Efficient Inhibition of HIV-1 Viral Entry Through a Novel Fusion Protein Including CD4
Description of Invention:
This invention relates to CD4 fusion proteins for use in the treatment of an immunodeficiency virus infection such as human immunodeficiency virus (HIV). These polypeptides have been shown by the inventors to inhibit the entry of primary isolates of HIV-1 into CD4+ T cells by targeting the gp120 subunit of the HIV-1 envelope. The invention claims recombinant polypeptides comprising a CD4 polypeptide ligated at its C-terminus with a portion of a human immunoglobulin comprising a hinge region and two constant domains of an immunoglobulin heavy chain. The portion of the IgG is fused at its C-terminus with a polypeptide comprising a tailpiece from the C terminus of the heavy chain of an IgA antibody. This protein is very large (greater than 800 kilodaltons), which may contribute to its ability to inhibit entry of primary isolates of HIV-1 into T cells. It presents twelve gp120 binding domains (D1D2) and can bind at least ten gp120s simultaneously. The inventors have shown that the construct efficiently neutralizes primary isolates from different HIV subgroups. Also claimed are use of the construct as a component of a vaccine and as a diagnostic.
Inventors:
James Arthos (NIAID) Claudia Cicala (NIAID) Anthony Fauci (NIAID)
Patent Status:
DHHS Reference No. E-337-2001/0 --
U.S. Provisional Application No. 60/346,231 filed 25 Oct 2001
PCT Application No. PCT/US02/34393 filed 24 Oct 2002
U.S. Patent Application No. 10/493,676 filed 23 Apr 2004
For Additional Information Please Contact: Robert M. Joynes J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)594-6565
Email: joynesr@mail.nih.gov
Fax: (301) 402-0220
