[Federal Register: April 19, 1996 (Volume 61, Number 77, Page 17309-17311]

National Institutes of Health

Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.


The inventions listed below are owned by agencies 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

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commercialization of results of federally funded research and
development. Foreign patent applications are filed on selected
inventions to extend market coverage for U.S. 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 contacting the indicated
licensing specialist 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.

Test Of HIV-Specific T Lymphocyte Function That Detects Exposure to HIV
Antigens and Possibly Early HIV Infection

Shearer, G.M., Berzofsky, J.A., Clerici, M. (NCI)
Filed 7 Jun 95
Serial No. 08/488,435 (CIP of 08/229,108)
Licensing Contact: George Keller, 301/496-7735 ext 246

This new diagnostic test is designed for early detection of
exposure to HIV or HIV antigens. The test measures activation of
peripheral blood mononuclear cells following incubation of those cells
with one or more synthetic epitopes of HIV. The test can detect HIV
exposure prior to seroconversion and is superior to standard HIV
antibody tests and PCR amplification of viral DNA. The new test may be
especially useful in screening the blood supply, and may also prove
useful as a diagnostic capable of detecting exposure of individuals to
HIV sooner after that exposure than current detection methods.
(portfolio: Infectious Diseases--Diagnostics, viral, AIDS)

Oligomeric HIV-1 Envelope Glycoproteins

Earl, P.L., Broder, C.C., Doms, R.W., Moss,B. (NIAID)
Filed 10 Dec 93
Serial No. 08/165,314
Licensing Contact: Cindy K. Fuchs, 301/496-7735 ext 232

This invention embodies a method for generating antibodies to HIV-1
envelope glycoproteins, which could hold powerful implications toward
both the diagnosis and the treatment of AIDS. Specifically, the method
involves the expression of a soluble protein, gp140, and the generation
of antibodies to this protein. gp140 is a recombinant version of gp160,
a protein which normally is cleaved in vivo to generate two
glycoprotein subunits which are expressed on the surface of the HIV-1
envelope. Unlike previously isolated versions of gp160, gp140 is
purified in a manner which preserves the quaternary structural elements
of the protein. Due to the conserved nature of these structural
elements, antibodies generated against gp140 may be more broadly
reactive against various forms of AIDS than other antibodies generated
to date. (portfolio: Infectious Diseases--Vaccines, viral, AIDS)

Pre-Binding of Retroviral Vector Particles With Complement Components
To Enable the Performance of Human Gene Therapy In Vivo

Mason, J.M., Safer, B., Anderson, W.F. (NHLBI)
Filed 28 Jul 93
Serial No. 08/098,944
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287

This invention relates to an improvement in the use of retroviral
vectors in gene therapy. The invention specifically relates to the use
of C1 complement subcomponents and antibody fragments to protect
retroviral vector particles produced in non-primate packaging lines
from attack by primate complement systems in vivo. Pharmaceutical
compositions containing retroviral vector particles prebound with C1
complement subcomponents, as well as gene therapy methods, are part of
this invention. (portfolio: Gene-Based Therapies--Therapeutics, viral

Cosalane and Related Compounds Having Activity Against AIDS and AIDS-
Related Infections

Cushman, M., Golebiewski, M., Haugwitz, R. (NCI)
Serial No. 08/029,415
Patent Issued 8 Aug 95
U.S. Patent No. 5,439,899
Licensing Contact: Cindy K. Fuchs, 301/496-7735 ext 232

A new series of potential anti-viral agents based upon the chemical
cosalane and its related derivatives may be the basis of a new
treatment for AIDS. Cosalane was developed by combining a fragment of
aurintricarboxylic acid (ATA), a compound originally used in the Swiss
dye industry, with cholestane, a steriod related to cholesterol. The
cholestane fragment is used to direct the drug to the T cell membrane
with the ATA fragment subsequently blocking binding of HIV gp120 to the
CD4 receptor site on the cell surface. Laboratory tests of cosalane
suggest it is effective in inhibiting both HIV-1 and HIV-2 infection
and is very effective at concentrations too weak to harm the T cells.
Other studies also suggest that cosalane may be able to suppress HIV
virus reproduction in patients without the toxic side effects
associated with current AIDS treatments. (portfolio: Infectious
Diseases--Therapeutics, antivirals, AIDS)

