[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2024130541A1 - ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION - Google Patents

ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION Download PDF

Info

Publication number
WO2024130541A1
WO2024130541A1 PCT/CN2022/140312 CN2022140312W WO2024130541A1 WO 2024130541 A1 WO2024130541 A1 WO 2024130541A1 CN 2022140312 W CN2022140312 W CN 2022140312W WO 2024130541 A1 WO2024130541 A1 WO 2024130541A1
Authority
WO
WIPO (PCT)
Prior art keywords
amino acid
seq
acid sequence
variable region
heavy chain
Prior art date
Application number
PCT/CN2022/140312
Other languages
English (en)
Chinese (zh)
Inventor
李竹石
朱燕
邓涛
赵真虎
龙杨洋
陈洪
王颖
Original Assignee
成都优洛生物科技有限公司
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
Application filed by 成都优洛生物科技有限公司 filed Critical 成都优洛生物科技有限公司
Priority to CN202280059497.7A priority Critical patent/CN117957250A/zh
Priority to PCT/CN2022/140312 priority patent/WO2024130541A1/fr
Publication of WO2024130541A1 publication Critical patent/WO2024130541A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/18—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

Definitions

  • the present application relates to the field of antibody drug development, and in particular, to anti-IL-1 ⁇ antibodies or antigen-binding fragments thereof, nucleic acids encoding the same, pharmaceutical compositions containing the same, and their uses in treating IL-1 ⁇ -related diseases.
  • Interleukin-1 is a cytokine belonging to the chemokine family, which can be synthesized and secreted by monocytes, macrophages, etc., including IL-1 ⁇ and IL-1 ⁇ .
  • IL-1 ⁇ is composed of 159 amino acids, encoded by the IL-1A gene, and can play an immunomodulatory role, such as activating CD4+T cells, promoting the formation of antibodies, improving antigen presentation by antigen presenting cells (APCs), and enhancing NK cell activity.
  • IL-1 ⁇ can induce the activation of key transcription factors associated with inflammation and immune responses, such as nuclear factor ⁇ B (NF- ⁇ B), activator protein-1 (AP-1), c-Jun N-terminal kinase (JNK), p38 and other mitogen-associated protein kinases (MAPK), extracellular signal-regulated kinases (ERK) and interferon-regulated genes.
  • NF- ⁇ B nuclear factor ⁇ B
  • AP-1 activator protein-1
  • JNK c-Jun N-terminal kinase
  • p38 mitogen-associated protein kinases
  • ERK extracellular signal-regulated kinases
  • IL-1 ⁇ In the extracellular space, released or membrane-bound IL-1 ⁇ binds to IL-1R1 on the cell surface and triggers a pro-inflammatory cascade.
  • IL-1 ⁇ is involved in autoimmune diseases, inflammatory diseases and cancer.
  • IL-1 ⁇ is involved in diseases characterized by tissue or organ inflammation (such as pericarditis, myositis), destruction of barrier epithelium (such as skin diseases, respiratory diseases, colitis), and endothelial damage or thromboembolic activation (such as Behcet's syndrome, vasculitis)
  • tissue or organ inflammation such as pericarditis, myositis
  • barrier epithelium such as skin diseases, respiratory diseases, colitis
  • endothelial damage or thromboembolic activation such as Behcet's syndrome, vasculitis
  • IL- IL-1 ⁇ is a highly proinflammatory cytokine in the tumor microenvironment that often increases tumor growth and invasiveness and has been reported as a candidate target for anti-cancer therapy (Peleg Rider et al., Seminars in Immunology, Interleukin-1 ⁇ , Vol. 25 (2013): 430-438; Kim Jun Cheng et al., Critical Reviews in Oncology/Hematology, IL-1 ⁇ and colorectal cancer pathogenesis: Enthralling candidate for anti-cancer therapy, Vol. 163: 103-398).
  • the present application relates to an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • HCDR1 (heavy chain CDR1), HCDR2 (heavy chain CDR2) and HCDR3 (heavy chain CDR3)
  • the HCDR1, HCDR2 and HCDR3 comprise the amino acid sequences set forth in SEQ ID NOs: 1, 2 and 3, respectively, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 1, 2 and 3;
  • HCDR1, HCDR2 and HCDR3 wherein the HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 11, 12 and 13, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 11, 12 and 13;
  • HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 21, 22 and 23, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 21, 22 and 23; or
  • HCDR1, HCDR2 and HCDR3 wherein the HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences shown in SEQ ID NOs: 31, 32 and 33, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences shown in SEQ ID NOs: 31, 32 and 33.
  • the present application relates to an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences shown in SEQ ID NOs: 1, 2 and 3 or are identical to SEQ ID NOs: NOs: 1, 2 and 3 have an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence shown in SEQ ID NOs: 108, 5 and 6, respectively, and the LCDR1, LCDR2 and LCDR3 comprise the amino acid sequence shown in SEQ ID NOs: 108, 5 and 6, respectively, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,
  • LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences shown in SEQ ID NOs: 24, 25 and 26, respectively, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences shown in SEQ ID NOs: 24, 25 and 26; or
  • the present application relates to an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region (VH), wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 47, 7, 17, 27, 37 or 39 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence shown in SEQ ID NO: 47, 7, 17, 27, 37 or 39.
  • VH heavy chain variable region
  • the present application relates to an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • a heavy chain variable region and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 47 or is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence shown in SEQ ID NO: 47.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 110;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:7
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:8, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:8;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:17, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:17
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:18, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:18;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:27, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:27
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:28, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:28;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:37, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:37
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:38, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:38;
  • (6) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 39 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 39.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 109 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 109;
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 39 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 39.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 110;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:45, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:45;
  • (9) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 47 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 47.
  • amino acid sequence wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 109 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence set forth in SEQ ID NO: 109; or
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 45 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 45.
  • the present application relates to an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:112, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:112;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:9, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:9
