Anti-PD-L1 antibodies, compositions and articles of manufacture

Patent metadata

Field	Value
Publication number	US-9920123-B2
Application number	US-201615335278-A
Country	US
Kind code	B2
Filing date	Oct 26, 2016
Priority date	Dec 9, 2008
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

The present application relates to anti-PD-L1 antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, including infection (e.g., acute and chronic) and tumor immunity.

First claim

What is claimed is:

1. An isolated anti-PD-L1 antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein:
(a) the heavy chain variable region comprises an HVR-H1, HVR-H2 and HVR-H3, wherein further:
(i) the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 15;
(ii) the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 16;
(iii) the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 3; and

(b) the light chain variable region comprises an HVR-L1, HVR-L2 and HVR-L3, wherein further:
(iv) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 17;
(v) the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 18;
(vi) the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 19;

wherein the antibody further comprises a human constant region.

2. The antibody of claim 1 , wherein:
(a) the heavy chain variable region amino acid sequence has at least 90% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region amino acid sequence has at least 90% sequence identity to the light chain variable region amino acid sequence of SEQ ID NO:21.

3. The antibody of claim 1 , wherein:
(a) the heavy chain variable region amino acid sequence has at least 95% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region amino acid sequence has at least 95% sequence identity to the light chain variable region amino acid sequence of SEQ ID NO:21.

4. The antibody of claim 3 , wherein the heavy chain variable region amino acid sequence has at least 99% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20.

5. The antibody of claim 4 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:21.

6. The antibody of claim 5 , wherein the constant region is IgG1.

7. The antibody of claim 6 , wherein the antibody comprises an effector-less Fc mutation, wherein the effector-less Fc mutation is N297A based on the Kabat numbering system.

8. A composition comprising the anti-PD-L1 antibody of claim 5 and at least one pharmaceutically-acceptable carrier.

9. An article of manufacture comprising the anti-PD-L1 antibody of claim 5 and at least one chemotherapeutic agent.

10. The antibody of claim 1 , wherein:
(a) the heavy chain variable region amino acid sequence has at least 98% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region amino acid sequence has at least 98% sequence identity to the light chain variable region amino acid sequence of SEQ ID NO:21.

11. The antibody of claim 10 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:21.

12. A composition comprising the anti-PD-L1 antibody of claim 11 and at least one pharmaceutically-acceptable carrier.

13. The antibody of claim 1 , wherein the antibody comprises an effector-less Fc mutation, wherein the effector-less Fc mutation is N297A based on the Kabat numbering system.

14. A composition comprising the anti-PD-L1 antibody of claim 1 and at least one pharmaceutically-acceptable carrier.

15. An article of manufacture comprising the anti-PD-L1 antibody of claim 1 and at least one chemotherapeutic agent.

16. The antibody of claim 1 , wherein the constant region is IgG1.

17. The antibody of claim 16 , wherein the antibody comprises an effector-less Fc mutation, wherein the effector-less Fc mutation is N297A based on the Kabat numbering system.

18. An isolated anti-PD-L1 antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein:
(a) the heavy chain variable region comprises an HVR-H1, HVR-H2 and HVR-H3, wherein further:
(i) the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 15;
(ii) the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 16;
(iii) the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 3; and

(b) the light chain variable region comprises an HVR-L1, HVR-L2 and HVR-L3, wherein further:
(iv) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 17;
(v) the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 18;
(vi) the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 19;

wherein the antibody further comprises variable region light chain framework sequences juxtaposed between the HVRs according to the formula: (LC-FR1)-(HVR-L1)-(LC-FR2)-(HVR-L2)-(LC-FR3)-(HVR-L3)-(LC-FR4), wherein one or more of the framework sequences is the following:
LC-FR1 comprises the amino acid sequence of SEQ ID NO: 11;
LC-FR2 comprises the amino acid sequence of SEQ ID NO: 12;
LC-FR3 comprises the amino acid sequence of SEQ ID NO: 13; and
LC-FR4 comprises the amino acid sequence of SEQ ID NO: 14.

19. The antibody of claim 18 , wherein the antibody further comprises variable region heavy chain framework sequences juxtaposed between the HVRs according to the formula: (HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4), wherein one or more of the framework sequences is the following:
HC-FR1 comprises the amino acid sequence of SEQ ID NO: 4;
HC-FR2 comprises the amino acid sequence of SEQ ID NO: 5;
HC-FR3 comprises the amino acid sequence of SEQ ID NO: 6; and
HC-FR4 comprises the amino acid sequence of SEQ ID NO: 7.

20. The antibody of claim 19 , wherein the antibody is a full-length antibody.

21. The antibody of claim 20 , wherein the antibody comprises a human constant region.

22. The antibody of claim 21 , wherein the constant region is IgG1.

23. The antibody of claim 22 , wherein the antibody comprises an effector-less Fc mutation, wherein the effector-less Fc mutation is N297A based on the Kabat numbering system.

24. A composition comprising the anti-PD-L1 antibody of claim 19 and at least one pharmaceutically-acceptable carrier.

25. The antibody of claim 18 , wherein the antibody is a full-length antibody.

26. The antibody of claim 25 further comprising a human constant region.

27. The antibody of claim 26 , wherein the constant region is IgG1.

28. The antibody of claim 27 , wherein the antibody comprises an effector-less Fc mutation, wherein the effector-less Fc mutation is N297A based on the Kabat numbering system.

29. A composition comprising the anti-PD-L1 antibody of claim 18 and at least one pharmaceutically-acceptable carrier.

30. An article of manufacture comprising the anti-PD-L1 antibody of claim 18 and at least one chemotherapeutic agent.

Assignees

• Genentech Inc

Inventors

• Irving Bryan
• Chiu Henry
• Maecker Heather
• Mariathasan Sanjeev
• Lehar Sophie M
• Wu Yan
• Cheung Jeanne

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P31/10

  Antimycotics · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title