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WO2023030501A1 - Anticorps capable de reconnaître de manière spécifique fcrn et son utilisation - Google Patents

Anticorps capable de reconnaître de manière spécifique fcrn et son utilisation Download PDF

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WO2023030501A1
WO2023030501A1 PCT/CN2022/116837 CN2022116837W WO2023030501A1 WO 2023030501 A1 WO2023030501 A1 WO 2023030501A1 CN 2022116837 W CN2022116837 W CN 2022116837W WO 2023030501 A1 WO2023030501 A1 WO 2023030501A1
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amino acid
seq
acid sequence
cdr2
cdr1
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PCT/CN2022/116837
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English (en)
Chinese (zh)
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张磊
张帅
晏丽
于茂荣
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舒泰神（北京）生物制药股份有限公司
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Priority to CN202280003350.6A priority Critical patent/CN116234827A/zh
Publication of WO2023030501A1 publication Critical patent/WO2023030501A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • the present invention relates to an antibody specifically recognizing neonatal Fc receptor (FcRn), its preparation method and use, including the method of using it to treat autoimmune disease and/or inflammatory disease.
  • FcRn neonatal Fc receptor
  • the neonatal Fc receptor (FcRn) is a major histocompatibility complex (MHC) class I-associated receptor.
  • MHC major histocompatibility complex
  • FcRn interacts with IgG class antibodies and binds to the constant region or Fc region of IgG. FcRn was originally found in the gut of neonatal rats.
  • FcRn plays an important role in regulating the dynamic behavior of IgG antibodies in vivo, including distribution, transport and persistence. The identification of these activities extended the role of FcRn well beyond its original role as a transporter of IgG from maternal to larvae, prompting extensive analysis of the molecular and cellular properties of FcRn. FcRn is widely expressed in parenchymal cells (endothelial cells, epithelial cells) and hematopoietic cells (Zhu, X. et al.
  • MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells .J.Immunol.166,3266–3276; Akilesh,S.et al.(2007) Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from metabolism.J.Immunol.179,4580–4588; Perez- Montoyo, H. et al. (2009) Conditional deletion of the MHC Class I-related receptor, FcRn, reveals the sites of IgG homeostasis in mice. Proc. Natl. Acad. Sci. U.S.A. 106, 2788–2793).
  • FcRn resides mainly in early acidic endosomes and binds to the Fc region of IgG in a pH-dependent manner: at pH 6.5 with micromolar to nanomolar affinity, whereas at physiological pH FcRn binds to Fc with very low affinity low and can be ignored.
  • FcRn regulates the concentration of serum IgG by binding to and protecting endocytosed monomeric IgG from degradation in the lysosomal compartment and by transporting IgG to the cell surface for neutralization. Released under extracellular physiological pH conditions. Through this mechanism, FcRn prolongs the half-life of IgG in serum; IgG not bound by FcRn enters the lysosomal pathway and is degraded (Raghavan, M.
  • FcRn binds not only the Fc region of IgG but also serum albumin (HSA). Like the binding of IgG, the binding of FcRn to HSA is also pH-dependent, and there is a binding effect in an acidic pH environment (usually less than pH 6, optimally pH 5), but not at neutral pH. The binding of FcRn to serum albumin can also protect HSA from being degraded, thereby prolonging the half-life of serum albumin.
  • HSA serum albumin
  • FcRn inhibitors a target for reducing the levels of symptom-causing antibodies in, for example, autoimmune or inflammatory diseases.
  • FcRn-deficient mice are more resistant to autoimmune diseases caused by pathogenic IgG autoantibodies because they cannot maintain high concentrations of pathogenic IgG (Christianson et al., 1996, J. Immunol. 156:4932-4939; Ghetie et al. , 1996, Eur. J. Immunol. 26:690-696; Israel et al., 1996, Immunol. 89:573-578).
  • FcRn-based inhibitors In nonhuman primates, studies and clinical trials of FcRn-based inhibitors have shown that they induce a sustained and significant decrease in endogenous IgG levels in healthy volunteers and are effective against the autoimmune disease muscular dystrophy. Positive effect (Nixon,A.E.et al.(2015)Fully human monoclonal antibody inhibitors of the neonatal Fc receptor reducing circulating IgG in non-human primates.Front.Immunol.6,176; Kiessling,P.et al.(2017)The FcRn inhibitor Rozanolixizumab reduces human serum IgG concentration: a randomized phase 1study.Sci.Transl.Med.9,eaan1208).
  • Anti-FcRn antibodies have been described in patents WO2014/19727, WO2015/71330. However, there remains a need for improved anti-FcRn antibodies.
  • an isolated anti-FcRn antibody comprising a heavy chain variable domain ( VH ) comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising TYSMN (SEQ ID NO:1); HC-CDR2, which comprises YISX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 is H or R, X 2 is G, K, R or S, X 3 is D or S, X 4 is I, K or L; and HC-CDR3, which comprises SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 is A, K, R or V, X 2 is A, I or V, X 3 is I, L or V; and a light chain variable domain (V L ), said V L comprising: a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX
  • an isolated anti-FcRn antibody comprising a VH comprising: HC- CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, said variant The body comprises a substitution of at most about 3 amino acids; HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 2-9 or a variant thereof, said variant comprising a substitution of at most about 3 amino acids; and HC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 10-17 or a variant thereof comprising a substitution of up to about 3 amino acids; and V L comprising: LC -CDR1, it comprises the amino acid sequence shown in any one of SEQ ID NOs:18-28 or its variant, and said variant comprises the substitution of at most about 3 amino acids; LC-CDR2, it comprises SEQ ID NO:29
  • the amino acid sequence shown in or its variant, described variant comprises the substitution of at most about 3 amino acids;
  • an isolated anti-FcRn antibody comprising: VH comprising HC- CDR1 comprised by VH as shown in any one of the amino acid sequences of SEQ ID NOs: 48-61, HC-CDR2 and HC-CDR3, and VL , said VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in VL as shown in any one of the amino acid sequences of SEQ ID NOs: 62-82.
  • an isolated anti-FcRn antibody comprising: (i) VH comprising HC-CDR1, HC-CDR2 and HC comprised by VH as shown in the amino acid sequence of SEQ ID NO:48 -CDR3; and V L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 contained in V L as shown in the amino acid sequence SEQ ID NO:62; (ii) V H , which comprises the amino acid sequence SEQ ID NO HC-CDR1, HC-CDR2 and HC-CDR3 contained in the V H shown in : 49; and V L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V H , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence SEQ ID NO:50; and V L , which comprises the amino acid sequence SEQ ID LC-CDR1,
  • an isolated anti-FcRn antibody comprising: (i) VH comprising: HC- CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:2, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:10, or variants of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and VL ,
  • the VL comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 18, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or The variant of the V L , comprising a substitution of up to about 5 amino acids in its LC-CDRs;
  • V H the V H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 1, HC- CDR2 comprising the amino acid sequence
  • HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11, or a variant of said VH comprising at most about 5 of its HC-CDRs amino acid substitutions; and a VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid Sequence SEQ ID NO: 31, or variants of said VL comprising up to about 5 amino acid substitutions in its LC-CDRs; (iv) VH comprising: HC- CDR1 comprising the amino acid sequence SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising in its HC-CDRs Substitutions of up to about 5 amino acids; and
  • HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or variants of said VH comprising at most about 5 of its HC-CDRs amino acid substitutions; and a VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid Sequence SEQ ID NO: 35, or variants of said V L comprising up to about 5 amino acid substitutions in its LC-CDRs; (viii) V H comprising: HC- CDR1 comprising the amino acid sequence SEQ ID NO: 1, HC-CDR2 , which comprises the amino acid sequence of SEQ ID NO: 6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs
  • any of the isolated anti-FcRn antibodies as described above comprising: V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 48-61 or a variant thereof, said variant Having at least about 80% sequence identity with the amino acid sequence shown in any of SEQ ID NOs: 48-61; and V L comprising the amino acid sequence shown in any of SEQ ID NOs: 62-82 or a variant thereof , the variant has at least about 80% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 62-82.
  • an isolated anti-FcRn antibody comprising: (i) a VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof having at least the amino acid sequence of SEQ ID NO: 48 about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 62; (ii) V H comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 49; and V L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:63; (iii) V H comprising the amino acid sequence SEQ ID NO:50 or a variant thereof, said variant Having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and V L comprising the amino
  • the isolated anti-FcRn antibody binds to human FcRn with a Kd value of 0.1 pM to 1 nM.
  • an isolated anti-FcRn antibody that competes with any of the isolated anti-FcRn antibodies described above for specific binding to FcRn.
  • an isolated anti-FcRn antibody is provided that specifically binds to the same epitope as any of the isolated anti-FcRn antibodies described above.
  • the isolated anti-FcRn antibody is a full length IgG antibody.
  • the isolated anti-FcRn antibody is a full length IgGl or IgG4 antibody.
  • the isolated anti-FcRn antibody is a chimeric, fully human or humanized antibody.
  • the isolated anti-FcRn antibody is an antigen-binding fragment selected from the group consisting of Fab, Fab', F(ab)' 2 , Fab'-SH, single chain Fv (scFv), Fv Fragments, dAbs, Fds, nanobodies, diabodies and linear antibodies.
  • an isolated nucleic acid molecule encoding any of the anti-FcRn antibodies described above is provided.
  • a vector comprising any one of the nucleic acid molecules described above.
  • a host cell comprising any of the above-mentioned anti-FcRn antibodies, any of the above-mentioned nucleic acid molecules, or any of the above-mentioned vectors.
  • a method for preparing an anti-FcRn antibody comprising: a) cultivating any one of the above-mentioned host cells under conditions capable of effectively expressing an anti-FcRn antibody; and b) obtaining the expressed anti-FcRn antibody from the host cell FcRn antibody.
  • a method of treating a disease or condition in an individual in need thereof comprising administering to said individual an effective amount of any one of the anti-FcRn antibodies described above.
  • use of any one of the anti-FcRn antibodies described above for the manufacture of a pharmaceutical composition for treating a disease or condition in an individual in need thereof.
  • use of any anti-FcRn antibody or a pharmaceutical composition comprising an anti-FcRn antibody as described above in the preparation of a medicament for treating a disease or disorder is provided.
  • the disease or disorder is associated with the FcRn signaling pathway, including an autoimmune disease or an inflammatory disease or disorder.
  • the disease or condition is selected from, for example, myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic Purpura, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus, type I or type II diabetes, multiple sclerosis, Raynaud's syndrome, autoimmune Immune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathy, experimental autoimmune encephalomyelitis, immune neutropenia, Juvenile-onset diabetes, immune responses associated with cytokines, T-lymphocyte
  • compositions, kits, and articles of manufacture comprising any of the anti-FcRn antibodies described above.
  • Figures 1A-1B show the binding affinities of exemplary anti-FcRn antibodies to different subunits FCGRT and B2M of human hFcRn analyzed by ELISA.
  • Figure 1A shows the binding affinities of exemplary anti-FcRn antibodies F02, F03, F14, F09 and F18 to the subunit FCGRT of human hFcRn analyzed by ELISA.
  • Figure IB shows the binding affinities of exemplary anti-FcRn antibodies F02, F03, F14, F09 and F18 to subunit B2M of human hFcRn analyzed by ELISA.
  • Figures 2A-2C show the cross-reactivity of exemplary anti-FcRn antibodies binding to different species of FcRn analyzed by ELISA.
  • Figure 2A shows the cross-reactivity of exemplary anti-FcRn antibodies F02, F03, F14, F09 and F18 for binding to cynomolgus monkey cyFcRn analyzed by ELISA.
  • Figure 2B shows the cross-reactivity of exemplary anti-FcRn antibodies F02, F03, F14, F09 and F18 for binding to rat rFcRn analyzed by ELISA.
  • Figure 2C shows the cross-reactivity of exemplary anti-FcRn antibodies F02, F03, F14, F09 and F18 for binding to mouse mFcRn analyzed by ELISA.
  • Figure 3 shows that exemplary anti-FcRn antibodies F02, F03, F14, F09 or F18 do not affect the content of HSA in cynomolgus monkeys.
  • FIG. 4 shows that exemplary anti-FcRn antibodies F02, F03, F14, F09, F18 and the control antibody Rozanolixizumab (UCB, anti-FcRn antibody) can rapidly reduce the IgG level in mice.
  • UB anti-FcRn antibody
  • the application provides anti-FcRn antibody molecules.
  • anti-FcRn antibody molecules Through a combination of natural yeast library screening, affinity maturation, and appropriately designed biochemical and biological experiments, highly effective antibody molecules capable of binding human FcRn and inhibiting the interaction of human FcRn with its receptors have been identified.
  • the results presented herein show that the antibodies of the present application proved to be even more effective or comparable to the known and widely used anti-FcRn antibody Rozanolixizumab (UCB) in various biological experiments.
  • UMB anti-FcRn antibody Rozanolixizumab
  • Anti-FcRn antibodies provided by the present application include, for example, full-length anti-FcRn antibodies, anti-FcRn single-chain antibodies (scFvs), anti-FcRn Fc fusion proteins, multispecific (such as bispecific) anti-FcRn antibodies, anti-FcRn immunoconjugates joints and whatnot.
  • the present application provides an anti-FcRn antibody comprising: a heavy chain variable domain ( VH ), said VH comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising TYSMN (SEQ ID NO:1); HC-CDR2, it comprises YISX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO:44), wherein X 1 is H or R, X 2 is G, K, R or S, X 3 is D or S, X 4 is I, K or L; and HC-CDR3, it comprises SWGX 1 X 2 GFDX 3 (SEQ ID NO:45), wherein X 1 is A, K, R or V, X 2 is A, I or V, X 3 is I, L or V; and a light chain variable domain (V L ), said V L comprising: a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X
  • nucleic acids encoding anti-FcRn antibodies are also provided.
  • compositions comprising anti-FcRn antibodies are also provided.
  • treatment is a method of obtaining a beneficial or desired result, including a clinical result.
  • the beneficial or desired clinical result Including, but not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, reducing the extent of the disease, stabilizing the disease (for example, preventing or delaying disease progression), preventing or delaying the spread of the disease (for example, metastasis) , preventing or delaying disease recurrence, delaying or slowing disease progression, improving disease state, remission of disease (partial or total), reducing dose of one or more other drugs needed to treat disease, delaying disease progression, improving or enhancing quality of life , increase body weight, and/or prolong survival.
  • treatment also includes the reduction of the pathological outcome of the disease.
  • the methods of the present application consider any one or more aspects of these treatments.
  • antibody includes full-length antibodies and antigen-binding fragments thereof.
  • Full-length antibodies include two heavy chains and two light chains.
  • the variable regions of the light and heavy chains are responsible for antigen binding.
  • the variable regions in both chains usually include 3 hypervariable loops called complementarity determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2 and LC-CDR3, heavy chain (HC ) CDRs include HC-CDR1, HC-CDR2 and HC-CDR3).
  • CDRs complementarity determining regions
  • the CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified by the Kabat, Chothia or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991).
  • the three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more conserved than the CDR regions and form a scaffold to support the hypervariable loops.
  • FRs flanking segments
  • the constant regions of the heavy and light chains are not involved in antigen binding, but exhibit various effector functions.
  • Antibodies are classified based on the amino acid sequence of the constant region of their heavy chains.
  • the five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG and IgM, characterized by heavy chains of the alpha, delta, epsilon, gamma and mu types, respectively.
  • major antibody classes are divided into subclasses such as IgG1 ( ⁇ 1 heavy chain), IgG2 ( ⁇ 2 heavy chain), IgG3 ( ⁇ 3 heavy chain), IgG4 ( ⁇ 4 heavy chain), IgA1 ( ⁇ 1 heavy chain) or IgA2 ( ⁇ 2 heavy chain).
  • antigen-binding fragment includes antibody fragments, for example, diabodies, Fab, Fab', F(ab') 2 , Fv fragments, disulfide bond-stabilized Fv fragments (dsFv), (dsFv) 2 , bispecific dsFv (dsFv-dsFv'), disulfide bond stabilized diabody (ds diabody), single chain Fv (scFv), scFv dimer (divalent diabody), Multispecific antibodies, single domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragments that are capable of binding to an antigen but do not contain the structure of a complete antibody, consisting of antibody fragments containing one or more CDRs .
  • an antigen-binding fragment is capable of binding the same antigen as a parent antibody or a fragment of a parent antibody (eg, a parent scFv).
  • Antigen-binding fragments also include fusion proteins comprising the antibody fragments described above.
  • an antigen-binding fragment may comprise one or more CDRs from a particular human antibody grafted into framework regions from one or more different human antibodies.
  • epitope refers to a specific atom or group of amino acids on an antigen to which an antibody or antibody portion binds. If two antibodies or antibody portions appear to compete for binding to an antigen, they likely bind the same epitope on the antigen.
  • the primary antibody when the first antibody inhibits the binding of the second antibody to the FcRn target by at least 50% (eg, at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%) at an equimolar concentration , 95%, 98%, or 99%), the primary antibody "competes" with the secondary antibody for binding to the FcRn target, and vice versa.
  • PCT publication WO 03/48731 describes a high-throughput antibody "epitope mapping" approach based on cross-competition.
  • the term “specifically binds”, “specifically recognizes” or “is specific for” refers to a measurable and reproducible interaction, for example binding of an antibody to a target can The presence of the target is determined in a heterogeneous population of molecules, including biomolecules.
  • the ability of an antibody to specifically recognize a certain target means that the antibody binds to the target with higher affinity, avidity, easier and/or longer duration than other targets.
  • an antibody that specifically recognizes an antigen reacts with one or more epitopes of the antigen with a binding affinity at least 10 times greater than its binding affinity for other targets.
