A Novel Chimeric Protein for Prevention and Treatment of HIV Infection
Description of Invention:
This invention relates to bispecific fusion proteins effective in viral neutralization. Specifically, the invention is a genetically engineered chimeric protein containing a soluble extracellular region of human CD4 attached via a flexible polypeptide linker to a single chain human monoclonal antibody directed against a CD4-induced, highly conserved HIV gp120 determinant involved in coreceptor interaction. Binding of the sCD4 moiety to gp120 induces a conformational change that enables the antibody moiety to bind, thereby blocking Env function and virus entry. This novel bispecific protein displays neutralizing activity against genetically diverse primary HIV-1 isolates, with potency at least 10-fold greater than the best described HIV-1 neutralizing monoclonal antibodies. The agent has considerable potential for prevention of HIV-1 infection, both as a topical microbicide and as a systemic agent to protect during and after acute exposure (e.g. vertical transmission, post-exposure prophylaxis). It also has potential utility for treatment of chronic infection. Such proteins, nucleic acid molecules encoding them, and their production and use in preventing or treating viral infections are claimed.
Inventors:
Edward A. Berger (NIAID) Christie M. Del Castillo
Patent Status:
DHHS Reference No. E-039-1999/0 --
U.S. Patent 7,115,262 issued 03 Oct 2006
U.S. Patent Application No. 11/535,957 filed 27 Sep 2006
