Anti-OX40 antibodies and methods of use
The invention provides anti-OX40 antibodies and methods of using the same.
1. An antibody that binds human OX40, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising (a) an HVR-H1 comprising the amino acid sequence of DSYMS (SEQ ID NO:2); (b) an HVR-H2 comprising the amino acid sequence of DMYPDNGDSSYNQKFRE (SEQ ID NO:3); and (c) an HVR-H3 comprising the amino acid sequence of APRWYFSV (SEQ ID NO:4); and
(2) a light chain variable domain (VL) comprising (d) an HVR-L1 comprising the amino acid sequence of RASQDISNYLN (SEQ ID NO:5); (e) an HVR-L2 comprising the amino acid sequence of YTSRLRS (SEQ ID NO:6); and (f) an HVR-L3 comprising the amino acid sequence of QQGHTLPPT (SEQ ID NO:7).
2. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
3. The antibody of claim 1 , wherein the antibody is a humanized antibody.
4. An antibody that binds human OX40, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56); and
(2) a light chain variable domain (VL) comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57).
5. The antibody of claim 4 , wherein the antibody is a monoclonal antibody.
6. An antibody that binds human OX40, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56);
(2) a light chain variable domain (VL) comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57); and
(3) a human IgG1 Fc region.
7. The antibody of claim 6 , wherein the antibody is a monoclonal antibody.
8. An immunoconjugate comprising an antibody that binds human OX40, wherein the antibody is conjugated to a cytotoxic agent or label, and wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising (a) an HVR-H1 comprising the amino acid sequence of DSYMS (SEQ ID NO:2); (b) an HVR-H2 comprising the amino acid sequence of DMYPDNGDSSYNQKFRE (SEQ ID NO:3); and (c) an HVR-H3 comprising the amino acid sequence of APRWYFSV (SEQ ID NO:4); and
(2) a light chain variable domain (VL) comprising (d) an HVR-L1 comprising the amino acid sequence of RASQDISNYLN (SEQ ID NO:5); (e) an HVR-L2 comprising the amino acid sequence of YTSRLRS (SEQ ID NO:6); and (f) an HVR-L3 comprising the amino acid sequence of QQGHTLPPT (SEQ ID NO:7).
9. The immunoconjugate of claim 8 , wherein:
(1) the heavy chain variable domain (VH) comprises the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56); and
(2) the light chain variable domain (VL) comprises the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57).
10. The immunoconjugate of claim 9 , wherein the antibody further comprises a human IgG1 Fc region.
11. The immunoconjugate of claim 8 , wherein the label is selected from the group consisting of a fluorescent label, a chromophoric label, an electron-dense label, a chemiluminescent label, a radioactive label, an enzyme, and a ligand.
12. The immunoconjugate of claim 9 , wherein the label is selected from the group consisting of a fluorescent label, a chromophoric label, an electron-dense label, a chemiluminescent label, a radioactive label, an enzyme, and a ligand.
13. The immunoconjugate of claim 10 , wherein the label is selected from the group consisting of a fluorescent label, a chromophoric label, an electron-dense label, a chemiluminescent label, a radioactive label, an enzyme, and a ligand.
14. The immunoconjugate of claim 8 , wherein the cytotoxic agent is selected from the group consisting of a radioactive isotope, a chemotherapeutic agent, and an antibiotic.
15. The immunoconjugate of claim 9 , wherein the cytotoxic agent is selected from the group consisting of a radioactive isotope, a chemotherapeutic agent, and an antibiotic.
16. The immunoconjugate of claim 10 , wherein the cytotoxic agent is selected from the group consisting of a radioactive isotope, a chemotherapeutic agent, and an antibiotic.
17. A composition comprising an antibody that binds human OX40 and a pharmaceutically acceptable carrier, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising (a) an HVR-H1 comprising the amino acid sequence of DSYMS (SEQ ID NO:2); (b) an HVR-H2 comprising the amino acid sequence of DMYPDNGDSSYNQKFRE (SEQ ID NO:3); and (c) an HVR-H3 comprising the amino acid sequence of APRWYFSV (SEQ ID NO:4); and
(2) a light chain variable domain (VL) comprising (d) an HVR-L1 comprising the amino acid sequence of RASQDISNYLN (SEQ ID NO:5); (e) an HVR-L2 comprising the amino acid sequence of YTSRLRS (SEQ ID NO:6); and (f) an HVR-L3 comprising the amino acid sequence of QQGHTLPPT (SEQ ID NO:7).
18. The composition of claim 17 , wherein the composition comprises a buffer, a surfactant, and a saccharide.
19. The composition of claim 18 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 100 mM-320 mM saccharide, 1 mM-50 mM histidine buffer, and has a pH of 5.0-6.0.
