Anti-PD-1 antibodies
Antibodies that bind to programmed cell death protein 1 (PD-1), compositions comprising such antibodies, and methods of making and using such antibodies are disclosed.
1. An isolated antibody that binds to programmed cell death protein 1 (PD-1), comprising a heavy chain variable region (HCVR) having complementarity determining regions (CDRs) selected from the group consisting of: CDRs 1-3 of SEQ ID NO: 1; and CDRs 1-3 of SEQ ID NO: 4, and a light chain variable region (LCVR) having CDRs selected from the group consisting of: CDRs 1-3 of SEQ ID NO: 27; and CDRs 1-3 of SEQ ID NO: 28.
2. The antibody according to claim 1 , wherein the antibody comprises a HCVR and LCVR pair selected from the group consisting of: a HCVR having the sequence set forth in SEQ ID NO: 4 and a LCVR having the sequence set forth in SEQ ID NO: 28 (244C7); a HCVR having the sequence set forth in SEQ ID NO: 4 and a LCVR having the sequence set forth in SEQ ID NO: 27 (244C7m1); a HCVR having the sequence set forth in SEQ ID NO: 1 and a LCVR having the sequence set forth in SEQ ID NO: 28 (244C8); and a HCVR having the sequence set forth in SEQ ID NO: 1 and a LCVR having the sequence set forth in SEQ ID NO: 27 (244C8m1).
3. The antibody according to claim 1 comprising a humanized or human framework region.
4. The antibody according to claim 1 , comprising a HCVR having the sequence set forth in SEQ ID NO: 85 and a LCVR having the sequence set forth in SEQ ID NO: 91; a HCVR having the sequence set forth in SEQ ID NO: 85 and a LCVR having the sequence set forth in SEQ ID NO: 93; or a HCVR having the sequence set forth in SEQ ID NO: 86 and a LCVR having the sequence set forth in SEQ ID NO: 91.
5. The antibody according to claim 1 , wherein the antibody binds to a sequence in PD-1 comprising amino acid residues 74-139 of SEQ ID NO: 97.
6. An isolated nucleic acid comprising a nucleotide sequence encoding the HCVR, the LCVR, or a combination thereof of claim 1 .
7. An expression vector comprising the nucleic acid of claim 6 .
8. A host cell transformed with an expression vector of claim 7 .
9. A method of producing an antibody comprising a HCVR, a LCVR, or a combination thereof, the method comprising:
(a) growing the host cell of claim 8 , under conditions such that the host cell expresses the antibody comprising the HCVR, the LCVR, or a combination thereof; and
(b) isolating the antibody comprising the HCVR, the LCVR, or combination thereof.
10. A method of treating cancer in a mammal in need thereof, comprising administering an effective amount of the antibody according to claim 1 to the mammal.
11. A method for increasing T cell effector function, comprising contacting a T cell with the antibody of claim 1 .
12. A method for increasing lymphocyte secretion of a cytokine selected from the group consisting of IL-6, IL-12, IL-18, TNF-α, IL-1β and GM-CSF in a human patient in need of increased T cell effector function, comprising administering to the patient a therapeutically effective amount of the antibody of claim 1 .
13. The antibody according to claim 1 , comprising a HCVR having CDRs 1-3 of SEQ ID NO: 1, and a LCVR having CDRs 1-3 of SEQ ID NO: 28.