IP Library › Granted Patent US 9,975,957
Granted Patent B2
US 9,975,957 · App. 14/673,792 · Granted May 22, 2018

Anti-OX40 antibodies and methods of use

Inventors: Changchun Du (South San Francisco, CA); Jeong Kim (San Francisco, CA); Jing Zhu (Moraga, CA); Jack Bevers, III (San Mateo, CA); Kevin Walsh (Walnut Creek, CA); Patricia De Almeida (Pleasant Hill, CA); James Andya (Millbrae, CA); Ye Shen (Daly City, CA)
Assignee: Genentech, Inc.
C07K16/2878A61K39/3955A61K39/39558A61K45/06A61K47/6803A61K47/6849C07K16/22C07K16/30C07K16/303C07K16/3015C07K16/3023C07K16/3038C07K16/3046C07K16/3069A61K48/00A61K2039/505A61K2039/507C07K2317/21C07K2317/24C07K2317/51C07K2317/515C07K2317/56C07K2317/71C07K2317/732C07K2317/75C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 9,975,957
App. No.
14/673,792
Granted
May 22, 2018
Kind
B2
Abstract

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

Claims (65)

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.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 13, 2015
From: GENENTECH, INC.
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 036781/0863 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 28, 2015
From: DU, CHANGCHUN; KIM, JEONG; ZHU, JING; BEVERS, JACK, III; WALSH, KEVIN; DE ALMEIDA, PATRICIA; ANDYA, JAMES; SHEN, YE
To: GENENTECH, INC.
Reel/Frame 036503/0604 →
Continuity (6)
Provisional Application 61973193 · Mar 31, 2014
Provisional Application 61989448 · May 6, 2014
Provisional Application 62073873 · Oct 31, 2014
Provisional Application 62080171 · Nov 14, 2014
Provisional Application 62113345 · Feb 6, 2015
Related Publication 20150307617A1 · Oct 29, 2015