Anti-cMET antibody

Patent metadata

Field	Value
Publication number	US-9469691-B2
Application number	US-201414248741-A
Country	US
Kind code	B2
Filing date	Apr 9, 2014
Priority date	Dec 2, 2008
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

Abstract

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.

First claim

The invention claimed is:

1. A monoclonal chimeric or humanized anti-cMet 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, respectively; and
a modified hinge region comprising the amino acid sequence SEQ ID No. 26.

2. The antibody of claim 1 , wherein the antibody is a chimeric antibody.

3. The antibody of claim 1 , wherein the antibody is a humanized antibody.

4. The antibody of claim 1 , or a divalent cMet-binding fragment thereof, wherein the antibody comprises:
a heavy chain variable domain of sequence comprising the amino acid sequence SEQ ID No. 4; and
a light chain variable domain of sequence comprising an amino acid sequence chosen from SEQ ID No. 8, 9, and 10.

5. The antibody of claim 1 , wherein the antibody comprises a human light chain constant and a human heavy chain constant region.

6. The antibody of claim 5 , wherein the human light chain constant region is of the IgG1 kappa isotype.

7. The antibody of claim 1 , or a divalent cMet-binding fragment thereof, wherein the antibody is chemically coupled to a mitotic inhibitor.

8. A pharmaceutical composition comprising the antibody according to claim 1 , or a divalent cMet-binding fragment thereof, and a pharmaceutically acceptable vehicle.

9. The composition of claim 8 further comprising an anti-tumoral antibody, wherein the monoclonal antibody, or a divalent cMet-binding fragment thereof, 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.

10. The composition of claim 8 , further comprising a cytotoxic/cytostatic agent, wherein the antibody, or a divalent cMet-binding fragment thereof, 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.

11. The composition of claim 9 , wherein at least one of the antibodies, or a divalent cMet-binding fragment of the monoclonal antibody, is conjugated with a cell toxin and/or a radioelement.

12. The composition of claim 10 , wherein the cytotoxic/cytostatic agent is coupled chemically to at least one of the antibodies, or the divalent cMet-binding fragment of the monoclonal antibody, for simultaneous use.

13. The composition of claim 11 , wherein said toxin and/or a radioelement is coupled chemically to at least one of the antibodies, for simultaneous use.

14. The composition of claim 9 , wherein the anti-tumoral antibody is an anti-HER2/neu antibody.

15. The composition of claim 9 , wherein the anti-tumoral antibody is an anti-VEGF antibody.

16. The composition of claim 9 , wherein the anti-tumoral antibody is an anti-EGFR antibody.

17. The composition of claim 10 , wherein the cytotoxic agent is chosen from gefitinib, erlotinib, and a combination thereof.

18. The composition of claim 10 , wherein the cytotoxic agent is chosen from carboplatin, paclitaxel, and a combination thereof.

19. The composition of claim 10 , wherein the cytotoxic agent is chosen from cisplatin, paclitaxel, and a combination thereof.

20. The composition of claim 10 , wherein the cytotoxic agent is chosen from cisplatin, gemcitabine, and a combination thereof.

21. The composition of claim 10 , wherein the cytotoxic agent is an antimetabolite.

22. The composition of claim 21 , wherein the antimetabolite is capecitabine.

23. 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, respectively; and
a hinge region comprising the amino acid sequence SEQ ID No. 26.

24. The antibody of claim 23 , wherein the antibody is a chimeric antibody.

25. The antibody of claim 23 , wherein the antibody is a humanized antibody.

26. The antibody of claim 23 , or a divalent cMet-binding fragment thereof, wherein the antibody comprises:
a heavy chain variable domain of sequence comprising the amino acid sequence SEQ ID No. 4; and
a light chain variable domain of sequence comprising an amino acid sequence chosen from SEQ ID No. 8, 9, and 10.

27. The antibody of claim 23 , wherein the antibody comprises a human light chain constant and a human heavy chain constant region.

28. The antibody of claim 27 , wherein the human light chain constant region is of the IgG1 kappa isotype.

29. The antibody of claim 23 , or a divalent cMet-binding fragment thereof, wherein the antibody is chemically coupled to a mitotic inhibitor.

Assignees

• Goetsch Liliane
• Wurch Thierry
• Bes Cédric
• Pf Medicament

Inventors

• Goetsch Liliane
• Wurch Thierry
• Bes Cédric

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K2317/53

  Hinge · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/555

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title