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IL274870B1 - Dual variable region antibody-like binding proteins having cross-over binding region orientation - Google Patents

Dual variable region antibody-like binding proteins having cross-over binding region orientation

Info

Publication number
IL274870B1
IL274870B1 IL274870A IL27487020A IL274870B1 IL 274870 B1 IL274870 B1 IL 274870B1 IL 274870 A IL274870 A IL 274870A IL 27487020 A IL27487020 A IL 27487020A IL 274870 B1 IL274870 B1 IL 274870B1
Authority
IL
Israel
Prior art keywords
length
amino acid
antibody
binding protein
acid residues
Prior art date
Application number
IL274870A
Other languages
Hebrew (he)
Other versions
IL274870B2 (en
IL274870A (en
Original Assignee
Sanofi Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=65657124&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL274870(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from PCT/US2012/030948 external-priority patent/WO2012135345A1/en
Application filed by Sanofi Sa filed Critical Sanofi Sa
Publication of IL274870A publication Critical patent/IL274870A/en
Publication of IL274870B1 publication Critical patent/IL274870B1/en
Publication of IL274870B2 publication Critical patent/IL274870B2/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • 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
    • A61P37/02—Immunomodulators
    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • C07K16/245—IL-1
    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • C07K16/247—IL-4
    • 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
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • 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
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • 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
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/522—CH1 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/624—Disulfide-stabilized antibody (dsFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/626—Diabody or triabody
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/66—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2318/00—Antibody mimetics or scaffolds

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (25)

