[Federal Register Volume 64, Number 14 (Friday, January 22, 1999)]
[Notices]
[Pages 3528-3530]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-1424]
[[Page 3528]]
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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 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 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
Amino-Terminus-Modified Eosinophil-Derived Neurotoxin and Its
Selective Toxicity to Kaposi's Sarcoma Cell Line, KS Y-1
Dr. Susanna M. Rybak and Dr. Dianne L. Newton (NCI)
Serial No. 60/106,732 filed 02 Nov 98
Licensing Contact: J.R. Dixon; 301/496-7056 ext. 206; e-mail:
jd212g@nih.gov
The invention described in this patent application is related to
the field of cancer/HIV therapeutics. More particularly, the invention
relates to the creation and identification of a compound which, in in
vitro assays, is selectively cytotoxic for Kaposi's sarcoma cells and
therefore may prove useful for developing a therapeutic treatment for
Kaposi's sarcoma. The compound, a derivative of human eosinophil-
derived neurotoxin (``EDN''), was obtained by altering the mature EDN
protein at its amino terminus. EDN, a ribonuclease, has previously been
shown to be cytotoxic when delivered to cells as an immunotoxin. The
EDN derivative of this patent application has been constructed by
adding to the NH2 terminus of the mature EDN protein the
four (4) naturally-occurring COOH terminal amino acids of the signal
sequence of EDN, SLHV. Normall, this signal sequence is cleaved from
EDN to obtain the mature, functional protein.
Tissue Microarray For Rapid Molecular Profiling
O Kallioniemi, G. Sauter (NHGRI)
DHHS Reference No. E-007-99/0 filed 28 Oct 98
Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail:
rr154z@nih.gov
Recent advances in molecular medicine have provided new
opportunities to understand cellular and molecular mechanisms of
disease and to select appropriate treatment regimens with the greatest
likelihood of success. The clinical application of novel molecular,
genetic and genomic discoveries has been impeded by the slow and
tedious process of evaluating biomarkets in large numbers of clinical
specimens. The present invention provides a method of high-throughput
molecular profiling of very large numbers of tissue specimens, such as
tumors, with minimal tissue requirements. This procedure provides a
target for rapid parrallel analysis of biological and molecular
characteristics (such as gene dosage and expression) from hundreds of
morphologically controlled tumor specimens. Multiple sections can be
obtained from such tissue microarrays (``tissue chips'') so that each
section contains hundreds or thousands of different tissue specimens
that maintain their assigned locations. Different in situ analyses,
such as histological, immunological, or molecular, are performed on
each section to determine the frequency and significance of multiple
molecular markers in a given set of tissues. This method can also be
combined with other technologies such as high-throughput genomics
surveys using NA microarrays. DNA microarrays enable analysis of
thousands of genes from one tissue specimen in a single experiment,
whereas the tissue microarrays make it possible to analyze hundreds or
thousands of tissue specimens in a single experiment using a single
gene or protein probe. Together the DNA and tissue microarray
technologies will be very powerful for the rapid analysis of markers
associated with disease prognosis or therapy outcome.
Inhibitors of Formation of Protease Resistant Prion Protein
B Chesebro, B Caughey, J Chabry, S Priola (NIAID)
Serial No. 09/128,450, filed 03 Aug 98
Licensing Contact: George Keller; 301/496-7735 ext. 246; e-mail:
gk40j@nih.gov.
The current invention provides peptides and pharmaceutical
compositions that are useful to inhibit formation of protease resistant
prion proteins (PrPres) such as the PrPres associated with
transmissible spongiform encephalopathies (TSE). Certain synthetic
peptides which incorporate the most amyloidogenic region of the PrP
protein can inhibit the formation of PrPres under conditions where it
would otherwise be formed. Such specific inhibition of the formation of
PrPres may prevent or slow the deposition of amyloid deposits in the
tissues of animals that have been exposed to a TSE or are suffering
from a neurodegenerative disorder having the characteristics of a
spongiform encephalopathy. For more information, see Chabry, Jr. et al.
(1998) Specific Inhibition of in vitro Formation of Protease-Resistent
Prion Protein by Specific Peptides, J. Biol. Chem. 273, 13203-13207.
Transcriptional Activation of the C-Mos Oncogene Is Associated With
Disease Progression in HIV Infection
DI Cohen (NCI)
Serial No. 60/093,121 filed 15 Jul 98
Licensing Contact: George Keller; 301/496-7735 ext. 246; e-mail:
gk40j@nih.gov
the current invention provides methods of diagnosing and staging
pathogenic lentivirus infections, specifically HIV, by detecting
activation of the c-mos gene. The binding of the HIV envelope
glycoprotein, during cell-cell infection, to CXC chemokine receptors,
leads to transcriptional activation of the c-mos gene. The invention
also provides a method for treating a cell proliferative disorder
associated with c-mos activity, such as HIV inspection, by treating a
subject having the disorder with a composition that regulates c-mos
activity or expression. In addition, compounds that modify c-mos
express in specific cells can be identified, using this invention.
