Anti-Properdin MoAb as a novel therapeutics for arthritis

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44AR048476-02
Agency Tracking Number: AR048476
Amount: $825,534.00
Phase: Phase II
Program: SBIR
Awards Year: 2006
Solicitation Year: 2006
Solicitation Topic Code: N/A
Solicitation Number: PHS2006-2
Small Business Information
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 (440) 477-9874
Business Contact
Phone: (440) 477-9874
Research Institution
DESCRIPTION (provided by applicant): Current therapeutic approaches for treating rheumatoid arthritis (RA) are not adequate to prevent the devastating inflammation and joint destruction. Complement activation contributes significantly to the inflammatory process in arthritic joints. While complement activation is vital to the body's defenses in fighting infections, unregulated complement activation significantly contributes to the pathogenesis of many inflammatory diseases, including RA. With complement activation, the anaphylatoxins C3a and C5a are released at sites of inflammation and are potent chemoattractants and activators of neutrophils, basophils, eosinophils, leukocytes, monocytes and macrophages that orchestrate and perpetuate the inflammatory response by producing pro-inflammatory mediators, such as cytokines. Recently developed humanized anti- 5 antibodies for inhibiting the downstream events of the complement cascade have highlighted the complement fragment C5a as a therapeutic target, but have neglected the essential role of C3a. Based on our preliminary data, therapeutic approaches that inhibit production of C3a, C5a and thus the final complement protein, the membrane attack complex (MAC) will completely inhibit the amplification loop of the alternative pathway (AP) and prevent its augmenting effect on activation of the classical complement pathway (CP). Such inhibitors should have greater potency than those that target only C5a in preventing cellular infiltration of cells, which direct the joint inflammation and destruction and to inhibit their activation and release of inflammatory mediators, such as TNF and IL-1. Consistent with this, C3a is known to regulate TNF and IL-1 production. The objective of this Phase II application is to further evaluate the efficacy of NM001(a blocking monoclonal antibody against factor B) and NM3014 (synthetic low molecular weight inhibitor of properdin function) in two well established models of RA; AIA rabbit model and CIA rat model. Similar to anti-properdin monoclonal antibodies both NM001 and NM3014 target the C3 convertase and prevent C3a, C5a and C5b-9 formation. We expect that such inhibitors will dramatically inhibit inflammation and joint destruction and will be an effective therapeutic approach for treating RA. NovelMed's approach appears to be more promising than current therapies because our approach is expected to inhibit the production of TNF and IL-1 instead of targeting each one separately. NovelMed has filed a patent on such inhibitors and additional patents are in preparation.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government