  • an "isolated" anti-FcRn antibody refers to an anti-FcRn antibody that is (1) not related to a naturally occurring protein, (2) free of other proteins of the same origin, (3) produced from a different species expressed by cells of the genus, or (4) does not exist in nature.
  • isolated nucleic acid refers to nucleic acid of genomic, cDNA or synthetic origin or combinations thereof. According to its source, the "isolated nucleic acid” refers to (1) not related to all or part of the polynucleotide in the "isolated nucleic acid” found in nature, (2) may be associated with polynucleotides that are not associated with it in nature. The nucleotides are operably linked, or (3) do not occur in nature as part of a longer sequence.
  • CDR or "complementarity determining region” means the non-contiguous antigen binding sites found within the variable domains of heavy and light chain polypeptides.
  • CDR or "complementarity determining region” means the non-contiguous antigen binding sites found within the variable domains of heavy and light chain polypeptides.
  • Kabat et al. J.Biol.Chem.252:6609-6616 (1977); Kabat et al., U.S. Dept. of Health and Human Services, "Sequences of proteins of immunological interest” (1991); Chothia et al. al., J. Mol. Biol. 196:901-917 (1987); Al-Lazikani B. et al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J.
  • chimeric antibody means that a part of the heavy chain and/or light chain is identical or homologous to the corresponding sequence in an antibody from a specific species or belonging to a specific antibody class or subclass, and this (s) chain The remaining part is identical or homologous to the corresponding sequence in antibodies from another genus or belonging to other antibody classes or subclasses, and fragments of such antibodies, as long as they have the biological activity in this application ( See U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).
  • Fv is the smallest antibody fragment that contains the complete antigen recognition and binding site. This fragment is a dimer formed by tight non-covalent linkage of one heavy chain variable domain and one light chain variable domain. Six hypervariable loops (3 loops each in the light and heavy chains) are derived from the folding of these two domains, which provide the antibody with amino acid residues for binding to the antigen and endow the antibody with the antigen binding specificity. However, even a single variable domain (or half of an Fv fragment, which contains only the 3 CDRs specific for an antigen) has the ability to recognize and bind antigen, albeit with a lower affinity than the full binding site.
  • Single-chain Fv also abbreviated “sFv” or “scFv”
  • sFv is an antibody fragment comprising the VH and VL antibody domains linked into a single polypeptide chain.
  • the scFv polypeptide further includes a linking polypeptide between the VH and VL domains , which allows the scFv to form a desired structure for antigen binding.
  • diabody is a small antibody fragment prepared by constructing a scFv fragment (see the above paragraph) using a short linker (for example, 5-10 residues) between the VH and VL domains. This allows for interchain rather than intrachain pairing of the variable domains, resulting in a bivalent fragment, ie, a fragment with two antigen-binding sites.
  • Bispecific diabodies are heterodimers of two "crossover" scFv fragments in which the VH and VL domains of the two antibodies are located on different polypeptide chains.
  • Diabodies are fully described in EP 404,097; WO 93/11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).
  • Humanized forms of non-human (eg, rodent) antibodies are chimeric antibodies, which include minimal sequence derived from the non-human antibody.
  • humanized antibodies are human immunoglobulins (recipient antibodies) in which the hypervariable region (HVR) residues of the recipient antibody are derived from a non-human species such as mouse, rat, rabbit or Non-human mammalian hypervariable region residues with desired antibody specificity, affinity and performance are substituted (donor antibody).
  • HVR hypervariable region residues of the recipient antibody
  • donor antibody Non-human mammalian hypervariable region residues with desired antibody specificity, affinity and performance are substituted (donor antibody).
  • residues in the framework regions of the human immunoglobulin are replaced by corresponding non-human residues.
  • humanized antibodies can include residues that are found neither in the recipient antibody nor in the donor antibody. These modifications can further improve antibody performance.
  • a humanized antibody will comprise substantially all, at least one, and usually two variable domains in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin, and all or Essentially all framework regions are human immunoglobulin sequences.
  • the human antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
  • Fc immunoglobulin constant region
  • Percent amino acid sequence identity or “homology” of the polypeptide and antibody sequences identified herein is defined: a sequence comparison is made where conservative substitutions are considered to be part of the sequence identity, and the candidate sequence is Compare the percentage of identical amino acid residues in polypeptide sequences. Percent amino acid sequence identity can be determined by various alignment methods that are within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.
  • percent amino acid sequence identity values are calculated using the sequence alignment computer program MUSCLE (Edgar, R.C., Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, R.C., BMC Bioinformatics 5(1) :113,2004) generated.
  • Fc receptor or "FcR” is used to describe a receptor that binds the Fc region of an antibody.
  • the FcR described herein is an FcR that binds an IgG antibody (a gamma receptor), including receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants of these receptors and available into spliced form.
  • FcyRII receptors include FcyRIIA ("activating receptor") and FcyRIIB ("inhibiting receptor”), which have similar amino acid sequences and differ mainly in the cytoplasmic domain.
  • the cytoplasmic domain of the activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine activation motif (ITAM).
  • the cytoplasmic domain of the inhibitory receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine inhibition motif (ITIM) (see M.in Annu. Rev. Immunol. 15:203-234 (1997)).
  • ITAM immunoreceptor tyrosine activation motif
  • ITIM immunoreceptor tyrosine inhibition motif
  • FcR in this application encompasses other types of FcRs, including FcRs identified in the future.
  • FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the neonate (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994 )).
  • FcRn refers to the neonatal Fc receptor (FcRn).
  • FcRn is structurally similar to the major histocompatibility complex (MHC) and consists of an alpha chain non-covalently bound to beta2 microglobulin.
  • MHC major histocompatibility complex
  • FcRn plays an important role in the passive transport of immunoglobulin IgGs from mother to neonate and in the regulation of serum IgG levels.
  • FcRn acts as a salvage receptor that binds and transports endocytosed IgG in intact form within and between cells and saves them from undergoing the default degradation pathway.
  • the "CH1 domain" of the human IgG heavy chain constant region typically extends from amino acid 118 to amino acid 215 (EU numbering system).
  • a "hinge region” is generally defined as extending from Glu 216 to Pro 230 of human IgGl (Burton, Molec. Immunol. 22:161-206 (1985)). Hinge regions of other IgG isotypes can be aligned with the IgGl sequence by placing the first and last cysteine residues that form inter-heavy chain disulfide bonds in the same position as IgGl.
  • the "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340.
  • the CH2 domain is unique in that it is not tightly paired with another region, but instead has two N-terminally linked branched sugar chains inserted between the two CH2 domains of the intact native IgG molecule. It has been speculated that sugars may act as a surrogate for domain-to-domain pairing, helping to keep the CH2 domain stable. Burton, Molec. Immunol. 22:161-206 (1985).
  • a "CH3" domain includes a stretch within the Fc region from the C-terminal residue to the CH2 domain (from amino acid 341 to the C-terminus of the antibody sequence, usually amino acid residue 446 or 447 of IgG).
  • a “functional Fc fragment” has the "effector function” that a native Fc region sequence has.
  • exemplary “effector functions” include Clq binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; Such as B cell receptor; BCR) and so on.
  • effector functions typically require binding of the Fc region to a binding domain (eg, antibody variable region) and can be assessed using a variety of assays well known in the art.
  • Antibodies of IgG Fc variants having "altered" FcR binding affinity or ADCC activity have increased or decreased FcR binding activity and/or ADCC activity compared to a parent polypeptide or a polypeptide comprising a native Fc sequence.
  • An Fc variant exhibiting "enhanced binding" to an FcR has a higher binding affinity for at least one FcR (e.g., a lower apparent Kd or IC50 value) than the parental polypeptide or a polypeptide comprising a native IgG Fc sequence. ).
  • the binding ability is increased by 3 times, such as 5, 10, 25, 50, 60, 100, 150, 200, even up to 500 times or the binding ability is increased by 25% to 1000% compared with the parental polypeptide.
  • An Fc variant that exhibits "reduced binding" to an FcR has a lower affinity for at least one FcR (eg, a higher apparent Kd or IC50 value) than a parental polypeptide.
  • the binding ability is reduced by 40% or more compared to the parental polypeptide.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • cytotoxic cells such as natural killer cells (NK), neutrophils
  • FcRs Fc receptors
  • NK cells only express Fc ⁇ RIII
  • monocytes express Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII.
  • FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991).
  • an in vitro ADCC assay can be performed, as described in US Patent No. 5,500,362 or 5,821,337. Suitable effector cells for such experiments include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK).
  • PBMC peripheral blood mononuclear cells
  • NK natural killer cells
  • the ADCC activity of a molecule of interest can also be assessed in vivo, for example as described in animal models as disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).
  • the polypeptide of the antibody is substantially the same in number as the wild-type IgG Fc polypeptide (or parental polypeptide) in the experiment, it can mediate ADCC more effectively in vitro or in vivo.
  • Such variants are typically identified using any in vitro ADCC assay known in the art, eg, assays or methods for identifying ADCC activity, eg, in animal models and the like. In some embodiments, such variants mediate ADCC 5 to 100 fold more efficiently, eg 25 to 50 fold, compared to wild type Fc (or parental polypeptide).
  • “Complement-dependent cytotoxicity” or “CDC” refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (Clq) to antibodies (subclasses of appropriate structure) that bind cognate antigens.
  • Clq first component of the complement system
  • a CDC assay can be performed as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996).
  • Polypeptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding ability are described in US Patent No. 6,194,551B1 and WO99/51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).
  • nucleotide sequence encoding an amino acid sequence includes all nucleotide sequences that are mutually degenerate forms and encode the same amino acid sequence.
  • a nucleotide sequence encoding a protein or RNA may also include introns, eg, a nucleotide sequence encoding a protein may, in some forms, include introns.
  • operably linked refers to a functional linkage between a regulatory sequence and a heterologous nucleotide sequence such that the latter is expressed.
  • a first nucleotide sequence is operably linked to a second nucleotide sequence when the first nucleotide sequence is in a functional relationship with the second nucleotide sequence.
  • a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence.
  • operably linked DNA sequences are contiguous and, when necessary, join two protein coding regions in the same reading frame.
  • “Homologous” refers to sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same position in the two compared sequences is the same base or amino acid monomer subunit, for example, the same position in the two DNA molecules is adenine, then the two DNA molecules are homologous at this position.
  • the percent homology between two sequences is a function of the ratio of the number of matching or homologous positions shared by the two sequences to the total number of positions multiplied by 100. For example, if 6 out of 10 positions in two sequences are matched or homologous, then the homology of the two sequences is 60%. For example, the DNA sequences ATTGCC and TATGGC share 50% homology. Generally speaking, when comparing two sequences, the comparison is performed with the aim of obtaining the maximum homology.
  • an “effective amount” of an anti-FcRn antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose.
  • An “effective amount” can be determined empirically and by methods known in relation to the purpose.
  • a therapeutically effective amount refers to the amount of the anti-FcRn antibody or composition thereof disclosed herein that can effectively treat the individual's disease or symptom.
  • a therapeutically effective amount of an anti-FcRn antibody or a composition thereof is capable of reducing the binding of IgG Fc to FcRn; reducing the half-life of circulating IgG; reducing the concentration of serum IgG; inhibiting (i.e. to a certain extent slow down or preferably stop) the reaction of the patient's autoantibodies with host tissues; suppress (ie slow down or preferably stop to some extent) the response of immune effector T cells to endogenous peptides and the resulting tissue destruction.
  • the therapeutically effective amount is an FcRn blocking amount that induces the breakdown of overall pathogenic antibodies and the clearance of multiple pathogenic antibodies.
  • a therapeutically effective amount refers to an amount that can prolong the survival of a patient.
  • a therapeutically effective amount refers to an amount that can improve the progression-free survival of a patient.
  • pharmaceutically acceptable refers to a material that has no biological activity or other undesired properties, for example, the material can be added to a pharmaceutical composition administered to a patient, and Does not cause significant adverse biological reactions, or interact in a deleterious manner with any other components contained in the composition.
  • Pharmaceutically acceptable carriers or excipients preferably meet the required criteria for toxicology or manufacturing testing and/or are included in the inactive ingredient guidelines prepared by the US Food and Drug Administration.
  • Embodiments of the application described herein are to be understood to include “consisting of” and/or “consisting essentially of” embodiments.
  • reference to "not" a value or parameter generally means and describes "other than” a value or parameter.
  • the method cannot be used to treat type X cancer, meaning that the method is usually used to treat other types of cancer than type X cancer.
  • the present application provides an anti-human or/and cynomolgus monkey FcRn antibody that specifically binds to FcRn.
  • the anti-FcRn antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy and/or light chain CDRs described herein.
  • the application provides an isolated antibody that binds to FcRn.
  • Contemplated anti-FcRn antibodies include, for example, full-length anti-FcRn antibodies (e.g., full-length IgGl or IgG4), anti-FcRn single-chain antibodies, anti-FcRn Fc fusion proteins, multispecific (e.g., bispecific) anti-FcRn antibodies, anti-FcRn Immunoconjugates, and whatnot.
  • the anti-FcRn antibody is a full-length antibody (eg, full-length IgGl or IgG4) or an antigen-binding fragment thereof that specifically binds FcRn.
  • the anti-FcRn antibody is Fab, Fab', F(ab)' 2 , Fab'-SH, single chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody (diabody) or linear antibody.
  • an antibody that specifically binds to FcRn refers to an antibody that binds to FcRn with an affinity at least 10 times that of a non-target binding affinity (including, for example, 10, 10 2 , 10 3 , 10 4 , 10 5 , 10 6 , or 10 7 times).
  • non-target refers to an antigen that is not FcRn.
  • Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis or radioimmunoprecipitation analysis (RIA).
  • Kd values can be determined by methods known in the art, such as surface plasmon resonance (SPR) techniques or biolayer interferometry (BLI).
  • non-human anti-FcRn antibodies comprising human sequences (eg, human heavy and light chain variable domains comprising human CDR sequences) are broadly discussed herein, non-human anti-FcRn antibodies are also contemplated.
  • the non-human anti-FcRn antibody comprises the human CDR sequences and non-human framework region sequences of the anti-FcRn antibodies described herein, and in some embodiments, the non-human framework region sequences comprise any of the human CDR sequences for use as described herein.
  • non-human anti-FcRn antibodies include anti-FcRn antibodies produced by grafting one or more human CDR sequences described herein into non-human framework regions (eg, murine or chicken framework region sequences).
  • the complete amino acid sequence of an exemplary human FcRn alpha chain comprises or consists of the amino acid sequence shown in SEQ ID NO:87.
  • the ⁇ 2-microglobulin (B2M) amino acid sequence of an exemplary human FcRn chain comprises or consists of the amino acid sequence set forth in SEQ ID NO:88.
  • an anti-FcRn antibody described herein specifically recognizes an epitope in human FcRn.
  • the anti-FcRn antibody cross-reacts with FcRn of a species other than human.
  • the anti-FcRn antibody is fully specific for human FcRn and does not cross-react with other non-human species.
  • the anti-FcRn antibody cross-reacts with at least one allelic variant of the FcRn protein (or fragment thereof).
  • the allelic variant has at most 30 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 , 15, 20, 25 or 30) amino acid substitutions (eg conservative substitutions).
  • the anti-FcRn antibody does not cross-react with any allelic variant of the FcRn protein (or fragment thereof).
  • the anti-FcRn antibody cross-reacts with at least one interspecies variant of the FcRn protein.
  • the FcRn protein (or fragment thereof) is human FcRn
  • the interspecies variant of the FcRn protein (or fragment thereof) is a variant in cynomolgus monkeys.
  • the anti-FcRn antibody does not cross-react with any interspecies variants of the FcRn protein.
  • any anti-FcRn antibody described herein comprising an antibody heavy chain constant region and an antibody light chain constant region.
  • the anti-FcRn antibody comprises an IgG1 heavy chain constant region.
  • the anti-FcRn antibody comprises an IgG2 heavy chain constant region.
  • the anti-FcRn antibody comprises an IgG3 type heavy chain constant region.
  • the anti-FcRn antibody comprises an IgG4 type heavy chain constant region.
  • the heavy chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 83.
  • the heavy chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 84.
  • the anti-FcRn antibody comprises a kappa light chain constant region.
  • the light chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 85.
  • the anti-FcRn antibody comprises a lambda light chain constant region.
  • the light chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 86.
  • the anti-FcRn antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.
  • the anti-FcRn antibody comprises a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising TYSMN (SEQ ID NO: 1); HC-CDR2, which comprises YISX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 is H or R, X 2 is G, K, R or S, X 3 is D or S, X 4 is I, K or L; and HC-CDR3, which comprises SWGX 1 X 2 GFDX 3 (SEQ ID NO: 45), wherein X 1 is A, K, R or V, X 2 is A, I or V, X 3 is I, L or V; and a light chain variable domain (V L ), said V L comprising: light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLX 1 X 2 X 3 X 4 GX 5 NYLD (SEQ ID NO
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any of SEQ ID NOs: 2-9 or a variant thereof comprising up to about 3 ( Such as 1, 2 or 3) amino acid substitutions; and HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 10-17 or a variant thereof comprising up to about 3 (eg 1, 2 or 3) amino acid substitutions.
  • the anti-FcRn antibody comprises VH , and the VH comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, HC-CDR2 comprising SEQ ID NOs: 2- The amino acid sequence shown in any one of 9, HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 10-17.
  • the anti-FcRn antibody comprises a V L comprising: LC- CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 18-28 or a variant thereof, the variant The body comprises at most about 3 (such as 1, 2 or 3) amino acid substitutions; LC-CDR2, it comprises the aminoacid sequence shown in SEQ ID NO:29 or its variant, and described variant comprises at most about 3 ( For example, 1, 2 or 3) amino acid substitutions; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 30-43 or a variant thereof comprising up to about 3 (eg 1, 2 or 3) amino acid substitutions.
