Anti-ICOS antibodies
Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Methods of producing anti-ICOS antibodies, including species cross-reactive antibodies, using transgenic knock-out mice.
1. An isolated antibody that binds the extracellular domain of human ICOS, comprising a heavy chain amino acid sequence SEQ ID NO: 410 and a light chain amino acid sequence SEQ ID NO: 417.
2. A composition comprising the isolated antibody of claim 1 and a pharmaceutically acceptable excipient.
3. The isolated antibody of claim 1 , wherein the antibody comprises an Fc effector positive constant region.
4. The isolated antibody of claim 1 , which is a multispecific antibody.
5. The isolated antibody of claim 1 , wherein the antibody is afucosylated.
6. The isolated antibody of claim 1 which is conjugated to a cytotoxic drug or pro-drug.
7. An isolated antibody that binds the extracellular domain of human ICOS, comprising a VH domain comprising an amino acid sequence SEQ ID NO: 408 and a VL domain comprising an amino acid sequence SEQ ID NO: 415, wherein the antibody is not a multispecific antibody.
8. A composition comprising the isolated antibody of claim 7 and a pharmaceutically acceptable excipient.
9. The isolated antibody of claim 7 , wherein the antibody comprises an Fc effector positive constant region.
10. The isolated antibody of claim 7 , wherein the antibody is afucosylated.
11. The isolated antibody of claim 7 which is conjugated to a cytotoxic drug or pro-drug.
12. An isolated antibody that is not multispecific and does not bind PD-L1 antigen, wherein the isolated antibody binds the extracellular domain of human ICOS, comprising a VH domain comprising amino acid sequence SEQ ID NO: 408, a VL domain comprising amino acid sequence SEQ ID NO: 415, and a human IgG1 constant region.
13. A composition comprising the isolated antibody of claim 12 and a pharmaceutically acceptable excipient.
14. The isolated antibody of claim 12 , wherein the antibody comprises an Fc effector positive constant region.
15. The isolated antibody of claim 12 , wherein the antibody is afucosylated.
16. The isolated antibody of claim 12 which is conjugated to a cytotoxic drug or pro-drug.
17. An isolated antibody that binds the extracellular domain of human ICOS, wherein said antibody is made by the process of (i) culturing a host cell comprising one or more vectors encoding a heavy chain amino acid sequence SEQ ID NO: 410 and a light chain amino acid sequence SEQ ID NO: 417; and (ii) recovering the antibody.
18. A composition comprising the isolated antibody of claim 17 and a pharmaceutically acceptable excipient.
19. The isolated antibody of claim 17 , which is a multispecific antibody.
20. The isolated antibody of claim 17 , wherein the antibody is afucosylated.
21. The isolated antibody of claim 17 which is conjugated to a cytotoxic drug or pro-drug.
22. A method of treating cancer in a human patient, the method comprising administering to the patient an antibody that binds the extracellular domain of human ICOS, comprising a heavy chain amino acid sequence SEQ ID NO: 410 and a light chain amino acid sequence SEQ ID NO: 417.
23. The method of claim 22 , wherein the cancer is a solid tumor or a hematological liquid tumor.
24. The method of claim 22 , wherein the cancer is renal cell cancer, head and neck cancer, melanoma, non-small cell lung cancer or diffuse large B-cell lymphoma, B cell lymphoma, or a T lymphocyte.
25. The method of claim 22 , wherein the cancer is head and neck cancer.
26. The method of claim 22 , wherein the cancer is not responsive to prior treatment with an immunooncology drug.
27. The method of claim 22 , wherein the cancer is resistant to treatment with an anti-CD20 antibody.
28. The method of claim 27 , wherein the anti-CD20 antibody is rituximab.
29. A method of treating cancer in a human patient, the method comprising administering to the patient an antibody that binds the extracellular domain of human ICOS, comprising a VH domain comprising an amino acid sequence SEQ ID NO: 408 and a VL domain comprising an amino acid sequence SEQ ID NO: 415, wherein the antibody is not a multispecific antibody.