Antigen Binding Proteins that Bind PD-1

Abstract

There is disclosed compositions and methods relating to or derived from anti-PD-1 antibodies. More specifically, there is disclosed fully human antibodies that bind PD-1, PD-1-binding fragments and derivatives of such antibodies, and PD-1-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PD-1 related disorders or conditions, including various inflammatory disorders and various cancers.

1 - 7 . (canceled) 
     
     
         8 . An anti-PD1 binding agent selected from the group consisting of:
 (i) an antibody that binds to a PD1 epitope, or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises   a heavy chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 33, and SEQ ID NO. 35; and   a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 34, and SEQ ID NO. 36;   (ii) an isolated anti-PD1 antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain comprising complementarity determining regions as set forth in a heavy chain variable domain amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 33, and SEQ ID NO. 35; and   comprising a light chain variable domain comprising complementarity determining regions as set forth in a light chain variable region amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 34, and SEQ ID NO. 36; and   (iii) an anti-PD1 single chain human antibody comprising a heavy chain variable domain and a light chain variable domain which are connected by a peptide linker, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 33, and SEQ ID NO. 35; and   a light chain variable domain sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO. 34, and SEQ ID NO. 36.   
     
     
         9 . The anti-PD1 binding agent of  claim 8 , comprising a heavy chain/light chain variable domain sequence selected from the group consisting of SEQ ID NO. 1/SEQ ID NO. 2, SEQ ID NO. 33/SEQ ID NO. 34, and SEQ ID NO. 35/SEQ ID NO. 36. 
     
     
         10 . The anti-PD1 binding agent of  claim 8 , wherein the antibody that binds to a PD1 epitope, or the isolated anti-PD1 antibody is a fully human antibody of an IgG class. 
     
     
         11 . The anti-PD1 binding agent of  claim 8 , wherein the antigen-binding fragment of the antibody that binds to a PD1 epitope, or the antigen-binding fragment of the isolated anti-PD1 antibody is a fully human antibody Fab fragment. 
     
     
         12 . The anti-PD1 binding agent of  claim 8 , which has a K D  of at least 1×10 −6  M. 
     
     
         13 . A pharmaceutical composition comprising the anti-PD1 binding agent of  claim 8 , and a pharmaceutically acceptable excipient. 
     
     
         14 . A method for treating a subject having cancer, the method comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 13 . 
     
     
         15 . The method of  claim 14 , wherein the cancer is selected from the group consisting of ovarian cancer, colon cancer, breast cancer, lung cancer, myeloma, a neuroblastic-derived CNS tumor, monocytic leukemia, B-cell derived leukemia, T-cell derived leukemia, B-cell derived lymphoma, T-cell derived lymphoma, skin cancer, small cell lung cancer, non-small cell lung cancer (NSCLC), head and neck cancer, pancreatic cancer, bladder cancer, brain cancer, colorectal cancer, thyroid cancer, prostate cancer, kidney cancer, stomach cancer, and cancer of the testes. 
     
     
         16 . One or more nucleic acids encoding the anti-PD1 binding agent of  claim 8 . 
     
     
         17 . The one or more nucleic acids of  claim 16 , wherein the antibody that binds to a PD1 epitope, or the antigen-binding fragment thereof, or the anti-PD1 single chain antibody comprises a heavy chain variable domain comprising complementarity determining regions (CDRs) as set forth in a heavy chain variable region amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 33, and SEQ ID NO: 35; and
 a light chain variable region comprising CDRs as set forth in a light chain variable region amino acid sequence selected from the group consisting of SEQ ID NO. 2, SEQ ID NO: 34, and SEQ ID NO: 36.   
     
     
         18 . One or more vectors comprising the one or more nucleic acids of  claim 17 . 
     
     
         19 . A host cell comprising the one or more nucleic acids of  claim 17 . 
     
     
         20 . A host cell comprising the one or more vectors of  claim 18 .