  • the anti-FcRn antibody comprises a V L comprising: LC- CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 18-28, LC-CDR2 comprising SEQ ID NOs: The amino acid sequence shown in ID NO:29, LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:30-43.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; HC-CDR2 comprising the amino acid sequence shown in any of SEQ ID NOs: 2-9 or a variant thereof comprising up to about 3 ( Such as 1, 2 or 3) amino acid substitutions; and HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 10-17 or a variant thereof comprising up to about 3 (eg 1, 2 or 3) amino acid substitutions; and V L , said V L comprising: LC-CDR1 comprising the amino acid sequence shown in any of SEQ ID NOs: 18-28 or a variant thereof, said variant
  • the body comprises at most about 3 (such as 1, 2 or 3) amino acid substitutions; LC-CDR2, it comprises the aminoacid sequence shown in SEQ ID NO:29 or its variant, and described variant comprises
  • the anti-FcRn antibody comprises VH , and the VH comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, HC-CDR2 comprising SEQ ID NOs: 2- The amino acid sequence shown in any one of 9, and HC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:10-17; And V L , said V L comprises: LC-CDR1, it comprises SEQ ID NOs: The amino acid sequence shown in any one of ID NOs:18-28, LC-CDR2, it comprises the aminoacid sequence shown in SEQ ID NO:29, and LC-CDR3, it comprises any one in SEQ ID NOs:30-43 The amino acid sequence shown.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 2, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 30, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 18, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:30.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:31.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 11, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:31.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 32, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:32.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 33, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 20, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:33.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:34.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 35, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:35.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 36, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 18, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:36.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 37, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 38, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:38.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 13, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 39, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:39.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 14, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 40, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 24, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:40.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 15, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 25, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 35, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 15; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:35.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 11, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:31.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 26, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 33, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 26, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:33.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 32, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:32.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 7, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 37, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 41, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:41.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 42, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 27, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 42, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 27, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 28, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 37, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 28, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 43, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 14, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 40, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:40.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or a variant of said V L , whose LC- CDRs contain up to about 5 amino acid substitutions.
  • the anti-FcRn antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:34.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC- CDR3; and VL , said VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in VL as shown in any one of the amino acid sequences of SEQ ID NOs: 62-82.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 48; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:62.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 49; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:50; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:64.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 52; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 53; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:67.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:54; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:68.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:54; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:69.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:70.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:55; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:71.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:56; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:72.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:57; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:73.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 58; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:74.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 52; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:75.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 59; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:76.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:77.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 52; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:78.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 52; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:79.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:80.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 60; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:81.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:56; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:82.
  • the anti-FcRn antibody comprises a VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO: 61; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibody comprises: V H , the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 48-61 or a variant thereof, and the variant is identical to SEQ ID NOs:
  • the amino acid sequences shown in any of 48-61 have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity
  • VL the V L comprises the amino acid sequence shown in any of SEQ ID NOs: 62-82 or a variant thereof, and the variant has at least about 80 amino acid sequences shown in any of SEQ ID NOs: 62-82 % (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence shown in any one of SEQ ID NOs:48-61, and a VL comprising SEQ ID NOs:62 The amino acid sequence shown in any one of -82.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof having at least about 80% the amino acid sequence of SEQ ID NO: 48 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 62 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:62.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:48, and a VL comprising the amino acid sequence of SEQ ID NO:62.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 49 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:49, and a VL comprising the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 50 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:50, and a VL comprising the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80% the amino acid sequence of SEQ ID NO:51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:64.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:64.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 52 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:65.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:52, and a VL comprising the amino acid sequence of SEQ ID NO:65.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80% the amino acid sequence of SEQ ID NO:51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 53 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 67 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:67.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:53, and a VL comprising the amino acid sequence of SEQ ID NO:67.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:54 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO:54 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:68.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:54, and a VL comprising the amino acid sequence of SEQ ID NO:68.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:54 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO:54 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:69.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:54, and a VL comprising the amino acid sequence of SEQ ID NO:69.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80% the amino acid sequence of SEQ ID NO:51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:70.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:70.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 55 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:71.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:55, and a VL comprising the amino acid sequence of SEQ ID NO:71.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 56 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:72.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:56, and a VL comprising the amino acid sequence of SEQ ID NO:72.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 57 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:73.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:57, and a VL comprising the amino acid sequence of SEQ ID NO:73.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 58 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:58, and a VL comprising the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80% the amino acid sequence of SEQ ID NO:51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:74.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:74.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 52 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:75.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:52, and a VL comprising the amino acid sequence of SEQ ID NO:75.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 59 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:76.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:59, and a VL comprising the amino acid sequence of SEQ ID NO:76.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:77.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:77.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:52, or a variant thereof having at least about 80% the amino acid sequence of SEQ ID NO:52 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:78.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:52, and a VL comprising the amino acid sequence of SEQ ID NO:78.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 52 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:79.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:52, and a VL comprising the amino acid sequence of SEQ ID NO:79.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:80.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:80.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 60 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 81 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:81.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:60, and a VL comprising the amino acid sequence of SEQ ID NO:81.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 56 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 82 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:82.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:56, and a VL comprising the amino acid sequence of SEQ ID NO:82.
  • the anti-FcRn antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 61 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:61, and a VL comprising the amino acid sequence of SEQ ID NO:66.
  • amino acid substitutions described above are limited to the "exemplary substitutions” shown in Table 4 herein. In some embodiments, amino acid substitutions are limited to the "preferred substitutions” shown in Table 4 herein.
  • functional epitopes can be resolved by combined alanine scanning methods.
  • combinatorial alanine scanning techniques can be used to identify amino acids in FcRn proteins that are essential for interaction with anti-FcRn antibodies.
  • the epitope is conformational, and the crystal structure of an anti-FcRn antibody bound to an FcRn protein can be used to identify the epitope.
  • the application provides antibodies that compete for binding to FcRn with any of the anti-FcRn antibodies described herein.
  • antibodies are provided that compete with any of the anti-FcRn antibodies described herein for binding to an epitope on FcRn.
  • anti-FcRn antibodies are provided that bind to the same epitope as an anti-FcRn antibody molecule comprising a VH and a VL , wherein the VH comprises amino acids set forth in any one of SEQ ID NOs: 48-61 sequence, and the V L comprises the amino acid sequence shown in any of SEQ ID NOs:62-82.
  • an anti-FcRn antibody that competes for binding to FcRn with an anti-FcRn antibody comprising a VH and a VL , wherein the VH comprises the amino acid sequence set forth in any one of SEQ ID NOs: 48-61 , and the V L comprises the amino acid sequence shown in any one of SEQ ID NOs:62-82.
  • competition assays can be used to identify monoclonal antibodies that compete for binding to FcRn with the anti-FcRn antibodies described herein. Competition experiments can determine whether two antibodies bind to the same epitope by recognizing identical or spatially overlapping epitopes or by one antibody competitively inhibiting binding of the other antibody to the antigen. In certain embodiments, such competing antibodies bind to the same epitope as the antibodies described herein.
  • Some exemplary competition assays include, but are not limited to, conventional assays as mentioned in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.).
  • each antibody is said to bind the same epitope if it blocks 50% or more of the binding of the other antibody.
  • antibodies that compete with the anti-FcRn antibodies described herein are chimeric, humanized, or fully human antibodies.
  • Exemplary anti-FcRn antibody sequences are shown in Table 2 and Table 3, wherein the CDRs are numbered according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms for predicting the location of CDRs and defining antibody light and heavy chain variable regions. Also within the scope of this application are antibodies comprising the CDRs, VH and/or VL sequences of antibodies as described herein, but based on prediction algorithms other than those exemplified in the table below.
  • the neonatal Fc receptor is a major histocompatibility complex (MHC) class I-associated receptor.
  • MHC major histocompatibility complex
  • FcRn interacts with IgG class antibodies and binds to the constant region or Fc region of IgG.
  • FcRn was initially identified as a transporter of IgG from mother to neonate (Leach et al., J. Immunol, 157:3317, 1996), and plays an important role in neonatal life.
  • FcRn is widely expressed in parenchymal cells (endothelial cells, epithelial cells) and hematopoietic cells. FcRn resides mainly in early acidic endosomes and binds to the Fc region of IgG in a pH-dependent manner: at pH 6.5 with micromolar to nanomolar affinity, whereas at physiological pH FcRn binds to Fc with very low affinity Weak and can be ignored. FcRn regulates the concentration of serum IgG by binding to and protecting endocytosed monomeric IgG from degradation in the lysosomal compartment and by transporting IgG to the cell surface for neutralization.
  • FcRn prolongs the half-life of IgG in serum; IgG not bound by FcRn enters the lysosomal pathway and is degraded.
  • FcRn-deficient mice are more resistant to autoimmune diseases caused by pathogenic IgG autoantibodies because they cannot maintain high concentrations of pathogenic IgG (Christianson et al., 1996, J. Immunol. 156:4932-4939; Ghetie et al. , 1996, Eur. J. Immunol. 26:690-696; Israel et al., 1996, Immunol. 89:573-578).
  • the anti-FcRn antibody is a full length anti-FcRn antibody.
  • the full length anti-FcRn antibody is IgA, IgD, IgE, IgG or IgM.
  • the full-length anti-FcRn antibody comprises an IgG constant region, such as the constant region of IgGl, IgG2, IgG3, IgG4, or variants thereof.
  • the full length anti-FcRn antibody comprises a lambda light chain constant region.
  • the full length anti-FcRn antibody comprises a kappa light chain constant region.
  • the full length anti-FcRn antibody is a full length human anti-FcRn antibody. In some embodiments, the full length anti-FcRn antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-FcRn antibody comprises an Fc sequence that has been altered or otherwise altered such that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity The effector function of action (CDC).
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • CDC complement-dependent cytotoxicity The effector function of action
  • a full length anti-FcRn antibody comprising an IgG1 constant region that specifically binds to FcRn.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG2 constant region that specifically binds to FcRn is provided.
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG3 constant region that specifically binds to FcRn is provided.
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region that specifically binds to FcRn is provided.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, said variant comprising at most about 3 (such as 1, 2 or 3) amino acid substitutions; HC-CDR2, which comprises SEQ ID NOs: The amino acid sequence shown in any of 2-9, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising SEQ ID NOs: 10 - the amino acid sequence shown in any one of 17 or a variant thereof, said variant comprising a substitution of up to about 3 (eg 1, 2 or 3) amino acids; and b) a light chain variable domain, said light chain variable domain
  • the chain variable domain comprises: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG2 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, said variant comprising at most about 3 (such as 1, 2 or 3) amino acid substitutions; HC-CDR2, which comprises SEQ ID NOs: The amino acid sequence shown in any of 2-9, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising SEQ ID NOs: 10 - the amino acid sequence shown in any one of 17 or a variant thereof, said variant comprising a substitution of up to about 3 (eg 1, 2 or 3) amino acids; and b) a light chain variable domain, said light chain variable domain
  • the chain variable domain comprises: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG3 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions, HC-CDR2 comprising SEQ ID NOs: The amino acid sequence shown in any of 2-9, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising SEQ ID NOs: 10 - the amino acid sequence shown in any one of 17 or a variant thereof, said variant comprising a substitution of up to about 3 (eg 1, 2 or 3) amino acids; and b) a light chain variable domain, said light chain variable domain
  • the chain variable domain comprises: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, said variant comprising at most about 3 (such as 1, 2 or 3) amino acid substitutions; HC-CDR2, which comprises SEQ ID NOs: The amino acid sequence shown in any of 2-9, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising SEQ ID NOs: 10 - the amino acid sequence shown in any one of 17 or a variant thereof, said variant comprising a substitution of up to about 3 (eg 1, 2 or 3) amino acids; and b) a light chain variable domain, said light chain variable domain
  • the chain variable domain comprises: LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:2-9, and HC-CDR3, which comprises SEQ ID NOs:10-17 Any one of the amino acid sequences shown, or a variant of the heavy chain variable domain, comprising up to about 5 (eg 1, 2, 3, 4 or 5) amino acid substitutions in its HC-CDR sequence; And b) light chain variable domain, said light chain variable domain comprises: LC-CDR1, it comprises the amino acid sequence shown in any one of SEQ ID NOs:18-28, LC-CDR2, it comprises SEQ ID The amino acid sequence shown in NO:29, and LC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises a) a heavy chain variable domain comprising: HC-CDR1, It comprises the amino acid sequence shown in SEQ ID NO:1, HC-CDR2, it comprises the amino acid sequence shown in any one of SEQ ID NOs:2-9, and HC-CDR3, it comprises SEQ ID NOs:10-17 Any of the amino acid sequences shown, or variants of said heavy chain variable domain, comprising up to about 5 (e.g., 1, 2, 3, 4 or 5) amino acid substitutions in the HC-CDR sequence; and B) light chain variable domain, said light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any one of SEQ ID NOs:18-28, LC-CDR2, comprises SEQ ID NO: The amino acid sequence shown in 29, and LC-CDR3, it comprises the aminoacid sequence shown in any one of SEQ ID NOs:30
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:2-9, and HC-CDR3, which comprises SEQ ID NOs:10-17
  • HC-CDR1 which comprises the amino acid sequence shown in SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:2-9, and HC-CDR3, which comprises SEQ ID NOs:10-17
  • b) light chain variable domain, described light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any of SEQ ID NOs:18-28 , LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:29, and LC-CDR
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:2-9, and HC-CDR3, which comprises SEQ ID NOs:10-17
  • HC-CDR1 which comprises the amino acid sequence shown in SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:2-9, and HC-CDR3, which comprises SEQ ID NOs:10-17
  • b) light chain variable domain, described light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any of SEQ ID NOs:18-28 , LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:29, and LC-CDR
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 2, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :30.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :31.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 4, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 11; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :31.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :32.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :33.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :34.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :35.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :36.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :37.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :38.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 13; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :39.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:14; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :40.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 15; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :35.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:11; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :31.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:26, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :33.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :32.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:7, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :37.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :41.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :42.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:27, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :42.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:28, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :37.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 8, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 16; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :43.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:14; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :40.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG1 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:9, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:17; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :34.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 2, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :30.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :31.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 4, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 11; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :31.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :32.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :33.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :34.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :35.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :36.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :37.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :38.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 13; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :39.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:14; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :40.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 15; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :35.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:11; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :31.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:26, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :33.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :32.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:7, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :37.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :41.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :42.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 12; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:27, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :42.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 10; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:28, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :37.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 8, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 16; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :43.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:3, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:14; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :40.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full length anti-FcRn antibody comprising an IgG4 constant region
  • said anti-FcRn antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:9, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:17; and b) a light chain variable domain
  • the light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :34.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: a heavy chain variable domain ( VH ), said VH comprising SEQ ID NOs: 48-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 48-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V L ), said V L comprising the amino acid sequence shown in any of SEQ ID NOs:62-82 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-82 , 98% or 99%) sequence identity.
  • VH heavy chain variable domain
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG2 constant region
  • the anti-FcRn antibody comprises: a heavy chain variable domain ( VH ), said VH comprising SEQ ID NOs: 48-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 48-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V L ), said V L comprising the amino acid sequence shown in any of SEQ ID NOs:62-82 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-82 , 98% or 99%) sequence identity.
  • VH heavy chain variable domain
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG3 constant region
  • the anti-FcRn antibody comprises: a heavy chain variable domain ( VH ), said VH comprising SEQ ID NOs: 48-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 48-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V L ), said V L comprising the amino acid sequence shown in any of SEQ ID NOs:62-82 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-82 , 98% or 99%) sequence identity.
  • VH heavy chain variable domain
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: a heavy chain variable domain ( VH ), said VH comprising SEQ ID NOs: 48-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 48-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V L ), said V L comprising the amino acid sequence shown in any of SEQ ID NOs:62-82 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-82 , 98% or 99%) sequence identity.
  • VH heavy chain variable domain
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: a heavy chain variable domain ( VH ), said VH comprising SEQ ID NOs: 48-61 Any of the amino acid sequences shown, and a light chain variable domain (V L ), said V L comprising the amino acid sequence shown in any of SEQ ID NOs: 62-82.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: a heavy chain variable domain ( VH ), said VH comprising SEQ ID NOs: 48-61 Any of the amino acid sequences shown, and a light chain variable domain (V L ), said V L comprising any of the amino acid sequences shown in SEQ ID NOs: 62-82.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:48 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:62 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:62 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 49 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 50 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 51 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 64 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:65 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:53 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:67 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:54 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:68 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:54 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:69 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:70 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:55 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:71 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:56 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:72 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:73 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:73 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:63 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:74 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:75 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:76 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:80 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:80 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:81 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:56 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:82 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:82 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG1 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:66 identity.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:48 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:62 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 49 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 50 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 51 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 64 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:65 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:53 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:67 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:54 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:68 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:54 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:69 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:70 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:55 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:71 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:56 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:72 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:73 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:73 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:63 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:74 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:75 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:76 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 52 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO: 78 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:80 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:80 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and V L , it comprises the amino acid sequence of SEQ ID NO:81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:81 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:56 has at least about 80% sequence identity; and VL , it comprises the amino acid sequence of SEQ ID NO:82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:82 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a full-length anti-FcRn antibody comprising an IgG4 constant region
  • the anti-FcRn antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and V L comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66 identity.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • Binding affinity is expressed as Kd, Koff, Kon or Ka.
  • Koff refers to the rate constant for dissociation of an antibody from an antigen/antibody complex, as determined by a kinetic selective device.
  • Kon refers to the association rate constant for the binding of an antibody to an antigen to form an antigen/antibody complex.
  • the equilibrium dissociation constant Kd used herein refers to the dissociation constant when a specific antibody-antigen interacts, and refers to the antigen concentration required when the antigen occupies half of all antibody binding sites and reaches equilibrium in the antibody molecule solution, which is equal to Koff /Kon. The determination of Kd assumes that all bound molecules are in solution.
