Cyanovirin-Based Topical Microbicides For Prevention Of Sexual Transmission Of HIV
Description of Invention:
The development of an effective anti-HIV topical microbicide, especially a female-controlled, vaginal microbicide, has been deemed an urgent global priority by numerous international agencies, including the World Health Organization, the U.S. Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and others.
Cyanovirin-N (CV-N) is a unique, 101 amino acid protein discovered1, by U.S. government scientists, as a constituent of a cultured cyanobacterium, Nostoc ellipsosporum. CV-N has subsequently been produced recombinantly in E. coli.3 Both the sequence1 and the 3-D solution structure2 of CV-N are unprecedented.
CV-N potently and irreversibly inactivates diverse primary strains of HIV-1, including M-tropic forms involved in sexual transmission of HIV, as well as T-tropic and dual-tropic forms; CV-N also blocks cell-to-cell transmission of HIV infection.1 CV-N is directly virucidal, interacting in an unusual manner with the viral envelope, apparently binding with extremely high affinity to poorly immunogenic epitopes on gp120.1,3
CV-N was benign in vivo when tested in the rabbit vaginal toxicity/irritancy model, and was not cytotoxic in vitro against human immune cells and lactobacilli (unpublished). CV-N is readily soluble in aqueous media, is remarkably resistant to physicochemical degradation,1 and, is amenable to very large-scale production by a variety of genetic engineering approaches.
Inventors:
Michael R. Boyd (NCI) Kirk R. Gustafson (NCI) Robert H. Shoemaker (NCI) James B. McMahon (NCI)
Patent Status:
DHHS Reference No. E-117-1995/0 --
U.S. Patent 5,843,882 issued 01 Dec 1998
U.S. Patent 6,015,876 issued 18 Jan 2000
Relevant Publication:
MR Boyd, KR Gustafson, JB McMahon, RH Shoemaker, BR O'Keefe, T Mori, RJ Gulakowski, L Wu, M Rivera, CM Laurencot, JH Cardellina II, RW Buckheit Jr., PL Nara, LK Pannell, RC Sowder II, LE Henderson. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob Agents Chemother. 1997 Jul;41(7):1521-1530. [PubMed abs]
CA Bewley, KR Gustafson, MR Boyd, DG Covell, A Bax, GM Clore, AM Gronenborn. Solution structure of cyanovirin-N, a potent HIV-inactivating protein. Nat Struct Biol. 1998 Jul;5(7):571-578. [PubMed abs]
T Mori, KR Gustafson, LK Pannell, RH Shoemaker, L Wu, JB McMahon, MR Boyd. Recombinant production of cyanovirin-N, a potent HIV (human immunodeficiency virus)-inactivating protein derived from a cultured cyanobacterium. Protein Expr Purif. 1998 Mar;12(2):151-158, 1998. [PubMed abs]
MT Esser, T Mori, I Mondor, Q Sattentau, B Dey, EA Berger, MR Boyd, JD Lifson. Cyanovirin-N binds to gp120 to interfere with CD4-dependent HIV-1 virion binding, infectivity, and fusion, but does not affect the CD4 binding site on gp120 or soluble CD4 induced conformational changes in gp120. J Virol. 1999 May;73(5):4360-4371. [PubMed abs]
Licensing Status: Exclusive or non-exclusive licensees are sought to develop and commercialize microbicidal compositions, formulations, devices and/or methods directly incorporating the unique, HIV-inactivating protein, cyanovirin-N (CV-N), for topical use to prevent sexual transmission of HIV infection and disease.
For Additional Information Please Contact: Sally Hu PhD MBA
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5606
Email: hus@mail.nih.gov
Fax: (301) 402-0220
