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. A method of treating an IL-6-associated disease or disorder selected from the group consisting of ovarian cancer, renal cell carcinoma, and
psoriasis, comprising administering to a subject in need of treatment thereof an effective amount of 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 method of claim 1 , wherein the antibody or antigen binding fragment thereof further comprises a human Fc domain comprising a H433K/N434F double mutation.
3. The method of claim 1 , wherein the VH domain comprises the amino acid sequence set forth as SEQ ID NO; 152.
4. The method of claim 3 , wherein the antibody or antigen binding fragment thereof further comprises a human Fc domain comprising a H433K/N434F double mutation.
5. The method of claim 3 , wherein the glutamine at position 1 of SEQ ID NO: 152 has been changed to glutamic acid.
6. The method of claim 5 , wherein the antibody or antigen binding fragment thereof further comprises a human Fc domain comprising a H433K/N434F double mutation.
7. The method of claim 1 , wherein the VL domain comprises the amino acid sequence set forth as SEQ ID NO: 416.
8. The method of claim 7 , wherein the antibody or antigen binding fragment thereof further comprises a human Fc domain comprising a H433K/N434F double mutation.
9. The method 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.
10. The method of claim 9 , wherein the antibody or antigen binding fragment thereof further comprises a human Fc domain comprising a H433K/N434F double mutation.
11. The method of claim 9 , wherein the glutamine at position 1 of SEQ ID NO: 152 has been changed to glutamic acid.
12. The method of claim 11 , wherein the antibody or antigen binding fragment further comprises a human Fc domain comprising a H433K/N434F double mutation.
13. The method of claim 1 , wherein the IL-6-associated disease or disorder is psoriasis.
14. The method of claim 1 , wherein the IL-6-associated disease or disorder is renal cell carcinoma.
15. The method of claim 1 , wherein the IL-6-associated disease or disorder is ovarian cancer.