Antibodies that Specifically Bind PD-1 and Methods of Use

Abstract

Antibodies that specifically bind PD-1 or antigen binding fragments thereof, polynucleotides encoding the antibodies or fragments, and methods of making and using the foregoing are useful in the treatment of an inflammatory or immune disorder.

We claim: 
     
         1 - 15 . (canceled) 
     
     
         16 . A method of downmodulating an immune response in a subject in need thereof, comprising administering to the subject an effective amount of an antibody that specifically binds PD-1 or an antigen binding fragment thereof, wherein the antibody or the antigen binding fragment thereof comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, a light chain complementarity determining region 1 (LCDR1), a LCDR2 and a LCDR3 of SEQ ID NOs: 2, 165, 4, 166, 6 and 7, respectively. 
     
     
         17 . The method of  claim 16 , wherein the antibody or the antigen binding fragment thereof comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of 
 a) SEQ ID NOs: 2, 3, 4, 5, 6 and 7, respectively;   b) SEQ ID NOs: 2, 145, 4, 5, 6, and 7, respectively;   c) SEQ ID NOs: 2, 146, 4, 5, 6, and 7, respectively;   d) SEQ ID NOs: 2, 147, 4, 5, 6, and 7, respectively;   e) SEQ ID NOs: 2, 3, 4, 148, 6 and 7, respectively;   f) SEQ ID NOs: 2, 3, 4, 149, 6 and 7, respectively;   g) SEQ ID NOs: 2, 145, 4, 148, 6 and 7, respectively;   h) SEQ ID NOs: 2, 146, 4, 148, 6 and 7, respectively;   i) SEQ ID NOs: 2, 147, 4, 148, 6 and 7, respectively;   j) SEQ ID NOs: 2, 145, 4, 149, 6 and 7, respectively;   k) SEQ ID NOs: 2, 146, 4, 149, 6 and 7, respectively; or   l) SEQ ID NOs: 2, 147, 4, 149, 6 and 7, respectively.   
     
     
         18 . The method of  claim 16 , wherein the antibody or the antigen binding fragment thereof comprises 
 a) a heavy chain variable region (VH) of SEQ ID NO: 118;   b) a light chain variable region (VL) of SEQ ID NO: 119; or   c) the VH and the VL of SEQ ID NOs: 118 and 119, respectively.   
     
     
         19 . The method of  claim 18 , wherein the antibody or the antigen binding fragment thereof comprises the VH of SEQ ID NO: 10 and the VL of SEQ ID NO: 16. 
     
     
         20 . The method of  claim 16 , wherein the antibody or the antigen binding fragment thereof comprises 
 a) the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 2, 3, 4, 5, 6 and 7, respectively;   b) the VH of SEQ ID NO: 10 and the VL of SEQ ID NO: 16; and/or   c) a heavy chain (HC) of SEQ ID NO: 22 and a light chain (LC) of SEQ ID NO: 28.   
     
     
         21 . The method of  claim 16 , wherein the antibody or the antigen binding fragment thereof is administered in combination with a second agent. 
     
     
         22 . The method of  claim 16 , wherein the antibody or the antigen binding fragment thereof comprises at least one mutation in the antibody Fc that modulates binding of the antibody to an Fc receptor (FcR). 
     
     
         23 . The method of  claim 16 , wherein the antibody or the antigen binding fragment thereof has a biantennary glycan structure with a fucose content of less than 15%. 
     
     
         24 . A method of suppressing activation of a PD-1 expressing T cell in a subject, comprising administering to the subject an antibody that specifically binds PD-1 or an antigen binding fragment thereof, for a time sufficient to suppress activation of the PD-1 expressing T cell, wherein the antibody or the antigen binding fragment thereof comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, a light chain complementarity determining region 1 (LCDR1), a LCDR2 and a LCDR3 of SEQ ID NOs: 2, 165, 4, 166, 6 and 7, respectively. 
     
