Inflammatory mediator antagonists

Abstract

The present invention relates to the use of an antagonist of OSM such as an antibody or small molecule in the manufacture of a medicament for the treatment or prophylaxis of an inflammatory arthropathy or inflammatory disorder, and the use of OSM in screening for such antagonists.

What is claimed is:  
     
         1 . A method of treating an inflammatory arthropathy or an inflammatory disorder comprising administering to a patient in need thereof an effective amount of an antagonist to oncostatin M (OSM) or an OSM receptor.  
     
     
         2 . The method according to  claim 1  wherein the antagonist is an antagonist to human OSM.  
     
     
         3 . The method according to  claim 2  wherein the antagonist interacts with one or more of the residues G120, Q16, Q20, N123 or N124 of human OSM in accordance with numbering shown in SEQ ID NO:12.  
     
     
         4 . The method according to  claim 1  wherein the antagonist is an antagonist of the OSM receptor gp130.  
     
     
         5 . The method according to  claim 1  wherein the antagonist is a small organic molecule.  
     
     
         6 . The method according to  claim 1  wherein the antagonist is an antibody.  
     
     
         7 . The method according to  claim 6  wherein the antibody is humanized or chimaerized.  
     
     
         8 . The method according to  claim 1  wherein the antagonist prevents or reduces collagen release from cartilage.  
     
     
         9 . The method according to  claim 1  wherein said inflammatory arthropathy or said inflammatory disorder is rheumatoid arthritis.  
     
     
         10 . A pharmaceutical composition comprising a unit dose of at least 1 mg, of an antagonist to oncostatin M (OSM), and a pharmaceutically acceptable carrier.  
     
     
         11 . The pharmaceutical composition according to  claim 10  wherein the antagonist is combined with an immunosuppressive, tolerance inducing, or anti-inflammatory agent.  
     
     
         12 . The method according to  claim 1  wherein the antagonist is administered in combination with an immunosuppressive, tolerance inducing, or anti-inflammatory agent.  
     
     
         13 . The pharmaceutical composition according to  claim 11  wherein the antagonist is combined with a CD4+ T cell inhibiting agent, an anti-CD23 antibody or a tumor necrosis factor (TNF) antagonist.  
     
     
         14 . The method according to  claim 12  wherein the antagonist is administered in combination with a CD4+ T cell inhibiting agent, an anti-CD23 antibody or a tumor necrosis factor (TNF) antagonist.  
     
     
         15 . An assay for the identification of an antagonist of oncostatin M (OSM) comprising combining OSM or an OSM binding moiety and an OSM receptor or receptor conjugate with a test agent and monitoring for blocking of the interaction between OSM or the OSM binding moiety and the OSM receptor or receptor conjugate.  
     
     
         16 . The assay according to  claim 15  wherein the receptor conjugate is a gp130-Fc fusion protein.  
     
     
         17 . The method according to  claim 1  wherein the antagonist is an aptamer.  
     
     
         18 . The composition according to  claim 10  wherein the antagonist is an aptamer.  
     
     
         19 . An aptamer selected from the group consisting of aptamers shown in FIG. 16.