The HIV co-culture system can be used to initiate c-mos dependent
cell death. Death in this system is dependent on the level of c-mos
induction. Pharmacological agents that either also induce c-mos, or
stabilize c-mos following its induction, would accelerate this death
process. Therefore, this technology defines a method of screen for
novel anti-proliferative drugs capable of interacting with this unique
c-mos death pathway.
2-Microglobulin Fusion Proteins and High
Affinity Variants
RK Ribaudo, M Shields (NCI)
Serial No. 60/088,813 filed 10 Jun 98
[[Page 3529]]
Licensing Conact: Peter Soukas; 301/496-7056 ext. 268; e-mail:
ps193c@nih.gov
This invention concerns fusion proteins comprising
(2M), a component of the MHC-1 complex, and
immunologically active proteins such as the co-stimulatory molecule B7.
The fusion proteins, and nucleic acids encoding them, have broad
utility activating Cytotoxic T Lymphocytes (CTLs) against viruses and
tumors. The fusion proteins locate to the surface of MHC-1 expressing
cells. They may be used as adjuvants to enhance the efficacy of MHC-1
binding peptides, from viruses or cancer antigens, as vaccines. The
fusion proteins can be used, in vivo or ex vivo, to enhance the
immunogenicity of cancer cells to cause their destruction by the immune
system. B7-2M is as effective at co-stimulating T-
cells in comparison to anti-CD28 monoclonal antibodies, whereas wild-
type 2M is ineffective at co-stimulating T-cells.
In addition, B7-2M induces better recognition and
killing of tumor cell lines compared to wild-type
2M. Another aspect of the invention is a mutant
human 2M that binds MHC-1 with higher affinity than
wild-type 2M. It can be used in place of wild-type
2M, including in the fusion proteins, to greater
effect.
Disubstituted Lavendustin a Analogs and Pharmaceutical Compositions
Comprising the Analogs
VL Narayanan, EA Sausville, G Kaur, R Varma (NCI)
Serial No. 60/076,330 filed 27 Feb 98
Licensing Contact: Girish Barua; 301/496-7056 ext. 263; e-mail:
gb18t@nih.gov
The invention discloses lavendustin A analogs that are protein
tyrosine kinase (PTK) inhibitors having antiproliferative activity. A
preferred compound, based on in vivo biological activity, is 4'-
adamantylmethylbenzoate-1'-N-1,4-dihydroxybenzylamine. Pharmaceutical
compositions comprising effective amounts of lavendustin are also
covered; such compositions also may comprise other active ingredients
and other materials typically used in such pharmaceutical formulations.
These compounds and compositions of the invention may be used for
treating subjects to, for example, inhibit the proliferation of living
cells for treatment of proliferative diseases.
Oligodeoxyribonucleotides Comprising O 6-Benzylguanine
and Their Use
R Moschel et al. (NCI)
Serial No. 09/023,726 filed 13 Feb 98
Licensing Contact: Girish Barua; 301/496-7056 ext. 263; e-mail:
gb18t@nih.gov
The invention provides single-stranded oligodeoxyribonucleotides
which are more potent than O6-benzylguanine in inactivating human O
6-alkylguanine-DNA alkyltransferase (AGT). The
oligodeoxyribonucleotides comprise from about 5 to 11 bases, at least
one of which is a substituted or an unsubstituted O 6-
benzylguanine. The oligodeoxyribonucleotides have several advantages
over O 6-benzylguanine. They can inactivate mutant human
AGTs that are either not inactivated or incompletely inactivated by O
6-benzylguanine. They have greater solubility in water than
O 6-benzylguanine, and they react much more rapidly with AGT
than does O 6-benzylguanine. The invention also provides
compositions comprising such oligodeoxyribonucleotides. In addition,
the invention provides a method of enhancing the effect of
antineoplastic alkylating agents that alkylate the O 6
position of guanine residues in DNA for the chemotherapeutic treatment
of cancer in a mammal.
Shielded Ultrasound Probe
H Wen, E Bennett (NHLBI)
DHHS Reference No. E-017-98/0 filed 12 Nov 97
Licensing Contact: John Fahner-Vihtelic; 301/496-7735 ext. 270; e-mail:
jf36z@nih.gov
The invention relates to the recently developed imaging method
called Hall Effect Imaging (HEI). HEI involves the use of a magnetic
field and electrical or ultrasound pulses applied to an object to
generate an image of the object. HEI has the potential to become a
novel medical imaging technique, revealing features not seen in
existing imaging methods. Performing HEI with conventional ultrasound
transducers is difficult due to electrical interference, though. The
present invention is a design for an ultrasonic transducer which
overcomes these difficulties. This design may be made as a modification
of a commercial ultrasound probe, thereby lowering the cost of
development and production.