  • the light chain comprises the amino acid sequence of SEQ ID NO:10, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:10;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:19, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:19
  • the light chain comprises the amino acid sequence of SEQ ID NO:20, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:20;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:29, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:29
  • the light chain comprises the amino acid sequence of SEQ ID NO:30, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:30;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:112, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:112;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:111, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:111;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:46, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:46;
  • a heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:48, and the light chain comprises the amino acid sequence of SEQ ID NO:111, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:111; or
  • (9) a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 48 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 48, and the light chain comprises the amino acid sequence of SEQ ID NO: 46 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 46.
  • the present application relates to a polynucleotide encoding an anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof described herein.
  • the present application relates to a recombinant vector comprising a polynucleotide described herein.
  • the present application relates to a host cell comprising the vector described herein or having the polynucleotide described herein integrated into its genome.
  • the present application relates to a pharmaceutical composition comprising the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described in the present application.
  • the present application relates to the use of the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, in the preparation of a medicament for preventing or treating a disease associated with IL-1 ⁇ .
  • the present application relates to the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, for preventing or treating a disease associated with IL-1 ⁇ .
  • the present application relates to a method for preventing or treating an IL-1 ⁇ -related disease, comprising administering the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein to a subject in need thereof.
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein can specifically bind to IL-1 ⁇ (affinity constant can be below 1.149 ⁇ 10 -10 M), thereby blocking the binding of IL-1 ⁇ to IL1R1 and IL1RAP.
  • affinity constant can be below 1.149 ⁇ 10 -10 M
  • the cross-binding of the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein to IL-1 ⁇ is very weak, indicating that the antibody or antigen-binding fragment thereof described in the present application can have good selective specificity.
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein can effectively block the release of IL-6, IL-8 and CCL20 induced by IL-1 ⁇ , and therefore can exhibit the desired in vivo efficacy.
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein can also exhibit good stability, low immunogenicity, and have good prospects for drugability.
  • FIG1 shows the activation effect of human IL-1 ⁇ on reporter gene cell lines.
  • FIG. 2 is a graph showing the results of detecting the activities of mouse antibodies and the positive control MABP1 by the reporter gene method.
  • FIG. 3 is a graph showing the results of detecting the activities of the chimeric antibody and the positive control MABP1 by the reporter gene method.
  • FIG4 is an SDS-PAGE profile of humanized antibodies and chimeric antibodies.
  • FIG. 5 is a graph showing the results of detecting the activities of humanized antibodies and the positive control MABP1 by a reporter gene method.
  • FIG. 6 is a graph showing the results of ELISA assays of the binding activities of humanized antibodies and the positive control MABP1 to human IL-1 ⁇ (upper left subgraph), cynomolgus monkey IL-1 ⁇ (upper right subgraph), mouse IL-1 ⁇ (lower left subgraph), and rat IL-1 ⁇ (lower right subgraph).
  • FIG. 7 is a graph showing the results of ELISA detection of the binding activities of humanized antibodies and positive control MABP1 to human IL-1 ⁇ .
  • FIG8 shows the affinity test results of humanized antibodies to human IL-1 ⁇ .
  • FIG. 9 shows the affinity test results of humanized antibodies to cynomolgus monkey IL-1 ⁇ .
  • FIG. 10 is a graph showing the results of detecting the activities of humanized antibodies and the positive control MABP1 by a cytokine method.
  • FIG. 11 is a graph showing the results of detecting the activities of humanized antibody mutants expressed in CHO-K1 cells and the positive control MABP1 by a reporter gene method.
  • FIG. 12 shows the blocking effect of humanized antibody mutants on human IL-1 ⁇ -induced mouse IL-6 release.
  • FIG. 13 shows the blocking effect of humanized antibody mutants on human IL-1 ⁇ -induced mouse IL-8 release.
  • FIG. 14 shows the blocking effect of humanized antibody mutants on human IL-1 ⁇ -induced mouse CCL20 release.
  • treatment means that after administration, the disease or its related symptoms can be inhibited, contained, alleviated, improved, mitigated, relieved or eliminated, the progression of the disease or its related symptoms can be delayed, postponed, slowed, stopped or terminated, or the recurrence of the disease or its related symptoms can be prevented, controlled or reduced.
  • the term "subject” as used herein encompasses any vertebrate, e.g., mammals and non-mammals, such as humans, non-human primates, sheep, dogs, cats, horses, cows, chickens, pigs, mice, etc.
  • the subject in the present application is a human.
  • the term "subject” as used herein can be used interchangeably with the term "patient”.
  • the percent identity (degree of homology) between sequences can be determined by comparing two sequences, for example, using freely available computer programs commonly used for this purpose on the World Wide Web (eg www.ncbi.nlm.nih.gov), such as BLASTp or BLASTn with default settings.
  • the present application provides an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • HCDR1 (heavy chain CDR1), HCDR2 (heavy chain CDR2) and HCDR3 (heavy chain CDR3)
  • the HCDR1, HCDR2 and HCDR3 comprise the amino acid sequences set forth in SEQ ID NOs: 1, 2 and 3, respectively, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 1, 2 and 3;
  • HCDR1, HCDR2 and HCDR3 wherein the HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 11, 12 and 13, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 11, 12 and 13;
  • HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 21, 22 and 23, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 21, 22 and 23; or
  • HCDR1, HCDR2 and HCDR3 wherein the HCDR1, HCDR2 and HCDR3 respectively comprise the amino acid sequences shown in SEQ ID NOs: 31, 32 and 33, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences shown in SEQ ID NOs: 31, 32 and 33.
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof provided herein further comprises:
  • LCDR1 light chain CDR1
  • LCDR2 light chain CDR2
  • LCDR3 light chain CDR3
  • LCDR1, LCDR2 and LCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 108, 5 and 6, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 108, 5 and 6;
  • LCDR1, LCDR2 and LCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 14, 15 and 16, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 14, 15 and 16;
  • LCDR1, LCDR2 and LCDR3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 24, 25 and 26, or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences set forth in SEQ ID NOs: 24, 25 and 26; or
