Anti-pd-1 antibodies, compositions comprising anti-pd-1 antibodies and methods of using anti-pd-1 antibodies

Abstract

Provided herein are antibodies that selectively bind to PD-1 and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

1 .- 20 . (canceled) 
     
     
         21 .- 67 . (canceled) 
     
     
         68 . A method of treating disease in a subject, comprising administering an effective amount of an antibody conjugate, or a pharmaceutical composition comprising the same, wherein the antibody conjugate comprises an antibody or antibody fragment of the IgG class comprising:
 three heavy chain CDRs of the V H  region SEQ ID NO: 252, or a variant thereof, and hree light chain CDRs of the V L  region SEQ ID NO: 276, or a variant thereof.   
     
     
         69 . A method of diagnosing a disease in a subject, comprising administering an effective amount of an antibody conjugate, or a pharmaceutical composition comprising the same, wherein the antibody conjugate comprises an antibody or antibody fragment of the IgG class comprising:
 three heavy chain CDRs of the V H  region SEQ ID NO: 252, or a variant thereof, and three light chain CDRs of the V L  region SEQ ID NO: 276, or a variant thereof.   
     
     
         70 . The method of  claim 68 , wherein the disease is cancer, an autoimmune disease or condition, infection, or any combination thereof. 
     
     
         71 . The method of  claim 68 , wherein the pharmaceutical composition comprises the antibody or antibody fragment of  claim 68  and a pharmaceutically acceptable carrier. 
     
     
         72 . The method of  claim 68 , wherein the pharmaceutical composition is substantially pure. 
     
     
         73 . The method of  claim 72 , wherein the pharmaceutical composition comprises an antibody that is at least 95% by mass of the total antibody or antibody fragment mass of said composition. 
     
     
         74 . The method of  claim 68 , wherein the pharmaceutical composition is administered intramuscularly, intradermally, intraperitoneally, intravenously, subcutaneously administration, or any combination thereof. 
     
     
         75 . The method of  claim 68 , wherein the antibody or antibody fragment comprises:
 a CDR-H1 comprising SEQ ID NO: 13; a CDR-H2 comprising SEQ ID NO: 66; a CDR-H3 comprising SEQ ID NO: 119; a CDR-L1 comprising SEQ ID NO: 148; a CDR-L2 comprising SEQ ID NO: 177; and a CDR-L3 comprising SEQ ID NO: 206; or   b. a CDR-H1 comprising SEQ ID NO: 37; a CDR-H2 comprising SEQ ID NO: 90; a CDR-H3 comprising SEQ ID NO: 119; a CDR-L1 comprising SEQ ID NO: 148; a CDR-L2 comprising SEQ ID NO: 177; and a CDR-L3 comprising SEQ ID NO: 206.   
     
     
         76 . The method of  claim 68 , wherein the variant of the V H  and V L  regions have 20 or fewer amino acid substitutions, and wherein the substitutions are conservative amino acid substitutions. 
     
     
         77 . The method of  claim 68 , wherein the antibody or antibody fragment further comprises at least one constant region domain. 
     
     
         78 . The antibody of  claim 77 , wherein the constant region domain comprises a sequence selected from SEQ ID NOs: 224-226 and 297. 
     
     
         79 . The method of  claim 68 , wherein the antibody or antibody fragment is a monoclonal antibody. 
     
     
         80 . The method of  claim 68 , wherein the antibody or antibody fragment is aglycosylated. 
     
     
         81 . The method of  claim 68 , wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′) 2  fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. 
     
     
         82 . The antibody fragment of  claim 81 , wherein the antibody fragment is an scFv fragment. 
     
     
         83 . The antibody fragment of  claim 81 , wherein the antibody fragment is an scFv-Fc fragment. 
     
     
         84 . The antibody fragment of  claim 83 , wherein the scFv-Fc fragment comprises a sequence selected from SEQ ID NO: 243 with AAGSDQEPK (SEQ ID NO: 301) removed from the sequence. 
     
     
         85 . The method of  claim 68 , wherein the antibody or antibody fragment has a k a  of about 4.74×10 4  M −1 ×sec −1  to about 1.23×10 6  M −1 ×sec −1  when associating with human PD-1 at a temperature of 25° C. 
     
     
         86 . The method of  claim 68 , wherein the antibody or antibody fragment has a k d  of about 1.87×10 −2  sec −1  to about 4.17×10 −4  sec −1  when dissociating from human PD-1 at a temperature of 25° C. 
     
     
         87 . The method of  claim 68 , wherein the antibody or antibody fragment has a K D  of about 3.85×10 −8  M to about 2.52×10 −10  M when bound to human PD-1 at a temperature of 25° C. 
     
     
         88 . The method of  claim 68 , wherein the antibody or antibody fragment specifically binds one or more of murine PD-1 and cynomolgus PD-1.