Anti-pd1 antibodies and their use as therapeutics and diagnostics

Abstract

Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) and inhibit PD1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD1-mediated functions.

1 . A method for treating cancer in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that specifically binds to human PD-1, wherein the antibody or antigen-binding fragment thereof comprises:
 a heavy chain variable region comprising a heavy chain complementary determining region (CDR) 1 comprising amino acid residues 6-10 of the sequence of SEQ ID NO: 31, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 32, and a heavy chain CDR3 comprising amino acid residues 3-12 of the sequence of SEQ ID NO: 33; and   a light chain variable region comprising a light chain CDR1 comprising the sequence of SEQ ID NO: 34, a light chain CDR2 comprising the sequence of SEQ ID NO: 35, and a light chain CDR3 comprising the sequence of SEQ ID NO: 36.   
     
     
         2 . The method of  claim 1 , wherein the heavy chain variable region comprises the sequence of SEQ ID NO: 24 and the light chain variable region comprises the sequence of SEQ ID NO: 26. 
     
     
         3 . The method of  claim 1 , wherein the antibody further comprises an IgG1 or an IgG4 heavy chain constant domain. 
     
     
         4 . The method of  claim 3 , wherein the antibody comprises an IgG4 heavy chain constant domain comprising the sequence of SEQ ID NO: 88. 
     
     
         5 . The method of  claim 1 , wherein the cancer is selected from lung cancer, liver cancer, stomach cancer, breast cancer, ovarian cancer, pancreatic cancer, esophageal cancer, and melanoma. 
     
     
         6 . A method for treating cancer in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that specifically binds to human PD-1, wherein the antibody or antigen-binding fragment thereof comprises:
 a heavy chain variable region comprising: a heavy chain complementary determining region (CDR) 1 comprising amino acid residues 1-8 of the sequence of SEQ ID NO: 31, a heavy chain CDR2 comprising amino acid residues 2-8 of the sequence of SEQ ID NO: 32, and a heavy chain CDR3 comprising the sequence of SEQ ID NO: 33; and   a light chain variable region comprising: a light chain CDR1 comprising amino acid residues 4-9 of the sequence of SEQ ID NO: 34, a light chain CDR2 comprising amino acid residues 1-3 of the sequence of SEQ ID NO: 35, and a light chain CDR3 comprising the sequence of SEQ ID NO: 36.   
     
     
         7 . The method of  claim 6 , wherein the heavy chain variable region comprises the sequence of SEQ ID NO: 24 and the light chain variable region comprises the sequence of SEQ ID NO: 26. 
     
     
         8 . The method of  claim 6 , wherein the antibody further comprises an IgG1 or an IgG4 heavy chain constant domain. 
     
     
         9 . The method of  claim 8 , wherein the antibody comprises an IgG4 heavy chain constant domain comprising the sequence of SEQ ID NO: 88. 
     
     
         10 . The method of  claim 6 , wherein the cancer is selected from lung cancer, liver cancer, stomach cancer, breast cancer, ovarian cancer, pancreatic cancer, esophageal cancer, and melanoma.