PD-1 antibodies
The present invention relates to antibodies that bind human programmed cell death 1 (PD-1), and may be useful for treating cancer alone and in combination with chemotherapy and other cancer therapeutics.
1. An antibody that binds human PD-1 (SEQ ID NO: 1), comprising a light chain (LC) and a heavy chain (HC), wherein the light chain comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences RASQGISSWLA (SEQ ID NO: 9), SAASSLQS (SEQ ID NO: 10), and QQANHLPFT (SEQ ID NO: 11), respectively, and wherein the heavy chain comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, wherein HCDR1 consists of the amino acid sequences KASGGTFSSYAIS (SEQ ID NO: 2) or KASGGTLSSYAIS (SEQ ID NO: 3), wherein HCDR2 consists of the amino acid sequences LIIPMFGTAGYAQKFQG (SEQ ID NO: 4), LIIPMFDTAGYAQKFQG (SEQ ID NO: 5) or LIIPMFGAAGYAQRFQG (SEQ ID NO: 6), and wherein HCDR3 consists of the amino acid sequences ARAEYSSTGTFDY (SEQ ID NO: 7) or ARAEHSSTGTFDY (SEQ ID NO:8).
2. The antibody of claim 1 , wherein LCDR1, LCDR2, and LCDR3 consist of the amino acid sequences RASQGISSWLA (SEQ ID NO: 9), SAASSLQS (SEQ ID NO: 10), and QQANHLPFT (SEQ ID NO: 11), respectively, and wherein HCDR1, HCDR2, and HCDR3 consist of the amino acid sequences KASGGTFSSYAIS (SEQ ID NO: 2), LIIPMFGTAGYAQKFQG (SEQ ID NO: 4), and ARAEYSSTGTFDY (SEQ ID NO: 7), respectively.
3. The antibody of claim 1 , wherein LCDR1, LCDR2, and LCDR3 consist of the amino acid sequences RASQGISSWLA (SEQ ID NO: 9), SAASSLQS (SEQ ID NO:10), and QQANHLPFT (SEQ ID NO: 11), respectively, and wherein HCDR1, HCDR2, and HCDR3 consist of the amino acid sequences KASGGTFSSYAIS (SEQ ID NO: 2), LIIPMFDTAGYAQKFQG (SEQ ID NO: 5), and ARAEHSSTGTFDY (SEQ ID NO: 8), respectively.
4. The antibody of claim 1 , wherein LCDR1, LCDR2, and LCDR3 consist of the amino acid sequences RASQGISSWLA (SEQ ID NO: 9), SAASSLQS (SEQ ID NO:10), and QQANHLPFT (SEQ ID NO: 11), respectively, and wherein HCDR1, HCDR2, and HCDR3 consist of the amino acid sequences KASGGTLSSYAIS (SEQ ID NO: 3), LIIPMFGAAGYAQRFQG (SEQ ID NO: 6), and ARAEHSSTGTFDY (SEQ ID NO: 8), respectively.
5. An antibody that binds human PD-1 (SEQ ID NO: 1), comprising a light chain (LC) and a heavy chain (HC), wherein the light chain comprises a light chain variable region (LCVR) and the heavy chain comprises a heavy chain variable region (HCVR), wherein the LCVR has the amino acid sequence given in SEQ ID NO: 15, and the HCVR has the amino acid sequence given in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.
6. The antibody of claim 5 , wherein the LCVR has the amino acid sequence given in SEQ ID NO: 15, and the HCVR has the amino acid sequence given in SEQ ID NO: 12.
7. The antibody of claim 5 , wherein the LCVR has the amino acid sequence given in SEQ ID NO: 15, and the HCVR has the amino acid sequence given in SEQ ID NO: 13.
8. The antibody of claim 5 , wherein the LCVR has the amino acid sequence given in SEQ ID NO: 15, and the HCVR has the amino acid sequence given in SEQ ID NO: 14.
9. The antibody of claim 5 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 16, SEQ 11 NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, or SEQ ID NO: 21.
10. The antibody of claim 9 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 16.
11. The antibody of claim 9 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 17.
12. The antibody of claim 9 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 18.
13. The antibody of claim 9 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 19.
14. The antibody of claim 9 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 20.
15. The antibody of claim 9 , wherein the LC has the amino acid sequence given in SEQ ID NO: 22, and the HC has the amino acid sequence given in SEQ ID NO: 21.
16. The antibody of claim 9 , comprising two light chains and two heavy chains, wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21.
17. The antibody of claim 16 , wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 16.
18. The antibody of claim 16 , wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 17.
19. The antibody of claim 16 , wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 18.
20. The antibody of claim 16 , wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 19.
21. The antibody of claim 16 , wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 20.
22. The antibody of claim 16 , wherein each light chain has the amino acid sequence given in SEQ ID NO: 22, and each heavy chain has the amino acid sequence given in SEQ ID NO: 21.
23. The antibody of claim 5 , wherein one of the heavy chains forms an inter-chain disulfide bond with one of the light chains, and the other heavy chain forms an inter-chain disulfide bond with the other light chain, and one of the heavy chains forms two inter-chain disulfide bonds with the other heavy chain.
24. The antibody of claim 23 , wherein the antibody is glycosylated.
25. A mammalian cell comprising a DNA molecule comprising a polynucleotide sequence encoding a polypeptide having an amino acid sequence of SEQ ID NO: 22 and a polynucleotide sequence encoding a polypeptide having an amino acid sequence of SEQ ID NO: 17 or SEQ ID NO:20, wherein the cell is capable of expressing an antibody comprising alight chain having an amino acid sequence of SEQ ID NO: 22 and a heavy chain having an amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 20 wherein the antibody binds human PD-1 (SEQ ID NO: 1).
26. A process for producing an antibody comprising a light chain having an amino acid sequence of SEQ ID NO: 22 and a heavy chain having an amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 20, comprising cultivating the mammalian cell of claim 25 under conditions such that the antibody is expressed, and recovering the expressed antibody wherein the antibody binds human PD-1 (SEQ ID NO:1).
27. An antibody produced by the process of claim 26 .
28. A pharmaceutical composition, comprising the antibody of claim 1 , and an acceptable carrier, diluent, or excipient.
29. A method of treating cancer, comprising administering to a patient in need thereof, an effective amount of the antibody of claim 1 .
30. The method of claim 29 , wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, or hepatocellular carcinoma.
31. The method of claim 30 , further comprising administering simultaneously, separately, or sequentially one or more anti-tumor agents.