Description of Invention:
The technology relates to a chimeric molecule, NCCG-gp41, in which the internal trimeric helical coiled-coil of the ectodomain of gp41 is fully exposed and stabilized by both fusion to a minimal ectodomain core of gp41 and by engineered intersubunit disulfide bonds. NCCG-gp41 inhibits HIV envelope mediated cell fusion at nanomolar concentrations with an IC50 of 16 nM. It is proposed that NCCG-gp41 targets the exposed C-terminal region of the gp41 ectodomain in its pre-hairpin intermediate state, thereby preventing the formation of the fusogenic form of the gp41 ectodomain that comprises a highly stable trimer of hairpins arranged in a six-helix bundle. Antibodies have been raised against NCCG-gp41 that inhibit HIV envelope mediated cell fusion.
Applications:
Entry inhibitor HIV therapeutic agent
HIV/AIDS vaccine
As a component of a high throughput screening assay for small molecule inhibitors of HIV envelope mediated cell fusion
Development Status:
The technology is currently in pre-clinical stage of development.
Patent Status:
DHHS Reference No. E-252-2001/0 --
U.S. Patent Application No. 10/499,094 filed 14 Jun 2004
EP application 02795951.9 and IN application 1535/CHENP/2004
Relevant Publication:
JM Louis et al. Design and properties of NCCG-gp41, a chimeric gp41 molecule with nanomolar HIV fusion inhibitory activity. J Biol Chem. 2001 Aug 3;276(31):29485-29489. [PubMed abs]
CA Bewley et al. Design of a novel peptide inhibitor of HIV fusion that disrupts the internal trimeric coiled-coil of gp41. J Biol Chem. 2002 Apr 19;277(16):14238-14245. [PubMed abs]
JM Louis et al. Covalent trimers of the internal N-terminal trimeric coiled-coil of gp41 and antibodies directed against them are potent inhibitors of HIV envelope-mediated cell fusion. J Biol Chem. 2003 May 30;278(22):20278-20285. [PubMed abs]
JM Louis et al. Characterization and HIV-1 fusion inhibitory properties of monoclonal Fabs obtained from a human non-immune phage library selected against diverse epitopes of the ectodomain of HIV-1 gp41. J Mol Biol. 2005 Nov 11;353(5):945-951. [PubMed abs]
Licensing Status: Available for non-exclusive or exclusive licensing.
For Additional Information Please Contact: Susan Ano Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5515
Email: anos@mail.nih.gov
Fax: (301) 402-0220