  • LCDR1, LCDR2 and LCDR3 respectively comprise the amino acid sequences shown in SEQ ID NOs: 34, 35 and 36 or amino acid sequences that are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequences shown in SEQ ID NOs: 34, 35 and 36.
  • the amino acid sequence QDIXSF shown in SEQ ID NO: 108 covers the sequence of the light chain CDR1 of the humanized antibody and the sequence of the mutated CDR1 obtained by mutating the asparagine residue (N) in the CDR1 to other amino acids.
  • the X can be selected from I, N, F, V, S, R, A, T, E, G, H, K, L, P, W, Y, C, M, Q or D; in some embodiments, the X can be selected from I, N, F, V, S, R, A, T, E, G, H, K, L, P, W or Y; preferably, the X can be I, F, V, S, R, A or T.
  • the LCDR1 may comprise an amino acid sequence selected from the group consisting of:
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof provided herein comprises:
  • CDR sequences numbered according to any one or more of the Kabat numbering rules, Chothia numbering rules, AbM numbering rules and Contact numbering rules (based on analysis of available complex crystal structures) also fall within the scope of protection of this application.
  • the present application provides an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NOs: 47, 7, 17, 27, 37 or 39 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence shown in SEQ ID NOs: 47, 7, 17, 27, 37 or 39.
  • the anti-IL-1 ⁇ antibody or its antigen-binding fragment provided by the present application further comprises a light chain variable region, which comprises the amino acid sequence shown in SEQ ID NOs: 110, 8, 18, 28, 38, 45 or 109, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence shown in SEQ ID NOs: 110, 8, 18, 28, 38, 45 or 109.
  • the present application relates to an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • a heavy chain variable region and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 47 or is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence shown in SEQ ID NO: 47.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 110;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:7
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:8, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:8;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:17, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:17
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:18, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:18;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:27, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:27
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:28, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:28;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:37, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:37
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:38, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:38;
  • (6) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 39 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 39.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 109 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 109;
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 39 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 39.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 110;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:45, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:45;
  • (9) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 47 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 47.
  • amino acid sequence wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 109 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence set forth in SEQ ID NO: 109; or
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 45 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 45.
  • the present application provides an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:95, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:95;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:7
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:8, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:8;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:17, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:17
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:18, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:18;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:27, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:27
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:28, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:28;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:37, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:37
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:38, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:38;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:40, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:40;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:43;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:45, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:45;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:40, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:40;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:43;
  • (11) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:45, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:45;
  • a heavy chain variable region and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 39 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, 125%, 126%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to an amino acid sequence, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:64, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:65, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:65;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:66, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:66;
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:67, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:67;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:68, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:68;
  • a heavy chain variable region and a light chain variable region comprising the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:69;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:70, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:71, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:72, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:72;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:73, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:73;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:74, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:74;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:75, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:75;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:76, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:76;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:77, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:77;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:39, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:39
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:78, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:78;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:94, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:94;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:96, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:96;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:97, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:97;
  • a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:98, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:98;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:99, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:99;
