Anti-Properdin MoAb as a Novel Therapeutic for Arthritis

DESCRIPTION (provided by applicant): The complement system is an important host defense system, however, inappropriate and/or excessive activation of the complement system has been implicated as contributing to the pathogenesis of many disease states, including rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is characterized by the occurrence of painful, swollen joints and none of the drugs currently administered to RA patients has been shown to cause regression of the disease. Therefore, there is a clinical need for potent new therapeutic agents for RA. There is evidence that the complement alternative pathway (AP) contributes significantly to the generation of pro-inflammatory agents in RA. Complement activation products such as C3a, C5a, and sMAC have been found within inflamed rheumatic joints and a positive correlation has been reported between the degree of complement activation and the severity of RA. Gliatech Inc. has identified a potent inhibitor of the AP, which consists of a blocking monoclonal antibody (GT6067) to properdin. Based on its ability to prevent AP activation in models of immune complex-mediated inflammation, there is reason to believe that such a MoAb holds great promise as an effective therapeutic agent for the treatment of RA. The focus of this study is to evaluate GT6067 in an antigen-induced model of arthritis in rabbits. This rabbit model possesses several key similarities with human rheumatoid arthritis and has been widely used in studies to identify novel RA therapeutic agents. Both Rekha Bansal, Ph.D. (P.I.) and James B. Parent are co-authors of the issued patent" Gupta-BansalR., Brunden, K. R. and Parent, J. B., A process of inhibiting complement activation via the alternative pathway. U.S. Patent 6,333,034B1, December, 2002 Key Words Complement; Monoclonal Antibodies; Properdin; Inflammation; Reverse Passive Arthus; Arthritis