Anti-OX40 antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-9975957-B2
Application number	US-201514673792-A
Country	US
Kind code	B2
Filing date	Mar 30, 2015
Priority date	Mar 31, 2014
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

The invention provides anti-OX40 antibodies and methods of using the same.

First claim

What is claimed is:

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

Assignees

• Genentech Inc

Inventors

• Du Changchun
• Kim Jeong
• Zhu Jing
• Bevers Iii Jack
• Walsh Kevin
• De Almeida Patricia
• Andya James
• Shen Ye

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12N15/79

  Vectors or expression systems specially adapted for eukaryotic hosts · CPC title

• C12N5/10

  Cells modified by introduction of foreign genetic material · CPC title

• C12N15/64

  General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host · CPC title