JPWO2020238998A5 - - Google Patents

Claims (15)

An antibody or antigen-binding fragment thereof capable of specifically recognizing TrkA, wherein the antibody is :
having at least 95% identity to heavy chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, or SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively Amino acid sequences or heavy chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, or at least 95% identical to SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively heavy chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, or SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively, and at least amino acid sequences with 95% identity, or heavy chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, or SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 11 and SEQ ID NO: 11, respectively Amino acid sequences having at least 95% identity to 12, or heavy chain variable region CDR1, CDR2, CDR3 sequences as shown in SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15, or SEQ ID NO: 13, SEQ ID NO: 14, respectively. and an amino acid sequence having at least 95% identity to SEQ ID NO: 15, or heavy chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO: 16, SEQ ID NO: 17 and SEQ ID NO: 18, or SEQ ID NO: 16, respectively, Amino acid sequences having at least 95% identity to SEQ ID NO: 17 and SEQ ID NO: 18, or heavy chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21, or sequences, respectively amino acid sequences having at least 95% identity to SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21; amino acid sequences having at least 95% identity to SEQ ID NO:22, SEQ ID NO:23 and SEQ ID NO:24, respectively; sequences, or amino acid sequences having at least 95% identity with SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively , and
Light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:28, SEQ ID NO:29 and SEQ ID NO:30, or amino acids having at least 95% identity to SEQ ID NO:28, SEQ ID NO:29 and SEQ ID NO:30, respectively or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:31, SEQ ID NO:32 and SEQ ID NO:33, or at least 95% identity to SEQ ID NO:31, SEQ ID NO:32 and SEQ ID NO:33, respectively or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:34, SEQ ID NO:35 and SEQ ID NO:36, or SEQ ID NO:34, SEQ ID NO:35 and SEQ ID NO:36 and at least 95, respectively amino acid sequences with % identity, or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:37, SEQ ID NO:38 and SEQ ID NO:39, or SEQ ID NO:37, SEQ ID NO:38 and SEQ ID NO:39, respectively or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42, or SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 41 and an amino acid sequence having at least 95% identity to SEQ ID NO:42, or a light chain variable region CDR1, CDR2, CDR3 sequence as set forth in SEQ ID NO:43, SEQ ID NO:44 and SEQ ID NO:45, or SEQ ID NO:43, sequence, respectively amino acid sequences having at least 95% identity to SEQ ID NO:44 and SEQ ID NO:45, or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:46, SEQ ID NO:47 and SEQ ID NO:48, or SEQ ID NO:48, respectively 46, SEQ ID NO:47 and SEQ ID NO:48, or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:49, SEQ ID NO:50 and SEQ ID NO:51, or respectively , SEQ ID NO:49, SEQ ID NO:50 and SEQ ID NO:51, or light chain variable region CDR1, CDR2, CDR3 sequences as set forth in SEQ ID NO:52, SEQ ID NO:53 and SEQ ID NO:54 or amino acid sequences having at least 95% identity to SEQ ID NO: 52, SEQ ID NO: 53 and SEQ ID NO: 54, respectively
An antibody or antigen-binding fragment thereof comprising a CDR sequence selected from at least one of The antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody has a heavy chain variable region of the amino acid sequence shown in any one of SEQ ID NOs:55 to 63. 2. The antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody has a light chain variable region of the amino acid sequence shown in any one of SEQ ID NO:64-SEQ ID NO:72. both the light chain constant region and the heavy chain constant region of said antibody are derived from human IgG4 ,
2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the Fc region of said antibody has S10P, F16A, L17A, R191K mutations and 229K deletion mutations compared to wild type. 2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the full-length sequence of said constant region of said antibody is set forth in SEQ ID NO:74 or SEQ ID NO:75. The claim that said antibody has a heavy chain of the amino acid sequence shown in any one of SEQ ID NO:76 to SEQ ID NO:84 and a light chain of the amino acid sequence shown in any one of SEQ ID NO:85 to SEQ ID NO:93. 2. The antibody or antigen-binding fragment thereof according to 1 . wherein the antibody is a single-chain antibody fragment, multimeric antibody, CDR-grafted antibody, or small molecule antibody ;
2. The antibody or antigen-binding fragment thereof according to claim 1 , wherein said antibody is a single-chain antibody fragment and said antibody has the amino acid sequence shown in SEQ ID NO:94 to SEQ ID NO:111. encoding the antibody or antigen-binding fragment thereof of any one of claims 1 to 7 ,
is DNA ,
a nucleotide sequence as set forth in any one of SEQ ID NOs: 112-120, or a nucleotide sequence as set forth in any one of SEQ ID NOs: 121-129, or a nucleotide sequence as set forth in any one of SEQ ID NOs: 130-147 A nucleic acid molecule having a nucleotide sequence as shown in any one. 8. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 7 , a nucleic acid molecule according to claim 8 . A kit for detecting TrkA, comprising the antibody of any one of claims 1-7 . A mouse B cell, wherein the genome of said B cell carries a sequence encoding a constant region, said constant region sequence having S108P, F114A, L115A, R289K mutations and Mouse B cell with 327K deletion mutation. Pain, cancer, inflammation or inflammatory diseases, neurodegenerative diseases, Sjögren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, pelvic pain syndrome, diseases associated with imbalance in the regulation of bone remodeling and connective tissue an antibody according to any one of claims 1 to 7 , a nucleic acid molecule according to claim 8 , for use in the preparation of a medicament for the treatment or prevention of diseases caused by abnormal signaling of growth factors ; or a pharmaceutical composition according to claim 9 . The pharmaceutical is neuropathic pain, inflammatory pain, cancer-related pain, fracture-related pain, surgery-related pain, inflammatory lung disease, interstitial cystitis, painful bladder syndrome, inflammatory bowel disease, inflammatory skin disease , Raynaud's syndrome, idiopathic pulmonary fibrosis, scarring (hypertrophy, keloid type and other forms), sclerosis, endomyocardial fibrosis, atrial fibrosis, myelofibrosis, progressive massive fibrosis (lung), kidney systemic fibrosis, scleroderma, systemic sclerosis, joint fibrosis, ocular fibrosis, non-small cell lung cancer, papillary thyroid cancer, glioblastoma multiforme, colorectal cancer, melanoma, bile duct 12. Used to treat or prevent cancer or sarcoma, acute myelogenous leukemia, large cell neuroendocrine carcinoma, neuroblastoma, prostate cancer, pancreatic cancer, melanoma, head and neck squamous cell carcinoma or gastric cancer. The antibody, nucleic acid molecule , or pharmaceutical composition according to . 8. An antibody according to any one of claims 1 to 7 , a nucleic acid molecule according to claim 8 , for use in preparing a kit for detecting TrkA or diagnosing a TrkA-associated disease. 12. Mouse B cells according to claim 11 for use in preparing monoclonal antibodies.