[Federal Register: December 9, 2003 (Volume 68, Number 236)]
[Notices]
[Page 68639-68641]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09de03-94]
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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, DHHS.
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.
Construction of Replication-Competent Chimeric Simian Immunodeficiency
Virus (SIV) Human Immunodeficiency Virus Type 1 (HIV-1) Viruses that
Replicate Using HIV-1 Reverse Transcriptase and Integrase (IN): A Model
System for Development and Testing of Antiviral Agents for the
Treatment of HIV-1 Infection
Vijay K. Pathak and Yijun Zhang (NCI). DHHS Reference No. E-019-
2004/0--Research Tool. Licensing Contact: Michael Ambrose; (301) 594-6565; ambrosea@mail.nih.gov.
Currently antiviral therapy is based on a cocktail that inhibits
viral replication. These drugs are targeted toward the Reverse
Transcriptase (RT) enzyme to inhibit such replication. However,
development of HIV drug resistance to these current therapies is the
leading blockage to successful treatment of such patients, and as such,
leads to the progression of AIDS and eventual death. The goal of
developing successful next generation drugs for HIV must contend with
(1) the alarming rate of mutation of HIV and (2) an animal model that
represents the natural disease in humans. This latter point must also
have as one of its properties; the natural occurring mutation and
resistance to the therapy in develop.
To address these questions, a chimeric virus was developed between
SIV and HIV. The SIV backbone is altered such that the HIV RT and
Integrase (IN) enzymes are expressed in infected cells. This allows the
use of the macaque as the animal model and having the RT and IN of HIV
as the potential drug targets. In this system, novel therapies can be
developed and studied in vivo, in single or in combination form, in a
manner more similar to the human HIV infection then is currently
available. Further, toxicity studies can be designed and results
obtained that are more relevant to the human disease condition.
One other advantage is the ability to use the macaque model to
discover additional generations of HIV therapies and tested in the same
system. This provides identical biological backgrounds to address
toxicity concerns of changing medications as one becomes resistant and
newer therapies are administered.
[[Page 68640]]
HIV-1/SIV Chimeras Promoting Trimerization of Soluble HIV-1 ENV
Bernard Moss (NIAID). U.S. Provisional Application filed 10 Oct
2003 (DHHS Reference No. E-356-2003/0-US-01). Licensing Contact: Susan Ano; (301) 435-5515; anos@mail.nih.gov.
The technology describes the replacement of the gp41 segment of
HIV-1 gp140 or just the N-terminal portion (85 amino acids) with the
corresponding region of SIV to promote efficient trimerization.
Functional, virion associated HIV-1 and SIV env have been shown to have
an almost exclusively trimeric structure. The chimera that contains
only the N-terminal portion of SIV in an HIV-1 background is
particularly interesting, since several broadly neutralizing HIV-1
epitopes are present in the C-terminal segment of gp41. Thus, the
current technology could be useful as an immunogen to elicit antibodies
that recognize a mimic of the native trimeric structure. The region of
HIV-1 replaced by SIV sequence contains no known targets of
neutralizing antibodies.
Use of a Statin To Kill EBV-Transformed B Cells
Jeffrey Cohen et al. (NIAID). U.S. Provisional Application filed 28
Oct 2003 (DHHS Reference No. E-312-2003/0-US-01). Licensing Contact: Susan Ano; (301) 435-5515; anos@mail.nih.gov.
This technology describes the use of certain natural and synthetic
statins, including simvastatin, other leukocyte function antigen-1
(LFA-1) inhibiting statins, and compounds derived from LFA-1 inhibiting
statins and statin-like compounds, for treatment or prevention of
Epstein-Barr Virus (EBV) associated tumors, including lymphomas that
express LFA-1 and transforming proteins. Such compounds could also be
used to treat tumors associated with other viruses that express LFA-1.
