Connective Tissue Growth Factor Antibodies

Abstract

The present invention relates to antibodies that bind to CTGF. The antibodies are particularly directed to regions of CTGF involved in biological activities associated with fibrosis. The invention also relates to methods of using the antibodies to treat disorders associated with CTGF including localized and systemic fibrotic disorders including those of the lung, liver, heart, skin, and kidney.

1 - 5 . (canceled) 
     
     
         6 . A method for treating a connective tissue growth factor (CTGF)-associated disorder or condition comprising administering to a subject in need thereof an effective amount of an antibody or fragment thereof, wherein the antibody, or fragment binds to a region of human connective tissue growth factor (CTGF) set forth as amino acids 134 to 158 of SEQ ID NO:2, thereby treating the CTGF-associated disorder or condition. 
     
     
         7 . The method of  claim 6 , wherein the antibody is a monoclonal antibody. 
     
     
         8 . The method of  claim 6 , wherein the affinity of the antibody for CTGF is at least about 10 −9  M. 
     
     
         9 . The method of  claim 6 , wherein the antibody is a single chain antibody. 
     
     
         10 . The method of  claim 6 , wherein the antibody is a humanized antibody. 
     
     
         11 . The method of  claim 6 , wherein the antibody is a human antibody. 
     
     
         12 . The method of  claim 6 , wherein the antibody is a chimeric antibody. 
     
     
         13 . The method of  claim 6 , wherein the antibody is a multivalent antibody. 
     
     
         14 . The method of  claim 6 , wherein the antibody is glycosylated. 
     
     
         15 . The method of  claim 6 , wherein the antibody is non-glycosylated. 
     
     
         16 . The method of  claim 6 , wherein the antibody fragment is selected from the group consisting of a Fab, a F(ab) 2 , and a F v  fragment. 
     
     
         17 . The method of  claim 6 , wherein the CTGF-associated disorder or condition is arthritis, atherosclerosis, retinopathy, nephropathy, transplant rejection, hypertrophic scarring, Crohn's disease, inflammatory bowel disease, keloids or macular degeneration. 
     
     
         18 . The method of  claim 17 , wherein the transplant rejection is the rejection of an organ selected from the group consisting of eye, heart, kidney, liver, lung and skin. 
     
     
         19 . The method of  claim 6 , wherein the CTGF-associated disorder is cancer. 
     
     
         20 . The method of  claim 19 , wherein the cancer is selected from the group consisting of acute lymphoblastic leukemia, angioleimyoma, angiolipoma, breast cancer, colorectal cancer, dermatofibromas, desmoplastic cancers, fibrosarcoma, gastrointestinal cancer, glioma, glioblastoma, liver cancer, ovarian cancer, pancreatic cancer, prostate cancer and rhabdomyosarcoma. 
     
     
         21 . The method of  claim 6 , wherein the CTGF-associated disorder or condition is a fibrotic disorder. 
     
     
         22 . The method of  claim 21 , wherein the fibrotic disorder is selected from the group consisting of cardiac fibrosis, interstitial fibrosis, liver fibrosis, kidney fibrosis, lung fibrosis, ocular fibrosis, osteoarthritis, scleroderma, skin fibrosis, systemic fibrosis, peridural fibrosis or peritoneal fibrosis. 
     
     
         23 . The method of  claim 22 , wherein the lung fibrosis is idiopathic pulmonary fibrosis. 
     
     
         24 . The method of  claim 21 , wherein the fibrotic disorder results from surgery, chemotherapy or radiation therapy. 
     
     
         25 . A pharmaceutical composition comprising an antibody, or fragment thereof, that binds to a region of human connective tissue growth factor (CTGF) set forth as amino acids 134 to 158 of SEQ ID NO:2. 
     
     
         26 . The pharmaceutical composition of  claim 25 , further comprising a carrier or excipient. 
     
     
         27 . A method of treating a CTGF-associated disorder or condition selected from the group consisting of arthritis, atherosclerosis, retinopathy, nephropathy, transplant rejection, hypertrophic scarring, Crohn's disease, inflammatory bowel disease, keloids or macular degeneration comprising administering the pharmaceutical composition of  claim 25 . 
     
     
         28 . A method of treating a CTGF-associated disorder or condition selected from the group consisting of cancer and fibrotic disorders comprising administering the pharmaceutical composition of  claim 25 .