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

Abstract

The present invention relates to blocking, inhibiting, reduceing, 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 antibody that binds to both IL-17A (SEQ ID NO:2) and IL-17F (SEQ ID NO:4).  
     
     
         2 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 23, 25, 27, 29 and 34 of SEQ ID NO:4.  
     
     
         3 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope comprises amino acid residues 20, 22, 24, 26 and 31 of SEQ ID NO:2.  
     
     
         4 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 23, 25, 27, 29 and 34 of SEQ ID NO:4 and an IL-17A epitope, wherein said epitope comprises amino acid residues 20, 22, 24, 26 and 31 of SEQ ID NO:2.  
     
     
         5 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 23-34 of SEQ ID NO:4.  
     
     
         6 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope comprises amino acid residues 20-31 of SEQ ID NO:2.  
     
     
         7 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 67-73 of SEQ ID NO:4.  
     
     
         8 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope comprises amino acid residues 69-75 of SEQ ID NO:2.  
     
     
         9 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 87-93 of SEQ ID NO:4 and an IL-17A epitope, wherein said epitope comprises amino acid residues 69-75 of SEQ ID NO:2.  
     
     
         10 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 79-85 of SEQ ID NO:4.  
     
     
         11 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope comprises amino acid residues 81-87 of SEQ ID NO:2.  
     
     
         12 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 79-85 of SEQ ID NO:4 and an IL-17A epitope, wherein said epitope comprises amino acid residues 81-87 of SEQ ID NO:2.  
     
     
         13 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 147-152 of SEQ ID NO:4.  
     
     
         14 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope comprises amino acid residues 149-154 of SEQ ID NO:2.  
     
     
         15 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope comprises amino acid residues 147-152 of SEQ ID NO:4 and an IL-17A epitope, wherein said epitope comprises amino acid residues 149-154 of SEQ ID NO:2.  
     
     
         16 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 105-109 and 147-152 of SEQ ID NO:4.  
     
     
         17 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 107-111 and 148-154 of SEQ ID NO:2.  
     
     
         18 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 105-109 and 147-152 of SEQ ID NO:4 and an IL-17A epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 107-111 and 148-154 of SEQ ID NO:2.  
     
     
         19 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 79-85, 119-122 and 130-134 of SEQ ID NO:4.  
     
     
         20 . The antibody of  claim 1 , wherein said antibody binds an IL-17A epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 81-87, 121-124 and 132-136 of SEQ ID NO:2.  
     
     
         21 . The antibody of  claim 1 , wherein said antibody binds an IL-17F epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 79-85, 119-122 and 130-134 of SEQ ID NO:4 and an IL-17A epitope, wherein said epitope is a discontinuous epitope comprising amino acid residues 81-87, 121-124 and 132-136 of SEQ ID NO:2.  
     
     
         22 . The antibody according to  claim 1 , wherein said antibody is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.  
     
     
         23 . The antibody according to  claim 1 , wherein said antibody is a monoclonal antibody.  
     
     
         24 . The antibody of  claim 23 , wherein said monoclonal antibody is selected from the group consisting of: murine, chimeric, humanized and human monoclonal antibodies.  
     
     
         25 . The antibody according to  claim 1 , wherein the antibody is a single chain monoclonal antibody.  
     
     
         26 . The antibody according to  claim 1 , wherein the antibody is a bispecific antibody.  
     
     
         27 . The antibody according to  claim 1 , wherein said antibody is a cross-reactive monoclonal antibody which binds to both IL-17A and IL-17F.  
     
     
         28 . Isolated antisera containing an antibody according to  claim 1 .  
     
     
         29 . A diagnostic kit comprising an antibody according to  claim 1  and means for detecting binding by that antibody.  
     
     
         30 . The diagnostic kit according to  claim 29  wherein said means for detecting binding comprises a detectable label that is linked to said antibody.  
     
     
         31 . A pharmaceutical composition for treating or preventing inflammation comprising an effective amount of the antibody according to  claim 1  and a pharmaceutically acceptable vehicle, carrier or excipient.  
     
     
         32 . The pharmaceutical composition according to  claim 31  wherein the infection treated or prevented is selected from the group consisting of: asthma, chronic inflammatory disease and acute inflammatory disease.  
     
     
         33 . The pharmaceutical composition according to  claim 32 , wherein disease is a chronic inflammatory disease comprising inflammatory bowel disease, ulcerative colitis, Crohn's disease, arthritis, atopic dermatitis, or psoriasis.  
     
     
         34 . The pharmaceutical composition according to  claim 32 , wherein disease is an acute inflammatory disease comprising endotoxemia, septicemia, toxic shock syndrome or infectious disease.  
     
     
         35 . A method of treating or preventing inflammation, comprising administering to a human or animal patient an effective amount of an antibody according to  claim 1 .  
     