Cancers associated with EBV that could be treated with the statins by
methods described herein include naspharyngeal carcinoma, Hodgkin's
disease, lymphoproliferative disease, T-cell lymphoma, and non-
Hodgkin's lymphoma.
HIV-Dependent Expression Vector
Drs. Jon Marsh and Yuntao Wu (NIMH). U.S. Provisional Application
No. 60/507,034 filed 28 Sep 2003 (DHHS Reference No. E-276-2003/0-US-
01). Licensing Contact: Sally Hu; (301) 435-5606; hus@mail.nih.gov.
This invention provides a DNA construct that can be useful for both
diagnostics and AIDS therapeutics. The construct can be incorporated
into a retrovirus or into a cell line. This construct mediates the
expression of a selected gene in the presence of HIV replication, but
is silent in the absence of HIV. The cell line with the incorporated
construct can be used as an indicator line for the presence of
replication-competent HIV. The virus containing the construct can be
used to co-infect a population of HIV-infected cells. If the construct-
encoded gene is a reporter, it would specifically identify cells that
are infected with HIV. If the construct-encoded gene is a cytotoxin, it
would specifically kill cells that are HIV-infected. This invention may
offer a novel approach to HIV elimination, as well as detection of HIV
infected cells or the presence of cell-free infectious HIV.
Polypeptide Multimers Having Antiviral Activity
Carol Weiss et al. (FDA). PCT Application filed 14 Aug 2003 (DHHS
Reference No. E-155-2003/0-PCT-01); U.S. Patent Application No. 09/
480,336 filed 07 Jan 2000 (DHHS Reference No. E-212-2001/0-US-02). Licensing Contact: Susan Ano; (301) 435-5515; anos@mail.nih.gov.
The technology describes polypeptide multimers that have antiviral
and immunogenic activity against HIV. These multimers consist of at
least one monomer of the highly conserved N and C heptad regions of
gp41 in a ratio of at least 2:1 N to C heptad, with the N and C heptads
being connected by linkers. The monomer forms homodimers and
homotrimers in solution and mimic fusion intermediate structure.
Further, the technology also describes a method of raising a broadly
neutralizing antibody response to HIV by administering the polypeptide
multimers mentioned above. Thus, these polypeptide multimers may be
used as antiviral (anti-HIV) agents. Because the structure of these
polypeptide multimers mimics the gp41 fusion intermediate, they can
also be used to identify compounds that may inhibit the fusion process.
Discovery of Novel Inhibitors of HIV-1 Integrase and/or RNase H That
Can Be Used for the Treatment of Retroviral Infection Including AIDS
Stuart F. J. Le Grice (NCI) et al. U.S. Provisional Application
filed 31 Oct 2003 (DHHS Reference No. E-022-2003/0-US-01).
Licensing Contact: Sally Hu; (301) 435-5606; e-mail: hus@mail.nih.gov.
This invention provides compounds and methods of treating
retroviral infection such as AIDS by administration of a
dioxtetrahydrobenzo[a]naphthacene compound, particularly a 8,13-dioxo-
5,6,8,13-tetrahydro-benzo[a]naphthacene compound, i.e. a
madurahydroxylactone compound. Retroviruses, such as HIV, need three
viral enzymes for replication: reverse transcriptase, protease, and
integrase. The prognosis of AIDS patients has recently been improved by
the discovery and associated therapeutic administration of reverse
transcriptase and/or protease inhibitors. However, a significant
portion of AIDS patients fail to respond to such treatments and viral
resistance remains a major problem.
It is known that HIV-1 integrase is a rational target for AIDS
therapy because genetic studies have demonstrated that the enzyme is
essential for viral replication, and because there is no cellular
equivalent. On the other hand, the reverse transcriptase RNase H active
site is another good target for antiviral therapeutic development
because elimination of the RNase H activity of reverse transcriptase
arrests virus replication. The compounds reported in this invention may
be capable of inhibiting both enzymes since the catalytic centers of
integrase and RNase H are structurally similar. As a consequence, this
invention can potentially avoid viral resistance, which limits the
efficacy of presently administered reverse transcriptase and/or
protease inhibitor therapeutic agents. Thus, the invention may be a
group of new small molecule agents for treating patients suffering from
retroviral infections, particularly patients suffering from Human
Immunodeficiency Virus (HIV).
