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

Inventors: Bryan Irving (San Francisco, CA); Henry Chiu (San Francisco, CA); Heather Maecker (Palo Alto, CA); Sanjeev Mariathasan (Millbrae, CA); Sophie M. Lehar (Montara, CA); Yan Wu (Foster City, CA); Jeanne Cheung (San Francisco, CA)

Assignee: Genentech, Inc.

C07K16/2827 A61K31/7068 A61K39/00 A61K39/3955 A61K39/39558 A61K45/06 C07K16/1063 C07K16/22 C07K16/28 C07K16/30 C07K16/3046 A61K2039/505 A61K2039/507 C07K2317/14 C07K2317/24 C07K2317/52 C07K2317/56 C07K2317/565 C07K2317/567 C07K2317/71 C07K2317/73 C07K2317/74 C07K2317/76 C07K2317/92

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Quick Facts

Patent No.: US 9,920,123
App. No.: 15/335,278
Granted: Mar 20, 2018
Kind: B2

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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.

Claims (62)

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: