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The Protein Cyanovirin Inactivates HIV and Influenza

Posted Jun 15 2010 5:00pm

Description of Invention:
Cyanovirin-N (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. CV-N interacts in an unusual manner with the viral envelope, binding with extremely high affinity to poorly immunogenic epitopes on gp120. Further, CV-N and homologous proteins and peptides potently inhibit diverse isolates of influenza viruses A and B, the two major types of influenza virus that infect humans.

The described technology includes glycosylation-resistant mutants, which code sequences to enable ultra large-scale recombinant production of functional CV-Ns in non-bacterial (yeast or insect) host cells or in transgenic animals or plants. Therefore, these glycosylation-resistant mutants may allow industry to produce CV-Ns on a large scale and make CV-Ns cheap enough for developing countries to benefit from this invention.

CV-N was benign in vivo when tested in the rabbit/monkey vaginal toxicity/irritancy model and was not cytotoxic in vitro against human immune cells and lactobacilli. CV-N is readily soluble in aqueous media, is remarkably resistant to physicochemical degradation and is amenable to very large-scale production by a variety of genetic engineering approaches.

Applications:
  • Therapeutics and prevention of HIV and influenza infections
  • Topical microbicide to protect HIV infection
  • Ex vivo devices incorporating CV-N to remove or inactivate HIV from fluid samples


Advantages:
  • Potent anti-HIV and anti-influenza activity
  • Can be applied both systematically or locally
  • Can be applied both in vivo and ex vivo
  • Inexpensive and large scale manufacturing


Development Status:
  • Preclinical (rabbit/monkey) data in microbicide field are available at this time.
  • Initial animal efficacy studies (both mouse and ferret) against influenza (H1N1) have been completed and published.


Inventors:
Michael R Boyd (NCI)
Kirk R Gustafson (NCI)
Robert H Shoemaker (NCI)
James B McMahon (NCI)
Barry R O'Keefe (NCI)


Patent Status:
HHS, Reference No. E-117-1995/0
US, , Patent No. 5,843,882, Issued 01 Dec 1998
US, , Patent No. 5,962,653, Issued 05 Oct 1999
US, , Patent No. 6,015,876, Issued 18 Jan 2000
US, , Patent No. 6,245,737, Issued 12 Jun 2001
US, , Patent No. 6,586,392, Issued 01 Jul 2003
US, , Patent No. 5,821,081, Issued 13 Oct 1998
US, , Patent No. 5,962,668, Issued 05 Oct 1999
US, , Patent No. 6,987,096, Issued 17 Jan 2006
US, , Patent No. 5,998,587, Issued 07 Dec 1999
US, , Patent No. 6,743,577, Issued 01 Jun 2004
US, , Patent No. 6,420,336, Issued 16 Jul 2002
US, , Patent No. 6,428,790, Issued 06 Aug 2002
US, , Patent No. 7,105,169, Issued 12 Sep 2006
US, , Patent No. 7,048,935, Issued 23 May 2006
PCT, Application No. PCT/US00/06247 filed 10 Mar 2000 , which published as WO 00/53213 on 14 Sep 2000; and related international patents/patent applications
US, , Patent No. 6,780,847, Issued 24 Aug 2004
US, , Patent No. 7,339,037, Issued 04 Mar 2008
US, Application No. 10/846,265 filed 14 May 2004
US, Application No. 12/377,875 filed 18 Feb 2009


Relevant Publication:
  1. B Giomarelli, R Provvedi, F Meacci, T Maggi, D Medaglini, G Pozzi, T Mori, JB McMahon, R Gardella, MR Boyd. The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1. AIDS. 2002 Jul 5;16(10):1351-1356. [ PubMed abs ]
  2. CC Tsai, P Emau, Y Jiang, MB Agy, RJ Shattock, A Schmidt, WR Morton, KR Gustafson, MR Boyd. Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses. 2004 Jan; 20(1):11-18. [ PubMed abs ]
  3. DF Smee, KW Bailey, MH Wong, BR O'Keefe, KR Gustafson, VP Mishin, LV Gubareva. Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Res. 2008 Dec;80(3):266-271. [ PubMed abs ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute, Molecular Targets Laboratory , is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Infectious Diseases - Therapeutics
Infectious Diseases - Vaccines
In-vivo Data



For Additional Information Please Contact:
Sally Hu Ph.D., M.B.A.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 21,
Rockville, MD 20852
United States
Email: hus@mail.nih.gov
Phone: 301-435-5606
Fax: 301-402-0220 Admin. Licensing Spec-InfectDis
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 21,
Rockville, MD 20852
United States6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: anos@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220


Ref No: 1980

Updated: 06/2010

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