274870/2 WHAT IS CLAIMED IS:
1. An antibody-like binding protein comprising four polypeptide chains that form four antigen binding sites, wherein two polypeptide chains have a structure represented by the formula:VL1-L1-VL2-L2-CL [I]and two polypeptide chains have a structure represented by the formula: VH2-L3-VH1-L4-CH1-Fc [II]wherein:V L1 is a first immunoglobulin light chain variable domain;V L2 is a second immunoglobulin light chain variable domain;V H1 is a first immunoglobulin heavy chain variable domain;VH2 is a second immunoglobulin heavy chain variable domain;CL is an immunoglobulin light chain constant domain;CH1 is the immunoglobulin CH1 heavy chain constant domain;Fc is the immunoglobulin hinge region and CH2, CH3 immunoglobulin heavy chain constant domains; andL1, L2, L3, and L4 are amino acid linkers, whereinL2 is at least 1 amino acid residue in length, andL4 is at least 1 amino acid residue in length;and wherein the polypeptides of formula I and the polypeptides of formula II form a cross-over light chain-heavy chain pair.
2. An antibody-like binding protein comprising two polypeptide chains that form two antigen binding sites, wherein a first polypeptide chain has a structure represented by the formula:VL1-L1-VL2-L2-CL [I]and a second polypeptide chain has a structure represented by the formula: VH2-L3-VH1-L4-CH1 [II]wherein:V L1 is a first immunoglobulin light chain variable domain; 274870/2 V L2 is a second immunoglobulin light chain variable domain;V H1 is a first immunoglobulin heavy chain variable domain;V H2 is a second immunoglobulin heavy chain variable domain;C L is an immunoglobulin light chain constant domain;C H1 is the immunoglobulin CH1 heavy chain constant domain; andL 1, L2, L3, and L4 are amino acid linkers, whereinL2 is at least 1 amino acid residue in length, andL4 is at least 1 amino acid residue in length;and wherein the first and second polypeptides form a cross-over light chain-heavy chain pair.
3. The antibody-like binding protein of either claim 1 or 2, wherein:L1 is 3 to 12 amino acid residues in length;L2 is 3 to 14 amino acid residues in length;L3 is 1 to 8 amino acid residues in length; andL4 is 1 to 3 amino acid residues in length.
4. The antibody-like binding protein of either claim 1 or 2, wherein:L1 is 5 to 10 amino acid residues in length;L2 is 5 to 8 amino acid residues in length;L3 is 1 to 5 amino acid residues in length; andL4 is 1 to 2 amino acid residues in length.
5. The antibody-like binding protein of either claim 1 or 2, wherein:L1 is 1 to 3 amino acid residues in length;L2 is 1 to 4 amino acid residues in length;L3 is 2 to 15 amino acid residues in length; andL4 is 2 to 15 amino acid residues in length.
6. The antibody-like binding protein of any one of claims 1 or 2, wherein:L1 is 7 amino acid residues in length; 274870/2 L2 is 5 amino acid residues in length;L3 is 1 amino acid residue in length; and L4 is 2 amino acid residues in length.
7. The antibody-like binding protein of either claim 1 or 2, wherein:L1 is 1 amino acid residue in length;L2 is 2 amino acid residues in length;L3 is 7 amino acid residues in length; and L4 is 5 amino acid residues in length.
8. The antibody-like binding protein of either claim 1 or 2, wherein one or more of L1 or L3 is 0 amino acid residues in length.
9. The antibody-like binding protein of either claim 1 or 2, wherein the bindingprotein is capable of specifically binding one or more antigen targets.
10. The antibody-like binding protein of claim 9, wherein the one or more antigen targets is selected from the group consisting of B7.1, B7.2, BAFF, BlyS, C3, C5, CCL11 (eotaxin), CCL15 (MIP-1d), CCL17 (TARC), CCL19 (MIP-3b), CCL(MCP-1), CCL20 (MIP-3a), CCL21 (MIP-2), SLC, CCL24 (MPIF-2/eotaxin-2), CCL25 (TECK), CCL26 (eotaxin-3), CCL3 (MIP-1a), CCL4 (MIP-1b), CCL(RANTES), CCL7 (MCP-3), CCL8 (mcp-2), CD3, CD19, CD20, CD24, CD40, CD40L, CD80, CD86, CDH1 (E-cadherin), Chitinase, CSF1 (M-CSF), CSF(GM-CSF), CSF3 (GCSF), CTLA4, CX3CL1 (SCYD1), CXCL12 (SDF1), CXCL13, EGFR, FCER1A, FCER2, HER2, IGF1R, IL-1, IL-12, IL13, IL15, IL17, IL18, IL1A, IL1B, IL1F10, IL1β, IL2, IL4, IL6, IL7, IL8, IL9, IL12/23, IL22, IL23, IL25, IL27, IL35, ITGB4 (b 4 integrin), LEP (leptin), MHC class II, TLR2, TLR4, TLR5, TNF, TNFα, TNFSF4 (OX40 ligand), TNFSF5 (CDligand), Toll-like receptors, TREM1, TSLP, TWEAK, XCR1 (GPR5/CCXCR1), DNGR-1(CLEC91), and HMGB1. 274870/2
11. The antibody-like binding protein of either claim 1 or 2, wherein the binding protein is bispecific and capable of binding two different antigen targets.
12. The antibody-like binding protein of claim 11, wherein the two different antigen targets are selected from the group consisting of IL4 and IL13, IGF1R and HER2, IGF1R and EGFR, EGFR and HER2, BK and IL13, PDL-1 and CTLA-4, CTLAand MHC class II, IL-12 and IL-18, IL-1α and IL-1β, TNFα and IL12/23, TNFα and IL-12p40, TNFα and IL1β, TNFα and IL-23, and IL17 and IL23.
13. The antibody-like binding protein of either claim 1 or 2, wherein at least one of the linkers selected from the group consisting of L1, L2, L3, and L4 contains at least one cysteine residue.
14. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the antibody-like binding protein of any one of claims 1-13.
15. An expression vector comprising the nucleic acid molecule of claim 14.
16. An isolated host cell comprising the nucleic acid molecule of claim 14 or the expression vector of claim 15.
17. The host cell of claim 16, wherein the host cell is a mammalian cell or an insect cell.
18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody-like binding protein of any one of claims 1-13.
19. A method for making the antibody-like binding protein of any one of claims 1-comprising expressing in a cell a nucleic acid molecule of claim 14. 274870/2
20. The method of claim 19, wherein the first antibody variable domain and the second antibody variable domain in the antibody-like binding protein are the same, wherein the first antibody variable domain is VL1 and VH1 and the second variable antibody domain is VL2 and VH2.
21. The antibody-like binding protein of either claim 1 or 2, wherein L2 and L4 are both at least one amino acid in length, and(a) the length of L2 is at least twice the length of L4; or(b) the length of L4 is at least twice the length of L2.
22. The antibody-like binding protein of claim 1, wherein at least one of the first or second polypeptide chains further comprises a Fc that is an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains derived from a Fc domain.
23. The antibody-like binding protein of claim 22, wherein the Fc is linked to the carboxyl terminal region of the polypeptide chain.
24. The antibody-like binding protein of claim 22, wherein the Fc is linked to CL and/or CH1.
25. The antibody-like binding protein of claim 24, wherein the Fc of the first polypeptide is linked to CL and/or the Fc of the second polypeptide is linked to the CH1.
IL274870A 2011-03-28 2020-05-24 Dual variable region antibody-like binding proteins having cross-over binding region orientation IL274870B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161468276P 2011-03-28 2011-03-28
FR1160311 2011-11-14
PCT/US2012/030948 WO2012135345A1 (en) 2011-03-28 2012-03-28 Dual variable region antibody-like binding proteins having cross-over binding region orientation