     
         36 . A method of reducing IL-17A-induced or IL-17F-induced inflammation comprising administering to a mammal with inflammation an amount of a composition of an antibody according to  claim 1 , sufficient to reduce inflammation.  
     
     
         37 . A method of reducing IL-17A-induced and IL-17F-induced inflammation comprising administering to a mammal with inflammation an amount of a composition of a antibody according to  claim 1 , sufficient to reduce inflammation.  
     
     
         38 . A method of treating a mammal afflicted with an inflammatory disease in which IL-17A or IL-17F plays a role, comprising: administering an antibody according to  claim 1 , wherein the inflammatory activity of either IL-17A (SEQ ID NO:2) or IL-17F (SEQ ID NO:4) is reduced.  
     
     
         39 . A method of treating a mammal afflicted with an inflammatory disease in which IL-17A and IL-17F plays a role, comprising: administering an antibody according to  claim 1 , wherein the inflammatory activity of either IL-17A (SEQ ID NO:2) and IL-17F (SEQ ID NO:4) is reduced.  
     
     
         40 . The method according to any of claims  36 - 39 , wherein the disease is asthma.  
     
     
         41 . The method according to any of claims  36 - 39 , wherein the disease is a chronic inflammatory disease.  
     
     
         42 . The method of  claim 41 , wherein the disease is a chronic inflammatory disease comprising inflammatory bowel disease, irritable bowel syndrome, ulcerative colitis, Crohn's disease, arthritis, atopic dermatitis, or psoriasis.  
     
     
         43 . The method according to any of claims  36 - 39 , wherein the disease is an acute inflammatory disease.  
     
     
         44 . The method of  claim 43 , wherein the disease is an acute inflammatory disease comprising endotoxemia, septicemia, toxic shock syndrome or infectious disease.  
     
     
         45 . A method of treating a pathological condition in a subject associated with IL-17A or IL-17F activity comprising administering an effective amount of an antibody according to  claim 1 , thereby treating said pathological condition.  
     
     
         46 . The method of  claim 45 , wherein said pathological condition is asthma.  
     
     
         47 . The method of  claim 46 , wherein said pathological condition is a chronic inflammatory condition.  
     
     
         48 . The method of  claim 47  wherein said chronic inflammatory condition comprising inflammatory bowel disease, irritable bowel syndrome, ulcerative colitis, Crohn's disease, arthritis, atopic dermatitis, or psoriasis.  
     
     
         49 . The method of  claim 45  wherein said pathological condition is an acute inflammatory condition.  
     
     
         50 . The method of  claim 49 , wherein said acute inflammatory condition comprises endotoxemia, septicemia, toxic shock syndrome, or infectious disease.  
     
     
         51 . A method of treating a mammal afflicted with an inflammatory disease in which IL-17A or IL-17F plays a role, comprising: an antibody according to  claim 1 , wherein the inflammatory activity is reduced.  
     
     
         52 . The method of  claim 51 , wherein the disease is asthma.  
     
     
         53 . The method of  claim 51 , wherein the disease is a chronic inflammatory disease.  
     
     
         54 . The method of  claim 53 , wherein the disease is a chronic inflammatory disease comprising inflammatory bowel disease, irritable bowel syndrome, ulcerative colitis, Crohn's disease, arthritis, atopic dermatitis, or psoriasis.  
     
     
         55 . The method of  claim 51 , wherein the disease is an acute inflammatory disease.  
     
     
         56 . The method of  claim 55 , wherein the disease is an acute inflammatory disease comprising endotoxemia, septicemia, toxic shock syndrome or infectious disease.  
     
     
         57 . An antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment reduces the pro-inflammatory activity of either either IL-17A (SEQ ID NO:2) or IL-17F (SEQ ID NO:4).  
     
     
         58 . The antibody or antibody fragment according to  claim 57 , wherein the antibody or antibody fragment reduces the pro-inflammatory activity of both IL-17A (SEQ ID NO:2) and IL-17F (SEQ ID NO:4).  
     
     
         59 . The antibody or antibody fragment according to  claim 58 , wherein the or antibody fragment is (a) a polyclonal antibody, (b) a murine monoclonal antibody, (c) a humanized antibody derived from (b), (d) an antibody fragment, or (e) a human monoclonal antibody.  
     
     
         60 . The antibody or antibody fragment according to  claim 59 , wherein the antibody further comprises a radionuclide, enzyme, substrate, cofactor, fluorescent marker, chemiluminescent marker, peptide tag, magnetic particle, drug, or toxin.  
     
     
         61 . The antibody of  claim 60  wherein the antibody further comprises PEGylation.  
     
     
         62 . The antibody or antibody fragment according to  claim 61 , wherein the or antibody fragment is (a) a polyclonal antibody, (b) a murine monoclonal antibody, (c) a humanized antibody derived from (b), (d) an antibody fragment, or (e) a human monoclonal antibody.