20. The composition of claim 18 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 100 mM-150 mM saccharide, 1 mM-25 mM histidine buffer, and has a pH of 5.0-6.0.
21. The composition of claim 18 , wherein the composition comprises 50 mg/mL-75 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 110 mM-130 mM saccharide, 20 mM-30 mM histidine buffer, and has a pH of 5.0-6.0.
22. The composition of claim 18 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.02%-0.06% (w/v) polysorbate, 100 mM-320 mM sucrose, 1 mM-50 mM histidine buffer, and has a pH of 5.0-6.0.
23. The composition of claim 18 , wherein the composition comprises 60 mg/mL antibody, 0.03% (w/v) polysorbate, 120 mM sucrose, 20 mM histidine acetate buffer, and has a pH of 5.5.
24. A composition comprising an antibody that binds human OX40 and a pharmaceutically acceptable carrier, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56); and
(2) a light chain variable domain (VL) comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57).
25. The composition of claim 24 , wherein the composition comprises a buffer, a surfactant, and a saccharide.
26. The composition of claim 25 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 100 mM-320 mM saccharide, 1 mM-50 mM histidine buffer, and has a pH of 5.0-6.0.
27. The composition of claim 25 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 100 mM-150 mM saccharide, 1 mM-25 mM histidine buffer, and has a pH of 5.0-6.0.
28. The composition of claim 25 , wherein the composition comprises 50 mg/mL-75 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 110 mM-130 mM saccharide, 20 mM-30 mM histidine buffer, and has a pH of 5.0-6.0.
29. The composition of claim 25 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.02%-0.06% (w/v) polysorbate, 100 mM-320 mM sucrose, 1 mM-50 mM histidine buffer, and has a pH of 5.0-6.0.
30. The composition of claim 25 , wherein the composition comprises 60 mg/mL antibody, 0.03% (w/v) polysorbate, 120 mM sucrose, 20 mM histidine acetate buffer, and has a pH of 5.5.
31. A composition comprising an antibody that binds human OX40 and a pharmaceutically acceptable carrier, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56);
(2) a light chain variable domain (VL) comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57); and
(3) a human IgG1 Fc region.
32. The composition of claim 31 , wherein the composition comprises a buffer, a surfactant, and a saccharide.
33. The composition of claim 32 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 100 mM-320 mM saccharide, 1 mM-50 mM histidine buffer, and has a pH of 5.0-6.0.
34. The composition of claim 32 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 100 mM-150 mM saccharide, 1 mM-25 mM histidine buffer, and has a pH of 5.0-6.0.
35. The composition of claim 32 , wherein the composition comprises 50 mg/mL-75 mg/mL antibody, 0.01%-0.1% (w/v) surfactant, 110 mM-130 mM saccharide, 20 mM-30 mM histidine buffer, and has a pH of 5.0-6.0.
36. The composition of claim 32 , wherein the composition comprises 10 mg/mL-100 mg/mL antibody, 0.02%-0.06% (w/v) polysorbate, 100 mM-320 mM sucrose, 1 mM-50 mM histidine buffer, and has a pH of 5.0-6.0.
37. The composition of claim 32 , wherein the composition comprises 60 mg/mL antibody, 0.03% (w/v) polysorbate, 120 mM sucrose, 20 mM histidine acetate buffer, and has a pH of 5.5.
38. A kit comprising a container containing an antibody that binds human OX40 and a pharmaceutically acceptable carrier, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising (a) an HVR-H1 comprising the amino acid sequence of DSYMS (SEQ ID NO:2); (b) an HVR-H2 comprising the amino acid sequence of DMYPDNGDSSYNQKFRE (SEQ ID NO:3); and (c) an HVR-H3 comprising the amino acid sequence of APRWYFSV (SEQ ID NO:4); and
(2) a light chain variable domain (VL) comprising (d) an HVR-L1 comprising the amino acid sequence of RASQDISNYLN (SEQ ID NO:5); (e) an HVR-L2 comprising the amino acid sequence of YTSRLRS (SEQ ID NO:6); and (f) an HVR-L3 comprising the amino acid sequence of QQGHTLPPT (SEQ ID NO:7).
39. A kit comprising a container containing an antibody that binds human OX40 and a pharmaceutically acceptable carrier, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56); and
(2) a light chain variable domain (VL) comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57).
40. A kit comprising a container containing an antibody that binds human OX40 and a pharmaceutically acceptable carrier, wherein the antibody comprises:
(1) a heavy chain variable domain (VH) comprising the amino acid sequence of EVQLVQSGAEVKKPGASVKVSCKASGYTFTDSYMSWVRQAPGQGLEWIGDMYPDNGDSS YNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAPRWYFSVWGQGTLVTVSS (SEQ ID NO:56);
(2) a light chain variable domain (VL) comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTSRLRSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKVEIK (SEQ ID NO:57); and
(3) a human IgG1 Fc region.