IP Library › Granted Patent US 11,111,300

Granted Patent B2

US 11,111,300 · App. 16/538,440 · Granted Sep 7, 2021

Anti PD-L1 antibodies

Inventors: Jiping Zha (Santa Clara, CA); Ziyong Sun (Santa Clara, CA); Junzhuan Qiu (Santa Clara, CA)

Assignee: APOLLOMICS INC.

C07K16/2827 A61K47/6849 C07K2317/24 C07K2317/565 C07K2317/74 C07K2317/76 C07K2317/92

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Quick Facts

Patent No.: US 11,111,300
App. No.: 16/538,440
Granted: Sep 7, 2021
Kind: B2

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Abstract

The present disclosure relates to antibodies and antigen-binding fragments thereof that bind to PD-L1, and to methods of using such antibodies and antigen-binding fragments. For example, the present invention provides humanized anti-PD-L1 antibodies and methods of use thereof.

Claims (75)

1. A method for treating a PD-L1 expressing cancer in a human subject having the PD-L1 expressing cancer, the method comprising administering to the subject an antibody or fragment thereof that binds to PD-L1, wherein the antibody or fragment thereof comprises:

(i) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 93, 94, and 95, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 96, 97, and 98, respectively;

(ii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 81, 82, and 83, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 84, 85, and 86, respectively;

(iii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 87, 88, and 89, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 90, 91, and 92, respectively;

(iv) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 99, 100, and 101, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 102, 103, and 104, respectively;

(v) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 105, 106, and 107, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 108, 109, and 110, respectively;

(vi) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 111, 112, and 113, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 114, 115, and 116, respectively;

(vii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 117, 118, and 119, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 120, 121, and 122, respectively;

(viii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 123, 124, and 125, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 126, 127, and 128, respectively;

(ix) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 129, 130, and 131, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 132, 133, and 134, respectively; or

(x) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 135, 136, and 137, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 138, 139, and 140, respectively.

2. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 93, 94, and 95, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 96, 97, and 98, respectively.

3. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 81, 82, and 83, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 84, 85, and 86, respectively.

4. The method of claim 1 , wherein the antibody or fragment thereof is humanized.

5. The method of claim 1 , wherein the antibody or fragment thereof comprises

(i) a heavy chain variable region comprising SEQ ID NO:10 and a light chain variable region comprising SEQ ID NO: 12;

(ii) a heavy chain variable region comprising SEQ ID NO: 2 and a light chain variable region comprising SEQ ID NO: 4;

(iii) a heavy chain variable region comprising SEQ ID NO: 6 and a light chain variable region comprising SEQ ID NO: 8;

(iv) a heavy chain variable region comprising SEQ ID NO: 14 and a light chain variable region comprising SEQ ID NO: 16;

(v) a heavy chain variable region comprising SEQ ID NO: 18 and a light chain variable region comprising SEQ ID NO: 20;

(vi) a heavy chain variable region comprising SEQ ID NO: 22 and a light chain variable region comprising SEQ ID NO: 24;

(vii) a heavy chain variable region comprising SEQ ID NO: 26 and a light chain variable region comprising SEQ ID NO: 28;

(viii) a heavy chain variable region comprising SEQ ID NO: 30 and a light chain variable region comprising SEQ ID NO: 32;

(ix) a heavy chain variable region comprising SEQ ID NO: 34 and a light chain variable region comprising SEQ ID NO: 36;

(x) a heavy chain variable region comprising SEQ ID NO: 38 and a light chain variable region comprising SEQ ID NO: 40;

(xi) a heavy chain variable region comprising SEQ ID NO: 42 and a light chain variable region comprising SEQ ID NO: 44; or

(xii) a heavy chain variable region comprising SEQ ID NO: 46 and a light chain variable region comprising SEQ ID NO: 48.

6. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region according to SEQ ID NO: 42 and a light chain variable region according to SEQ ID NO: 44.

7. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region according to SEQ ID NO: 46 and a light chain variable region according to SEQ ID NO: 48.

8. The method claim 1 , wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 70 and a light chain according to SEQ ID NO: 74.

9. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 72 and a light chain according to SEQ ID NO: 74.

10. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 76 and a light chain according to SEQ ID NO: 80.

11. The method of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain according to SEQ ID NO: 78 and a light chain according to SEQ ID NO: 80.

12. The method of claim 1 , wherein the antibody or fragment thereof is selected from the group consisting of a monoclonal antibody, an scFv, a Fab fragment, an Fab′ fragment, and an F(ab)′ fragment.

13. The method of claim 1 , wherein the antibody or fragment thereof is linked or conjugated to a therapeutic agent.

14. The method of claim 13 , wherein the therapeutic agent is a cytotoxic drug, a radioactive isotope, an immunomodulator, or an antibody.

15. The method of claim 1 , wherein the method further comprises administering the antibody or fragment thereof to the subject in combination with an additional therapeutic agent.

16. The method of claim 1 , wherein the cancer is selected from the group consisting of lymphoma, leukemia, melanoma, glioma, breast cancer, lung cancer, colon cancer, bone cancer, ovarian cancer, bladder cancer, kidney cancer, liver cancer, stomach cancer, rectal cancer, testicular cancer, salivary cancer, thyroid cancer, thymic cancer, epithelial cancer, head or neck cancer, gastric cancer, and pancreatic cancer; or any combination thereof.

17. A method for reducing PD-L1 expressing tumors or inhibiting the growth of PD-L1 expressing tumor cells in a subject, the method comprising administering to the subject an antibody or fragment thereof that binds to PD-L1, wherein the antibody or fragment thereof comprises:

(i) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 93, 94, and 95, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 96, 97, and 98, respectively;

18. The method of claim 17 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 93, 94, and 95, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 96, 97, and 98, respectively.

19. The method of claim 17 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 81, 82, and 83, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 84, 85, and 86, respectively.

20. The method of claim 17 , wherein the antibody or fragment thereof is humanized.

21. The method of claim 17 , wherein the antibody or fragment thereof comprises