Tweak receptor

Abstract

The present invention provides the TWEAK receptor and methods for identifying and using agonists and antagonists of the TWEAK receptor. In particular, the invention provides methods of screening for agonists and antagonists and for treating diseases or conditions mediated by angiogenesis, such as solid tumors and vascular deficiencies of cardiac or peripheral tissue.

What is claimed is: 
     
         1 . An isolated anti-TWEAK antibody that reduces binding of TWEAK to the TWEAK receptor, wherein the TWEAK receptor comprises the sequence of SEQ ID NO:4. 
     
     
         2 . The isolated anti-TWEAK antibody of  claim 1 , wherein said anti-TWEAK antibody reduces binding of TWEAK-coated beads to COS cells expressing the TWEAK receptor. 
     
     
         3 . The isolated anti-TWEAK antibody of  claim 1 , wherein said anti-TWEAK antibody reduces signalling through the TWEAK receptor. 
     
     
         4 . The isolated anti-TWEAK antibody of  claim 1 , wherein said anti-TWEAK antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a transgenic antibody, or a human antibody. 
     
     
         5 . The isolated anti-TWEAK antibody of  claim 1 , wherein said anti-TWEAK antibody is a humanized monoclonal antibody. 
     
     
         6 . An isolated nucleic acid encoding the light chain, the heavy chain, or both the light chain and the heavy chain of said anti-TWEAK antibody of  claim 1 . 
     
     
         7 . An isolated vector comprising said nucleic acid  claim 6 . 
     
     
         8 . The isolated vector of  claim 7 , wherein said vector is an expression vector. 
     
     
         9 . An isolated cell comprising said nucleic acid of  claim 6 . 
     
     
         10 . A method of producing an anti-TWEAK antibody comprising incubating said isolated cell of  claim 9  under conditions that allow said cell to express said anti-TWEAK antibody. 
     
     
         11 . A method of treating inflammation in a subject, comprising administering to said subject an effective amount of said anti-TWEAK antibody of  claim 1 . 
     
     
         12 . The method of  claim 12 , wherein said subject is a human. 
     
     
         13 . The method of  claim 11 , wherein said anti-TWEAK antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a transgenic antibody, or a human antibody. 
     
     
         14 . The method of  claim 11 , wherein said anti-TWEAK antibody is a humanised monoclonal antibody. 
     
     
         15 . The method of  claim 11 , wherein said subject has arthritis, rheumatism, or psoriasis. 
     
     
         16 . A method of reducing angiogenesis in a subject, comprising administering to said subject an effective amount of said anti-TWEAK antibody of  claim 1 . 
     
     
         17 . A method of treating an ocular disorder in a subject, comprising administering to said subject an effective amount of said anti-TWEAK antibody of  claim 1 . 
     
     
         18 . The method of  claim 17  wherein said ocular disorder is diabetic retinopathy, retinopathy of prematurity, neovascular glaucoma, retinoblastoma, retrolental fibroplasias, rubeosis, uveitis, macular degeneration, or corneal graft neovascularisation. 
     
     
         19 . The method of  claim 11 , wherein said subject has a cell proliferative disorder. 
     
     
         20 . The method of  claim 19 , wherein said cell proliferative disorder is a malignant condition or a metastatic condition. 
     
     
         21 . The method of  claim 19 , wherein said cell proliferative disorder is a solid tumor. 
     
     
         22 . The method of  claim 21 , wherein said solid tumor is a primary sarcoma, a metastatic sarcoma, a primary carcinoma, or a secondary carcinoma. 
     
     
         23 . The method of  claim 11 , wherein said subject has a benign tumor, a preneoplastic condition, myocardial angiogenesis, haemophilic joints, scleroderma, vascular adhesions, atherosclerotic plaque neovascularisation, telangiectasia, or wound granulation.