     
         25 . The method of  claim 24 , wherein the antibody or the antigen binding fragment thereof comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of 
 a) SEQ ID NOs: 2, 3, 4, 5, 6 and 7, respectively;   b) SEQ ID NOs: 2, 145, 4, 5, 6, and 7, respectively;   c) SEQ ID NOs: 2, 146, 4, 5, 6, and 7, respectively;   d) SEQ ID NOs: 2, 147, 4, 5, 6, and 7, respectively;   e) SEQ ID NOs: 2, 3, 4, 148, 6 and 7, respectively;   f) SEQ ID NOs: 2, 3, 4, 149, 6 and 7, respectively;   g) SEQ ID NOs: 2, 145, 4, 148, 6 and 7, respectively;   h) SEQ ID NOs: 2, 146, 4, 148, 6 and 7, respectively;   i) SEQ ID NOs: 2, 147, 4, 148, 6 and 7, respectively;   j) SEQ ID NOs: 2, 145, 4, 149, 6 and 7, respectively;   k) SEQ ID NOs: 2, 146, 4, 149, 6 and 7, respectively; or   l) SEQ ID NOs: 2, 147, 4, 149, 6 and 7, respectively.   
     
     
         26 . The method of  claim 24 , wherein the antibody or the antigen binding fragment thereof comprises 
 a) the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 2, 3, 4, 5, 6 and 7, respectively;   b) the VH of SEQ ID NO: 10 and the VL of SEQ ID NO: 16; and/or   c) a heavy chain (HC) of SEQ ID NO: 22 and a light chain (LC) of SEQ ID NO: 28.   
     
     
         27 . The method of  claim 24 , wherein the antibody or the antigen binding fragment thereof is administered in combination with a second agent. 
     
     
         28 . The method of  claim 24 , wherein the antibody or the antigen binding fragment thereof comprises at least one mutation in the antibody Fc that modulates binding of the antibody to an Fc receptor (FcR). 
     
     
         29 . The method of  claim 24 , wherein the antibody or the antigen binding fragment thereof has a biantennary glycan structure with a fucose content of less than 15%. 
     
     
         30 . A method of treating an immune disorder, comprising administering to a subject in need thereof an effective amount of an antibody that specifically binds PD-1 or an antigen binding fragment thereof, wherein the antibody or the antigen binding fragment thereof comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, a light chain complementarity determining region 1 (LCDR1), a LCDR2 and a LCDR3 of SEQ ID NOs: 2, 165, 4, 166, 6 and 7, respectively. 
     
     
         31 . The method of  claim 30 , wherein the antibody or the antigen binding fragment thereof comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of 
 a) SEQ ID NOs: 2, 3, 4, 5, 6 and 7, respectively;   b) SEQ ID NOs: 2, 145, 4, 5, 6, and 7, respectively;   c) SEQ ID NOs: 2, 146, 4, 5, 6, and 7, respectively;   d) SEQ ID NOs: 2, 147, 4, 5, 6, and 7, respectively;   e) SEQ ID NOs: 2, 3, 4, 148, 6 and 7, respectively;   f) SEQ ID NOs: 2, 3, 4, 149, 6 and 7, respectively;   g) SEQ ID NOs: 2, 145, 4, 148, 6 and 7, respectively;   h) SEQ ID NOs: 2, 146, 4, 148, 6 and 7, respectively;   i) SEQ ID NOs: 2, 147, 4, 148, 6 and 7, respectively;   j) SEQ ID NOs: 2, 145, 4, 149, 6 and 7, respectively;   k) SEQ ID NOs: 2, 146, 4, 149, 6 and 7, respectively; or   l) SEQ ID NOs: 2, 147, 4, 149, 6 and 7, respectively.   
     
     
         32 . The method of  claim 30 , wherein the antibody or the antigen binding fragment thereof comprises 
 a) the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 2, 3, 4, 5, 6 and 7, respectively;   b) the VH of SEQ ID NO: 10 and the VL of SEQ ID NO: 16; and/or   c) a heavy chain (HC) of SEQ ID NO: 22 and a light chain (LC) of SEQ ID NO: 28.   
     
     
         33 . The method of  claim 30 , wherein the antibody or the antigen binding fragment thereof is administered in combination with a second agent. 
     
     
         34 . The method of  claim 30 , wherein the antibody or the antigen binding fragment thereof comprises at least one mutation in the antibody Fc that modulates binding of the antibody to an Fc receptor (FcR). 
     
     
         35 . The method of  claim 30 , wherein the antibody or the antigen binding fragment thereof has a biantennary glycan structure with a fucose content of less than 15%.