Il-17 homologous polypeptides and therapeutic uses thereof

Abstract

The present invention is directed to novel polypeptides having sequence identity with IL-17 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.

1 . A method of treating a degenerative cartilaginous disorder, comprising administering a therapeutically effective amount of a polypeptide having at least 95% amino acid sequence identity to:
 (a) the polypeptide of SEQ ID NO:3;   (b) the polypeptide of SEQ ID NO:3 lacking its associated signal peptide; or   (c) the polypeptide encoded by the cDNA clone deposited as ATCC deposit number 203552,   wherein said polypeptide is capable of inducing release of TNFa from THP-1 cells and/or increasing matrix breakdown and inhibiting matrix synthesis in articular cartilage explants.   
     
     
         2 . The method of  claim 1 , comprising administering a therapeutically effective amount of a polypeptide having at least 99% amino acid sequence identity to:
 (a) amino acid residues 1 to 197 of SEQ ID NO: 3;   (b) amino acid residues 19 to 177 of SEQ ID NO: 3; or   (c) the polypeptide encoded by the cDNA clone deposited as ATCC deposit number 203552,   wherein said polypeptide is capable of inducing release of TNFa from THP-1 cells and/or increasing matrix breakdown and inhibiting matrix synthesis in articular cartilage explants.   
     
     
         3 . A method of treating a degenerative cartilaginous disorder, comprising administering a therapeutically effective amount of a polypeptide comprising:
 (a) amino acid residues 1 to 197 of SEQ ID NO: 3;   (b) amino acid residues 19 to 177 of SEQ ID NO: 3; or   (c) the polypeptide encoded by the cDNA clone deposited as ATCC deposit number 203552.   
     
     
         4 . The method of  claim 3  wherein the polypeptide comprises amino acid residues 1 to 197 of SEQ ID NO: 3. 
     
     
         5 . The method of  claim 3  wherein the polypeptide comprises amino acid residues 19 to 177 of SEQ ID NO: 3. 
     
     
         6 . The method of  claim 3  wherein the polypeptide comprises the polypeptide encoded by the cDNA clone deposited as ATCC deposit number 203552. 
     
     
         7 . The method of any one of  claims 1 - 6  wherein the degenerative cartilaginous disorder is arthritis. 
     
     
         8 . A method of treating a degenerative cartilaginous disorder, comprising administering a therapeutically effective amount of a chimeric polypeptide comprising
 (a) amino acid residues 1 to 197 of SEQ ID NO: 3;   (b) amino acid residues 19 to 177 of SEQ ID NO: 3; or   (c) the polypeptide encoded by the cDNA clone deposited as ATCC deposit number 203552.   fused to an Fc region of an immunoglobulin, wherein said chimeric polypeptide is capable of inducing release of TNFa from THP-1 cells and/or increasing matrix breakdown and inhibiting matrix synthesis in articular cartilage explants.   
     
     
         9 . The method of  claim 8  wherein the chimeric polypeptide comprises amino acid residues 1 to 197 of SEQ ID NO: 3 fused to an Fc region of an immunoglobulin. 
     
     
         10 . The method of  claim 8  wherein the chimeric polypeptide comprises amino acid residues 19 to 177 of SEQ ID NO: 3, lacking its associated signal peptide, fused to an Fc region of an immunoglobulin. 
     
     
         11 . The method of  claim 8  wherein the chimeric polypeptide comprises the polypeptide encoded by the cDNA clone deposited as ATCC deposit number 203552, fused to an Fc region of an immunoglobulin. 
     
     
         12 . The method of any one of  claims 8 - 11  wherein the degenerative cartilaginous disorder is arthritis.