Glycosides of Cyclodextrin, and Processes for Their Preparation

Pitha, J., Wimmer, T. (NIA)
Serial No. 08/016,449
U.S. Patent 5,426,184 issued 20 Jun 95
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287

A novel method for preparing cyclodextrin glycosides is
particularly useful for solubilizing substances that are sparingly
soluble in water. Previous methods for preparing cyclodextrin
derivatives have been hampered by the high reaction temperature used,
which leads to unwanted by-products and makes working up and
purification of the reaction products quite difficult. This new process
employs an anhydrous acid medium with subsequent treatment of the
reaction products with a mild base. The reaction takes place at
relatively low temperatures (between 40 deg.C and 80 deg.C), providing
a high yield of desired products. It also is much easier to prepare the
reaction compared to previous processes, and purification of products
is accomplished through standard methods. (portfolio: Internal

Novel Serine Protease Inhibitors and Genes Encoding Same

Kotwal, G.J., Moss, B. (NIAID)
Serial No. 07/906,983
U.S. Patent 5,187,268 issued 16 Feb 93 (DIV of 07/285,510, U.S. Patent
5,151,509 issued 29 Sep 92; CIP of 07/239,208, U.S. Patent 5,257,110
issued 20 Oct 92)
Licensing Contact: Carol Lavrich, 301/496-7735 ext 287

Novel proteins having a substantial degree of homology to the
serine protease inhibitor superfamily could be valuable for treating
conditions such as emphysema, cirrhosis, and liver cancer. Serine
protease activity has been associated with the accelerated failure of
certain diseased organs and tissues. There have previously been no
known synthetic or microbial proteins capable of specifically
inhibiting serine proteases. (portfolio: Internal Medicine--
Therapeutics, cardiology, antithrombotic)

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Adenovirus Mediated Transfer of Genes to the Gastrointestinal Tract

Crystal, R.G. (NHLBI)
Filed 16 Oct 91
Serial No. 07/776,057
Licensing Contact: Larry Tiffany, 301/496-7056 ext 206

A novel method of producing a chosen protein in the
gastrointestinal tract of a human has been invented by and is available
for licensing from the Public Health Service. The technology allows for
the systemic long-term administration of a therapeutic protein to a
patient without the need for periodic injections or suppositories. In
comparison to alternative delivery systems, such as retroviral vectors,
this methodology allows the gene of interest to be directly transferred
to targeted cells even if these cells are not actively dividing. The
technology is the subject of a pending patent application. (portfolio:
Gene-Based Therapies--Therapeutics, vectors, viral; Gene-Based
Therapies--Therapeutics, therapeutic genes)

Cytosine Deaminase Negative Selection System for Gene Transfer
Techniques and Therapies

Mullen, C.A., Blaese, R.M. (NCI)
Serial No. 07/725,076
U.S. Patent No. 5,358,866 issued 25 Nov 94
Licensing Contact: Larry Tiffany, 301/496-7056 ext 206

