Antibodies that bind both il-17a and il-17f and methods of using the same

Abstract

The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, as well as methods of using the same in inflammation.

1 . An isolated, cross-reactive monoclonal antibody that binds to both IL-17A (SEQ ID NO:2) and IL-17F (SEQ ID NO:4), wherein said antibody binds to
 (a) an IL-17F epitope comprising amino acid residues 67-73 of SEQ ID NO:4 and an IL-17A epitope comprising amino acid residues 69-75 of SEQ ID NO:2;   (b) an IL-17F epitope comprising amino acid residues 79-85 of SEQ ID NO:4 and an IL-17A epitope comprising amino acid residues 81-87 of SEQ ID NO:2;   (c) an IL-17F epitope comprising amino acid residues 146-152 of SEQ ID NO:4 and an IL-17A epitope comprising amino acid residues 148-154 of SEQ ID NO:2;   (d) a discontinuous IL-17F epitope comprising amino acid residues 105-109 and 147-152 of SEQ ID NO:4 and a discontinuous IL-17A epitope comprising amino acid residues 107-111 and 149-154 of SEQ ID NO:2; or   (e) a discontinuous IL-17F epitope comprising amino acid residues 79-85, 119-122, and 130-134 of SEQ ID NO:4 and a discontinuous IL-17A epitope comprising amino acid residues 81-87, 121-124, and 132-136 of SEQ ID NO:2;   and wherein said antibody reduces the pro-inflammatory activity of both IL-17A and IL-17F.   
     
     
         2 . The antibody of  claim 1 , wherein said antibody is selected from the group consisting of a murine antibody, a chimeric antibody, a humanized antibody, and a human antibody. 
     
     
         3 . The antibody of  claim 1 , wherein said antibody is a single chain antibody. 
     
     
         4 . The antibody of  claim 1 , wherein said antibody is an antibody fragment. 
     
     
         5 . The antibody of  claim 4 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2 , and Fv antibody fragments. 
     
     
         6 . A pharmaceutical composition comprising:
 an effective amount of the antibody according to  claim 1 ; and   a pharmaceutically acceptable vehicle, carrier, or excipient.   
     
     
         7 . A diagnostic kit comprising an antibody according to  claim 1  and means for detecting binding by that antibody. 
     
     
         8 . The diagnostic kit according to  claim 7 , wherein said means for detecting binding comprises a detectable label that is linked to said antibody. 
     
     
         9 . A method for diagnosing an immune disease in a mammal, the method comprising (a) contacting an antibody according to  claim 1  with a test sample of tissue cells obtained from the mammal, (b) detecting the formation of a complex between the antibody and either or both of IL-17A and IL-17F in the test sample, and (c) comparing said complex formation with complex formation in a control sample of normal tissue cells of the same cell type, wherein the formation of a larger quantity of complexes formed in the test sample is indicative of the presence of the immune disease in the mammal. 
     
     
         10 . A method of reducing inflammation in a mammal, the method comprising:
 administering to a mammal with inflammation an effective amount of an antibody according to  claim 1 .   
     
     
         11 . A method of treating or preventing an inflammatory disease, the method comprising:
 administering to a patient having the inflammatory disease an effective amount of an antibody according to  claim 1 .   
     
     
         12 . The method of  claim 11 , wherein the inflammatory disease is a chronic inflammatory disease. 
     
     
         13 . The method of  claim 12 , wherein the chronic inflammatory disease is selected from the group consisting of an inflammatory bowel disease (IBD), arthritis, atopic dermatitis, and psoriasis. 
     
     
         14 . The method of  claim 11 , wherein the inflammatory disease is an acute inflammatory disease. 
     
     
         15 . The method of  claim 14 , wherein the acute inflammatory disease is selected from the group consisting of endotoxemia, septicemia, toxic shock syndrome, and infectious disease. 
     
     
         16 . The method of  claim 11 , wherein the inflammatory disease is an autoimmune disease. 
     
     
         17 . The method of  claim 16 , wherein the autoimmune disease is selected from the group consisting of type I diabetes (IDDM), multiple sclerosis (MS), systemic lupus erythematosus (SLE), myasthenia gravis, rheumatoid arthritis, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). 
     
     
         18 . The method of  claim 11 , wherein the inflammatory disease is an arthritic disease. 
     
     
         19 . The method of  claim 18 , wherein the arthritic disease is selected from the group consisting of psoriatic arthritis, rheumatoid arthritis, osteoarthritis, and juvenile chronic arthritis. 
     
     
         20 . The method of  claim 11 , wherein the inflammatory disease is an inflammatory bowel disease (IBD). 
     
     
         21 . The method of  claim 20 , wherein the inflammatory bowel disease is selected from the group consisting of ulcerative colitis and Crohn's disease. 
     
     
         22 . The method of  claim 11 , wherein the inflammatory disease is a demyelinating disease of the central or peripheral nervous system. 
     
     
         23 . The method of  claim 22 , wherein the demyelinating disease is selected from the group consisting of multiple sclerosis, idiopathic demyelinating polyneuropathy, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyneuropathy. 
     
     
         24 . The method of  claim 11 , wherein the inflammatory disease is a hepatobiliary disease. 
     
     
         25 . The method of  claim 24 , wherein the hepatobiliary disease is selected from the group consisting of infectious, autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, and sclerosing cholangitis. 
     
     
         26 . The method of  claim 11 , wherein the inflammatory disease is an autoimmune or immune-mediated skin disease. 
     
     
         27 . The method of  claim 26 , wherein the autoimmune or immune-mediated skin disease is selected from the group consisting of a bullous skin disease, erythema multiforme, atopic dermatitis, contact dermatitis, psoriasis, and neutrophilic dermatoses. 
     
     
         28 . The method of  claim 11 , wherein the inflammatory disease is an allergic disease. 
     
     
         29 . The method of  claim 28 , wherein the allergic disease is selected from the group consisting of allergic asthma, allergic rhinitis, food hypersensitivity, and urticaria. 
     
     
         30 . The method of  claim 11 , wherein the inflammatory disease is an immunologic disease of the lung. 
     
     
         31 . The method of  claim 30 , wherein the immunologic disease of the lung is selected from the group consisting of eosinophilic pneumonia, idiopathic pulmonary fibrosis, adult respiratory disease (ARD), acute respiratory distress syndrome(ARDS), asthma, chronic obstructive pulmonary disease (COPD), airway hyper-responsiveness, chronic bronchitis, allergic asthma, and hypersensitivity pneumonitis. 
     
     
         32 . The method of  claim 11 , wherein the inflammatory disease is a transplantation-associated disease. 
     
     
         33 . The method of  claim 32 , wherein the transplantation-associated disease is selected from the group consisting of transplant rejection and graft-versus-host disease (GVHD).