  • the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 47 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence shown in SEQ ID NO: 47.
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 100;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:64, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:64;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:65, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:65;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:66, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:66;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:67, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:67;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO:68, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:68;
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 69 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 69 Amino acid sequence; or
  • the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 47
  • the light chain variable region comprises the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 70.
  • the present application provides an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 37, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 38;
  • (6) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 40;
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 43;
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 45;
  • (11) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 47, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 45;
  • a heavy chain variable region and a light chain variable region wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 67;
  • (21) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 73;
  • (22) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 74;
  • (25) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 39, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 77;
  • (31) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 47, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 99;
  • (32) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 47, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 100;
  • (39) a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region has the amino acid sequence shown in SEQ ID NO: 47, and the light chain variable region has the amino acid sequence shown in SEQ ID NO: 70.
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof provided by the present application further comprises a heavy chain constant region and a light chain constant region.
  • the heavy chain constant region is the constant region of human IgG1, IgG2, IgG3 or IgG4 (preferably the constant region of human IgG1 or IgG4)
  • the light chain constant region is the constant region of human antibody ⁇ chain or ⁇ chain; more preferably, the heavy chain constant region comprises the amino acid sequence shown in SEQ ID NO: 117 or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 1177, 118%, 119%
  • the present application provides an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:102, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:102;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:9, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:9
  • the light chain comprises the amino acid sequence of SEQ ID NO:10, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:10;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:19, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:19
  • the light chain comprises the amino acid sequence of SEQ ID NO:20, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:20;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:29, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:29
  • the light chain comprises the amino acid sequence of SEQ ID NO:30, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:30;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:42;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:44, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:44;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:46, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:46;
  • a heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48, and the light chain comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:42;
  • (9) a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48, and the light chain comprises the amino acid sequence of SEQ ID NO:44, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:44;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:46, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:46;
  • (11) a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:79, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:79;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:80, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:80;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:81, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:81;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:82, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:82;
  • a heavy chain and a light chain comprising the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:83, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:83;
  • a heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41, and the light chain comprises the amino acid sequence of SEQ ID NO:84, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:84;
  • a heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41, and the light chain comprises the amino acid sequence of SEQ ID NO:85, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:85;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:86, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:86;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:87, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:87;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:88, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:88;
  • (21) a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:89, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:89;
  • (22) a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41, and the light chain comprises the amino acid sequence of SEQ ID NO:90, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:90;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:91, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:91;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:92, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:92;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:41
  • the light chain comprises the amino acid sequence of SEQ ID NO:93, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:93;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:101, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:101;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:103, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:103;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:104, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:104;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:105, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:105;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:106, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:106;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:107, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:107;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:79, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:79;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:80, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:80;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:81, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:81;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:82, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:82;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:83, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:83;
