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Uses of Cyanovirin-N for Anti-Hiv and Anti-Influenza Therapeutics and Prophylactics

Keywords: Therapeutics, Vaccines, HIV, Influenza, Cyanovirin-N (CV-N)

Background:
The National Cancer Institute's Molecular Targets Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cyanovirin-N HIV and influenza therapeutics and vaccines.

Technology:
Inventors at NCI have discovered that the cyanovirin-N (CV-N) protein potently and irreversibly inactivates diverse primary strains of HIV-1, including forms involved in sexual transmission of HIV. 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 including H1N1 strains.

Also described in this technology platform are 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 production of CV-Ns on a large scale and reduce the cost of CV-Ns sufficiently for developing countries to benefit from this invention.

Since CV-N inhibits HIV at a concentration that is10,000 times smaller than its toxic concentration to cells, it may be used to develop safe and effective HIV therapeutics.  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 stable, and is amenable to very large-scale production by a variety of genetic engineering approaches. CV-N has been shown to be 100% effective in inhibiting the transmission of SIV in macaque sexual transmission studies and 100% effective in inhibiting death due to infection by H1N1 influenza following intranasal administration.

Potential Commercial Applications/Possible Markets Identified:

• Therapeutics and prevention of HIV and influenza infections 
• Topical microbicide to prevent sexual transmission of HIV
• Ex vivo devices incorporating CV-N to remove or inactivate HIV from fluid samples

• Potent anti-HIV and anti-influenza activity
• Can be applied both systematically or locally
• CV-N is 10,000 times more toxic to HIV than it is to cells
• Can be applied both in vivo and ex vivo
• Inexpensive and large scale manufacturing
• Readily soluble in aqueous media
• Resistant to physicochemical degradation

• Successful pre-clinical in vivo proof of concept (rabbit/monkey)as a topical microbicide against HIV infection.  Initial animal efficacy studies (both mouse and ferret) against influenza (H1N1) have been completed and published.

• GMP production
• Formulation studies for both topical and aerosol administration
•  Additional animal efficacy studies

This opportunity is also listed under the following categories:

• Therapeutics