Interleukin-21 receptor binding proteins

Abstract

The present invention provides binding proteins and antigen-binding fragments thereof that specifically bind to the human interleukin-21 receptor (IL-21R). The binding proteins can act as, e.g., antagonists of IL-21R activity, thereby modulating immune responses in general, and those mediated by IL-21R in particular. The disclosed compositions and methods may be used, e.g., in diagnosing and/or treating IL-21R-associated disorders, e.g., inflammatory disorders, autoimmune diseases, allergies, transplant rejection, cancer, and other immune system disorders.

1 . An isolated binding protein or antigen-binding fragment thereof that binds to IL-21R, wherein the binding protein or antigen-binding fragment thereof comprises at least one amino acid sequence that is at least about 95% identical to an amino acid sequence(s) selected from the group consisting of:
 (a) SEQ ID NO:163;   (b) SEQ ID NO:164;   (c) SEQ ID NO:169;   (d) SEQ ID NO:194;   (e) SEQ ID NO:195;   (f) SEQ ID NO:176;   (g) SEQ ID NO:219;   (h) SEQ ID NO:219 from amino acid 1 to 118;   (i) SEQ ID NO:220; and   (j) SEQ ID NO:221.   
     
     
         2 - 6 . (canceled) 
     
     
         7 . An isolated binding protein or antigen-binding fragment thereof that binds to IL-21R, wherein the binding protein or antigen-binding fragment thereof comprises at least one amino acid sequence encoded by a nucleotide sequence that is at least about 95% identical to a nucleotide sequence(s) selected from the group consisting of:
 (a) SEQ ID NO:239 from nucleotide 148 to 165;   (b) SEQ ID NO:239 from nucleotide 208 to 255;   (c) SEQ ID NO:239 from nucleotide 352 to 378;   (d) SEQ ID NO:97 from nucleotide 124 to 156;   (e) SEQ ID NO:97 from nucleotide 202 to 222;   (f) SEQ ID NO:97 from nucleotide 319 to 354;   (g) SEQ ID NO:239 from nucleotide 58 to 1401;   (h) SEQ ID NO:239 from nucleotide 58 to 411;   (i) SEQ ID NO:97 from nucleotide 58 to 702; and   (j) SEQ ID NO:97 from nucleotide 58 to 384.   
     
     
         8 - 22 . (canceled) 
     
     
         23 . An isolated binding protein or antigen-binding fragment thereof that binds to IL-21R, wherein the binding protein or antigen-binding fragment thereof comprises a light chain and a heavy chain, and wherein the light chain comprises at least one amino acid sequence selected from the group consisting of:
 (a) SEQ ID NO:194;   (b) SEQ ID NO:195;   (c) SEQ ID NO:176;   (d) SEQ ID NO:220; and   (e) SEQ ID NO:221.   
     
     
         24 . (canceled) 
     
     
         25 . The binding protein or antigen-binding fragment of  claim 23 , wherein the binding protein or antigen-binding fragment comprises a V L  domain and a V H  domain, and wherein the V L  domain comprises at least one amino acid sequence selected from the group consisting of:
 (a) SEQ ID NO:194;   (b) SEQ ID NO:195;   (c) SEQ ID NO:176; and   (d) SEQ ID NO:221.   
     
     
         26 . (canceled) 
     
     
         27 . An isolated binding protein or antigen-binding fragment thereof that binds to an IL-21R epitope that is recognized by AbS, wherein the binding protein or antigen-binding fragment competitively inhibits the binding of AbS to human IL-21R. 
     
     
         28 . The binding protein or antigen-binding fragment of  claim 27 , comprising a heavy chain, a light chain, or an F v  fragment comprising an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NO:163;   (b) SEQ ID NO:164;   (c) SEQ ID NO:169;   (d) SEQ ID NO:194;   (e) SEQ ID NO:195;   (f) SEQ ID NO:176;   (g) SEQ ID NO:219;   (h) SEQ ID NO:219 from amino acid 1 to 118;   (i) SEQ ID NO:220; and   (j) SEQ ID NO:221.   
     
     
         29 . The binding protein or antigen-binding fragment of  claim 27 , comprising a heavy chain, a light chain, or an F v  fragment comprising an amino acid sequence encoded by a nucleotide sequence selected from the group consisting of:
 (a) SEQ ID NO:239 from nucleotide 148 to 165;   (b) SEQ ID NO:239 from nucleotide 208 to 255;   (c) SEQ ID NO:239 from nucleotide 352 to 378;   (d) SEQ ID NO:97 from nucleotide 124 to 156;   (e) SEQ ID NO:97 from nucleotide 202 to 222;   (f) SEQ ID NO:97 from nucleotide 319 to 354;   (g) SEQ ID NO:239 from nucleotide 58 to 1401;   (h) SEQ ID NO:239 from nucleotide 58 to 411;   (i) SEQ ID NO:97 from nucleotide 58 to 702; and   (j) SEQ ID NO:97 from nucleotide 58 to 384.   
     
     
         30 - 39 . (canceled) 
     
     
         40 . An isolated nucleic acid encoding the binding protein or antigen-binding fragment of  claim 1 . 
     
     
         41 . An expression vector comprising the nucleic acid of  claim 40 . 
     
     
         42 . A host cell transformed with the vector of  claim 41 . 
     
     
         43 . The host cell of  claim 42 , wherein the host cell is a bacteria, mammalian cell, yeast cell, plant cell, or insect cell. 
     
     
         44 - 49 . (canceled) 
     
     
         50 . An isolated nucleic acid encoding the binding protein or antigen-binding fragment of  claim 27 .