Anti-cMET antibody
Antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.
1. A method for inhibiting the growth and/or the proliferation of tumor cells, the method comprising the administration to a subject in need thereof of a monoclonal antibody comprising:
a heavy chain comprising complementarity determining regions (CDR) CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;
a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; and
a modified hinge region comprising the amino acid sequence SEQ ID No. 28.
2. The method of claim 1 , wherein the antibody is a chimeric antibody.
3. The method of claim 1 , wherein the antibody is a human antibody.
4. The method of claim 1 , wherein the antibody is a humanized antibody.
5. The method of claim 1 , wherein the antibody comprises:
a heavy chain variable domain comprising the amino acid sequence SEQ ID No. 4; and
a light chain variable domain comprising amino acid sequence SEQ ID No. 10.
6. The method of claim 5 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
7. The method of claim 6 , wherein the human light chain constant region is of the IgG1 kappa isotype.
8. The method of claim 1 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
9. The method of claim 8 , wherein the human light chain constant region is of the IgG1 kappa isotype.
10. The method of claim 6 , wherein the antibody is chemically coupled to a mitotic inhibitor.
11. The method of claim 8 , wherein the antibody is chemically coupled to a mitotic inhibitor.
12. A method for treating cancer, the method comprising administering to a subject in need thereof a monoclonal antibody comprising:
a heavy chain comprising complementarity determining regions (CDR) CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;
a light chain comprising CDR-L1, CDR-L2, and CDR-L3 , comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; and
a modified hinge region comprising the amino acid sequence SEQ ID No. 28.
13. The method of claim 12 , wherein the antibody is a chimeric antibody.
14. The method of claim 12 , wherein the antibody is a human antibody.
15. The method of claim 12 , wherein the antibody is a humanized antibody.
16. The method of claim 12 , wherein the antibody comprises:
a heavy chain variable domain comprising the amino acid sequence SEQ ID No. 4; and
a light chain variable domain comprising amino acid sequence SEQ ID No. 10.
17. The method of claim 16 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
18. The method of claim 17 , wherein the human light chain constant region is of the IgG1 kappa isotype.
19. The method of claim 12 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
20. The method of claim 19 , wherein the human light chain constant region is of the IgG1 kappa isotype.
21. The method of claim 17 , wherein the antibody is chemically coupled to a mitotic inhibitor.
22. The method of claim 19 , wherein the antibody is chemically coupled to a mitotic inhibitor.
23. The method according to any one of claims 1 - 22 , wherein the cancer is chosen from prostate cancer, osteosarcoma, lung cancer, breast cancer, endometrial cancer, glyoblastoma, and colon cancer.
24. The method according to any one of claims 1 - 22 , wherein the cancer is a c-Met-activation-related cancer chosen from c-Met-activation-related cancers that are HGF-dependent, HGF-independent, or both.
25. A method for inhibiting the growth and/or the proliferation of tumor cells, the method comprising administering to a subject in need thereof a composition comprising a pharmaceutically acceptable vehicle and a monoclonal antibody comprising:
a heavy chain comprising complementarity determining regions (CDR) CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;
a light chain comprising CDR-L1, CDR-L2, and CDR-L3 , comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; and
a modified hinge region comprising the amino acid sequence SEQ ID No. 28.
26. The method of claim 25 , wherein the antibody is a chimeric antibody.
27. The method of claim 25 , wherein the antibody is a human antibody.
28. The method of claim 25 , wherein the antibody is a humanized antibody.
29. The method of claim 25 , wherein the antibody comprises:
a heavy chain variable domain comprising the amino acid sequence SEQ ID No. 4; and
a light chain variable domain comprising amino acid sequence SEQ ID No. 10.
30. The method of claim 29 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
31. The method of claim 30 , wherein the human light chain constant region is of the IgG1 kappa isotype.
32. The method of claim 25 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
33. The method of claim 32 , wherein the human light chain constant region is of the IgG1 kappa isotype.
34. The method of claim 30 , wherein the antibody is chemically coupled to a mitotic inhibitor.
35. The method of claim 32 , wherein the antibody is chemically coupled to a mitotic inhibitor.
36. A method for treating cancer, the method comprising administering to a subject in need thereof a composition comprising a pharmaceutically acceptable vehicle and a monoclonal antibody comprising:
a heavy chain comprising complementarity determining regions (CDR) CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;
a light chain comprising CDR-L1, CDR-L2, and CDR-L3 , comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; and
a modified hinge region comprising the amino acid sequence SEQ ID No. 28.
37. The method of claim 36 , wherein the antibody is a chimeric antibody.
38. The method of claim 36 , wherein the antibody is a human antibody.
39. The method of claim 36 , wherein the antibody is a humanized antibody.
40. The method of claim 36 , wherein the antibody comprises:
a heavy chain variable domain comprising the amino acid sequence SEQ ID No. 4; and
a light chain variable domain comprising amino acid sequence SEQ ID No. 10.
41. The method of claim 40 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
42. The method of claim 41 , wherein the human light chain constant region is of the IgG1 kappa isotype.
43. The method of claim 36 , wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
44. The method of claim 43 , wherein the human light chain constant region is of the IgG1 kappa isotype.
45. The method of claim 41 , wherein the antibody is chemically coupled to a mitotic inhibitor.
46. The method of claim 43 , wherein the antibody is chemically coupled to a mitotic inhibitor.
47. The method according to any one of claims 25 - 46 , wherein the cancer is chosen from prostate cancer, osteosarcoma, lung cancer, breast cancer, endometrial cancer, glyoblastoma, and colon cancer.
48. The method according to any one of claims 25 - 46 , wherein the cancer is a c-Met-activation-related cancer chosen from c-Met-activation-related cancers that are HGF-dependent, HGF-independent, or both.
49. The method according to any one of claims 1 - 22 , further comprising administering an anti-tumoral antibody in a simultaneous, separate, or sequential fashion.
50. The method according to any one of claims 1 - 22 , further comprising administering cytotoxic/cytostatic agent in a simultaneous, separate, or sequential fashion.
51. The method according to any one of claims 25 - 46 , further comprising administering an anti-tumoral antibody in a simultaneous, separate, or sequential fashion.
52. The method according to any one of claims 25 - 46 , further comprising administering cytotoxic/cytostatic agent in a simultaneous, separate, or sequential fashion.
53. The method according to claim 49 , wherein at least one of said antibodies is conjugated with a cell toxin and/or a radioelement.
54. The method according to claim 50 , wherein said cytotoxic/cytostatic agent is coupled chemically to the antibody.
55. The method according to claim 51 , wherein at least one of said antibodies is conjugated with a cell toxin and/or a radioelement.
56. The method according to claim 52 , wherein at least one of said antibodies is conjugated with a cell toxin and/or a radioelement.