  • the corresponding equilibrium dissociation rate constant is expressed in terms of EC50 , which is a good approximation of Kd.
  • the affinity association constant Ka is the reciprocal of the dissociation constant Kd.
  • the dissociation constant (Kd) can be used as an indicator of the affinity of the antibody moiety for the antigen.
  • simple analysis can be performed by the Scatchard method using antibodies labeled with various markers, and a Biacore instrument (manufactured by Amersham Biosciences), and the interaction between biomolecules can be analyzed by surface plasmon resonance according to the user's manual or the attached kit .
  • Kd values obtained using these methods are expressed in units of M.
  • Antibodies that specifically bind to a target may have, for example, ⁇ 10 -7 M, ⁇ 10 -8 M, ⁇ 10 -9 M, ⁇ 10 -10 M, ⁇ 10 - 11 M, ⁇ 10 -12 M, or ⁇ 10 - Kd value of 13M .
  • the binding specificity of an antibody can be determined experimentally by methods known in the art. These methods include, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore tests, and peptide scans, among others.
  • the anti-FcRn antibody specifically binds an FcRn target with a Kd value of 10 ⁇ 7 M to 10 ⁇ 13 M (e.g., 10 ⁇ 7 M to 10 ⁇ 13 M, 10 ⁇ 8 M to 10 ⁇ 13 M, 10 -9 M to 10 -13 M or 10 -10 M to 10 - 12 M).
  • the Kd value of the binding between the anti-FcRn antibody and FcRn is 10 ⁇ 7 M to 10 ⁇ 13 M, 1 ⁇ 10 ⁇ 7 M to 5 ⁇ 10 ⁇ 13 M, 10 ⁇ 7 M to 10 -12 M, 10 -7 M to 10 -11 M, 10 -7 M to 10 - 10 M, 10 -7 M to 10 -9 M, 10 -8 M to 10 -13 M, 1 ⁇ 10 -8 M to 5 ⁇ 10 -13 M, 10 -8 M to 10 -12 M, 10 -8 M to 10 -11 M, 10 -8 M to 10 -10 M, 10 -8 M to 10 -9 M, 5 ⁇ 10-9 M to 1 ⁇ 10-13 M, 5 ⁇ 10-9 M to 1 ⁇ 10-12 M, 5 ⁇ 10-9 M to 1 ⁇ 10-11 M, 5 ⁇ 10-9 M to 1 ⁇ 10 -10 M, 10 -9 M to 10 -13 M, 10 -9 M to 10 -12 M, 10 -9 M to 10 -11 M, 10 -9 M to 10 -10 M, 5 ⁇
  • the Kd value for the binding of the anti-FcRn antibody to a non-target is higher than the Kd value of the anti-FcRn antibody to the target, and in some embodiments cited herein, the Kd value of the anti-FcRn antibody to the target (e.g., FcRn)
  • the binding affinity is higher than that of anti-FcRn antibodies to non-targets.
  • non-target refers to an antigen other than FcRn.
  • the Kd value of the anti-FcRn antibody (for FcRn) binding to a non-FcRn target differs by at least 10 times, such as 10-100 times, 100-1000 times, 10 3 -10 4 times, 10 4 -10 5 times, 10 5 -10 6 times, 10 6 -10 7 times, 10 7 -10 8 times, 10 8 -10 9 times , 10 9 -10 10 times, 10 10 -10 11 times, 10 11 -10 12 times .
  • the non-target binding Kd value of the anti-FcRn antibody is 10 ⁇ 1 M to 10 ⁇ 6 M (for example, 10 ⁇ 1 M to 10 ⁇ 6 M, 10 ⁇ 1 M to 10 ⁇ 5 M, 10 -2 M to 10 -4 M).
  • the non-target refers to an antigen other than FcRn.
  • the Kd value for binding between an anti-FcRn antibody and a non-FcRn target is 10 ⁇ 1 M to 10 ⁇ 6 M, 1 ⁇ 10 ⁇ 1 M to 5 ⁇ 10 ⁇ 6 M, 10 ⁇ 1 M to 10 -5 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -5 M, 10 -1 M to 10 -4 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -4 M, 10 -1 M to 10 -3 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -3 M, 10 -1 M to 10 -2 M, 10 -2 M to 10 -6 M, 1 ⁇ 10 -2 M to 5 ⁇ 10 -6 M, 10 -2 M to 10 -5 M, 1 ⁇ 10 -2 M to 5 ⁇ 10 -5 M, 10 -2 M to 10 -4 M, 1 ⁇ 10 -2 M to 5 ⁇ 10 -4 M, 10 -2 M to 10 -3 M, 10 -3 M to 10 -6 M, 1 ⁇ 10 -3 M to 5 ⁇ 10 -6 M, 10 -3 M to 10 -6 M, 1
  • an anti-FcRn antibody when an anti-FcRn antibody specifically recognizes an FcRn target with high binding affinity and binds a non-target with low binding affinity, the anti-FcRn antibody binds to an FcRn target with a Kd value of 10 ⁇ 7 M to 10 -13 M (for example, 10 -7 M to 10 -13 M, 10 -8 M to 10 -13 M, 10 -9 M to 10 -13 M, 10 -10 M to 10 -12 M), and with The Kd value for non-target binding is 10 ⁇ 1 M to 10 ⁇ 6 M (eg, 10 ⁇ 1 M to 10 ⁇ 6 M, 10 ⁇ 1 M to 10 ⁇ 5 M, 10 ⁇ 2 M to 10 ⁇ 4 M).
  • a Kd value for non-target binding is 10 ⁇ 1 M to 10 ⁇ 6 M (eg, 10 ⁇ 1 M to 10 ⁇ 6 M, 10 ⁇ 1 M to 10 ⁇ 5 M, 10 ⁇ 2 M to 10 ⁇ 4 M).
  • the binding affinity of the anti-FcRn antibody is compared to the binding affinity of a control anti-FcRn antibody (eg, Rozanolixizumab).
  • the Kd value of the binding between the control anti-FcRn antibody and FcRn may be at least 2 times, such as 2 times, 3 times, 4 times, the Kd value of the binding between the anti-FcRn antibody described herein and FcRn , 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 10-100 times, 100-1000 times, 10 3 -10 4 times.
  • nucleic acid molecules encoding anti-FcRn antibodies are also contemplated.
  • a nucleic acid (or set) encoding a full-length anti-FcRn antibody is provided, including any one of the full-length anti-FcRn antibodies described herein.
  • the nucleic acid (or a set of nucleic acids) of the anti-FcRn antibody described herein may also include a nucleic acid sequence encoding a polypeptide tag (eg, protein purification tag, His tag, HA tag).
  • an isolated host cell comprising an anti-FcRn antibody, an isolated nucleic acid encoding an anti-FcRn antibody polypeptide component, or a vector comprising a nucleic acid encoding an anti-FcRn antibody polypeptide component described herein.
  • a variant includes a nucleotide sequence that hybridizes to a nucleic acid sequence encoding an anti-FcRn antibody of the present application at least under moderately stringent hybridization conditions.
  • the present application also provides a vector into which the nucleic acid sequence of the present application can be inserted.
  • a natural or synthetic nucleic acid encoding an anti-FcRn antibody is inserted into a suitable expression vector such that the nucleic acid is operably linked to 5' and 3' regulatory elements, including, for example, promoters (e.g., lymphocyte-specific promoter) and 3' untranslated region (UTR), can express anti-FcRn antibody (such as full-length anti-FcRn antibody).
  • promoters e.g., lymphocyte-specific promoter
  • UTR 3' untranslated region
  • the vectors are suitable for replication and integration in eukaryotic host cells.
  • Typical cloning and expression vectors contain transcriptional and translational terminators, initiation sequences and promoters to regulate the expression of the nucleic acid sequence of interest.
  • nucleic acids described herein can also be used in nucleic acid immunization and gene therapy by using standard gene delivery protocols. Methods of nucleic acid delivery are known in the art. See, eg, U.S. Pat. Nos. 5,399,346, 5,580,859, 5,589,466, the entire contents of which are incorporated herein by reference. In some embodiments, the present application also provides gene therapy vectors.
  • Nucleic acids can be cloned into many types of vectors.
  • nucleic acids can be cloned into vectors including, but not limited to, plasmids, phagemids, phage derivatives, animal viruses, and cosmids.
  • Vectors of particular interest include expression vectors, replication vectors, probe generation vectors and sequencing vectors.
  • expression vectors can be provided to cells in the form of viral vectors.
  • Viral vector technology is well known in the art and described, for example, in Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), among other virology or molecular biology manuals.
  • Viruses that can be used as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses.
  • suitable vectors include an origin of replication functional in at least one organism, a promoter sequence, convenient restriction enzyme sites, and one or more selectable markers (see, e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193).
  • retroviruses provide a convenient platform for gene delivery systems.
  • the selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art.
  • the recombinant virus is then isolated and delivered to cells of the subject either in vivo or in vitro.
  • Many retroviral systems are known in the art.
  • adenoviral vectors are used.
  • Many adenoviral vectors are known in the art.
  • lentiviral vectors are used.
  • Vectors derived from retroviruses are suitable tools for long-term gene transfer because they allow long-term stable integration of the transgene and propagation in progeny cells.
  • Lentiviral vectors have an additional advantage over tumor-derived retroviruses such as murine leukemia virus in that they can transduce non-dividing cells such as hepatocytes. At the same time, it has the added advantage of low immunogenicity.
  • promoter elements such as enhancers, regulate transcription initiation frequency. Typically they are located 30-110 bp upstream of the initiation site, although it has recently been discovered that many promoters also contain functional elements downstream of the initiation site.
  • the spacing between promoter elements is usually flexible so that promoter function is maintained when elements are swapped or moved relative to each other. In the thymidine kinase (tk) promoter, activity begins to decline when the spacing between promoter elements increases to 50 bp.
  • tk thymidine kinase
  • a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence.
  • the promoter sequence is a strong constitutive promoter sequence, which can drive high-level expression of any polynucleotide sequence operably linked to it.
  • Another example of a suitable promoter is the elongation factor 1 alpha (EF-1 alpha) promoter.
  • constitutive promoters can also be used, including but not limited to Simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus long terminal repeat (HIV-LTR) promoter , MoMuLV promoter, avian leukemia virus promoter, Epstein-Barr virus immediate early promoter, Rous sarcoma virus promoter and human gene promoter, for example including but not limited to actin promoter, myosin promoter, Hemoglobin promoter and creatine kinase promoter.
  • SV40 Simian virus 40
  • MMTV mouse mammary tumor virus
  • HV-LTR human immunodeficiency virus long terminal repeat
  • MoMuLV promoter avian leukemia virus promoter
  • Epstein-Barr virus immediate early promoter Epstein-Barr virus immediate early promoter
  • Rous sarcoma virus promoter Rous sarcoma virus promoter
  • human gene promoter for example including but not limited to actin
  • an inducible promoter provides a molecular switch that turns on expression of a polynucleotide sequence to which it is operably linked when such expression is desired and turns off expression when it is not.
  • Inducible promoters include, but are not limited to, the metallothionein promoter, the glucocorticoid promoter, the progesterone promoter, and the tetracycline promoter.
  • expression of anti-FcRn antibodies is inducible.
  • the nucleic acid sequence encoding the anti-FcRn antibody is operably linked to an inducible promoter, including any of the inducible promoters described herein.
  • an inducible promoter provides a molecular switch that turns on expression of a polynucleotide sequence to which it is operably linked when expression is desired and turns off expression when expression is not desired.
  • exemplary inducible promoters suitable for use in eukaryotic cells include, but are not limited to, hormone regulatory elements (see, e.g., Mader, S. and White, J.H. (1993) Proc. Natl. Acad. Sci. USA 90:5603-5607 ), synthetic ligand regulatory elements (seeing Spencer, D.M.et al (1993) Science 262:1019-1024) and ionizing radiation regulatory elements (seeing Manome, Y.et al.
  • the inducible promoter system used to express the anti-FcRn antibody is the Tet system.
  • the inducible promoter system used to express anti-FcRn antibodies is the E. coli lac repression system.
  • an exemplary inducible promoter system employed herein is the Tet system.
  • the system is based on the Tet system described by Gossen et al. (1993).
  • the polynucleotide of interest is controlled by a promoter comprising one or more Tet operator (TetO) sites.
  • TetO Tet operator
  • TetR Tet repressor
  • the activated state e.g., in the presence of inducers such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox) or their active analogs, the inducer releases TetR from TetO, resulting in transcription .
  • inducers such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox) or their active analogs
  • Doxycycline is a member of the tetracycline antibiotic family with the chemical name 1-dimethylamino-2,4a,5,7-pentahydroxy-11-methyl-4,6-dioxy-1,4a , 11,11a,12,12a-Hexahydrotetraene-3-carboxamide.
  • TetR is codon optimized for expression in mammalian cells, such as mouse or human cells. Due to the degeneracy of the genetic code, most amino acids are encoded by more than one codon, resulting in a large number of variants in the sequence of a given nucleic acid without any change in the amino acid sequence it encodes. However, many organisms differ in their codon usage, also known as "codon bias" (ie, the preference for a given amino acid to use a particular codon). Codon bias is often associated with the presence of dominant tRNA species for specific codons, which in turn increases the efficiency of mRNA translation. A coding sequence derived from a particular species (eg, prokaryotes) can thus be tailored by codon optimization to enhance its expression in a different species (eg, eukaryotes).
  • Tet-Off transcription is inactivated in the presence of Tc or Dox.
  • a tetracycline-regulated transcriptional activator consisting of TetR fused to the strong transcriptional activation domain of herpes simplex virus VP16, regulates the expression of target nucleic acids under the transcriptional control of a tetracycline-responsive promoter element (TRE).
  • the TRE element consists of a TetO sequence fused in tandem to a promoter (usually a minimal promoter sequence derived from the immediate early promoter of human cytomegalovirus).
  • Tc or Dox binds TRE and activates transcription of target genes.
  • tTA cannot bind TRE and target genes cannot be expressed.
  • rtTA is a fusion protein consisting of the TetR repressor and the VP16 transcriptional activation domain.
  • a change of 4 amino acids in the DNA-binding region of TetR altered the binding properties of rtTA so that it could only recognize the tetO sequence on the target transgenic TRE in the presence of Dox. Therefore, in the Tet-On system, rtTA can activate the transcription of TRE-regulated target genes only in the presence of Dox.
  • lac repressor system of E. coli (see Brown et al., Cell 49:603-612 (1987)).
  • the Lac repressor system functions by regulating the transcription of a polynucleotide of interest operably linked to a promoter comprising the lac operator (lacO).
  • lacO lac operator
  • lacR lac repressor
  • lacR lacR
  • lacR lacR
  • Expression of the polynucleotide of interest is induced by a suitable inducer, for example, isopropyl- ⁇ -Dthiogalactopyranoside (IPTG).
  • IPTG isopropyl- ⁇ -Dthiogalactopyranoside
  • the expression vector to be introduced into the cells may also contain a selectable marker gene or a reporter gene or both to facilitate the identification and selection of expressing cells from a population of cells transfected or infected with the viral vector.
  • selectable markers can be carried on separate DNA fragments and used in co-transfection experiments. Either a selectable marker gene or a reporter gene can be flanked by appropriate regulatory sequences to enable its expression in the host cell.
  • Useful selectable markers include, for example, antibiotic resistance genes such as neo and the like.
  • Reporter genes can be used to identify potentially transfected cells and evaluate the function of regulatory sequences.
  • a reporter gene is a gene not present in or expressed by a recipient organism or tissue that encodes a polypeptide whose expression is manifested by some readily detectable property, such as enzymatic activity. After the DNA is introduced into the recipient cells, the expression of the reporter gene is detected at an appropriate time.
  • Suitable reporter genes may include genes encoding luciferase, ⁇ -galactosidase, chloramphenicol acetyltransferase, secreted alkaline phosphatase, or green fluorescent protein (see, Ui-Tel et al., 2000 FEBS Letters 479 :79-82).
  • Suitable expression systems are known and can be prepared by known techniques or obtained commercially.
  • the construct with the smallest 5' flanking region that exhibits the highest expression level of the reporter gene is considered a promoter.
  • Such a promoter region can be linked to a reporter gene and used to assess the ability of certain substances to regulate transcription driven by the promoter.
  • nucleic acid encoding any of the full-length anti-FcRn antibodies described herein is provided.
  • the nucleic acid comprises one or more nucleic acid sequences encoding full-length anti-FcRn antibody heavy and light chains.
  • each of the one or more nucleic acid sequences is contained in a separate vector.
  • at least some of the nucleic acid sequences are contained within the same vector.
  • all nucleic acid sequences are contained within the same vector.
  • the vector can be selected, for example, from mammalian expression vectors and viral vectors (such as vectors derived from retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses).
  • mammalian expression vectors such as vectors derived from retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses.
  • vectors can be readily introduced into host cells, such as mammalian, bacterial, yeast or insect cells, by any method in the art.
  • expression vectors can be introduced into host cells by physical, chemical or biological methods.
  • polynucleotides are introduced into host cells by calcium phosphate transfection.
  • Biological methods for introducing polynucleotides of interest into host cells include the use of DNA and RNA vectors.
  • Viral vectors especially retroviral vectors, have become the most widely used method for inserting genes into mammalian cells, such as human cells.
  • Other viral vectors can be derived from lentiviruses, poxviruses, herpes simplex virus type 1, adenoviruses, and adeno-associated viruses, among others. See, eg, U.S. Pat. Nos. 5,350,674 and 5,585,362.
  • Chemical methods for introducing polynucleotides into host cells include colloidal dispersion systems such as polymer complexes, nanocapsules, microspheres, magnetic beads and lipid-based systems including oil-in-water emulsions, micelles, mixed gels clumps and liposomes.
