Antibodies Directed Against Programmed Death-1(PD-1)

Abstract

The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to a programmed death-1 (PD-1) protein. The invention provides a PD-1-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using the PD-1-binding agent to treat a cancer or an infectious disease.

1 - 52 . (canceled) 
     
     
         53 . An isolated programmed cell death-1 protein (PD-1) binding agent comprising an immunoglobulin heavy chain polypeptide comprising a complementarity determining region 1 (CDR) amino acid sequence, a CDR2 amino acid sequence, and a CDR3 amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. 
     
     
         54 . An isolated programmed cell death-1 protein (PD-1) binding agent comprising an immunoglobulin light chain polypeptide comprising a complementarity determining region 1 (CDR) amino acid sequence, a CDR2 amino acid sequence, and a CDR3 amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 40. 
     
     
         55 . An isolated programmed cell death-1 protein (PD-1) binding agent comprising: (i) an immunoglobulin heavy chain polypeptide according to  claim 53 ; and (ii) an immunoglobulin light chain polypeptide according to  claim 54 . 
     
     
         56 . The isolated programmed cell death-1 protein (PD-1) binding agent according to  claim 55  wherein the binding agent is an antibody, and antibody conjugate, or an antigen-binding fragment thereof. 
     
     
         57 . The PD-1 binding agent of  claim 56  wherein the binding agent is an antibody and the framework region thereof is an IgG1 or IgG4 framework region. 
     
     
         58 . The PD-1 binding agent of  claim 57  wherein the antibody is a humanized IgG4 antibody. 
     
     
         59 . An isolated or purified nucleic acid sequence encoding the PD-1 binding agent of  claim 55 . 
     
     
         60 . An isolated cell comprising the nucleic acid of  claim 59 . 
     
     
         61 . A composition comprising the isolated PD-1 binding agent of  claim 55  and a pharmaceutically acceptable carrier. 
     
     
         62 . A method of treating a cancer in a human patient, the method comprising administering an effective amount of the composition of  claim 61  to the human patient whereupon the cancer is treated in the human patient. 
     
     
         63 . The method of  claim 62  further comprising (i) an antibody that binds to a TIM-3 protein and (ii) a pharmaceutically acceptable carrier. 
     
     
         64 . The method of  claim 62  further comprising (i) an antibody that binds to a LAG-3 protein and (ii) a pharmaceutically acceptable carrier. 
     
     
         65 . The method of  claim 62  wherein the PD-1 binding agent binds to PD-1 with a KD between about 1 picomolar (pM) and about 100 micromolar (µM). 
     
     
         66 . The method of  claim 62  wherein the half-life of the PD-1 binding agent is between 30 minutes and 45 days. 
     
     
         67 . The isolated programmed cell death-1 protein (PD-1) binding agent of  claim 55  comprising the immunoglobulin heavy chain polypeptide of SEQ ID NO: 6 and the immunoglobulin light chain polypeptide of SEQ ID NO:29. 
     
     
         68 . The isolated programmed cell death-1 protein (PD-1) binding agent of  claim 55  comprising the immunoglobulin heavy chain polypeptide of SEQ ID NO: 7 and the immunoglobulin light chain polypeptide of SEQ ID NO:29. 
     
     
         69 . The isolated programmed cell death-1 protein (PD-1) binding agent of  claim 55  comprising the immunoglobulin heavy chain polypeptide of SEQ ID NO: 8 and the immunoglobulin light chain polypeptide of SEQ ID NO:29. 
     
     
         70 . The isolated programmed cell death-1 protein (PD-1) binding agent of  claim 55  comprising the immunoglobulin heavy chain polypeptide of SEQ ID NO: 9 and the immunoglobulin light chain polypeptide of SEQ ID NO:29. 
     
     
         71 . The isolated programmed cell death-1 protein (PD-1) binding agent of  claim 55  comprising the immunoglobulin heavy chain polypeptide of SEQ ID NO: 10 and the immunoglobulin light chain polypeptide of SEQ ID NO:29. 
     
     
         72 . An isolated programmed cell death-1 protein (PD-1) binding agent comprising: (i) an immunoglobulin heavy chain polypeptide of SEQ ID NO: 23; and (ii) an immunoglobulin light chain polypeptide of SEQ ID NO: 29.