Anti-PD-1 antibodies and methods of use thereof
The instant disclosure provides antibodies that specifically bind to human PD-1 and antagonize PD-1 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.
1. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the amino acid sequences of SEQ ID NOs: 1, 2, and 7, respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16.
2. The isolated antibody of claim 1 , wherein the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 16.
3. The isolated antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 19.
4. The isolated antibody of claim 3 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 19.
5. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 20; and a light chain variable region comprising complementarity determining regions CDRL1, CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively.
6. The isolated antibody of claim 5 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 20.
7. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 17; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16.
8. The isolated antibody of claim 7 , wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 17; and the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 16.
9. The isolated antibody of claim 7 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 53.
10. The isolated antibody of claim 9 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 53.
11. The isolated antibody of claim 7 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 20.
12. The isolated antibody of claim 11 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 20.
13. The isolated antibody of claim 7 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 19.
14. The isolated antibody of claim 13 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 23.
15. The isolated antibody of claim 13 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 19.
16. An isolated antibody that specifically binds to human PD-1, comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 53; and the light chain comprises the amino acid sequence of SEQ ID NO: 19.
17. The isolated antibody of claim 16 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 53.
18. The isolated antibody of claim 16 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 20.
19. The isolated antibody of claim 18 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 20.
20. The isolated antibody of claim 16 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 19.
21. The isolated antibody of claim 16 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 53, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 19.
22. The isolated antibody of claim 16 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 20, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 19.
23. The isolated antibody of claim 22 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 20, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 19.
24. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.
25. A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier or excipient.
26. A pharmaceutical composition comprising the antibody of claim 7 and a pharmaceutically acceptable carrier or excipient.
27. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier or excipient.
28. A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier or excipient.
29. A pharmaceutical composition comprising the antibody of claim 21 and a pharmaceutically acceptable carrier or excipient.
30. A pharmaceutical composition comprising the antibody of claim 23 and a pharmaceutically acceptable carrier or excipient.