  • colloidal dispersion systems such as polymer complexes, nanocapsules, microspheres, magnetic beads and lipid-based systems including oil-in-water emulsions, micelles, mixed gels clumps and liposomes.
  • An exemplary colloidal system used as a delivery vehicle in vivo and in vitro is a liposome (eg, an artificial membrane vesicle).
  • an exemplary delivery vehicle is a liposome.
  • lipid formulations to introduce nucleic acids into host cells (in vitro, ex vivo, or in vivo).
  • the nucleic acid can be bound to a lipid.
  • Lipid-bound nucleic acids can be encapsulated into the aqueous interior of liposomes, dispersed within the lipid bilayer of liposomes, attached to liposomes via linker molecules that bind liposomes and oligonucleotides, and include Buried in liposomes, complexed with liposomes, dispersed in lipid-containing solutions, mixed with lipids, associated with lipids, suspended in lipids, contained in or mixed with micelles , or otherwise bind to lipids.
  • Lipid, lipid/DNA or lipid/expression vector-related compositions are not limited to any particular structure in solution. For example, they may exist in bilayer structures, in micelles or in "collapsed" structures.
  • Lipids are fatty substances, either naturally occurring or synthetic.
  • lipids include fat droplets naturally present in the cytoplasm, as well as a class of compounds containing long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, aminoalcohols, and aldehydes.
  • experiments can be performed to confirm the presence of the recombinant DNA sequence in the host cell.
  • Such experiments include, for example, "molecular biology” experiments well known to those skilled in the art. Examples include Southern and Northern blotting, RT-PCR, and PCR; "biochemical” assays, such as detection of the presence or absence of a specific polypeptide, e.g. identified by immunological methods (ELISAs and Western blots) or by assays described herein All fall within the scope of this application.
  • the anti-FcRn antibody is or is derived from a monoclonal antibody. In some embodiments, the anti-FcRn antibody comprises VH and VL from a monoclonal antibody, or a variant thereof. In some embodiments, the anti-FcRn antibody further comprises CH1 and CL regions from a monoclonal antibody, or a variant thereof.
  • Monoclonal antibodies can be prepared using, for example, methods known in the art, including hybridoma cell methods, phage display methods, or using recombinant DNA methods. Additionally, exemplary phage display methods are described herein and in the Examples below.
  • lymphocytes In the hybridoma cell method, hamsters, mice or other suitable host animals are usually immunized with an immunizing agent to induce lymphocytes that produce or are capable of producing antibodies that specifically bind to the immunizing agent.
  • lymphocytes can be immunized in vitro. Immunizing agents may include polypeptides or fusion proteins of the protein of interest.
  • PBLs peripheral blood lymphocytes
  • splenocytes or lymph node cells are used if cells of non-human mammalian origin are desired.
  • Lymphocytes are fused with an immortal cell line using an appropriate fusion agent, such as polyethylene glycol, to form hybridoma cells.
  • Immortal cell lines are usually transformed mammalian cells, especially myeloma cells of rodent, bovine and human origin. Typically rat or mouse myeloma cell lines are used.
  • Hybridoma cells can be cultured in a suitable medium, which preferably contains one or more substances that inhibit the growth or survival of unfused immortalized cells.
  • a suitable medium which preferably contains one or more substances that inhibit the growth or survival of unfused immortalized cells.
  • the parental cells lack hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT)
  • the hybridoma cell culture medium usually includes hypoxanthine, aminopterin, and thymidine (HAT medium), which can Prevents the growth of HGPRT-deficient cells.
  • the immortalized cell lines fuse efficiently, ensure high-level stable expression of antibodies by the selected antibody-producing cells, and are sensitive to certain media, such as HAT media.
  • the immortal cell line is a mouse myeloma cell line available from, for example, the Salk Cell Collection, San Diego, California, and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human hybrid myeloma cell lines are also described for the production of human monoclonal antibodies.
  • the medium in which the hybridoma cells are grown can then be assayed for the presence of monoclonal antibodies directed against the polypeptide.
  • the binding specificity of monoclonal antibodies produced by hybridoma cells can be determined by immunoprecipitation or in vitro binding assays, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques or analytical methods are known in the art.
  • the binding affinity of monoclonal antibodies can be determined by Scatchard analysis as described, for example, in Munson and Pollard, Anal. Biochem., 107:220 (1980).
  • hybridoma cells After the desired hybridoma cells have been identified, the clones of interest can be subcloned by limiting dilution and cultured by standard methods. Suitable media for this purpose include, for example, Modified Eagle's Medium (DMEM) and RPMI-1640 medium. Alternatively, hybridoma cells can be grown in ascites in mammals.
  • DMEM Modified Eagle's Medium
  • RPMI-1640 medium RPMI-1640
  • Monoclonal antibodies secreted by subclones can be isolated or purified from culture medium or ascitic fluid by conventional immunoglobulin purification methods, such as protein A-Sepharose, hydroxyapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
  • the anti-FcRn antibody comprises a sequence selected from a clone of an antibody library, eg, a phage library displaying scFv or Fab fragments.
  • a clone of an antibody library eg, a phage library displaying scFv or Fab fragments.
  • Such clones can be identified by screening a combinatorial library of antibody fragments having the desired activity. For example, various methods are known in the art for generating phage display libraries and screening these libraries for antibodies with desired binding properties.
  • the repertoires of the VH and VL genes are cloned separately by polymerase chain reaction (PCR), randomly recombined in a phage library, and then screened for antigen-binding phage, as in Winter et al. ., Ann. Rev. Immunol., 12:433-455 (1994).
  • Phage typically display antibody fragments as scFv fragments or as Fab fragments.
  • Immune-derived library phages provide high-affinity antibodies against the immunogen without the need to construct hybridoma cells.
  • natural repertoires e.g.
  • the anti-FcRn antibody is prepared by phage display screening the anti-FcRn antibody part in the library that can specifically bind to the target FcRn.
  • the library can be a human scFv phage display library with at least 1 ⁇ 10 9 (e.g. at least 1 ⁇ 10 9 , 2.5 ⁇ 10 9 , 5 ⁇ 10 9 , 7.5 ⁇ 10 9 , 1 ⁇ 10 10 , 2.5 ⁇ 10 10 , 5 ⁇ 10 10 , 7.5 ⁇ 10 10 , or 1 ⁇ 10 11 ) diversity of unique human antibody fragments.
  • the library is a natural human library constructed from DNA extracted from PMBCs and spleens of healthy subjects, comprising all human heavy and light chain subfamilies.
  • the library is a human natural library constructed by DNA extracted from PMBCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients and patients with infectious diseases.
  • the library is a semi-synthetic human library in which the heavy chain CDR3s are completely randomized, with all amino acids (except cysteine) present at any given position with equal probability. (See eg, Hoet, RM et al., Nat. Biotechnol. 23(3):344-348, 2005).
  • the semi-synthetic human library has a heavy chain CDR3 length between 5 and 24 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
  • the library is a fully synthetic phage display library. In some embodiments, the library is a non-human phage display library.
  • Phage clones with high affinity to target FcRn can be screened by iterative binding of phage to target FcRn bound to a solid support (e.g. beads for solution panning or mammalian cells for cell panning). ), followed by removal of unbound phage and elution of specifically bound phage. Subsequently, bound phage clones are eluted and used to infect suitable host cells, such as E.coli XL1-Blue, for expression and purification. Phage clones that specifically bind FcRn can be enriched by multiple rounds of panning (eg, 2, 3, 4, 5, 6 or more rounds), such as solution panning, cell panning, or a combination of both. Specific binding of the enriched phage clones to the target FcRn can be detected by any method known in the art, including, for example, ELISA and FACS.
  • Another way to screen antibody libraries is to display proteins on the surface of yeast cells.
  • Wittrup et al. (US Patents 6,699,658 and 6,696,251) developed a method for displaying libraries in yeast cells.
  • one component includes the yeast lectin protein (Aga1) anchored on the yeast cell wall, and the other component includes the second subunit of the lectin protein Aga2, which can Combined with Aga1 protein and displayed on the surface of yeast cells.
  • the Agal protein is expressed by integrating the Agal gene into the yeast chromosome. After transformation of a single-chain variable fragment (scFv) library fused to the Aga2 gene in a yeast display plasmid, the library is retained in yeast due to the presence of an additional nutritional marker. Both Aga1 and Aga2 proteins are expressed under the control of a galactose-inducible promoter.
  • scFv single-chain variable fragment
  • VH and VK fragments Human antibody V gene repertoires ( VH and VK fragments) were obtained by the PCR method using a set of degenerate primers (Sblattero, D. and Bradbury, A. Immunotechnology 3, 271-278 1998).
  • PCR templates were derived from commercially available RNA or cDNA, including PBMC, spleen, lymph node, bone marrow and tonsil. After combining independent VH and VK PCR libraries, they were assembled into scFv format by overlap extension PCR (Sheets, MD et al, Proc. Natl. Acad. Sci. USA 95, 6157-6162 1998).
  • yeast scFv display library To construct a yeast scFv display library, the resulting scFv PCR product was cloned into a yeast display plasmid in yeast by homologous recombination. (Chao, G, et al, Nat Protoc. 2006; 1(2):755-68. Miller KD, et al. Current Protocols in Cytometry 4.7.1-4.7.30, 2008).
  • Anti-FcRn antibodies can be screened using a mammalian cell display system, wherein antibody portions are displayed on the cell surface and antibodies specifically targeting FcRn are isolated by antigen-directed screening methods (as described in U.S. Patent No. 7,732,195B2).
  • a library of Chinese hamster ovary (CHO) cells displaying a large number of human IgG antibody genes can be created and used to discover clones expressing high-affinity antibody genes.
  • An alternative display system has been developed that enables simultaneous cell surface display and secretion of the same protein through alternative splicing, where the displayed protein phenotype remains genotype-related, enabling simultaneous biophysical and cellular function-based analysis The secreted soluble antibody was characterized in .
  • This method overcomes many limitations of previous mammalian cell displays and enables direct screening and maturation of antibodies in the form of full-length, glycosylated IgGs (Peter M. Bowers, et al, Methods 2014, 65: 44-56) .
  • Transient expression systems are suitable for single rounds of antigen selection prior to antibody gene restoration and are therefore most useful for selecting antibodies from smaller libraries.
  • Stable exosome vectors offer an attractive option. Exosome vectors can be efficiently transfected and stably maintained at low copy numbers, allowing multiple rounds of panning and resolution of more complex antibody repertoires.
  • the IgG library is constructed based on the ligation of germline sequence V gene segments isolated from a panel of human donors with rearranged (D)J regions. RNA collected from 2000 human blood samples was reverse transcribed into cDNA, V H and V K fragments were amplified using V H and V K specific primers, and purified by gel extraction. IgG libraries were prepared by subcloning VH and VK fragments into display vectors containing IgG1 or K constant regions, respectively, and then electroporating or transducing 293T into cells.
  • VH and VK were ligated to generate scFv, which was then subcloned into a display vector, which was then electroporated or transduced into 293T cells.
  • IgG libraries are constructed based on germline sequence V gene fragments and rearranged (D)J regions isolated from a group of donors, such as mice, rats, rabbits or monkeys.
  • Monoclonal antibodies can also be prepared by recombinant DNA methods, such as described in U.S. Patent No. 4,816,567.
  • DNA encoding the monoclonal antibodies described in this application can be easily isolated and sequenced by conventional methods (eg, by oligonucleotide probes that can specifically bind to genes encoding the light and heavy chains of murine antibodies).
  • Hybridoma cells as described above or FcRn-specific phage clones of the present application can be used as a source of such DNA.
  • the DNA can be placed in an expression vector, which is then transfected into host cells, such as simian COS cells, Chinese hamster ovarian cancer (CHO) cells, or non-immunoglobulin-producing myeloma cells, to obtain Monoclonal antibodies synthesized in cells.
  • host cells such as simian COS cells, Chinese hamster ovarian cancer (CHO) cells, or non-immunoglobulin-producing myeloma cells.
  • the DNA can also be modified, for example by replacing human heavy and light chain constant regions with coding sequences and/or by replacing homologous non-human sequences with framework regions (U.S. Patent No. 4,816,567; Morrison et al., supra), or by A coding sequence of a non-immunoglobulin polypeptide covalently linked to all or part of a coding sequence of an immunoglobulin.
  • This non-immunoglobulin polypeptide can replace the constant region of the antibody of
  • the antibody can be a monovalent antibody.
  • Methods of making monovalent antibodies are known in the art. For example, one method involves recombinant expression of an immunoglobulin light chain and a modified heavy chain. Heavy chains are typically truncated anywhere in the Fc region to prevent cross-linking of the heavy chains to each other. Alternatively, the relevant cysteine residues are substituted with other amino acid residues or deleted to prevent cross-linking.
  • In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce antibody fragments, particularly Fab fragments, can be accomplished using any method known in the art.
  • Antibody variable domains with the desired binding specificity can be fused to immunoglobulin constant regions.
  • the fusion is preferably to an immunoglobulin heavy chain constant region, which includes at least part of the hinge, CH2 and CH3 regions.
  • the first heavy chain constant region (CH1) comprising the site necessary for light chain binding is present in at least one fusion.
  • DNA encoding the fusion of the immunoglobulin heavy chain and, if desired, the DNA encoding the light chain of the immunoglobulin is inserted into a separate expression vector and co-transfected into a suitable host organism.
  • the anti-FcRn antibody (such as a full-length anti-FcRn antibody) can be a fully human antibody or a humanized antibody.
  • Humanized forms of non-human (e.g., mouse) antibody portions are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (e.g., Fv, Fab, Fab', F(ab') 2 , scFv, or other fragments of antibodies).
  • Antigen-binding subsequences which generally include minimal sequence derived from non-human immunoglobulins.
  • Humanized antibodies include human immunoglobulins, immunoglobulin chains or fragments thereof (recipient antibodies) in which residues from the recipient CDRs are replaced by non-human (donor antibody) CDRs having the desired specificity, affinity and properties. Residue substitutions, such as mouse, rat or rabbit CDRs. In some embodiments, human immunoglobulin Fv framework region residues are substituted by corresponding non-human residues. Humanized antibodies may also comprise amino acid residues that are found neither in the recipient antibody nor in imported CDR or framework region sequences.
  • humanized antibodies will comprise at least one, and usually two, variable domains in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and in which all or substantially all of the framework regions are common to human immunoglobulins. sequence.
  • humanized antibodies typically contain one or more amino acid residues that have been introduced from a non-human source. Those non-human amino acid residues are often referred to as "imported” residues, usually from an "imported” variable domain.
  • humanization can basically be carried out according to the following method of Winter and its colleagues (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 ( 1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of human antibodies.
  • such "humanized” antibody portions U.S. Patent No.
  • a humanized antibody portion is that portion of a typically human antibody in which some CDR residues and possibly some framework region residues are substituted by residues from analogous sites in rodent antibodies.
  • Fully human antibodies are an alternative to humanization.
  • transgenic animals eg, mice
  • mice that are capable of producing a fully human antibody library upon immunization but not endogenous immunoglobulins are currently produced.
  • JH antibody heavy-chain joining region
  • human germline immunoglobulin gene arrays into such germline mutant mice produces human antibodies upon antigen stimulation, see, e.g., akobovits et al., PNAS USA, 90:2551 (1993); Jakobovits et al ., Nature, 362:255-258 (1993); Bruggemann et al., Year in Immunol., 7:33 (1993); U.S. Patent Nos. 5,545,806, 5,569,825, 5,591,669, 5,545,807; and WO 97/17852.
  • fully human antibodies can be prepared by introducing human immunoglobulin loci into transgenic animals (eg, mice in which endogenous immunoglobulin genes have been partially or fully silenced).
  • Fully human antibodies can also be produced by in vitro activation of B cells (see U.S. Patents 5,567,610 and 5,229,275) or by using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J.Mol.Biol., 227:381 (1991); Marks et al., J.Mol.Biol., 222:581 (1991). Techniques of Cole et al. and Boerner et al. It can also be used to prepare fully human monoclonal antibodies. See Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991).
  • the amino acid sequences of anti-FcRn antibody variants provided herein are also contemplated.
  • the amino acid sequences of antibody variants can be prepared by introducing appropriate modifications into the antibody-encoding nucleotide sequence or by peptide synthesis. Such modifications include, for example, deletions and/or insertions and/or substitutions of residues in the antibody amino acid sequence.
  • the final construction can be accomplished by any combination of amino acid residue deletions, insertions, and substitutions to impart the desired characteristics. For example, antigen binding.
  • anti-FcRn antibody variants having one or more amino acid substitutions are provided.
  • Target sites for substitution mutations include hypervariable regions (HVRs) and framework regions (FRs).
  • Amino acid substitutions can be introduced in the antibody of interest and the product screened for desired activity, for example, improved biological activity, retained/improved antigen binding ability, reduced immunogenicity, or improved ADCC or CDC.
  • Amino acids are divided into different classes according to their side chain properties:
  • Acidic amino acids aspartic acid Asp, glutamic acid Glu;
  • Aromatic amino acids tryptophan Trp, tyrosine Tyr, phenylalanine Phe.
  • Substitution of non-conservative amino acids involves substitution of one of the above classes for another class.
  • An exemplary substitution variant is an affinity matured antibody, which can be conveniently generated using, for example, phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated, the variant antibody portions are displayed on phage, and variants are screened for specific biological activity (eg, biological activity or binding affinity based on IgG cycling assays). Alterations (eg, substitutions) can be made in regions of the HVRs to achieve improved biological activity or binding affinity based on IgG cycling assays. Alterations can be produced in HVR "hotspots", i.e. residues encoded by codons that are highly mutated during somatic maturation (see, e.g., Chowdhury, Methods Mol. Biol.