Publications (3)

Publication Number Publication Date
IL274870A IL274870A (en) 2020-07-30
IL274870B1 true IL274870B1 (en) 2023-01-01
IL274870B2 IL274870B2 (en) 2023-05-01

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IL24936916A IL249369B (en) 2011-03-28 2016-12-04 Dual variable region antibody-like binding proteins having cross-over binding region orientation
IL274876A IL274876A (en) 2011-03-28 2020-05-24 Dual variable region antibody-like binding proteins having cross-over binding region orientation
IL274870A IL274870B2 (en) 2011-03-28 2020-05-24 Dual variable region antibody-like binding proteins having cross-over binding region orientation

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IL24936916A IL249369B (en) 2011-03-28 2016-12-04 Dual variable region antibody-like binding proteins having cross-over binding region orientation
IL274876A IL274876A (en) 2011-03-28 2020-05-24 Dual variable region antibody-like binding proteins having cross-over binding region orientation

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KR (1) KR102240802B1 (en)
CL (1) CL2013002763A1 (en)
ES (1) ES2859906T3 (en)
HR (1) HRP20210240T1 (en)
HU (1) HUE053139T2 (en)
IL (3) IL249369B (en)
LT (1) LT3199547T (en)
MX (2) MX366923B (en)
PH (1) PH12018501305A1 (en)
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Publication number Priority date Publication date Assignee Title
WO1997014719A1 (en) * 1995-10-16 1997-04-24 Unilever N.V. A bifunctional or bivalent antibody fragment analogue
CN107226864A (en) * 2007-06-21 2017-10-03 宏观基因有限公司 Covalent diabodies and application thereof
EP2050764A1 (en) * 2007-10-15 2009-04-22 sanofi-aventis Novel polyvalent bispecific antibody format and uses thereof
TW201109438A (en) * 2009-07-29 2011-03-16 Abbott Lab Dual variable domain immunoglobulins and uses thereof

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PH12018501305A1 (en) 2020-01-27
KR20190049902A (en) 2019-05-09
HUE053139T2 (en) 2021-06-28
IL249369B (en) 2019-11-28
IL274876A (en) 2020-07-30
PT3199547T (en) 2021-02-02
MX2019009016A (en) 2019-09-10
CL2013002763A1 (en) 2014-03-07
ES2859906T3 (en) 2021-10-04
KR102240802B1 (en) 2021-04-16
IL274870B2 (en) 2023-05-01
LT3199547T (en) 2021-02-25
HRP20210240T1 (en) 2021-04-02
IL274870A (en) 2020-07-30
IL249369A0 (en) 2017-02-28
MX366923B (en) 2019-07-31
RU2019122155A (en) 2020-03-16

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