  • the heavy chain comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:48
  • the light chain comprises the amino acid sequence of SEQ ID NO:84, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:84; or
  • a heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 48 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 48, and the light chain comprises the amino acid sequence of SEQ ID NO: 85 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 85.
  • an amino acid sequence that has at least 80% identity with the amino acid sequence shown in SEQ ID NO: may mean that the amino acids in the region other than CDR (such as the framework region or constant region) in the heavy chain/heavy chain variable region or the light chain/light chain variable region are changed, and after comparison with the sequence before the change, the changed sequence has at least 80% identity.
  • the present application provides an isolated anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, comprising:
  • a heavy chain and a light chain wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 41, and the light chain has the amino acid sequence shown in SEQ ID NO: 46;
  • (11) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 41, and the light chain has the amino acid sequence shown in SEQ ID NO: 79;
  • (21) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 41, and the light chain has the amino acid sequence shown in SEQ ID NO: 89;
  • (22) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 41, and the light chain has the amino acid sequence shown in SEQ ID NO: 90;
  • (25) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 41, and the light chain has the amino acid sequence shown in SEQ ID NO: 93;
  • (26) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 48, and the light chain has the amino acid sequence shown in SEQ ID NO: 101;
  • (31) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 48, and the light chain has the amino acid sequence shown in SEQ ID NO: 107;
  • (32) a heavy chain and a light chain, wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 48, and the light chain has the amino acid sequence shown in SEQ ID NO: 79;
  • a heavy chain and a light chain wherein the heavy chain has the amino acid sequence shown in SEQ ID NO: 48, and the light chain has the amino acid sequence shown in SEQ ID NO: 85.
  • the anti-IL-1 ⁇ antibody provided herein is a murine antibody, a chimeric antibody, or a humanized antibody.
  • the anti-IL-1 ⁇ antibody or its antigen-binding fragment may also be conservatively modified.
  • Conservative modification refers to amino acid modification that does not significantly affect or change the binding properties of the antibody.
  • conservative amino acid substitution may be substitution with another amino acid of the same type (having similar chemical properties or functions).
  • amino acids can be divided into the following categories according to their side chain properties: (1) non-polar amino acids: Ala (A), Val (V), Leu (L), Ile (I), Pro (P), Phe (F), Trp (W), Met (M); (2) uncharged polar amino acids: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N), Gln (Q); (3) acidic amino acids: Asp (D), Glu (E); (4) basic amino acids: Lys (K), Arg (R), His (H).
  • amino acids can be divided based on common side chain properties: (1) hydrophobic amino acids: Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic amino acids: Cys, Ser, Thr, Asn, Gln; (3) acidic amino acids: Asp, Glu; (4) basic amino acids: His, Lys, Arg; (5) amino acids that affect chain orientation: Gly, Pro; (6) aromatic amino acids: Trp, Tyr, Phe.
  • anti-IL-1 ⁇ antibodies or antigen-binding fragments thereof and variants thereof described in the present application can specifically bind to IL-1 ⁇ .
  • the antibodies or antigen-binding fragments thereof provided herein are selected from monoclonal antibodies, Fab fragments, Fab' fragments, F(ab')2 fragments, Fd fragments, Fv fragments, dAb fragments, isolated CDR regions, scFv and nanobodies.
  • the anti-IL-1 ⁇ antibodies or antigen-binding fragments thereof described herein may exhibit a combination of one or more of the following properties:
  • the present application provides a pharmaceutical composition comprising the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described in the present application.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
  • pharmaceutically acceptable excipient refers to any excipient known in the art that has no obvious irritation to an organism, is biocompatible with an active ingredient, and does not impair the activity and properties of the active ingredient.
  • the pharmaceutical composition of the present application may be suitable for parenteral, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal administration.
  • administration may be by injection or infusion, but is not limited thereto.
  • the active ingredient may be coated in different suitable materials to protect it from irritants (e.g., acids, alkalis, metal ions) and other natural conditions (e.g., high temperature, high humidity) that may inactivate it.
  • irritants e.g., acids, alkalis, metal ions
  • other natural conditions e.g., high temperature, high humidity
  • the pharmaceutical composition of the present application may be in the form of a sterile aqueous solution or dispersion.
  • the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described in the present application may also be formulated in a microemulsion (also known as a nanoemulsion) or a liposome.
  • the appropriate dosage of the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described in the present application can be determined by a clinician according to factors such as the age, weight, sex, general condition, and severity of the disease of the subject.
  • the dosage of the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof of the present application can be administered within a dosage range of about 0.0001 to 3000 mg/kg, such as 0.001 mg/kg, 0.01 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg, 1 mg/kg, 3 mg/kg, 5 mg/kg, 10 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg, 500 mg/kg, 1000 mg/kg, 1200 mg/kg, 1500 mg/kg, 1800 mg/kg, 2000 mg/kg.
  • a single large dose can be administered, multiple divided doses can be administered over time, or the single dose can be reduced or increased in proportion to the severity of the treatment situation.
  • the antibody when administered as a sustained release formulation, it can be administered at a reduced frequency.
  • the present application provides a polynucleotide encoding an anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof as described herein.
  • the polynucleotide comprises a polynucleotide encoding a heavy chain variable region or/and a light chain variable region of an anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof as described herein, respectively.
  • the polynucleotide comprises a polynucleotide encoding a heavy chain and a light chain of an anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof, respectively.
  • the present application provides a recombinant vector comprising the polynucleotide.
  • the vector is a cloning vector; in other embodiments, the vector is an expression vector.
  • the expression vector may optionally be any expression vector capable of expressing the antibody or antigen-binding fragment thereof described herein.
  • the present application provides a host cell comprising the vector or having the polynucleotide integrated into its genome.
  • the host cell herein may be any suitable host cell for expressing an anti-IL-1 ⁇ antibody or an antigen-binding fragment thereof.
  • the host cell is a prokaryotic cell.
  • the host cell is a eukaryotic cell.
