[Federal Register Volume 68, Number 236 (Tuesday, December 9, 2003)]
[Notices]
[Pages 68639-68641]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-30498]


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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; [email protected].

    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; [email protected].
    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; [email protected].
    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; [email protected].
    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; [email protected].
    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: 
[email protected].
    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; 
[email protected].
    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; 
[email protected].
    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; [email protected].
    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