University of Virginia Patent Foundation

Donna J Webb

Ronald P Taylor

William M Sutherland

Craig Reist

Eleanor L Wright

Steven L Gonias

Ronald Labuguen

The present invention relates to a composition and method for inhibiting TGF-&bgr; activity. The composition comprises a TGF-&bgr; neutralizing peptide derived from &agr;,-macroglobulin that binds to TGF-&bgr; and inhibits TGF-&bgr; activity.

Transforming growth factor-&bgr; binding site

Chemically modified .alpha.-macroglobulin is conformationally locked by cross-linking .alpha..sub.2 M with a bi-functional peptide crosslinker, and then modified with methylamine, to provide conformational intermediates with limited conformational change. These modified compounds have a high binding affinity for inflammatory cytokines including TNF-.alpha. and IL-1.beta.. When administered in vivo, the modified .alpha..sub.2 M (MAC) protects against development of septic shock, and is an effective treatment aid in treating mammals with established septic shock.

Chemically modified a-macroglobulins, methods of making, and methods of

Mammalian red blood cells are used to safely and rapidly neutralize and/or clear antigens or immunogens from the circulatory system by binding to the RBC a monoclonal antibody specific for a receptor (CR1) on the RBC, which monoclonal antibody is chemically bound to a second Mab specific for the antigen to be cleared from the circulatory system. These chemically cross-linked monoclonal antibody heteropolymers may be injected directly into the patient's circulatory system. Alternatively, red blood cells, extracted from the patient or provided by a suitable donor, are bound to the Mab complex and returned to the system.

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Charlottesville, VA, United States of America

Donna J Webb