Particles for Imaging Cells
Kathleen Hinds, Cynthia Dunbar (NHLBI). U.S. Patent Application No.
10/313,304 filed 06 Dec 2002 (DHHS Reference No. E-185-2002/0-US-01).
Licensing Contact: Michael Shmilovich; (301) 435-5019; shmilovm@mail.nih.gov.
Available for licensing are NIH patent pending contrast particles
for use in MRI and flow cytometry to track cells migration in real
time. Present cell-tracking studies rely on labeling cells with ultra-
small dextran-coated iron particles that are endocytosed. The contrast
agent of the present invention uses larger iron oxide particles,
approximately 1 [mu]m, situated in a tri-layer structure. The inner
structure is a magnetic molecular complex of FITC (a fluorescent
marker) encased in a layer of superparamagnetic microparticles, which
is then covered with a shell of
[[Page 68641]]
inert polystyrene and di-vinyl benzene coated with soluble -COOH
groups. Accordingly, the particle is labeled with both a magnetic and
fluorescent marker. This dual labeling permits monitoring of the
molecule on multiple spatial scales, from intracellular distribution to
distribution throughout the animal.
Methods for Detecting Cancer Cells
Thomas Ried, Evelin Schrock, Bijan M. Ghadimi (NHGRI). U.S.
Provisional Application No. 60/127,637 filed 01 Apr 1999 (DHHS
Reference No. E-211-1998/0-US-01); PCT Application No. PCT/US00/08588
filed 31 Mar 2000 (DHHS Reference No. E-211-1998/0-PCT-02); U.S. Patent
Application No. 09/937,864 filed 31 Dec 2000 (DHHS Reference No. E-211-
1998/0-US-03). Licensing Contact: Michael Ambrose; (301) 594-6565; ambrosem@mail.nih.gov.
The present application describes a highly sensitive assay for
distinguishing between cancer and non-cancer epithelial cells in the
blood. It provides an improved diagnostic technique for detecting
cancer and determining the organ-origin of the cancer. This assay can
be used to prove the neoplastic nature of cells and predict when shed
tumor cells have or will become metastatic. A major advantage of the
present invention is that tumor cells can also be recovered as viable
cells. Thus, the tumor cells can be kept alive in vitro for a
sufficient period of time to determine the effect of particular anti-
tumor pharmaceuticals on the cells. Furthermore, the assay provides an
early detector of treatment success or failure and thereby allows a
treatment regimen to be customized for an individual patient with
advanced primary cancer.
Method for Detecting Transmissible Spongiform Encephalopathies
Gary E. Hsich, Kimbra Kenney, Clarence J. Gibbs, Michael G.
Harrington (NINDS). U.S. Patent 5,998,149 issued on 07 Dec 1999 (DHHS
Reference No. E-055-1996/0-US-01); U.S. Patent 6,406,860 issued on 18
Jul 2002 (DHHS Reference No. E-055-1996/0-US-02). Licensing Contact: Michael Ambrose; (301) 594-6565; ambrosem@mail.nih.gov.
Improved assays for the detection of transmissible spongiform
encephalopathies (TSEs) in humans and non-human mammals have been
developed. The assays involve detecting the presence or absence of 14-
3-3 proteins in cerebrospinal fluid. Elevated levels of these proteins
are indicative of TSEs, in particular Creutzfeldt-Jacob disease in
humans and animals with these diseases. This invention is available for
licensing on a non-exclusive basis.
Dated: December 1, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 03-30498 Filed 12-8-03; 8:45 am]
BILLING CODE 4140-01-P