Anti-trka antibodies, derivatives and uses thereof

Abstract

The present invention relates to an antibody, recombinant or synthetic antigen-binding fragments thereof able to recognise and bind an epitope comprised in the TrkA amino acid sequence, medical uses thereof and a pharmaceutical composition comprising at least one of the above antibody, recombinant or synthetic antigen-binding fragments thereof.

1 . An antibody, recombinant or synthetic antigen-binding fragments thereof which is able to recognise and bind a sequence having at least 80% identity to an epitope comprising the sequence from amino acid residue 294 to amino acid residue 299 of the human TrkA amino acid sequence of SEQ ID NO: 65. 
     
     
         2 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , which is an NGF antagonist. 
     
     
         3 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , wherein said epitope consists of the sequence from amino acid residue 294 to amino acid residue 299 of the human TrkA amino acid sequence of SEQ ID NO: 65. 
     
     
         4 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising at least one heavy chain complementary determining region (CDRH3) amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 64, 43, 46, 49, 52, 55, 58 and 61. 
     
     
         5 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising at least one heavy chain complementary determining region (CDRH1) amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 62, 41, 44, 47, 50, 53, 56 and 59. 
     
     
         6 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising at least one heavy chain complementary determining region (CDRH2) amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 63, 42, 45, 48, 51, 54, 57 and 60. 
     
     
         7 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 6 , comprising a CDRH1 amino acid sequence having at least 80% identity to SEQ ID NO: 62, a CDRH2 amino acid sequence having at least 80% identity to SEQ ID NO: 63 and a CDRH3 amino acid sequence having at least 80% identity to SEQ ID NO: 64. 
     
     
         8 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising at least one light chain complementary determining region (CDRL3) amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 40, 19, 22, 25, 28, 31, 34 and 37. 
     
     
         9 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising at least one light chain complementary determining region (CDRL1) amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 38, 17, 20, 23, 26, 29, 32 and 35. 
     
     
         10 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising at least one light chain complementary determining region (CDRL2) amino acid sequence having at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 39, 18, 21, 24, 27, 30, 33 and 36. 
     
     
         11 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 10 , comprising a CDRL1 amino acid sequence having at least 80% identity to SEQ ID NO: 38, a CDRL2 amino acid sequence having at least 80% identity to SEQ ID NO: 39 and a CDRL3 amino acid sequence having at least 80% identity to SEQ ID NO: 40. 
     
     
         12 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising a heavy chain variable region comprising SEQ ID NOs: 15, 1, 3, 5, 7, 9, 11 or 13. 
     
     
         13 . The antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , comprising a light chain variable region comprising SEQ ID NOs: 16, 2, 4, 6, 8, 10, 12 or 14. 
     
     
         14 . A method for treating pain, cancer, neuronal disorders, inflammation-related diseases, or diabetes, in a subject in need thereof comprising administering an effective amount of at least one of an antibody, recombinant or synthetic antigen-binding fragments thereof, according to  claim 1 . 
     
     
         15 . A pharmaceutical composition comprising at least one antibody, recombinant or synthetic antigen-binding fragments thereof according to  claim 1 , and pharmaceutically acceptable excipients. 
     
     
         16 . A method of inhibiting TrkA in a subject in need thereof, comprising administering an effective amount of at least one of an antibody, recombinant or synthetic antigen-binding fragments thereof, according to  claim 1 . 
     
     
         17 . The antibody according to  claim 1 .