Methods for Use of Interleukin-4 (IL-4) and Tumor Necrosis Factor-
Alpha (TNF-) To Treat Human Immunodeficiency Virus (HIV)
Infection
George N. Pavlakis, Antonio Valentin, Barbara K. Felber (NCI)
DHHS Reference No. E-160-96/1 filed 18 Sep 98 (claiming priority of
U.S. Provisional 60/059,359 filed 19 September 1997)
Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264; e-mail:
jk141n@nih.gov
AIDS (acquired immunodeficiency syndrome), first reported in the
United States in 1981, has become a worldwide epidemic, crossing all
geographic and demographic boundaries. More than 475,000 cases of AIDS
have been reported in the United States since 1981 and more than
295,000 deaths have resulted in the U.S. from AIDS. Over 1.5 million
Americans are thought to be infected with HIV (human immunodeficiency
virus), the causative agent of AIDS.
The subject invention relates to the interactions of the cytokines,
interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-),
with HIV and HIV targets in the body. The invention provides methods
for characterizing isolates of HIV according to susceptibility to the
viral replication inhibiting effects of IL-4 and methods for use of
TNF-, IL-4, IL-4 analogs, and/or inhibitors of IL-4 to treat
patients infected with specific isolates of HIV. The methods include a
method for determining the prognosis of a patient infected with HIV, a
method for down-regulating CCR5 expression in a cell, and methods for
treating patients infected with CCR5 dependent isolate of HIV or CXCR4
dependent isolate of HIV.
Novel FUSE-Binding Protein and cDNA
DL Levens, RC Duncan, MI Avigan (NCI)
U.S. Patent 5,580,760 issued 03 Dec 96; U.S. Patent 5,734,016 issued 31
Mar 98; PCT/US97/21679 filed 21 Nov 97
Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail:
rr154z@nih.gov
This invention includes the gene sequence for a novel proto-
oncogene binding protein that is valuable for studying the regulation
of genes responsible for transforming normal cells to cancer cells. The
c-myc proto-oncogene plays a central role in normal cell proliferation
and programmed cell death; factors that inhibit its expression thus
contribute to the formation of a variety of tumors. This newly isolated
gene sequence encodes a protein that binds to the far-upstream element
(FUSE) of the c-myc gene, which has been shown to be required to its
maximal transcription. The FUSE-binding protein gene sequence may be
used to analyze mutations, translocations, and other genetic
derangements that are associated with abnormalities of the FUSE protein
or c-myc expression. Such DNA probes also may be useful for diagnosing
a variety of physiologic and pathologic
[[Page 3530]]
conditions, such as the transformation of normal cells to tumor cells.
The FUSE-binding protein also may be used for developing mAbs that can
be used to detect and quantitate the protein in biologic samples.
Fluorescent Hybridization Probes not Requiring Separation of
Products
ME Hawkins, W Pfleiderer, MD Davis, FM Balis (NCI)
U.S. Patent 5,525,711 issued 11 Jun 96; U.S. Patent 5,612,468 issued 18
Mar 97; DHHS Reference No. E-155-96/1;
PCT/US97/22448 filed 10 Dec 97
Licensing Contact: L. Manja R. Blazer; 301/496-7056 ext. 224; e-mail:
mb379c@nih.gov
Fluorescent guanosine analogs (excitation at 340 nm, emission at
450 nm) are incorporated into oligonucleotides through a native
deoxyribose linkage using automated DNA synthesis which allows them to
base stack with native bases. As a result, slight changes in DNA
structure can cause significant changes in spectral properties. These
compounds are highly fluorescent as monomers in solution, but lose
intensity in oligonucleotides. The use of these fluorophores as hairpin
hybridization probes is based on the dramatic fluorescence increase
that occurs upon them being squeezed out of the strand during annealing
where the probe has not been provided with a base-pairing partner in
the complementary strand. The degree of increase depends on the
oligonucleotide sequence and the annealing strands' concentration. It
allows the detection of specific DNA sequences in a mixture without
separation of annealed and labeled products. These stable probes are
treated as normal phosphoramidites during the DNA synthesis and
subsequent de-blocking procedures.
This research has been published in Nucleic Acids Research, 23
(1995) 2872-2880 and Analytical Biochemistry, 244 (1997) 86-95.
Dated: January 13, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer.
[FR Doc. 99-1424 Filed 1-21-99; 8:45 am]
BILLING CODE 4140-01-M
