Il-17 homologous polypeptides and therapeutic uses thereof

Abstract

The present invention is directed to novel polypeptides having sequence identity with IL-17, IL-17 receptors and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

What is claimed is: 
     
         1 . A method of treating an IL-17E-associated inflammatory or degenerative cartilaginous disorder in a mammal in need thereof comprising administering to said mammal an antagonist antibody of a polypeptide comprising
 (i) amino acids 1 to 502 of SEQ ID NO:12; or   (ii) the amino acid sequence of the polypeptide encoded by the full-length coding sequence of the cDNA deposited under ATCC accession number PTA-20;   wherein the antagonist antibody binds to said polypeptide and blocks binding of IL-17E to said polypeptide.   
     
     
         2 . The method of  claim 1 , wherein the IL-17E-associated inflammatory or degenerative cartilaginous disorder is rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, a spondyloarthropathy, inflammatory bowel disease, an autoimmune or immune-mediated skin disease, contact dermatitis, psoriasis, an allergic disease, or asthma. 
     
     
         3 . The method of  claim 1  wherein said antagonist antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a human antibody. 
     
     
         4 . The method of  claim 1  wherein said antagonist antibody is a Fab, Fab′, Fv, or F(ab′) 2  fragment. 
     
     
         5 . A method of treating an IL-17E-associated inflammatory or degenerative cartilaginous disorder in a mammal in need thereof comprising administering to said mammal an antagonist antibody of a polypeptide comprising
 (i) amino acids 1 to 502 of SEQ ID NO:12; or   (ii) the amino acid sequence of the polypeptide encoded by the full-length coding sequence of the cDNA deposited under ATCC accession number PTA-20;   wherein the antagonist antibody binds to said polypeptide and inhibits induction of cytokine expression that results from stimulation of said polypeptide by IL-17E in a mammalian cell.   
     
     
         6 . The method according to  claim 5  wherein the cytokine expression that is inhibited is that of IL-6 or IL-8. 
     
     
         7 . The method of  claim 5 , wherein the IL-17E-associated inflammatory or degenerative cartilaginous disorder is rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, a spondyloarthropathy, inflammatory bowel disease, an autoimmune or immune-mediated skin disease, contact dermatitis, psoriasis, an allergic disease, or asthma. 
     
     
         8 . The method of  claim 5  wherein said antagonist antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a human antibody. 
     
     
         9 . The method of  claim 5  wherein said antagonist antibody is a Fab, Fab′, Fv, or F(ab′) 2  fragment. 
     
     
         10 . The method of  claims 6 , wherein the IL-17E-associated inflammatory or degenerative cartilaginous disorder is rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, a spondyloarthropathy, inflammatory bowel disease, an autoimmune or immune-mediated skin disease, contact dermatitis, psoriasis, an allergic disease, or asthma. 
     
     
         11 . The method of  claim 6  wherein said antagonist antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a human antibody. 
     
     
         12 . The method of  claim 6  wherein said antagonist antibody is a Fab, Fab′, Fv, or F(ab′) 2  fragment. 
     
     
         13 . A method of treating an IL-17E-associated inflammatory or degenerative cartilaginous disorder in a mammal in need thereof comprising administering to said mammal an antagonist antibody of a polypeptide comprising
 (i) amino acids 1 to 502 of SEQ ID NO:12; or   (ii) the amino acid sequence of the polypeptide encoded by the full-length coding sequence of the cDNA deposited under ATCC accession number PTA-20;   wherein the antagonist antibody binds to said polypeptide and inhibits the activation of NF-κB that results from stimulation of said polypeptide by IL-17E in a mammalian cell.   
     
     
         14 . The method of  claim 13 , wherein the IL-17E-associated inflammatory or degenerative cartilaginous disorder is rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, a spondyloarthropathy, inflammatory bowel disease, an autoimmune or immune-mediated skin disease, contact dermatitis, psoriasis, an allergic disease, or asthma. 
     
     
         15 . The method of  claim 13  wherein said antagonist antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a human antibody. 
     
     
         16 . The method of  claim 13  wherein said antagonist antibody is a Fab, Fab′, Fv, or F(ab′) 2  fragment. 
     
     
         17 . A method of treating an IL-17E-associated degenerative cartilaginous disorder in a mammal in need thereof comprising administering to said mammal an antagonist antibody of a polypeptide comprising
 (i) amino acids 1 to 502 of SEQ ID NO:12; or   (ii) the amino acid sequence of the polypeptide encoded by the full-length coding sequence of the cDNA deposited under ATCC accession number PTA-20;   wherein the antagonist antibody binds to said polypeptide and blocks the inhibition of matrix synthesis in a mammal resulting from stimulation of said polypeptide by IL-17E.   
     
     
         18 . The method of  claim 17 , wherein the IL-17E-associated degenerative cartilaginous disorder is rheumatoid arthritis. 
     
     
         19 . The method of  claim 17  wherein said antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a human antibody. 
     
     
         20 . The method of  claim 17  wherein said antibody is a Fab, Fab′, Fv, or F(ab′) 2  fragment.