  • variable genes selected for affinity maturation are introduced into the variable genes selected for affinity maturation by any of a variety of methods (e.g., error-prone PCR, strand shuffling, or oligonucleotide-directed mutagenesis) . Secondary libraries are then created. This library is screened to identify antibody variants with the desired affinity. Another method of introducing diversity involves an HVR-mediated approach, in which several HVR residues (eg, 4-6 residues at a time) are randomized. HVR residues involved in antigen binding are specifically identified, for example, using alanine scanning mutagenesis or modeling. Often the CDR-H3 and CDR-L3 regions in particular are key targets.
  • HVR-mediated approach in which several HVR residues (eg, 4-6 residues at a time) are randomized. HVR residues involved in antigen binding are specifically identified, for example, using alanine scanning mutagenesis or modeling. Often the CDR-H3 and CDR-L3 regions in particular are key targets.
  • substitutions, insertions, or deletions may occur within one or more of the HVRs, so long as such alterations do not substantially reduce the ability of the antibody to bind antigen.
  • conservative changes eg, conservative substitutions provided herein
  • HVRs that do not substantially reduce binding affinity. These changes may occur outside of HVR "hot spots" or SDRs.
  • each HVR is either unchanged or comprises no more than 1, 2 or 3 amino acid substitutions.
  • a useful method for identifying amino acid residues or regions of an antibody that can be targeted for mutation is called "alanine scanning mutagenesis" as described in Cunningham and Wells (1989) Science, 244:1081-1085 .
  • target residues e.g., charged residues such as arginine, aspartic acid, histidine, lysine, and glutamic acid
  • neutral or negatively charged amino acids e.g., , alanine or glutamic acid
  • the contact sites between the antibody and the antigen are identified by the crystal structure of the antigen-antibody complex. These contact residues and neighboring residues can be targeted or eliminated as candidates for substitution. Variants are screened to determine whether they possess the desired properties.
  • Amino acid sequence insertions including amino-terminal and/or carboxy-terminal fusions, ranging in length from 1 residue to polypeptides containing 100 or more residues, also include intrasequence insertions of 1 or more amino acid residues base.
  • terminal insertions include antibodies with a methionyl residue at the N-terminus.
  • Other insertional variants of antibody molecules include fusions to the N-terminus or C-terminus of the antibody molecule of an enzyme (eg, ADEPT) or a polypeptide that increases the serum half-life of the antibody.
  • one or more amino acid modifications are introduced into the Fc region of an antibody described herein (eg, a full-length anti-FcRn antibody or an anti-FcRn antibody fusion protein), resulting in an Fc region variant.
  • Fc region variants have enhanced ADCC potency, typically associated with Fc-binding receptors (FcRs).
  • the Fc region variant has reduced ADCC potency.
  • ADCC Antibody-dependent cell-mediated cytotoxicity
  • NK cells activated by antibodies.
  • NK cells express the Fc receptor CD16. This receptor recognizes and binds the Fc portion of an antibody molecule bound to the surface of a target cell.
  • the most common Fc receptors on the surface of NK cells are CD16 or Fc ⁇ RIII.
  • Binding of Fc receptors to the Fc region of an antibody results in activation of NK cells, release of cytolytic granules, and subsequent apoptosis of target cells.
  • the killing effect of ADCC on tumor cells can be determined by the specific experiment of NK-92 cells transfected with high-affinity FcR. The results were compared with wild-type NK-92 not expressing FcR.
  • the present application also provides anti-FcRn antibody variants (eg, full-length anti-FcRn antibody variants) comprising an Fc region with some but not all effector functions, such that they have an extended half-life in vivo, however specific For effector functions (such as CDC or ADCC) that are dispensable or deleterious, such anti-FcRn antibodies are ideal candidates for this application.
  • anti-FcRn antibody variants eg, full-length anti-FcRn antibody variants
  • Fc region with some but not all effector functions such that they have an extended half-life in vivo, however specific For effector functions (such as CDC or ADCC) that are dispensable or deleterious, such anti-FcRn antibodies are ideal candidates for this application.
  • the reduction/elimination of CDC and/or ADCC activity is confirmed by in vitro and/or in vivo cytotoxicity assays.
  • an Fc receptor (FcR) binding assay is used to confirm that the antibody lack
  • NK cells express only Fc ⁇ RIII, while monocytes express Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII.
  • FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet Annu. Rev. Immunol. 9:457-492 (1991).
  • Non-limiting examples of in vitro assessment of ADCC activity of target molecules are described in US Pat. ) and Hellstrom, I et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); US Pat. No. 5,821,337 (see Bruggemann, M. et al., J. Exp. Med.
  • non-radioactive detection methods can be used (see, for example, the ACTI TM Flow Cytometry Non-Radioactive Cytotoxicity Assay (Cell Technology, Inc. Mountain View, Calif.) and the CYTOTOX 96 TM Non-Radioactive Cytotoxicity Assay. Toxicity assays (Promega, Madison, Wis.). Effector cells used in such assays include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK).
  • PBMC peripheral blood mononuclear cells
  • NK natural killer cells
  • ADCC activity of the molecule of interest is performed in vivo Assay, e.g., in an animal model, as described in Clynes et al.Proc.Nat'l Acad.Sci.USA 95:652-656 (1998).
  • a C1q binding assay can also be performed to confirm that the antibody cannot bind to C1q , thus lacking CDC activity. See, for example, C1q and C3c binding ELISA in WO 2006/029879 and WO 2005/100402.
  • a CDC assay can be performed (see, for example, Gazzano-Santoro et al., J. Immunol.
  • Antibodies with reduced effector function include substitutions of one or more residues at residues 238, 265, 269, 270, 297, 327, and 329 of the Fc region (U.S. Pat. No. 6,737,056). These Fc variants include Fc variants with substitutions of two or more residues at positions 265, 269, 270, 297, and 327, including Fc variants known as "DANA", which have residues at positions 265 and 297 The base is substituted with alanine (U.S. Pat. No. 7,332,581).
  • a variant of an anti-FcRn antibody comprising a variant of the Fc region with one or more amino acid substitutions capable of enhancing ADCC effect.
  • the Fc region variant comprises one or more amino substitutions capable of enhancing the ADCC effect, and these substitutions are at positions 298, 333 and/or 334 (EU residue numbering) of the Fc region.
  • the anti-FcRn antibody (eg, full-length anti-FcRn antibody) variant comprises amino acid substitutions at positions S298A, E333A, and K334A of the Fc region.
  • alterations in the Fc region result in alterations (i.e., enhancement or attenuation) of Clq binding and/or complement-dependent cytotoxicity (CDC), see U.S. Pat. No. 6,194,551, WO 99/51642, and Idusogie et al. al., J. Immunol. 164:4178-4184 (2000).
  • CDC complement-dependent cytotoxicity
  • an anti-FcRn antibody eg, a full-length anti-FcRn antibody
  • a variant of the Fc region with one or more amino acid substitutions capable of extending half-life or enhancing interaction with an Fc receptor (FcRn ) combination comprising a variant of the Fc region with one or more amino acid substitutions capable of extending half-life or enhancing interaction with an Fc receptor (FcRn ) combination.
  • Antibodies with extended half-life and improved FcRn binding are described in US 2005/0014934A1 (Hinton et al.). These antibody Fc regions contain one or more amino acid substitutions that enhance the binding of the Fc region to FcRn.
  • Fc variants comprise 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or One or more substitutions in residue 434, eg, substitution of residue 434 in the Fc region (U.S. Pat. No. 7,371,826).
  • anti-FcRn antibodies eg, full-length anti-FcRn antibodies
  • anti-FcRn antibodies comprising any one of the Fc variants described herein, or combinations thereof.
  • an anti-FcRn antibody provided herein is altered to increase or decrease the degree of glycosylation of the anti-NGF antibody.
  • Addition or deletion of glycosylation sites on the anti-FcRn antibody can be conveniently achieved by changing the amino acid sequence of the anti-NGF antibody or its polypeptide portion to add or remove one or more glycosylation sites.
  • the sugar attached to it can be altered.
  • Native antibodies produced by mammalian cells typically comprise branched biantennary oligosaccharides, usually N-linked to the Fc region CH2 domain Asn297, see e.g. Wright et al., TIBTECH 15:26-32 (1997) .
  • the oligosaccharides may comprise a variety of sugars such as mannose, N-acetylglucosamine (GlcNAc), galactose and sialic acid, as well as trehalose linked to the GlcNAc in the "stem" of the biantennary oligosaccharide structure.
  • oligosaccharide modifications can be made to the anti-FcRn antibodies of the present application to generate anti-FcRn antibody variants with certain improved properties.
  • N-glycans linked to the CH2 domain of the Fc region are heterogeneous.
  • Antibodies or Fc fusion proteins produced in CHO cells are fucosylated by fucosyltransferase activity, see Shoji-Hosaka et al., J. Biochem. 2006, 140:777-83.
  • a small fraction of naturally occurring non-fucosylated IgGs can be detected in human serum.
  • N-glycosylation of the Fc region is important for its binding to Fc ⁇ Rs; non-fucosylated N-glycans enhance the binding ability of Fc to Fc ⁇ RIIIa.
  • Enhanced binding to FcRIIIa results in enhanced ADCC effect, which is advantageous in certain antibody therapeutic applications where cytotoxicity is required.
  • enhanced effector functions may be detrimental when Fc-mediated cytotoxicity is not desired.
  • the Fc fragment or CH2 domain is aglycosylated.
  • glycosylation is prevented by mutating the N-glycosylation site in the CH2 domain.
  • anti-FcRn antibody e.g., full-length anti-FcRn antibody
  • variants comprise an Fc region, wherein the carbohydrate structure attached to the Fc region has reduced fucose or lacks fucose, which may ADCC function will be enhanced.
  • anti-FcRn antibodies that have reduced fucose relative to the same anti-FcRn antibodies produced by wild-type CHO cells. That is, they are characterized by having a lower amount of fucose than antibodies produced by native CHO cells (eg, CHO cells producing native glycosylated forms, CHO cells containing the native FUT8 gene).
  • the N-linked glycans of the anti-FcRn antibody have less than 50%, 40%, 30%, 20%, 10%, or 5% fucose.
  • the fucose content of the anti-FcRn antibody may be 1%-80%, 1%-65%, 5%-65%, or 20%-40%.
  • the N-linked glycans of the anti-FcRn antibody do not comprise fucose, ie, wherein the anti-FcRn antibody is completely free of fucose, or has no fucose, or is afucosylated.
  • the content of fucose was calculated by calculating the average content of fucose in the sugar chain attached to Asn297 relative to the total of all sugar structures (such as complex, hybrid or mannose structures) attached to Asn297 measured by MALDI-TOF mass spectrometry. Quantities are determined as described in WO 2008/077546. Asn297 refers to the asparagine residue located at position 297 of the Fc region (EU Fc region residue numbering system). However, Asn297 can also be located ⁇ 3 amino acids upstream or downstream of position 297, ie between positions 294 and 300, due to minor sequence variations of the antibody. These fucosylated variants may have enhanced ADCC function. See, eg, US Patent Publication Nos.
  • Cell lines capable of producing afucosylated antibodies include Lec13CHO cells lacking protein fucosylation function (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003 /0157108 A1, Presta, L; and WO 2004/056312 A1, Adams et al., especially Example 11), and gene knockout cell lines, such as the ⁇ -1,6-fucosyltransferase gene, FUT8 Gene knockout CHO cells (see Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006); and WO2003/085107).
  • Anti-FcRn antibody (eg, full-length anti-FcRn antibody) variants further provide bisected oligosaccharides, eg, wherein the biantennary oligosaccharide attached to the Fc region of the anti-FcRn antibody is bisected by GlcNAc.
  • Such anti-FcRn antibody (eg, full-length anti-FcRn antibody) variants may have reduced fucosylation and/or enhanced ADCC function. Examples of such antibody variants are in WO 2003/011878 (Jean-Mairet et al.); U.S. Pat. No.
  • anti-FcRn antibody eg, full-length anti-FcRn antibody
  • anti-FcRn antibody variants having at least one galactose residue in the oligosaccharide linked to the Fc region.
  • anti-FcRn antibody variants may have enhanced CDC function.
  • Such variants are described, for example, in WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.).
  • the anti-FcRn antibody (eg, full-length anti-FcRn antibody) variant comprises an Fc region that binds Fc ⁇ RIII.
  • said anti-FcRn antibody (e.g., full-length anti-FcRn antibody) variant comprising an Fc region has ADCC activity in the presence of human effector cells (e.g., T cells), or is combined with other antibodies having a human wild-type IgG1 Fc region. Enhanced ADCC activity in the presence of human effector cells compared to the same anti-FcRn antibody (eg, full-length anti-FcRn antibody).
  • cysteine-engineered anti-FcRn antibodies eg, full-length anti-FcRn antibodies
  • substituted residues occur at sites accessible to anti-FcRn antibodies.
  • cysteine By substituting cysteine for those residues, a reactive sulfhydryl group located at an accessible site of the anti-FcRn antibody can be used to conjugate the anti-FcRn antibody to other moieties, such as drug moieties or linker-drug moieties, to prepare anti-FcRn immunoconjugates as further described herein.
  • Cysteine-engineered anti-FcRn antibodies eg, full-length anti-FcRn antibodies
  • the anti-FcRn antibodies provided herein can be further modified to include other non-protein moieties known in the art and readily available.
  • Moieties suitable for derivatizing anti-FcRn antibodies include, but are not limited to, water soluble polymers.
  • Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), ethylene glycol/propylene glycol copolymers, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1 ,3-dioxolane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyamino acid (homopolymer or random copolymer), dextran or poly(n- vinylpyrrolidone) polyethylene glycol, propylene glycol homopolymer, propylene oxide/ethylene oxide copolymer, polyoxyethylated polyols (eg glycerol), polyvinyl alcohol and mixtures thereof.
  • PEG polyethylene glycol
  • ethylene glycol/propylene glycol copolymers carboxymethylcellulose
  • dextran polyvinyl alcohol
  • polyvinylpyrrolidone poly-1 ,3-dioxo
  • Polyethylene glycol propionaldehyde has advantages in manufacturing due to its stability in water.
  • the polymers can be of any molecular weight and can be branched or unbranched.
  • the number of polymers attached to the anti-FcRn antibody can vary, and if more than one polymer is attached, they can be the same or different molecules.
  • the amount and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the need to improve the properties or function of the anti-FcRn antibody, whether the anti-FcRn antibody derivative is useful in a particular condition, treatment etc.
  • compositions comprising any of an anti-FcRn antibody (e.g., a full-length anti-FcRn antibody), a nucleic acid encoding an antibody, a vector comprising a nucleic acid encoding an antibody, or a host cell comprising a nucleic acid or vector described herein. substances, also referred to herein as preparations).
  • an anti-FcRn antibody e.g., a full-length anti-FcRn antibody
  • a nucleic acid encoding an antibody e.g., a full-length anti-FcRn antibody
  • a vector comprising a nucleic acid encoding an antibody
  • a host cell comprising a nucleic acid or vector described herein.
  • a pharmaceutical composition comprising any anti-FcRn antibody described herein and a pharmaceutically acceptable carrier.
  • a suitable anti-FcRn antibody can be obtained by mixing an anti-FcRn antibody of the desired purity with optionally a pharmaceutically acceptable carrier, excipient or stabilizer (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)).
  • Antibody preparations are prepared in the form of lyophilized preparations or liquid preparations.
  • Acceptable carriers, excipients, or stabilizers that are nontoxic to recipients at the dosages and concentrations employed include buffers such as: phosphates, citric acid, and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives such as Octadecyldimethylbenzylammonium chloride; Hexamethylammonium chloride; Benzalkonium chloride; Benzethonium chloride; Phenol; Butanol or benzyl alcohol; Alkylparabens such as p-hydroxybenzoate Methyl formate or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol and m-cresol); low molecular weight (fewer than 10 residues) polypeptides; proteins such as serum Albumin, gelatin, or immunoglobulin; hydrophilic polymers, such as polyvinylpyrrolidone; amino acids, such as glycine, glutamine,
  • Lyophilized formulations suitable for subcutaneous administration are described in WO97/04801. Such lyophilized formulations can be reconstituted with a suitable diluent into a high protein concentration formulation, and the reconstituted formulation can be administered subcutaneously to the individual to be treated herein. Cationic liposomes or liposomes can be used to deliver the anti-FcRn antibodies of the present application to cells.
  • the preparations described herein may also contain one or more other active substances necessary for the treatment of specific diseases, preferably substances with complementary activities and no adverse reactions to each other .
  • active substances preferably substances with complementary activities and no adverse reactions to each other .
  • monoclonal antibody therapy nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, inhibitors of the complement system, immunosuppressants, immunomodulatory agents or combinations thereof.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • the anti-FcRn antibody (e.g., full-length anti-FcRn antibody) can also be embedded in microcapsules prepared, e.g., by coacervation techniques and interfacial polymerization, e.g., in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, respectively). , microemulsions, nanoparticles and nanocapsules) or in macroemulsions of hydroxymethylcellulose or gelatin-microcapsules and poly(methyl methacrylate) microcapsules. Sustained release formulations can be prepared.
  • sustained release formulations of anti-FcRn antibodies can be prepared.
  • suitable examples of sustained release formulations include semipermeable matrices of solid hydrophobic polymers containing the antibody (or fragment thereof) in the form of shaped articles, eg, films or microcapsules.
  • sustained release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol)), polylactic acid (U.S. Pat. No.
  • L-glutamine Acid and ethyl L-glutamate copolymer non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymer such as LUPRON DEPOTTM (composed of lactic acid-glycolic acid copolymer and leuprolide acetate can injection microspheres) and poly-D(-)-3-hydroxybutyrate. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid can release molecules for more than 100 days, certain hydrogels can release proteins for a shorter period of time.
