[Federal Register Volume 71, Number 102 (Friday, May 26, 2006)]
[Notices]
[Pages 30430-30431]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-8176]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Influenza DNA Vaccine That Protects Against Lethal H5N1 Challenge

    Description of Technology: Concerns about a potential influenza 
pandemic and its prevention dominate health news, with new cases of 
bird (avian) influenza (H5N1 strain) cases being reported on a daily 
basis. Vaccination is one of the most effective ways to minimize 
suffering and death from influenza. Currently, there is not an 
effective vaccine to protect against the H5N1 strain, thought to be a 
leading pandemic candidate. The technology described here relates to a 
DNA influenza vaccine encoding the matrix 2 (M2) protein, which is 
highly conserved among different influenza strains. The M2 component 
can be used either alone or in combination with other influenza 
components. Specifically, mouse studies showed that the use of M2 from 
H1N1 strain protected against a lethal challenge with H5N1 strain. The 
current technology offers several advantages over traditional influenza 
vaccine approaches, including (a) ease and speed of production without 
need for eggs, (b) no surveillance to determine dominant strain(s), and 
(c) no potential for antigenic shift as observed for the components (HA 
and NA) of current influenza vaccines.
    Inventors: Suzanne L. Epstein et al. (CBER/FDA).
    Patent Status: U.S. Provisional Application No. 60/785,152 filed 
March 27, 2006 (HHS Reference No. E-076-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, PhD.; 301/435-5515; 
[email protected].
    Collaborative Research Opportunity: The Food and Drug 
Administration's Center for Biologics Evaluation and Research (CBER) is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact Beatrice Droke at 301/827-7008 or 
[email protected] for more information.

Methods for Inhibiting HIV and Other Viral Infections by Modulating 
Ceramide Metabolism

    Description of Technology: This invention provides methods of 
inhibiting or preventing HIV-1 infections by inducing either the de 
novo biosynthesis of ceramide, or by activating enzymes (e.g., 
sphingomyelinase) involved in the generation of ceramide at the plasma 
membrane, or by direct incorporation of exogenous ceramide into target 
cell membranes. The invention describes methods for administration a 
retinamide compound particularly an N-(aryl) retinamide compound such 
as N-(4-hydroxyphenyl) retinamide (4-HPR) resulting in increased plasma 
membrane ceramide levels, which results in the inhibition of HIV-1 
infection in monocyte/macrophages by perturbing membrane organization. 
In addition, because of its low toxicity in non-tumor cells, 4-HPR and 
related compounds are particularly suitable for long-term preventative 
or therapeutic administration to subjects suffering from an HIV 
infection or who are at risk of contracting an HIV infection. Thus, 
this invention provides a novel means of treating or inhibiting HIV and 
other viral infections by administering a retinamide compound to a 
patient suffering from or susceptible to such a viral infection.
    Inventors: Robert P. Blumenthal et al. (NCI).
    Publications:
    1. C.M. Finnegan et al., ``Ceramide, a target for antiretroviral 
therapy,'' Proc. Natl. Acad. Sci. USA. (2004 Oct 26) 101(43):15452-
15457.
    2. C.M. Finnegan and R. Blumenthal, ``Fenretinide inhibits HIV 
infection by promoting viral endocytosis,'' Antiviral Res. (2006 Feb) 
69(2):116-123.
    Patent Status: U.S. Provisional Application No. 60/528,411 filed 
December 9, 2003 (HHS Reference No. E-265-2003/0-US-01); PCT 
Application No. PCT/US2004/41512 filed December 9, 2004, which 
published as WO 2005/072091 on August 11, 2005 (HHS Reference No. E-
265-2003/0-PCT-02).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Sally Hu, PhD., M.B.A.; 301/435-5606; 
[email protected]
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research Nanobiology Program, is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the clinical 
potential of sphingolipid-based antiviral therapies. Please contact 
Melissa Maderia at [email protected] or by phone at 301/846-5465 
for more information.