  • the host cell is selected from yeast cells, mammalian cells, or other cells suitable for preparing antibodies or antigen-binding fragments thereof.
  • Mammalian cells are, for example, Chinese hamster ovary cells (CHO), human kidney epithelial cell line 293 cells, or 293T cells.
  • the present application relates to the use of the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, in the preparation of a medicament for blocking the release of inflammatory cytokines.
  • the present application relates to the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, for blocking the release of inflammatory cytokines.
  • the present application relates to a method for blocking the release of inflammatory cytokines in a subject, comprising administering the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, to a subject in need thereof.
  • the inflammatory cytokines are IL-6, IL-8 and CCL20.
  • the present application relates to the use of the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, in the preparation of a medicament for preventing or treating a disease associated with IL-1 ⁇ .
  • the present application relates to the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein, for preventing or treating a disease associated with IL-1 ⁇ .
  • the present application relates to a method for preventing or treating an IL-1 ⁇ -related disease, comprising administering the anti-IL-1 ⁇ antibody or antigen-binding fragment thereof described herein, or the pharmaceutical composition described herein to a subject in need thereof.
  • the IL-1 ⁇ -related disease can be selected from atopic dermatitis, hidradenitis suppurativa, pyoderma gangrenosum, Sweet syndrome, Sjögren's syndrome ( syndrome), systemic sclerosis, progressive fibrosis, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, bronchopulmonary dysplasia, pericarditis, myositis, myocarditis, myocarditis, myocardial infarction, ischemia-reperfusion injury, respiratory diseases, colitis, Behcet's syndrome, Erdheim-Chester disease, vasculitis, IL-1Ra deficiency (DIRA), Kawasaki disease, aneurysm, lung cancer (non-small cell and small cell), kidney cancer, thyroid cancer, neuroendocrine cancer, pseudomyxoma peritonei, Castleman disease, rectal cancer, pancreatic cancer, and colorectal cancer.
  • the subject is a mammal, such as a human.
  • the nucleic acid sequence information of the coding regions of human IL1R1 and IL1RAP was obtained from the UniProt database, and the genes were synthesized and subcloned into lentiviral expression vectors. Lentivirus was prepared (see, for example, Neha Tandon et al., Bio Protoc. 2018 Nov 5; 8(21): e3073), and 293 cells were infected respectively.
  • the recombinant cell lines that stably overexpressed IL1R1 and IL1RAP were screened using 2 ⁇ g/mL puromycin antibiotics, and the cells were further infected with Lenti-NF- ⁇ B-Luciferase-Hygro lentivirus, and 200 ⁇ g/mL Hygromycin B was added to screen the stable transfected cell lines to obtain the 293F-IL1RI-IL1RAP-NFkB-Luc reporter gene cell line.
  • the activation effect of IL-1 ⁇ on the reporter gene cell line was verified according to the following steps.
  • Human IL-1 ⁇ was adjusted to a concentration of 0.2 ⁇ g/mL using HybGro serum-free medium, and then diluted 10-fold in a series of 9 dilutions (2 ⁇ 10 -1 to 2 ⁇ 10 -9 ⁇ g/mL).
  • the 96-well plate was removed, 20 ⁇ L of Bright-Glo TM detection reagent (purchased from Promega) was added, and the plate was placed at room temperature away from light for 5 min.
  • the Luciferase fluorescence value was read using a Tecan M1000 multifunctional microplate reader. The data are shown in FIG1 , indicating that the reporter gene cell line can be activated by human IL-1 ⁇ in a dose-dependent manner.
  • mice Take 10 Balb/c and 10 CD1 mice, use 50 ⁇ g of human and cynomolgus monkey IL-1 ⁇ emulsified with Freund's adjuvant, and immunize the mice subcutaneously at multiple points, for a total of 3 immunizations, with an interval of 14 days. Take mice with good immune titer detection for shock immunization, and kill them by cervical dislocation 3 days later. Obtain the mouse spleen under sterile conditions, prepare B cell single cell suspension, and mix it with SP2/0 myeloma cells in a ratio of 1:1, and use BTX cell electrofusion instrument for cell fusion.
  • DMEM complete culture medium
  • FBS FBS
  • HAT complete culture medium
  • the hybridomas of monoclonal 14-D8-A6-D7, 30-E12-E4-G9, 17-B12-C9, and 48-G12-G2 obtained from the above two rounds of subclone screening were amplified and cultured, and then the mouse antibodies were purified by protein A column affinity chromatography.
  • the purified antibodies were detected by the reporter gene method according to the following steps, and the IC50 value was calculated, wherein Xbiotech's IL-1 ⁇ antibody Bermekimab (MABP1) was used as a positive control, and the amino acid sequence of MABP1 was derived from patent CN200980125033, as shown below.
  • the purified mouse antibody or positive control antibody MABP1 was diluted 10-fold starting from the highest concentration of 400 ⁇ g/mL, and 9 dilutions were made in succession (4 ⁇ 10 2 to 4 ⁇ 10 -6 ⁇ g/mL).
  • 2 ⁇ 10 6 293F-IL1RI-IL1RAP-NFkB-Luc cells in the logarithmic growth phase were transferred to a 15 mL centrifuge tube, centrifuged at 500 g for 5 min, the supernatant was removed, 10 mL PBS was added for resuspending, centrifuged at 500 g for 5 min, the supernatant was removed, and the cells were resuspended in 10 mL HybGro serum-free medium. After thorough mixing, 100 ⁇ L of the cell suspension was aspirated and added to a 96-well plate. 200 ⁇ L HybGro serum-free medium was added to the blank background well. The plates were cultured at 37°C and 5% CO 2 for 18 h.
  • Table 1 shows the activity detection results of the reporter gene method, in which the candidate mouse antibodies can block the fluorescence signal induced by IL-1 ⁇ .
  • the representative results are shown in Figure 2, and it can be seen that the activity of the mouse antibody 30-E12-E4-G9 is significantly better than the positive control MABP1.
  • the amino acid sequences of the light chain and heavy chain variable regions of the mouse antibodies 30-E12-E4-G9, 17-B12-C9-D6, and 48-G12-G2 with higher activity were obtained by hybridoma sequencing.
  • the heavy chain variable region was subcloned into the pcDNA3.4-hIgG1 expression vector, and the light chain variable region was subcloned into the pcDNA3.4-hIgKc expression vector to obtain the heavy chain expression vector and the light chain expression vector.
  • the DNA/LVTransm complex obtained above was added to 100 mL of 293F cells (cell density 1 ⁇ 10 6 /mL) and gently shaken to mix thoroughly.
  • the cells were placed in a carbon dioxide shaker and cultured continuously for 7 days at 37°C, 5% CO 2 , and 130 rpm.
  • the culture supernatant was collected by centrifugation, filtered with a 0.45 ⁇ m filter membrane, and the chimeric antibody was purified by protein A affinity chromatography.
  • the chimeric antibody was tested by reporter gene method according to the steps described above. Table 2 shows the activity test results. It can be seen that the activity of 30-E12-E4-G9 chimeric antibody and 48-G12-G2-G2 chimeric antibody is still significantly better than the positive control MABP1.
  • the representative results are shown in Figure 3.
  • the chimeric antibody 30-E12-E4-G9 with the highest activity was humanized.
  • the humanization design was based on the amino acid sequence of the heavy and light chains of the mouse antibody, and the CDR region sequence of the original antibody was kept unchanged. According to the results of germline alignment and antibody structure simulation, different humanized antibody templates were selected for the heavy and light chains, and the framework regions were back mutated after humanization to design candidate humanized antibody sequences.
