[Federal Register Volume 61, Number 77 (Friday, April 19, 1996)]
[Notices]
[Pages 17309-17311]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-9614]



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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, HHS.

ACTION: Notice.

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    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

[[Page 17310]]

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 
vectors)

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 
Medicine--Miscellaneous)

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)

[[Page 17311]]

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 
subject.
    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 
Pathway

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]
BILLING CODE 4140-01-M