  • the anti-FcRn antibody (e.g., a full-length anti-FcRn antibody) is formulated in the presence of citrate, sodium chloride, acetate, succinate, glycine, polysorbate 80 (Tween 80), or in any combination of the above buffers.
  • Preparations for in vivo administration must be sterile. This is readily accomplished, for example, by filtration using sterile filtration membranes.
  • Anti-FcRn antibodies e.g., full-length anti-FcRn antibodies
  • compositions described herein can be administered to an individual (e.g., a mammal, such as a human) to facilitate clearance of autoantibodies in a subject, inhibit the subject's Presentation of antigens, blocking of an immune response (eg, blocking activation of an immune complex-based immune response in a subject), treatment of immunological diseases (eg, autoimmune diseases) and inflammatory diseases in a subject.
  • Autoimmune disease refers to a class of diseases in which a subject's autoantibodies react with host tissues, or immune effector T cells have a spontaneous response to endogenous autologous peptides and cause tissue destruction.
  • the immune response is directed against the subject's own antigens (called self-antigens).
  • self-antigen refers to the antigen of normal host tissue. Normal host tissue does not include tumor cells. These disorders include, but are not limited to, myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic Lupus erythematosus, Graves' disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus, type I or type II diabetes, multiple sclerosis, Raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease , vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondylo
  • the present application provides a method for a disease and/or disorder (eg, an autoimmune disease or an inflammatory disease) as described above, comprising administering to an individual an effective amount of an antibody comprising an anti-FcRn (eg, A composition (e.g., a pharmaceutical composition) of a full-length anti-FcRn antibody), such as any one of the anti-FcRn antibodies described herein (e.g., a full-length anti-FcRn antibody), in some embodiments, the individual is Humanity.
  • an anti-FcRn eg, A composition (e.g., a pharmaceutical composition) of a full-length anti-FcRn antibody
  • the individual is Humanity.
  • a method of regulating the interaction between FcRn and IgG Fc comprising combining FcRn in a cell or a subject with an anti-FcRn antibody or antigen-binding fragment, or an effective amount of an anti-FcRn comprising any one of the anti-FcRn
  • a composition eg, a pharmaceutical composition
  • an antibody eg, a full-length anti-FcRn antibody
  • the modulation inhibits the interaction between FcRn and IgG Fc.
  • a method of promoting the degradation of antibodies in a cell or in an individual is provided.
  • the antibody is an autoantibody.
  • the individual is a human.
  • a method of treating or ameliorating an individual suffering from an IgG-mediated disease comprising administering to said individual an anti-FcRn antibody or antigen-binding fragment, or comprising any of said anti-FcRn antibodies (e.g., full-length anti-FcRn antibody) compositions (eg, pharmaceutical compositions).
  • the IgG-mediated diseases include pathogenic IgG antibody-related diseases, including coagulopathy, vascular disease, collagen disease, skin disease, neuropathy, inflammatory bowel disease and organ-specific disease.
  • the individual is a human.
  • a method of blocking transplacental transmission of pathogenic antibodies comprising administering to a pregnant mammal in need thereof a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment, or comprising any of said anti- Compositions (eg, pharmaceutical compositions) of FcRn antibodies (eg, full-length anti-FcRn antibodies).
  • a method of inhibiting FcRn from binding to an immune complex comprising combining FcRn in a cell or an individual with an anti-FcRn antibody or an antigen-binding fragment, or comprising any of the anti-FcRn antibodies (such as , a composition (eg, a pharmaceutical composition) of a full-length anti-FcRn antibody).
  • IC immune complex
  • APCs antigen presenting cells
  • the individual is a human.
  • a method of increasing IC clearance in an individual comprising administering to an individual in need thereof an anti-FcRn antibody, an antigen-binding fragment, or any anti-FcRn antibody (e.g., a full-length anti-FcRn antibody) comprising the same Compositions (such as pharmaceutical compositions).
  • the methods are useful for treating IC-mediated vasculitis.
  • the individual is a human.
  • a method of inhibiting the secretion of inflammatory cytokines from antigen-presenting cells comprising combining APCs with an anti-FcRn antibody, an antigen-binding fragment, or any anti-FcRn antibody (e.g., full-length anti-FcRn antibody) composition (such as a pharmaceutical composition) contact.
  • Inflammatory cytokines include, but are not limited to, interleukin-12 (IL-12), interleukin-6 (IL-6), and interferon gamma (IFNy).
  • a method of inhibiting antigen-presenting cells from activating T cells comprising combining antigen-presenting cells with an anti-FcRn antibody, an antigen-binding fragment, or any anti-FcRn antibody (e.g., a full-length anti-FcRn antibody ) composition (such as a pharmaceutical composition).
  • an anti-FcRn antibody e.g., an antigen-binding fragment, or any anti-FcRn antibody (e.g., a full-length anti-FcRn antibody ) composition (such as a pharmaceutical composition).
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of an antibody comprising an anti-FcRn (e.g., a full-length anti-FcRn antibody), wherein said antibody comprises: a heavy chain variable domain ( VH ), said VH comprising: a heavy chain complementarity determining region (HC-CDR) 1, which comprising TYSMN (SEQ ID NO: 1); HC-CDR2 comprising YISX 1 X 2 SX 3 X 4 IYYADSVKG (SEQ ID NO: 44), wherein X 1 is H or R, X 2 is G, K, R or S, X 3 is D or S, X 4 is I, K or L; and HC-CDR3, it comprises SWGX 1 X 2 GFDX 3 (SEQ ID NO:45), wherein X 1 is A, K, R or
  • the anti-FcRn antibody is a full length antibody. In some embodiments, the full length anti-FcRn antibody is an IgGl or IgG4 antibody.
  • the disease or condition is selected from, for example, myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic Purpura, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus, type I or type II diabetes, multiple sclerosis, Raynaud's syndrome, autoimmune Immune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease,
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises V H , and the V H comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, HC-CDR2 comprising any of SEQ ID NOs: 2-9 and HC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 10-17, or variants of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs and V L , said V L comprising: LC-CDR, which comprises the amino acid sequence 1 shown in any one of SEQ ID NOs:18-28, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:29 , and LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs:
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein said antibody comprises: V H , said V H comprising the amino acid sequence shown in any of SEQ ID NOs:48-61 or a variant thereof, said variant being identical to any of SEQ ID NOs:48-61 A shown amino acid sequence having at least about 80% sequence identity; and V L , said V L comprising any one of SEQ ID NOs: 62-82 shown in the amino acid sequence or a variant thereof, said variant being identical to SEQ ID NOs: 62-82
  • the amino acid sequences shown in any one of ID NOs: 62-82 have at least about 80% sequence identity.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 30, or variants of said V L , in which LC-CDRs Substitutions of up to about 5
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 48 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:62.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said VL , in its LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 49 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein said antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 11, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:31, or variants of said V L , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 50, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 50 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 32, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:64.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:33, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 52 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:65.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 35, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 53 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 18, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 36, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein said antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:37, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:69.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:38, or variants of said V L , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:70.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 13, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 39, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:71.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 14, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:40, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:72.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein said antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 15, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:25, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:35, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:73.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 11, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:31, or variants of said V L , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 26, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 33, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:74.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 32, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 52 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:75.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:37, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 59 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:76.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 41, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:42, or variants of said V L , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 12, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:27, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:42, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 10, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO:28, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:37, or variants of said VL , in which LC-CDRs Substitutions of up
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO: 80 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 80.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 16, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 43, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:81 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:81.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein the antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 14, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 40, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:82 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:82.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • a method for treating an individual with a disease or disorder as described above comprising administering to the individual an effective amount of a combination comprising an anti-FcRn antibody wherein said antibody comprises: VH , said VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and HC-CDR3, It comprises the amino acid sequence of SEQ ID NO: 17, or a variant of said VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: LC-CDR1 comprising amino acid Sequence SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or variants of said V L , in which LC-CDRs Substitutions of up to about
  • an anti-FcRn antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80 % sequence identity; and a VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66.
  • the anti-FcRn antibodies described herein are full-length anti-FcRn antibodies comprising an IgGl or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:84. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:85. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:86.
  • the individual is a mammal (eg, a human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc.). In some embodiments, the individual is a human. In some embodiments, the individual is a clinical patient, a clinical trial volunteer, an experimental animal, or the like. In some embodiments, the individual is less than 60 years old (including, for example, less than 50, 40, 30, 25, 20, 15, or 10 years old). In some embodiments, the individual is greater than 60 years old (including, for example, greater than 70, 80, 90, or 100 years old).
  • the individual is diagnosed with or is genetically predisposed to have one or more diseases or conditions described herein (eg, an autoimmune disease or an inflammatory disease). In some embodiments, the individual has one or more risk factors associated with one or more diseases or conditions described herein.
  • diseases or conditions described herein eg, an autoimmune disease or an inflammatory disease.
  • the individual has one or more risk factors associated with one or more diseases or conditions described herein.
  • the application provides a method of delivering an anti-FcRn antibody (e.g., any of the anti-FcRn antibodies described herein, e.g., an isolated anti-FcRn antibody) to a cell in an individual that expresses FcRn on its surface, the The method comprises administering to the individual a composition comprising an anti-FcRn antibody.
  • an anti-FcRn antibody e.g., any of the anti-FcRn antibodies described herein, e.g., an isolated anti-FcRn antibody
  • autoimmune or inflammatory diseases or any other disease exhibiting aberrant expression of FcRn, and the clinical description of these diseases are known in the art.
  • diagnostic methods include, but are not limited to, eg, immunohistochemistry, PCR, and fluorescence in situ hybridization (FISH).
  • an anti-FcRn antibody eg, a full-length anti-FcRn antibody
  • a second, third, or fourth agent including, eg, a monoclonal antibody for the treatment of an immune-mediated disease
  • NSAIDs non-steroidal anti-inflammatory drugs
  • corticosteroids inhibitors of the complement system
  • immunosuppressants immunomodulators, or combinations thereof
  • a therapeutic effect refers to ameliorating or preventing a target disease or condition, or exhibiting a detectable therapeutic or preventive effect.
  • the effect is a reduction in circulating IgG levels.
  • the reduction in circulating IgG levels can be restored within 1 week or more after administration of the anti-FcRn antibody.
  • Dosages of anti-FcRn antibody (eg, isolated anti-FcRn antibody) compositions administered to an individual may vary depending on the particular composition, mode of administration, and type of disease being treated.
  • the amount of the composition eg, a composition comprising an anti-FcRn antibody
  • an objective response eg, a partial response or a complete response
  • the amount of anti-FcRn antibody composition is sufficient to produce a complete response in an individual.
  • the amount of anti-FcRn antibody composition is sufficient to produce a partial response in the individual.
  • the anti-FcRn antibody composition is administered at a dose (e.g., when administered alone) sufficient to produce greater than 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85%, or 90% overall response rate.
  • a dose e.g., when administered alone
  • An individual's response to the treatment methods described herein can be determined, for example, by FcRn binding activity to IgG Fc, circulating IgG levels, and/or half-life.
  • the amount of the composition is sufficient to prolong progression-free survival in the individual. In some embodiments, the amount of the composition is sufficient to prolong the overall survival of the individual. In some embodiments, the amount of the composition (eg, when administered alone) is sufficient to produce greater than 50%, 60%, 70%, or 77% clinical benefit in a population of individuals treated with an anti-FcRn antibody composition.
  • the amount of a composition (e.g., a composition comprising an isolated anti-FcRn antibody), used alone or in combination with a second, third, and/or fourth agent, is that before treatment or with Sufficient to reduce FcRn binding activity to IgG Fc, shorten half-life of circulating IgG, and/or reduce circulating IgG levels by at least 10%, 20%, 30%, 40% compared to corresponding activity in other subjects not receiving treatment , 50%, 60%, 70%, 80%, 90%, 95%, or 100%.
  • the magnitude of this therapeutic effect can be measured using standard methods, such as in vitro assays of purified enzymes, cell-based assays, animal models, or human trials.
  • the amount of anti-FcRn antibody (e.g., full-length anti-FcRn antibody) in the composition is below that which causes a toxic effect (i.e., a level of toxicity above a clinically acceptable level). effect), or at a level at which potential side effects can be managed or tolerated.
  • the amount of the composition approximates the maximum tolerated dose (MTD) of the composition. In some embodiments, the amount of the composition is greater than 80%, 90%, 95%, or 98% of the MTD.
  • the amount of anti-FcRn antibody (eg, full-length anti-FcRn antibody) in the composition ranges from 0.001 ⁇ g to 1000 ⁇ g.
  • the effective amount of the anti-FcRn antibody (eg full-length anti-FcRn antibody) in the composition is in the range of 0.1 ⁇ g/kg to 100 mg/kg based on body weight.
  • Anti-FcRn antibody compositions can be administered to an individual (e.g., a human) by a variety of routes, including, for example, intravenous injection, intraarterial administration, intraperitoneal injection, intrapulmonary administration, oral administration, inhalation administration, intravascular administration, Intramuscular, intratracheal, subcutaneous, intraocular, intrathecal, mucosal or transdermal.
  • sustained release formulations of the compositions are used.
  • the composition is administered intravenously.
  • the composition is administered arterially.
  • the composition is administered intraperitoneally.
  • the composition is administered intrahepatically.
  • the composition is administered by hepatic artery infusion.
  • the composition is administered at a site remote from the first lesion.
  • an article of manufacture comprising a substance that can be used to treat a disease or disorder as described above (e.g., an autoimmune disease or an inflammatory disease), or with For delivering an anti-FcRn antibody (eg, a full-length anti-FcRn antibody) to cells expressing FcRn on their surface.
  • the article of manufacture may comprise a container and a label or package insert on or accompanying the container.
  • Suitable containers include, for example, bottles, vials, syringes, and the like. Containers can be made from a variety of materials such as glass or plastic.
  • the container contains a composition effective to treat a disease or condition described herein and has a sterile port (eg, the container may be an IV bag or a vial with a hypodermic needle-pierceable cap). At least one active substance in the composition is the anti-FcRn antibody described in this application.
  • the label or package insert identifies the particular condition that the composition may be used to treat.
  • the label or package insert further comprises instructions for administering the anti-FcRn antibody composition to a patient. Articles of manufacture and kits comprising combination therapies are contemplated herein.
  • Package insert refers to the instructions commonly included in commercial packages of therapeutic products that contain indications, usage, dosage, administration, contraindications and/or warning information pertaining to the use of such therapeutic products.
  • the package insert indicates that the composition can be used to treat a disease or condition as described above (eg, an autoimmune disease or an inflammatory disease).
  • the package insert indicates that the composition can be used to treat the following diseases, including myasthenia gravis, pemphigus vulgaris, neuromyelitis optica, Guillain-Barré syndrome, lupus, idiopathic thrombocytopenic purpura , thrombotic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, autoimmune myocarditis, membranous glomerulonephritis, diabetes mellitus, type I or type II diabetes, multiple sclerosis, Raynaud's syndrome, autoimmune thyroiditis, gastritis, celiac disease, vitiligo, hepatitis, primary biliary cirrhosis, inflammatory bowel disease, spondyloarthropathy, experimental autoimmune encephalomyelitis, immune neutropenia Agranulocytopenia, juvenile-onset diabetes mellitus,
  • diseases including
  • the article of manufacture may further comprise a second container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Greene's solution, or dextrose solution.
  • a pharmaceutically acceptable buffer such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Greene's solution, or dextrose solution.
  • kits that can be used for various purposes, such as for the treatment of diseases or conditions as described above (such as autoimmune diseases or inflammatory diseases), or for the delivery of anti-FcRn antibodies (such as full-length anti-FcRn antibodies) to In cells expressing FcRn on the surface, optionally combined with preparations.
  • Kits of the present application include one or more containers comprising an anti-FcRn antibody composition (or single dosage form and/or preparation) and, in some embodiments, further comprising another agent (e.g., an agent described herein ) and/or instructions for use consistent with any of the methods described herein.
  • the kit may further include instructions for selecting an individual for treatment.
  • the instructions for use attached to the kit in the present application are usually written instructions on the label or package insert (such as paper sheets included in the kit), machine-readable instructions (such as instructions on a magnetic or optical storage disc) is also acceptable.
  • the kit includes a composition comprising an anti-FcRn antibody (eg, a full-length anti-FcRn antibody).
  • the kit comprises: a) a composition comprising any one of the anti-FcRn antibodies described herein, and b) at least one effective amount of another agent capable of enhancing the effect of the anti-FcRn antibody (e.g., therapeutic effect, detection effect).
  • the kit comprises: a) a composition comprising any of the anti-FcRn antibodies described herein, and b) administering the anti-FcRn antibody composition to an individual for the treatment of a disease associated with the FcRn signaling pathway (e.g.
  • the kit comprises: a) a composition comprising any one of the anti-FcRn antibodies described herein, and b) at least one effective amount of another agent capable of enhancing the effect of the anti-FcRn antibody (e.g., therapeutic effect, detecting effect) and c) instructions for administering to an individual an anti-FcRn antibody composition and other substances for the treatment of a disease or disorder as described above (eg, an autoimmune disease or an inflammatory disease).
  • the anti-FcRn antibody and other substances may be present in separate containers or in the same container.
  • the kit may include one particular composition or two or more compositions, where one composition includes an anti-FcRn antibody and the other composition includes another agent.
  • the kit comprises a nucleic acid (or set) encoding an anti-FcRn antibody (eg, a full-length anti-FcRn antibody).
  • the kit comprises: a) a nucleic acid (or set of nucleic acids) encoding an anti-FcRn antibody (e.g., a full-length anti-FcRn antibody), and b) a host expressing the nucleic acid (or set of nucleic acids) cell.