A DNA construct has been developed which permits efficient
expression of a modified bacterial cytosine deaminase (CD) gene in
mammalian cells. The presence and expression of the gene has no
apparent deleterious effects upon the transfected cells unless they are
exposed to 5-fluorocytosine (5FC). Because CD has the ability to
convert 5FC to a toxic antimetabolite, 5-fluorouracil, cells which have
been transformed with the DNA construct can be selectively killed by
treating them with 5FC. By modifying the specifity or method of
delivering the DNA construct to cells, or by modifying the vector
carrying the DNA construct to correspond to a tissue-specific promoter,
specific cell or tissue types may be selectively eliminated from a
Potential uses of the CD negative selective system (CDNSS) include
gene therapy, immunotherapy, and bone marrow transplant applications.
The CDNSS could be used to regulate the biological activity of a
transformed cell type as a part of a gene therapy application. For
example, the CDNSS might be incorporated within a transformed cell type
which also expresses a gene of therapeutic interest. The transformed
cell type could then be administered to a subject. The biological
activity expressed by the transformed cell type might be regulated by
administering a measured dose of 5FC to the subject such that a portion
of the transformed cell type is eliminated. Alternately, the
transformed cell type might be eliminated from the subject by
administering to the subject a dose of 5FC that would be toxic to the
transformed cell type.
The CDNSS could also be used to impart immunity against a virus or
a specific cell type, including a bacterium, a protozoan, or a type of
tumor cell. For example, a cell type or virus harboring the CDNSS might
be introduced into a subject to elicit an immune response against that
cell type or virus. The introduced cell type or cells harboring the
virus might be selectively killed after an immune response was elicited
by administering 5FC to the subject.
The CDNSS could be used in conjunction with bone marrow transplant
procedures to eliminate a specific cell type or virus from the bone
marrow. For example, bone marrow cells from a subject might be
transduced with a vector which harbors the CDNSS and which is specific
for a certain cell type or for cells harboring a specific virus. The
transformed bone marrow cells might then be treated with 5FC to
selectively eliminate (or purge) the transduced cells, after which the
treated bone marrow could be introduced into a subject.
Other uses for the CDNSS are not fully described here, including
its use as a double negative selection vector and its use as a
diagnostic indicator of homologous recombination. Further information
regarding these and other applications is available.
A corresponding group of divisional patent applications claiming
different aspects of this technology (e.g. a vaccine for mammals
against tumors) have also been filed and are available for licensing.
(portfolio: Gene-Based Therapies--Therapeutics, vectors, control
sequences/genes; Gene-Based Therapies--Therapeutics, vectors, viral)

Dominant Negative Transcription Regulatory Proteins Created by Acidic
Amphipathic Alpha-Helical Extension of the Leucine Zipper

Vinson, C.R. (NCI)
Filed 31 Jul 95
Serial No. 60/001,654
Licensing Contact: Allan Kiang, 301/496-7735 ext 270

Members of the transcription factor family of molecules termed
basic-region leucine zipper (bZIP) proteins are characterized by the
fact that they contain two regions--a hepted repeat of leucine residues
(the leucine zipper) and a region rich in basic amino acids.
Dimerization with other protein molecules occurs by interactions with
the leucine zipper domains allowing interaction of DNA regulatory
sequences with the basic domain, thereby stabilizing the dimer. This
invention embodies the creation of dominant negative (DN) transcription
factors modified to increase the stability of the dimerization reaction
between the leucine zipper regions of the bZIP proteins. This results
in a DN factor that has the ability to inhibit DNA binding and then
transactivation, thereby preventing the production of other proteins or
the expression of genes that are detrimental. A transgenic animal model
has been produced expressing a DN factor that interacts and inhibits a
cellular factor indicating the utility of this approach. (portfolio:
Gene-Based Therapies--Therapeutics, other)

Method of Identifying Inhibitors of the Jak-STAT Signal Transduction

Leonard, W.J. (NHLBI)
DHHS Reference No. E-176-95/0
Licensing Contact: Allan Kiang, 301/496-7735 ext 270

The invention provides identification methods for agents which
inhibit the Jak-STAT signaling transduction pathway. Drugs identified
by these methods are candidates for the treatment of proliferative
disorders dependent on the Jak-STAT pathway, including those caused by
HTLV-1. In addition, such agents may be potent immunosuppressive drugs
with potential applications not only for organ transplantation but also
for treatment of autoimmune diseases. (portfolio: Cancer--Therapeutics,
miscellaneous; Internal Medicine--Miscellaneous)

Dated: April 11, 1996.
Barbara M. McGarey, J.D.,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-9614 Filed 4-18-96; 8:45 am]