Anti-cMet antibody
Antibodies capable of binding to the human c-Met receptor and/or capable of inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, the antibodies comprising a modified hinge region. A composition comprising one or more of such antibodies antagonist to c-Met and its use as a medicament for treating cancer.
1. 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 antibody of claim 1 , wherein the antibody is a chimeric antibody.
3. The antibody of claim 1 , wherein the antibody is a human antibody.
4. The antibody of claim 1 , wherein the antibody is a humanized antibody.
5. The antibody 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 antibody of claim 5 ,
wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
7. The antibody of claim 6 ,
wherein the human light chain constant region is of the IgG1 kappa isotype.
8. The antibody of claim 1 ,
wherein the antibody comprises a human light chain constant region and a human heavy chain constant region.
9. The antibody of claim 8 ,
wherein the human light chain constant region is of the IgG1 kappa isotype.
10. The antibody of claim 7 , wherein the antibody
is chemically coupled to a mitotic inhibitor.
11. The antibody of claim 9 , wherein the antibody
is chemically coupled to a mitotic inhibitor.
12. A pharmaceutical composition comprising the antibody according to one of claims 1 , and 2 to 11 and a pharmaceutically acceptable vehicle.
13. The composition of claim 12 , further comprising an anti-tumoral antibody,
wherein the monoclonal antibody and the anti-tumoral antibody are in a single dosage form or in separate dosage forms, and wherein the separate dosage forms can be administered at the same time or sequentially.
14. The composition of claim 12 , further comprising a cytotoxic/cytostatic agent,
wherein the antibody and the cytotoxic/cytostatic agent are in a single dosage form or in separate dosage forms, and wherein the separate dosage forms can be administered at the same time or sequentially.
15. The composition of claim 13 , wherein at least one of the antibodies is conjugated with a cell toxin and/or a radioelement.
16. The composition of claim 14 , wherein the cytotoxic/cytostatic agent is coupled chemically to at least one of the antibodies for simultaneous use.
17. The composition of claim 15 , wherein said toxin and/or a radioelement is coupled chemically to at least one of the antibodies, for simultaneous use.
18. The composition of claim 13 , wherein the anti-tumoral antibody is an anti-HER2/neu antibody.
19. The composition of claim 13 , wherein the anti-tumoral antibody is an anti-VEGF antibody.
20. The composition of claim 13 , wherein the anti-tumoral antibody is an anti-EGFR antibody.
21. The composition of claim 14 , wherein the cytotoxic agent is chosen from gefitinib, erlotinib, and a combination thereof.
22. The composition of claim 14 , wherein the cytotoxic agent is chosen from carboplatin, paclitaxel, and a combination thereof.
23. The composition of claim 14 , wherein the cytotoxic agent is chosen from cisplatin, paclitaxel, and a combination thereof.
24. The composition of claim 14 , wherein the cytotoxic agent is chosen from cisplatin, gemcitabine, and a combination thereof.
25. The composition of claim 14 , wherein the cytotoxic agent is an anti-metabolite.
26. The composition of claim 25 , wherein the anti-metabolite is capecitabine.
27. A recombinant antibody capable of inhibiting c-Met dimerization, wherein the antibody comprises:
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 hinge region comprising the amino acid sequence SEQ ID No. 28.