Methods and Compositions for the Inhibition of HIV-1 Replication

    Description of Technology: This invention relates to methods and 
compositions for the attenuation of HIV-1 replication in human cells, 
and especially in CD4+ human peripheral blood mononuclear cells, such 
as blood monocyte-derived macrophages by targeting a host cell protein. 
HIV-1 infected macrophages typically resist cell death, support viral 
replication, and facilitate HIV-1 transmission. We found that the gene 
encoding cyclin-dependent kinase inhibitor 1A (CDKN1A) is consistently 
expressed following virus binding, and re-expressed at the peak of HIV-
1 replication. The protein encoded by this gene, also known as p21, is 
associated with cell cycle regulation, anti-apoptotic response and cell 
differentiation. Increased levels of p21 may enhance survival and long-
term persistence of HIV-1 infected macrophages. Following 
identification of p21 as a candidate molecule in facilitating viral 
replication, efforts to curtail its role were investigated as a mode of 
blunting infection in macrophages. RNA interference (siRNA) represents 
a tool to regulate gene expression and when siRNA specific for p21 or 
p21-specific oligonucleotides were transfected into primary macrophages 
to silence the expression of p21, HIV infection was aborted, thereby 
validating p21 as a cellular factor essential to productive HIV 
infection in this population. Extending these observations, a

[[Page 30431]]

pharmacologic agent known to influence p21 expression, the synthetic 
triterpenoid and peroxisome proliferator-activated receptor gamma 
(PPARg) ligand, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) or 
its derivative di-CDDO, was shown to moderate virally-induced p21 
expression and concurrently dampen HIV infection. CDDO is part of a 
class of synthetic triterpenoids based on natural products resembling 
steroids in their biogenesis and in their pleiotropic actions. A newly 
developed CDDO derivative, which is orally bioavailable, also 
suppresses HIV. These results, coupled with the evidence that 
macrophage p21 is a requisite macrophage facilitator of viral 
replication, intensify the interest to further develop these compounds 
as antiretroviral agents. The anti-retroviral effect of CDDO was 
evident when peripheral blood mononuclear cells (PBMC) were infected 
with a T-tropic (X4) or dual tropic viral (R5X4) strain of HIV-1. These 
studies suggest that these triterpenoids may aid in the control of 
retroviral replication. Neither p21 oligonucleotides nor CDDO were 
toxic to the cultured macrophages or peripheral blood mononuclear 
cells. Thus, p21 inhibitors could be safe and effective anti-HIV 
therapeutic candidates to be used independently and/or in conjunction 
with current anti-retroviral therapy. In this regard, CDDO will be 
entered into human trials for the first time in the near future for its 
anti-cancer indications, thereby determining its maximally tolerated 
dose for use in subsequent HIV/AIDS clinical trials. Current anti-
retroviral therapy, often characterized by high toxicity and the 
emergence of drug resistant virus strains, may be augmented through the 
identification of these and other new anti-viral agents targeting host 
cellular molecules less prone to mutational events.
    Inventors: Sharon M. Wahl, Nancy Vazquez-Maldonado, Teresa 
Greenwell-Wild (NIDCR).
    Publications:
    1. S.M. Wahl et al., ``HIV accomplices and adversaries in 
macrophage infection,'' J. Leukoc. Biol. 2006, in press.
    2. N. Vazquez et al., ``Human immunodeficiency virus type 1-induced 
macrophage gene expression includes the p21 gene, a target for viral 
regulation,'' J. Virol. (2005 Apr) 79(7):4479-4491.
    Patent Status: U.S. Provisional Application No. 60/516,794 filed 
November 4, 2003 (HHS Reference No. E-114-2003/0-US-01); PCT 
Application No. PCT/US2004/36492 filed November 3, 2004, which 
published as WO 2005/046732 on May 26, 2005 (HHS Reference No. E-114-
2003/0-PCT-02)
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Sally Hu, PhD., M.B.A.; 301/435-5606; 
[email protected]
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research, Oral Infection and Immunity Branch, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize this technology. Please contact David W. Bradley, PhD., 
at [email protected] or by phone at 301/402-0540 for more 
information.

    Dated: May 18, 2006.
David R. Sadowski,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
 [FR Doc. E6-8176 Filed 5-25-06; 8:45 am]
BILLING CODE 4140-01-P