  • the kit comprises: a) a (or set of) nucleic acid encoding an anti-FcRn antibody (e.g., a full-length anti-FcRn antibody), and b) instructions for use in: i) in a host cell Expressing an anti-FcRn antibody, ii) preparing a composition comprising the anti-FcRn antibody, and iii) administering the composition comprising the anti-FcRn antibody to an individual to treat a disease or disorder as described above (eg, an autoimmune or inflammatory disease).
  • a disease or disorder as described above (eg, an autoimmune or inflammatory disease).
  • the kit comprises: a) a nucleic acid (or set of nucleic acids) encoding an anti-FcRn antibody (e.g., a full-length anti-FcRn antibody), b) a host cell expressing the nucleic acid (or set of nucleic acids) , and c) instructions for use, suitable for: i) expressing the anti-FcRn antibody in a host cell, ii) preparing a composition comprising the anti-FcRn antibody, and iii) administering the composition comprising the anti-FcRn antibody to an individual for the treatment of diseases or conditions (such as autoimmune or inflammatory diseases).
  • diseases or conditions such as autoimmune or inflammatory diseases.
  • kits described herein are packaged in a suitable form.
  • suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (eg, sealed mylar or plastic bags), and the like. Kits may optionally provide other components, such as buffers and instructional information. Accordingly, the present application also provides articles of manufacture including vials, bottles, jars, flexible packaging (eg, sealed mylar or plastic bags), and the like.
  • the instructions for use of the anti-FcRn antibody composition usually include some information, such as dose, administration cycle and administration route.
  • the container can be unit dose, bulk (eg, multi-dose package) or subunit dose.
  • a kit comprising a sufficient dose of an anti-FcRn antibody as described herein (e.g., a full-length anti-FcRn antibody) is provided for long-term effective treatment of an individual, e.g., one week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months or longer time. Kits may also comprise multiple unit doses of anti-FcRn antibody, pharmaceutical compositions and instructions for use, and be packaged in quantities sufficient for storage and use in pharmacies, eg, hospital pharmacies and compounding pharmacies.
  • FcRn Neonatal Fc receptor, neonatal Fc receptor
  • hFCGRT human FCGRT, human FcRn-alpha
  • hB2M human ⁇ 2-microglobulin
  • cyFcRn crab-eating monkey FcRn-alpha
  • mFcRn mimFcRn
  • rFcRn rat FcRn-alpha
  • Bavih-hFCGRT Biotin-hFCGRT-Avi-10His
  • Example 1 Preparation of recombinant FcRn antigen and screening of anti-FcRn single-chain antibody (scFv)
  • FcRn is a non-covalent heterodimer composed of an alpha chain (FCGRT) and a beta2-microglobulin (B2M). Codon-optimized coding sequences of hFCGRT (NP_001129491.1), hB2M (NP_004039.1), cyFcRn (NP_001271480.1), mFcRn (NP_001344046.1) and rFcRn (NP_203502.1) were synthesized and fused with the His tag Constructed into the mammalian cell expression vector pTTa1, respectively construct the following expression vectors: pTTa1-hFCGRT-10His, pTTa1-hFCGRT-Avi-10His, pTTa1-hB2M-10His, pTTa1-cyFcRn-10His, pTTa1-mFcRn-10His, pTTa1- rFcRn-10His. Where "his or
  • the recombinant FcRn described above was expressed and purified according to the manufacturer's instructions. Briefly, the expression vectors were transfected into 293F cells, and the cells were cultured at 37°C, 8% CO 2 , and 120rpm for 5 days. For the purification of His-tag protein, the cell culture fluid was collected, the supernatant was loaded into a Histrap column, and equilibrated with 20mM sodium phosphate buffer (pH7.4) containing 0.25M NaCl and 5mM imidazole (pH8.0).
  • hFCGRT-Avi-10His was biotinylated using biotinylated ligase B0101A (GeneCopoeia). Briefly, hFCGRT-Avi-10His antigen was incubated at 30°C for 2 hours after addition of buffer A/B and BirA ligase. Biotinylated FCGRT (ie Biotin-hFCGRT-Avi-10His) was named Bavih-hFCGRT. Biotinylation efficiency was detected by ELISA method. In short, the initial concentration of Bavih-hFCGRT was set to 500ng/ml, and it was diluted in a ratio of 1:2, and then coated with an ELISA plate. SA-HRP was used for detection, and biotinylated standard was used as control. The biotinylation efficiency of Bavih-hFCGRT was 70%.
  • Preparation of phage display library and screening of scFv antibodies Use scFv-F and scFv-R primers to perform PCR amplification on the plasmids obtained from the yeast library, clone the obtained scFvs antibody fragments into the phage display vector pDAN5 through SfiI, and transform after ligation TG1 phage display electroporation competent cells to obtain scFv antibody phage display library. After a series of repeated screening steps, the scFv antibody specifically binding to hFCGRT was isolated from the phage display library.
  • helper phages were added and cultured overnight at 28° C. and 200 rpm on a shaker. The culture medium was collected the next day, and the supernatant was obtained after centrifugation, and entered into the next round of screening until a positive scFv antibody library was obtained.
  • the scFv single chain antibody was screened by ELISA binding assay.
  • the enriched phages after MACS panning were subjected to ELISA binding test to screen scFv single-chain antibodies.
  • human hFCGRT antigen was dissolved in PBS solution, coated with 0.1 ⁇ g/well of 96-well plate, and left overnight at 4°C. Wash the 96-well plate with PBST solution before adding the antibody. Add 90 ⁇ L of PBS containing 4% skimmed milk powder to each well, then add 10 ⁇ L of phage supernatant expressing scFv to the corresponding well, and incubate at 37° C. for 1-2 hours.
  • IgG blocking assay Screening of scFv single-chain antibodies by IgG blocking assay: positive scFv antibodies with inhibitory IgG-FcRn binding activity were screened by IgG blocking assay. Briefly, commercial hIgG (Jackson ImmunoResearch, 009-000-003) was coated onto a 96-well microtiter plate (Corning, 9018) overnight at 4°C. Afterwards, it was blocked with 1% BSA and incubated at room temperature for 1 hour to block non-specific binding.
  • IgG blocking assay commercial hIgG (Jackson ImmunoResearch, 009-000-003) was coated onto a 96-well microtiter plate (Corning, 9018) overnight at 4°C. Afterwards, it was blocked with 1% BSA and incubated at room temperature for 1 hour to block non-specific binding.
  • V L and V H were amplified and constructed into eukaryotic expression vectors pTT5-K (containing kappa constant region) or pTT5-L (containing lambda constant region), and pTT5-H1 (containing IgG1 heavy chain constant region) or pTT5- H4 (contains IgG4 heavy chain constant region).
  • the plasmids expressing light and heavy chains were extracted respectively, co-transfected into 293F cells, cultured at 37°C, 8% CO 2 , 120rpm for 5 days, and the culture solution was purified by protein A affinity chromatography. Briefly, the protein A column was first equilibrated with 6 column volumes of 50 mM PBS buffer (pH 7.2) containing 0.15M NaCl at a flow rate of 150 cm/h. The culture supernatant (adjusted to pH 7.2) was passed through the column at a flow rate of 150 cm/h. After further equilibration, 50 mM citric acid-sodium citrate buffer (pH 3.5) was used for elution, and the eluate was collected. Among the constructed full-length antibodies, F01 was selected as the lead antibody.
  • a Fab yeast display library containing mutations in the CDR regions was prepared using F01 Fab.
  • the biological activity of antibody variants that bind hFcRn with high affinity is evaluated.
  • Fab antibody with improved hFcRn binding activity was selected to construct full-length antibody.
  • a new round of screening was performed on full-length antibodies. The selected optimized antibodies are then subjected to further biochemical and biological analysis.
  • lead antibody F01 molecules were affinity matured.
  • two yeast display libraries were constructed for the lead antibody F01, namely the L1L3H2H3 antibody library (with a library capacity of 3 ⁇ 10 8 ) and the L3H3 antibody library (with a library capacity of 2 ⁇ 10 7 ).
  • the yeast display library preparation steps are as described above.
  • FACS sorting was used to sort the positive antibody group that strongly binds to the hFCGRT antigen under the binding condition of pH 6.0.
  • Extract positive yeast population plasmids construct them on IgG secretion expression vectors, extract plasmids and transfect 293 cells, perform ELISA binding detection on cell supernatants, pick positive well plasmids that strongly bind to hFCGRT antigen, and obtain a series of optimized antibodies ( F02-F24).
  • ELISA was used to evaluate the affinity of the lead antibody F01 and the optimized antibody (reconstituted into human IgG4) to hFcRn. Briefly, a 96-well microtiter plate was coated with 1 ⁇ g/mL hFcRn antigen (human FCGRT&B2M heterodimeric recombinant protein, SinoBiological, cat#CT009-H08H) and left overnight at 4°C. Remove the coating solution, add blocking buffer containing 1% BSA, and incubate at room temperature for 1 hour. Wash the plate 3 times, add the antibody in serial dilution, and react at 37°C for 1 hour.
  • hFcRn antigen human FCGRT&B2M heterodimeric recombinant protein, SinoBiological, cat#CT009-H08H
  • Antibody EC50 (nM) Antibody EC50 (nM) F01 2.55 F13 0.34 F02 1.11 F14 0.15 F03 0.69 F15 2.61 F04 0.99 F17 0.21 F05 0.82 F18 1.21 F06 0.93 F19 0.93 F07 0.29 F20 1.09 F08 0.27 F21 1.00 F09 0.61 F22 0.27 F10 0.37 F23 0.29 F11 0.11 F24 0.37 F12 0.15 the the same
  • the inhibitory activity of the lead antibody F01 and the optimized antibody (reconstituted into human IgG4) on the binding of IgG to FcRn was detected by ELISA method. Briefly, commercial hIgG (Jackson ImmunoResearch, 009-000-003) was coated onto a 96-well microtiter plate overnight at 4°C. 1% BSA was used to block at room temperature for 1 hour, after washing the plate, Bavih-hFCGRT and the antibody after gradient dilution were added successively, and reacted at 37°C for 1 hour. Then add 100 ⁇ L/well of HRP-labeled streptavidin (1:20000) and react at 37°C for 1 hour.
  • the results are shown in Table 6.
  • the lead antibody F01 and the optimized antibody (reconstituted into human IgG4) can block the binding of IgG to human FcRn, and the inhibitory activity on the binding of IgG to FcRn in vitro is significantly better than that of the control antibody Rozanolixizumab (UCB, anti-FcRn Antibody).
  • Antibody IC 50 (nM) Antibody IC 50 (nM) F01 6.29 F14 6.68 F02 6.67 F15 2.83 F03 4.45 F16 3.30 F04 4.27 F17 4.92 F05 3.71 F18 3.81 F06 4.15 F19 3.42 F07 4.85 F20 4.05 F08 2.35 F21 3.25 F09 2.08 F22 3.67 F10 2.90 F23 7.34 F11 5.12 F24 1.75 F12 5.39 Rozanolixizumab 8.74 F13 2.58 the the the following:
  • FcRn has the property of binding IgG antibodies in a pH-dependent manner, and is a key receptor for maintaining the metabolic level of IgG immunoglobulins in vivo.
  • MDCK cells are model cells for studying IgG transport by FcRn.
  • MDCK cells stably transfected with two subunits of human FcRn (hFCGRT and hB2M) can transport human IgG, and anti-FcRn antibody can block this activity.
  • the inhibitory activity of anti-FcRn antibody can be evaluated by measuring IgG concentration.
  • MDCK-4# cells were seeded in a 96-well plate. After the cells reached the polarity requirement, the complete cell culture medium was removed, and HBSS buffer (pH 7.4) containing 1% BSA was added to wash.
  • HBSS buffer pH 7.4 containing 1% BSA was added to each well, and placed in an incubator for pre-equilibration for 20 minutes.
  • Add the diluted anti-FcRn antibody place in a 37°C, 5% CO 2 conditional incubator, and incubate for 1 hour.
  • the antibody diluent was removed, and 100 ⁇ L of HBSS buffer (pH 5.9) containing 1% BSA was added to each well to wash, and the prepared biotinylated IgG (Jackson ImmunoResearch, 009-060-003) was added to the cell plate, and placed for 37 °C, 5% CO 2 conditional incubator for 1 hour. Wash with HBSS buffer (pH 5.9).
  • add 100 ⁇ L of HBSS buffer (pH 7.4) to each well, place in a 37° C., 5% CO 2 conditional incubator and incubate for 2 hours. Cell supernatants were collected for ELISA experiments.
  • a commercial goat anti-human IgG Fc antibody (Southern Biotech, 2014-01) was coated on the microtiter plate and incubated overnight at 4°C.
  • the results are shown in Table 7.
  • the lead antibody and the optimized antibody can inhibit the circulation of human IgG, and the inhibitory activity on the circulation of IgG is comparable to that of the positive control antibody Rozanolixizumab (UCB, anti-FcRn antibody), and even better than the control antibody.
  • UB positive control antibody Rozanolixizumab
  • anti-FcRn antibody anti-FcRn antibody
  • Antibody IC 50 (nM) Antibody IC 50 (nM) F01 9.526 F10 3.56 F02 11.46 F11 11.78 F03 14.78 F12 7.28 F04 8.60 F13 2.42 F05 9.035 F14 2.77 F06 16.63 F15 12.87 F07 8.86 F16 16.59 F08 1.73 Rozanolixizumab 12.89 F09 1.53 the the
  • hFCGRT and hB2M antigens were respectively coated onto 96-well ELISA plates, overnight at 4°C, then blocked with 1% BSA, and incubated at room temperature for 1 hour. After washing the plate, add serially diluted anti-FcRn antibodies F02, F03, F14, F09 or F18, and react at 37°C for 1 hour.
  • Rozanolixizumab (UCB, anti-FcRn antibody) was used as a positive control antibody, and FY38 (an antibody that does not bind to FcRn, derived from Shutaishen) was used as a negative control antibody; in the B2M binding experiment, Anti-B2M (SinoBiological, cat#11976-MM35) is the positive control antibody, and Rozanolixizumab (UCB, anti-FcRn antibody) is the negative control antibody.
  • HRP-labeled goat anti-human IgG Fab secondary antibody was added and reacted at 37°C for 1 hour, followed by TMB for color development at room temperature. After the color development was completed, 2M sulfuric acid was added to terminate the reaction. The OD450 was read, and the binding curve was generated by PRISM, and the EC50 value was calculated.
  • the cross-binding activity of anti-FcRn antibody to FcRn of different species including cynomolgus monkey, mouse and rat was detected by ELISA method.
  • cyFcRn, mFcRn or rFcRn antigens were respectively coated onto 96-well ELISA plates, overnight at 4°C, and then blocked with 1% BSA. After washing the plates, serially diluted anti-FcRn antibodies F02 and F03 to be tested were added respectively.
  • Rozanolixizumab (UCB, anti-FcRn antibody) is a positive control antibody
  • FY38 is a negative control antibody (an antibody that does not bind to FcRn, derived from Shutaishen)
  • M281 Johnson&Johnson, anti-FcRn antibody
  • Rozanolixizumab (UCB, anti-FcRn antibody) was used as a negative control antibody.
  • Biacore T200 was used to characterize the binding affinity of anti-FcRn antibody (reconstituted into human IgG4). A full-length anti-FcRn antibody was immobilized on the sensor chip CM5. Affinity to different concentrations of hFCGRT was measured. Concentration ranges included 10, 5, 2.5, 1.25, 0.625, 0.3125, 0.15625, 0.078, 0.039, 0.0195 and OnM, where 0.625 and OnM were repeated once. On- and off-rates were measured using SPR techniques, and binding affinities were determined.
  • Example 8 Effect of anti-FcRn antibody on HSA content in cynomolgus monkeys
  • FcRn not only binds to IgG, but also binds to serum albumin (HSA).
  • HSA serum albumin
  • the inhibitory activity of anti-FcRn antibodies on the binding of HSA to FcRn was detected by bromocresol green method.
  • cynomolgus monkeys were intravenously injected with 10 mg/kg of the control antibody Rozanolixizumab (UCB, anti-FcRn antibody) and the antibody to be tested, respectively, at 0h, 4h, 8h, 24h, 32h, 48h, 72h, 96h, 120h blood samples were collected from each animal. After centrifugation, the HSA content in plasma was analyzed by bromocresol green method.
  • mice expressing hFcRn were used as a group in this experiment. On day 0, all mice were pre-injected with hIgG at a concentration of 500 mg/kg intravenously. Twenty-four hours after hIgG injection, mice were injected with anti-FcRn antibodies F02, F03, F14, F09 or F18 (reconstituted into human IgG4) at a concentration of 30 mg/kg.
  • Rozanolixizumab was used as a positive control, and PBS buffer was used as a negative control.
  • Blood samples from each animal were collected at 0h (ie 24 hours after hIgG injection, before anti-FcRn antibody injection), 0.25h, 24h, 48h, 72h, 96h, 144h and 196h after antibody injection. After centrifugation, hIgG concentrations in plasma were analyzed by ELISA. The plasma concentration of mice at 0h (24 hours after hIgG injection, before anti-FcRn antibody injection) was defined as 1.0, and the change factor of hIgG concentration relative to 0h was calculated according to the plasma IgG concentration at different time points.
  • anti-FcRn antibody molecules F02, F03, F14, F09 and F18 can rapidly reduce the level of IgG in mice, and their activity is better than that of the control antibody Rozanolixizumab.

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Abstract

L'invention concerne un anticorps ou un fragment de liaison à l'antigène capable de reconnaître de manière spécifique un récepteur Fc néonatal (FcRn), son procédé de préparation et son utilisation.
PCT/CN2022/116837 2021-09-03 2022-09-02 Anticorps capable de reconnaître de manière spécifique fcrn et son utilisation WO2023030501A1 (fr)

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CN108025066A (zh) * 2015-05-12 2018-05-11 Synt免疫公司 人源化亲和力成熟的抗FcRn抗体
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