Il-21 antagonists

Abstract

Monoclonal antibodies are identified that bind the IL-21 protein. These antibodies are used to identify regions of the IL-21 protein to where binding neutralizes IL-21 activity. Hybridomas and methods of producing anti-IL-21 monoclonal antibodies are described. The monoclonal antibodies are useful in treating IL-21-mediated diseases, which may include autoimmune and inflammatory diseases such as pancreatitis, type I diabetes (IDDM), Graves Disease, inflammatory bowel disease (IBD), Crohn's Disease, ulcerative colitis, irritable bowel syndrome, multiple sclerosis, rheumatoid arthritis, diverticulosis, systemic lupus erythematosus, psoriasis, ankylosing spondylitis, scleroderma, systemic sclerosis, psoriatic arthritis, osteoarthritis, atopic dermatitis, vitiligo, graft vs. host disease (GVHD), cutaneous T cell lymphoma (CTCL), Sjogren's syndrome, glomerulonephritis, IgA nephropathy, graft versous host disease, transplant rejection, atopic dermatitis, anti-phospholipid syndrome, and asthma, and other autoimmune diseases.

1 . An anti-IL-21 monoclonal antibody that binds to an antigenic region of human IL-21.  
     
     
         2 . The anti-IL-21 monoclonal antibody of  claim 1 , wherein the antigenic region of human IL-21 is shown in SEQ ID NO: 6 from amino acid residues 97-122.  
     
     
         3 . The anti-IL-21 monoclonal antibody of  claim 2 , wherein the antibody neutralizes a human IL-21 protein activity, binds a human IL-21-Fc protein, binds a human IL-21 mutein-Fc protein, and binds a mouse IL-21-mouse Fc protein.  
     
     
         4 . The anti-IL-21 monoclonal antibody of  claim 1 , wherein the antigenic region of human IL-21 is shown in SEQ ID NO: 6 from amino acid residues 145 to 148.  
     
     
         5 . The anti-IL-21 monoclonal antibody of  claim 4 , wherein the antibody also binds antigenic region as shown in SEQ ID NO: 6 from amino acid residue 154 to 162.  
     
     
         6 . The anti-IL-21 monoclonal antibody of  claim 4 , wherein the antibody neutralizes a human IL-21 protein activity, binds a human IL-21-Fc protein, does not bind a human IL-21 mutein-Fc protein, and binds a mouse IL-21-mouse Fc protein.  
     
     
         7 . The anti-IL-21 monoclonal antibody of  claim 1 , wherein the antigenic region of human IL-21 is shown in SEQ ID NO: 6 from amino acid residues 30 to 50.  
     
     
         8 . The anti-IL-21 monoclonal antibody of  claim 7 , wherein the antibody neutralizes a human IL-21 protein activity, binds a human IL-21-Fc protein, binds a human IL-21 mutein-Fc protein, and binds a mouse IL-21-mouse Fc protein.  
     
     
         9 . The anti-IL-21 monoclonal antibody of  claim 1 , wherein the antigenic region of human IL-21 is shown in SEQ ID NO: 6 from amino acid residues 40 to 50.  
     
     
         10 . The anti-IL-21 monoclonal antibody of  claim 9 , wherein the antibody neutralizes a human IL-21 protein activity, binds a human IL-21-Fc protein, binds a human IL-21 mutein-Fc protein, and binds a mouse IL-21-mouse Fc protein.  
     
     
         11 . A bin that is capable of competition with monoclonal antibody 272.21.1.13.4.2 (ATCC Accession No. PTA-7142) for binding a human IL-21 antigen.  
     
     
         12 . A bin that is capable of competition with monoclonal antibody 268.5.1.11.42.1.4.3.9 (ATCC Accession No. PTA-7143) for binding a human IL-21 antigen.  
     
     
         13 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody specifically binds to the epitope to which monoclonal antibody 272.21.1.13.4.2 (ATCC Accession No. PTA-7142) binds.  
     
     
         14 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody specifically binds to the epitope to which monoclonal antibody 268.5.1.11.42.1.4.3.9 (ATCC Accession No. PTA-7143) binds.  
     
     
         15 . The monoclonal antibody of according to claims  1 ,  2 ,  4 ,  7 ,  9 ,  13  or  14  labeled with a detectable marker.  
     
     
         16 . The monoclonal antibody of according to claims  1 ,  2 ,  4 ,  7 ,  9 ,  13  or  14  labeled with a detectable marker selected from the group consisting of a radioactive isotope, enzyme, dye and biotin.  
     
     
         17 . A hybridoma cell producing the monoclonal antibody according to claims  1 ,  2 ,  4 ,  7 ,  9 ,  13  or  14 .  
     
     
         18 . The hybridoma cell producing the monoclonal antibody of  claim 17 .  
     
     
         19 . A method of producing the monoclonal antibody according to claims  1 ,  2 ,  4 ,  7 ,  9 ,  13  or  14  comprising: 
 (a) providing a hybridoma capable of producing the monoclonal antibody; and    (b) culturing the hybridoma under conditions that provide for production of the monoclonal antibody by the hybridoma.    
     
     
         20 . A method of treating an autoimmune disease comprising administering a therapeutically effective amount of an anti-IL-21 monoclonal antibody according to claims  1 ,  2 ,  4 ,  7 ,  9 ,  13  or  14  to a patient.  
     
     
         21 . The method of  claim 20 , wherein the autoimmune disease is selected from the group consisting of pancreatitis, type I diabetes (IDDM), Graves Disease, inflammatory bowel disease (IBD), Crohn's Disease, ulcerative colitis, irritable bowel syndrome, multiple sclerosis, rheumatoid arthritis, diverticulosis, systemic lupus erythematosus, psoriasis, ankylosing spondylitis, scleroderma, systemic sclerosis, psoriatic arthritis, osteoarthritis, atopic dermatitis, vitiligo, graft vs. host disease (GVHD), cutaneous T cell lymphoma (CTCL), Sjogren's syndrome, glomerulonephritis, IgA nephropathy, graft versous host disease, transplant rejection, atopic dermatitis, anti-phospholipid syndrome, and asthma, and other autoimmune diseases.