Anti-PD-1 antibodies, compositions comprising anti-PD-1 antibodies and methods of using anti-PD-1 antibodies
Provided herein are antibodies that selectively bind to PD-1 and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.
1. An isolated antibody that specifically binds to PD-1 comprising:
three heavy chain CDRs and three light chain CDRs comprised within a V H region of SEQ ID NO: 252 and a V L region of SEQ ID NO: 276.
2. The antibody of claim 1 that specifically binds to PD-1, wherein the antibody comprises:
m. a CDR-H1 comprising SEQ ID NO: 13; a CDR-H2 comprising SEQ ID NO: 66; a CDR-H3 comprising SEQ ID NO: 119; a CDR-L1 comprising SEQ ID NO: 148; a CDR-L2 comprising SEQ ID NO: 177; and a CDR-L3 comprising SEQ ID NO: 206;
n. a CDR-H1 comprising SEQ ID NO: 37; a CDR-H2 comprising SEQ ID NO: 90; a CDR-H3 comprising SEQ ID NO: 119; a CDR-L1 comprising SEQ ID NO: 148; a CDR-L2 comprising SEQ ID NO: 177; and a CDR-L3 comprising SEQ ID NO: 206.
3. An isolated antibody that specifically binds to PD-1, wherein the antibody comprises:
g. a V H comprising: a CDR-H1 comprising one or more of SEQ ID NOs: 13 and 37; a CDR-H2 comprising one or more of SEQ ID NOs: 66 and 90; and a CDR-H3 comprising SEQ ID NO: 119; and a V L region comprising: a CDR-L1 comprising SEQ ID NO: 148; a CDR-L2 comprising SEQ ID NO: 177; and a CDR-L3 comprising SEQ ID NO: 206.
4. The antibody of claim 3 , wherein the antibody comprises a Vu region selected from:
a SEQ ID NO: 252, or a variant thereof having 4 or fewer amino acid substitutions;
wherein the substitutions are conservative amino acid substitutions.
5. The antibody of claim 3 , wherein the antibody comprises a V L region selected from:
a. SEQ ID NO: 276 or a variant thereof having 20 or fewer amino acid substitutions,
wherein the substitutions are conservative amino acid substitutions.
6. The antibody of claim 3 , wherein:
g. the V H region is SEQ ID NO: 252, and the V L region is SEQ ID NO: 276.
7. The antibody of claim 3 , further comprising at least one constant region domain.
8. The antibody of claim 7 , wherein the constant region domain comprises a sequence selected from SEQ ID NOs: 224-226 and 297.
9. The antibody of claim 3 , wherein the antibody is a monoclonal antibody.
10. The antibody of claim 3 , wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM.
11. The antibody of claim 3 , wherein the antibody is aglycosylated.
12. The antibody of claim 3 , wherein the antibody is an antibody fragment.
13. The antibody of claim 12 , wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′) 2 fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment.
14. The antibody of claim 13 , wherein the antibody is an scFv fragment.
15. The antibody of claim 13 , wherein the antibody is an scFv-Fc fragment.
16. The antibody of claim 15 , wherein the scFv-Fc fragment comprises a sequence selected from SEQ ID NO: 243 with AAGSDQEPK (SEQ ID NO: 301) removed from the sequence.
17. The antibody of claim 3 , wherein the antibody has a k a of about 4.74×10 4 M −1 ×sec −1 to about 1.23×10 6 M −1 ×sec −1 when associating with human PD-1 at a temperature of 25° C.
18. The antibody of claim 3 , wherein the antibody has a k d of about 1.87×10 −2 sec −1 to about 4.17×10 −4 sec −1 when dissociating from human PD-1 at a temperature of 25° C.
19. The antibody of claim 3 , wherein the antibody has a K D of about 3.85×10 −8 M to about 2.52×10 −10 M when bound to human PD-1 at a temperature of 25° C.
20. The antibody of claim 3 , wherein the antibody specifically binds one or more of murine PD-1 and cynomolgus PD-1.
21. A kit comprising an antibody of claim 3 , and instructions for use of the antibody.
22. A polynucleotide encoding an antibody of claim 3 .
23. A vector comprising the polynucleotide of claim 22 .
24. A host cell comprising the vector of claim 23 .
25. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier.
26. A method of treating a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody of claim 3 , or a pharmaceutical composition of claim 25 .
27. The method of claim 26 , wherein the disease or condition is cancer.
28. A polynucleotide encoding an antibody of claim 1 .
29. A vector comprising the polynucleotide of claim 28 .
30. A host cell comprising the vector of claim 29 .
31. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
32. A method of treating a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody of claim 1 .
33. A method of treating a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition of claim 31 .
34. The method of claim 32 , wherein the disease or condition is cancer.
35. The method of claim 33 , wherein the disease or condition is cancer.