  • the heavy and light chains of the designed humanized antibodies were gene synthesized separately, and the heavy chain was subcloned into the pcDNA3.4-hIgG1 expression vector, and the light chain was subcloned into the pcDNA3.4-hIgKc expression vector.
  • Figure 4 shows that the purity of humanized antibodies 30-E12-1, 30-E12-2, 30-E12-3, 30-E12-4, 30-E12-5, and 30-E12-6 was greater than 90%.
  • the chimeric antibodies and humanized antibodies 30-E12-1, 30-E12-2, 30-E12-4 and 30-E12-5 with higher activity were selected to detect the binding activity with different species of IL-1 ⁇ and homologous protein human IL-1 ⁇ by ELISA method.
  • the experimental steps are as follows:
  • Antigen coating dilute the antigen to 1 ⁇ g/mL with coating solution (1 ⁇ CBS), add 100 ⁇ L/well to the ELISA plate, and place it at 4°C for overnight coating;
  • Blocking Take out the ELISA plate, discard the solution in the wells, add 300 ⁇ L PBST buffer (1 ⁇ ), soak for 5 seconds, wash the plate once, and pat the remaining droplets on the plate on absorbent paper as much as possible after washing. Add 200 ⁇ l of blocking solution (2% BSA/PBST) to each well, cover the plate with a sealing film, and block at 37°C for 2h;
  • Anti-IL-1 ⁇ antibody gradient dilution dilute the anti-IL-1 ⁇ antibody 3.5 times from the highest concentration of 10 ⁇ g/mL (take 50 ⁇ L of the test sample stock solution and add it to 125 ⁇ L of diluent (0.5% BSA/PBST) and perform gradient dilution in sequence), and dilute 11 gradients continuously (10000, 2857.14, 816.33, 233.24, 66.64, 19.04, 5.44, 1.55, 0.44, 0.13, 0.036, 0 ng/ml);
  • Sample addition transfer the gradient diluted anti-IL-1 ⁇ antibody solution to the ELISA plate, 100 ⁇ L/well, cover with sealing film, and incubate at 37°C for 1 hour;
  • Secondary antibody dilution dilute Anti-human IgG-HRP 50,000 times with diluent;
  • Color development Add 100 ⁇ L/well of TMB substrate solution to the ELISA plate, cover with sealing film, and incubate at 37°C in the dark for 10 minutes for color development;
  • Termination Add 100 ⁇ L/well of the stop solution to the ELISA plate to terminate the reaction;
  • the test results are shown in Table 4, Figure 6 and Figure 7.
  • the humanized antibody has strong cross-binding with human and cynomolgus monkey IL-1 ⁇ , and weak cross-binding with mouse and rat IL-1 ⁇ .
  • the cross-binding of the humanized antibody to IL-1 ⁇ , a homologous protein of IL-1 ⁇ is very weak, indicating that the humanized antibody has good selective specificity.
  • the Fortebio instrument moved the sensor to read in the analyte wells of each concentration gradient, and the binding and dissociation of the antibody to be tested with IL-1 ⁇ were monitored in real time, with an equilibrium time of 150s, a binding time of 180s, a dissociation time of 300s, and a detection temperature of 25°C.
  • the experimental data were fitted using the instrument supporting software in the Steady affinity mode.
  • test results show that the humanized antibody has a very high affinity for human IL-1 ⁇ , with the highest KD reaching the pM order of magnitude, and also has a very high affinity for cynomolgus monkey IL-1 ⁇ .
  • the results are shown in Table 5, Figures 8 and 9.
  • the functional activity of humanized antibodies was evaluated by detecting the release of cytokine IL-8 from MRC-5 cells.
  • the experimental steps are as follows:
  • MRC-5 cells in the logarithmic growth phase (purchased from the Chinese Academy of Sciences) and add them to a 15 mL centrifuge tube, mix them, and centrifuge them at 200 g for 5 min. After centrifugation, resuspend the cells in DMEM + 10% FBS medium. After sufficient mixing, adjust the cell suspension density to 1 ⁇ 10 5 cells/mL, take 200 ⁇ L of the cell suspension, add it to a 96-well plate, and add 2 ⁇ 10 4 cells per well. Transfer the 96-well plate to a carbon dioxide incubator and continue to culture at 37°C and 5% CO 2 for 18 h.
  • IL-1 ⁇ protein human IL-1 ⁇ (purchased from Suzhou Nearshore Protein Technology Co., Ltd.) was adjusted to 0.02 ⁇ g/mL using DMEM basal medium;
  • Humanized antibody gradient dilution The humanized antibody and the positive control MABP1 were diluted 3.5 times from the highest concentration of 20 ⁇ g/mL, and 10 gradients were continuously diluted (20, 5.71, 1.63, 0.47, 0.13, 0.038, 0.011, 0.0031, 0.00089, 0.00025 ⁇ g/mL).
  • Example 11 In vivo efficacy test of humanized antibody mutants in mice
  • the in vivo efficacy of the humanized antibody mutants was evaluated by detecting the blocking effect of two humanized antibody mutants 30-E12-4-I and 30-E12-2-V on the release of mouse cytokines IL-6, IL-8, and CCL20 induced by human IL-1 ⁇ .
  • Antibody 1 low-dose group 10 ⁇ g/kg human IL-1 ⁇ (purchased from Suzhou Nearshore Protein Technology Co., Ltd.) was intraperitoneally injected, followed by 1 mg/kg humanized antibody mutant 30-E12-4-I was subcutaneously injected.
  • Antibody 1 high-dose group intraperitoneal injection of 10 ⁇ g/kg human IL-1 ⁇ , followed by subcutaneous injection of 3 mg/kg humanized antibody mutant 30-E12-4-I.
  • Antibody 2 low-dose group intraperitoneal injection of 10 ⁇ g/kg human IL-1 ⁇ , followed by subcutaneous injection of 1 mg/kg humanized antibody mutant 30-E12-2-V.
  • Antibody 2 high-dose group intraperitoneal injection of 10 ⁇ g/kg human IL-1 ⁇ , followed by subcutaneous injection of 3 mg/kg humanized antibody mutant 30-E12-2-V.
  • Positive control low-dose group intraperitoneal injection of 10 ⁇ g/kg human IL-1 ⁇ , followed by subcutaneous injection of 1 mg/kg positive control MABP1.
  • Positive control high-dose group intraperitoneal injection of 10 ⁇ g/kg human IL-1 ⁇ , followed by subcutaneous injection of 3 mg/kg positive control MABP1.
  • Negative control group intraperitoneal injection of 10 ⁇ g/kg human IL-1 ⁇ , followed by subcutaneous injection of sterile PBS (purchased from Beijing Zhongshan Jinqiao Biotechnology Co., Ltd., pH 7.3).
  • Blank control group sterile PBS was injected intraperitoneally and then subcutaneously.
  • mice in all groups were killed 2 hours later and blood was collected.
  • the blood samples were centrifuged at 4000g for 10 min at 4°C to separate the serum and store at -80°C.
  • the corresponding commercial ELISA kits (all purchased from Hangzhou Lianke Biotechnology Co., Ltd.) were used to detect the content of mouse IL-6, IL-8 and CCL20 in each serum according to the instructions provided by the manufacturer.
  • the test results are shown in Table 9 and Figures 12 to 14.
  • the results of this experiment showed that the humanized antibody mutants and the positive control MABP1 were able to significantly block the release of mouse cytokines IL-6, IL-8 and CCL20 induced by human IL-1 ⁇ in a dose-dependent manner, among which the blocking effects of the antibody mutants 30-E12-4-I and 30-E12-2-V were higher than those of the positive control MABP1, especially for the release of mouse CCL20.
  • X can be I, N, F, V, S, R, A, T, E, G, H, K, L, P, W, Y, C, M, Q or D.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un anticorps anti-IL-1α isolé ou un fragment de liaison à l'antigène de celui-ci, un acide nucléique codant pour celui-ci et une composition pharmaceutique le comprenant, et l'utilisation de l'anticorps ou du fragment de liaison à l'antigène de celui-ci, de l'acide nucléique et de la composition pharmaceutique pour le traitement de maladies associées à IL-1α.
PCT/CN2022/140312 2022-12-20 2022-12-20 ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION WO2024130541A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN202280059497.7A CN117957250A (zh) 2022-12-20 2022-12-20 一种靶向IL-1α的抗体或其抗原结合片段及其应用
PCT/CN2022/140312 WO2024130541A1 (fr) 2022-12-20 2022-12-20 ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/140312 WO2024130541A1 (fr) 2022-12-20 2022-12-20 ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION

