[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]



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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: 
[email protected]

    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: 
[email protected]

    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: 
[email protected].

    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: 
[email protected]

    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

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Licensing Conact: Peter Soukas; 301/496-7056 ext. 268; e-mail: 
[email protected]

    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: 
[email protected]

    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: 
[email protected]

    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: 
[email protected]

    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: 
[email protected]

    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: 
[email protected]

    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: 
[email protected]

    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