Pd-1 binding proteins and methods of use thereof

Abstract

Provided herein are compositions, methods and uses involving antibodies that specifically bind to Programmed Death-1 (PD-1) and modulate the expression and/or activity of PD-1.

1 . An antibody or antigen-binding fragment thereof that
 (a) binds to an epitope of human PD-1 recognized by an antibody comprising a light chain variable region having an amino acid sequence of SEQ ID NO:8 and a heavy chain variable region having an amino acid sequence of SEQ ID NO: 13; or   (b) competes for the binding to human PD-1 with an antibody comprising a light chain variable region having an amino acid sequence of SEQ ID NO:8 and a heavy chain variable region having an amino acid sequence of SEQ ID NO: 13.   
     
     
         2 .- 69 . (canceled) 
     
     
         70 . A polynucleotide comprising nucleotide sequences encoding a VH, a VL, or both a VH and a VL of the antibody of  claim 1 . 
     
     
         71 . (canceled) 
     
     
         72 . The polynucleotide of  claim 70 , wherein the polynucleotide is operably linked to a promoter. 
     
     
         73 . A vector comprising the polynucleotide of  claim 70 . 
     
     
         74 . A cell comprising the polynucleotide of  claim 70 . 
     
     
         75 . A cell comprising the vector of  claim 73 . 
     
     
         76 . An isolated cell producing the antibody or antigen-binding fragment of  claim 1 . 
     
     
         77 . A kit comprising the antibody or antigen-binding fragment of  claim 1 . 
     
     
         78 . A method of making an antibody or antigen-binding fragment which specifically binds to an epitope of human PD-1, comprising culturing the cell of  claim 74  to express the antibody or antigen-binding fragment. 
     
     
         79 . A method of making an antibody or antigen-binding fragment thereof which specifically binds to an epitope of human PD-1, comprising expressing the polynucleotide of  claim 70 . 
     
     
         80 . A method of attenuating activity of a T cell, comprising contacting the T cell with an effective amount of an antibody or antigen binding fragment of  claim 1 . 
     
     
         81 .- 85 . (canceled) 
     
     
         86 . A method of downregulating PD-1 expression on the surface of a T cell, comprising contacting the T cell with an effective amount of an antibody or antigen binding fragment of  claim 1 . 
     
     
         87 .- 90 . (canceled) 
     
     
         91 . A method of inhibiting cytokine production by a T cell, comprising contacting the T cell with an effective amount of an antibody or antigen binding fragment of  claim 1 . 
     
     
         92 . The method of  claim 91 , wherein the cytokine is IL-1, IL-2, IL-6, IL-12, IL-17, IL-22, IL-23, GM-CSF, TNF-α, IFN-γ, or any combination thereof. 
     
     
         93 .- 104 . (canceled) 
     
     
         105 . The method of  claim 78 , wherein the antibody or antigen binding fragment comprises:
 a light chain variable region (VL) comprising:
 a VL complementarity determining region 1 (CDR1) comprising SEQ ID NO: 1 or SEQ ID NO:7, 
 a VL CDR2 comprising SEQ ID NO:2, and 
 a VL CDR3 comprising SEQ ID NO:3; and 
   a heavy chain variable region (VH) comprising:
 a VH CDR1 comprising SEQ ID NO:4, 
 a VH CDR2 comprising SEQ ID NO:5, and 
 a VH CDR3 comprising SEQ ID NO:6. 
   
     
     
         106 . The method of  claim 79 , wherein the antibody or antigen binding fragment comprises:
 a light chain variable region (VL) comprising:
 a VL complementarity determining region 1 (CDR1) comprising SEQ ID NO: 1 or SEQ ID NO:7, 
 a VL CDR2 comprising SEQ ID NO:2, and 
 a VL CDR3 comprising SEQ ID NO:3; and 
   a heavy chain variable region (VH) comprising:
 a VH CDR1 comprising SEQ ID NO:4, 
 a VH CDR2 comprising SEQ ID NO:5, and 
 a VH CDR3 comprising SEQ ID NO:6. 
   
     
     
         107 . The method of  claim 80 , wherein the antibody or antigen binding fragment comprises:
 a light chain variable region (VL) comprising:
 a VL complementarity determining region 1 (CDR1) comprising SEQ ID NO: 1 or SEQ ID NO:7, 
 a VL CDR2 comprising SEQ ID NO:2, and 
 a VL CDR3 comprising SEQ ID NO:3; and 
   a heavy chain variable region (VH) comprising:
 a VH CDR1 comprising SEQ ID NO:4, 
 a VH CDR2 comprising SEQ ID NO:5, and 
 a VH CDR3 comprising SEQ ID NO:6. 
   
     
     
         108 . The method of  claim 86 , wherein the antibody or antigen binding fragment comprises:
 a light chain variable region (VL) comprising:
 a VL complementarity determining region 1 (CDR1) comprising SEQ ID NO: 1 or SEQ ID NO:7, 
 a VL CDR2 comprising SEQ ID NO:2, and 
 a VL CDR3 comprising SEQ ID NO:3; and 
   a heavy chain variable region (VH) comprising:
 a VH CDR1 comprising SEQ ID NO:4, 
 a VH CDR2 comprising SEQ ID NO:5, and 
 a VH CDR3 comprising SEQ ID NO:6. 
   
     
     
         109 . The method of  claim 91 , wherein the antibody or antigen binding fragment comprises:
 a light chain variable region (VL) comprising:
 a VL complementarity determining region 1 (CDR1) comprising SEQ ID NO: 1 or SEQ ID NO:7, 
 a VL CDR2 comprising SEQ ID NO:2, and 
 a VL CDR3 comprising SEQ ID NO:3; and 
   a heavy chain variable region (VH) comprising:
 a VH CDR1 comprising SEQ ID NO:4, 
 a VH CDR2 comprising SEQ ID NO:5, and 
 a VH CDR3 comprising SEQ ID NO:6.