Publications (1)

Publication Number Publication Date
WO2024130541A1 true WO2024130541A1 (fr) 2024-06-27

Family

ID=90795074

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/140312 WO2024130541A1 (fr) 2022-12-20 2022-12-20 ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION

Country Status (2)

Country Link
CN (1) CN117957250A (fr)
WO (1) WO2024130541A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040103007A (ko) * 2003-05-30 2004-12-08 한국생명공학연구원 인간 ｐｒｏＩＬ－１α와 ＩＬ－１α에 대한단일클론항체, 이를 생산하는 융합세포주 및단일클론항체의 제조방법
CN102112495A (zh) * 2008-06-03 2011-06-29 雅培制药有限公司 双重可变结构域免疫球蛋白及其用途
CN102112154A (zh) * 2008-05-30 2011-06-29 埃克斯生物科技公司 IL-1α抗体及使用方法
CN102296050A (zh) * 2011-05-30 2011-12-28 苏州大学 抗人IL-1α单克隆抗体及其应用
CN102369217A (zh) * 2009-01-29 2012-03-07 雅培制药有限公司 Il-1结合蛋白
US20130171146A1 (en) * 2006-12-29 2013-07-04 Abbott Laboratories Dual-specific il-1a/ il-1b antibodies
WO2020219506A1 (fr) * 2019-04-24 2020-10-29 Janssen Biotech, Inc. Formulation d'anticorps
WO2022073102A1 (fr) * 2020-10-07 2022-04-14 Xbiotech Inc. ANTICORPS HUMAIN VÉRITABLE SPÉCIFIQUE DE L'INTERLEUKINE 1 ALPHA (IL-1α)

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040103007A (ko) * 2003-05-30 2004-12-08 한국생명공학연구원 인간 ｐｒｏＩＬ－１α와 ＩＬ－１α에 대한단일클론항체, 이를 생산하는 융합세포주 및단일클론항체의 제조방법
US20130171146A1 (en) * 2006-12-29 2013-07-04 Abbott Laboratories Dual-specific il-1a/ il-1b antibodies
CN102112154A (zh) * 2008-05-30 2011-06-29 埃克斯生物科技公司 IL-1α抗体及使用方法
CN102112495A (zh) * 2008-06-03 2011-06-29 雅培制药有限公司 双重可变结构域免疫球蛋白及其用途
CN102369217A (zh) * 2009-01-29 2012-03-07 雅培制药有限公司 Il-1结合蛋白
CN102296050A (zh) * 2011-05-30 2011-12-28 苏州大学 抗人IL-1α单克隆抗体及其应用
WO2020219506A1 (fr) * 2019-04-24 2020-10-29 Janssen Biotech, Inc. Formulation d'anticorps
WO2022073102A1 (fr) * 2020-10-07 2022-04-14 Xbiotech Inc. ANTICORPS HUMAIN VÉRITABLE SPÉCIFIQUE DE L'INTERLEUKINE 1 ALPHA (IL-1α)

Also Published As

Publication number Publication date
CN117957250A (zh) 2024-04-30

Similar Documents

Publication Publication Date Title
KR20210018336A (ko) 항인터류킨-17a 항체, 그의 약학 조성물 및 용도
TWI636063B (zh) 結合ｉｌ－２３之抗體
WO2020135710A1 (fr) Anticorps dirigé contre il-4 ra humain et son utilisation
EP4289861A1 (fr) Anticorps contre la tslp humaine et leur utilisation
TW202023612A (zh) 結合人ｉｌ－４ｒ的抗體、其抗原結合片段及其醫藥用途
WO2023274286A1 (fr) Anticorps anti-crtam et son utilisation
JP2021500856A (ja) Ｉｌ−６ｒ抗体およびその抗原結合フラグメントならびに医薬としての使用
CN112041347A (zh) 结合人il-4r的抗体、其制备方法和用途
KR20230116857A (ko) 항 tslp 항체의 약학 조성물 및 이의 용도
CN104045713B (zh) 一种抗Blys的单克隆抗体及含有该抗体的药物组合物
CN115433275A (zh) 抗胸腺基质淋巴细胞生成素（tslp）抗体及其用途
CN112638940B (zh) 抗-il-25抗体及其用途
WO2024130541A1 (fr) ANTICORPS CIBLANT L'IL-1α OU FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET LEUR UTILISATION
WO2019238074A1 (fr) Anticorps lag-3 ayant une affinité élevée et une haute activité biologique, et utilisation associée
EP3878867A1 (fr) Anticorps se liant à l'il-1 ? humaine, son procédé de préparation et son utilisation
CN113817058B (zh) 一种抗人il-17rc的单克隆抗体及其应用
Li et al. Development and characterization of anti-IL-5 monoclonal antibody Fab fragment for blocking IL-5/IL-5Rα binding
TWI827980B (zh) 結合人il-33的抗體、其製備方法和用途
CN113698480B (zh) 一组il-23单克隆抗体及其医药用途
RU2825460C1 (ru) Антитела к TSLP человека и их применение
WO2023036127A1 (fr) Anticorps ou fragment de liaison à l'antigène de celui-ci ciblant il-23p19, et son utilisation
WO2023236844A1 (fr) Anticorps bispécifique ciblant her2 et pd-l1, son procédé de préparation et son utilisation
CN112079922B (zh) 抗人p40蛋白域抗体及其用途
CN109705217A (zh) 抗il-13抗体及其用途
KR20170076332A (ko) 항 Ang2 항체를 포함하는 면역강화제

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22968844

Country of ref document: EP

Kind code of ref document: A1