IL-6 binding molecules
The present invention provides binding molecules (e.g., antibodies or antigen binding fragments thereof) that specifically bind to and inhibit the biological activity of IL-6 (e.g., human, mouse and non-human primate IL-6). In a preferred embodiment, the antibodies or antigen binding fragments of the invention bind to IL-6 and inhibit its binding to an IL-6 receptor. Such antibodies or antigen binding fragments are particularly useful for treating IL-6-associated diseases or disorders (e.g., inflammatory disease and cancer).
1. An antibody or antigen binding fragment thereof that specifically binds to IL-6, comprising:
a VH domain comprising
the HCDR3 amino acid sequence set forth as SEQ ID NO: 497;
the HCDR2 amino acid sequence set forth as SEQ ID NO: 501; and
the HCDR1 amino acid sequence set forth as SEQ ID NO: 508, and
a VL domain comprising
the LCDR3 amino acid sequence set forth as SEQ ID NO: 513;
the LCDR2 amino acid sequence set forth as SEQ ID NO: 525; and
the LCDR1 amino acid sequence set forth as SEQ ID NO: 536.
2. The antibody or antigen binding fragment thereof of claim 1 , wherein the VH domain comprises the amino acid sequence set forth as SEQ ID NO: 152.
3. The antibody or antigen binding fragment thereof of claim 2 , wherein the glutamine at position 1 of SEQ ID NO: 152 has been changed to glutamic acid.
4. The antibody or antigen binding fragment thereof of claim 1 , wherein the VL domain comprises the amino acid sequence set forth as SEQ ID NO: 416.
5. The antibody or antigen binding fragment thereof of claim 1 , wherein the VH domain comprises the amino acid sequence set forth as SEQ ID NO: 152, and the VL domain comprises the amino acid sequence set forth as SEQ ID NO: 416.
6. The antibody or antigen binding fragment thereof of claim 5 , wherein the glutamine at position 1 of SEQ ID NO: 152 has been changed to glutamic acid.
7. An antibody or antigen binding fragment thereof that specifically binds to IL-6, comprising a VH domain comprising the amino acid sequence set forth as SEQ ID NO: 152.
8. The antibody or antigen binding fragment thereof of claim 7 , wherein the glutamine at position 1 of SEQ ID NO: 152 has been changed to glutamic acid.
9. An antibody or antigen binding fragment thereof that specifically binds to IL-6, comprising a VL domain comprising the amino acid sequence set forth as SEQ ID NO: 416.
10. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 1 and a pharmaceutically acceptable carrier.
11. The antibody or antigen binding fragment thereof according to claim 1 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
12. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 11 and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 2 and a pharmaceutically acceptable carrier.
14. The antibody or antigen binding fragment thereof according to claim 2 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
15. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 14 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 3 and a pharmaceutically acceptable carrier.
17. The antibody or antigen binding fragment thereof according to claim 3 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
18. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 17 and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 4 and a pharmaceutically acceptable carrier.
20. The antibody or antigen binding fragment thereof according to claim 4 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
21. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 20 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 5 and a pharmaceutically acceptable carrier.
23. The antibody or antigen binding fragment thereof according to claim 5 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
24. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 23 and a pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 6 and a pharmaceutically acceptable carrier.
26. The antibody or antigen binding fragment thereof according to claim 6 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
27. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 26 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 7 and a pharmaceutically acceptable carrier.
29. The antibody or antigen binding fragment thereof according to claim 7 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
30. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 29 and a pharmaceutically acceptable carrier.
31. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 8 and a pharmaceutically acceptable carrier.
32. The antibody or antigen binding fragment thereof according to claim 8 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
33. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 32 and a pharmaceutically acceptable carrier.
34. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 9 and a pharmaceutically acceptable carrier.
35. The antibody or antigen binding fragment thereof according to claim 9 , further comprising a human Fc domain comprising a H433K/N434F double mutation.
36. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 35 and a pharmaceutically acceptable carrier.