[Federal Register Volume 64, Number 37 (Thursday, February 25, 1999)]
[Notices]
[Pages 9338-9339]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-4659]
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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 contacting Richard U.
Rodriguez, M.B.A., at the Office of Technology Transfer, National
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville,
Maryland 20852-3804; telephone: 301/496-7056 ext. 287; fax: 301/402-
0220; e-mail: rr154z@nih.gov. A signed Confidential Disclosure
Agreement will be required to receive copies of the patent
applications.
Use Of Calreticulin And Calreticulin Fragments To Inhibit
Endothelial Cell Growth And Angiogenesis, And Suppress Tumor Growth
G Tosato, SE Pike (FDA), DHHS Reference No. E-082-98/0 filed 06 Oct. 98
Tumor growth and invasion into normal tissues is dependent upon an
adequate blood supply, and agents that target tumor blood supply have
been shown to prevent or delay tumor formation and to promote the
regression or dormancy of established tumors in preclinical models. It
has been shown that EBV-immortalized cell lines can promote regression
of experimental Burkitt's lymphoma, colon carcinoma and other human
malignancies established in athymic mice through a vascular-based
process. The inventors analyzed the cultured-media from EBV-
immortalized cells and isolated a unique and potent factor which
inhibits angiogenesis and tumor cell growth. This novel compound was
named vasostatin. Vasostatin is an NH2-terminal fragment of
human calreticulin, and it can inhibit endothelial cell proliferation
in vitro, suppress neovascularization in vivo and prevent or reduce
growth of experimental tumors while having minimal effect on other cell
types. Vasostatin is the most conserved domain among calrecticulins so
far cloned and has no homology to other protein sequences. Data
suggests that the antitumor effects of vasostatin are related to
inhibition of new vessel formation rather than to a toxic effect on
established tumor vascular structures. Vasostatin has key differences
from other inhibitors of angiogenesis. It is small and soluble, and it
is stable for greater than 19 months in aqueous solution. It is easily
produced and delivered. By comparison, angiostatin, endostatin and
thrombospondin can be difficult to isolate, purify and deliver.
Additionally, studies have shown that the effective dose of vasostatin
is 4-10 fold lower than the effective doses of endostatin and
angiostatin. Therefore, this new and potent anti-angiogenic molecule
should prove highly useful for the prevention and treatment of human
cancers.
Polynucleotide Inhibition Of RNA Destabilization And Sequestration
DJ Lipman (NLM)
DHHS Reference No. 3-130-97/1 filed 19 Aug 98; PCT/US98/17261
A variety of mechanisms are available in eukaryotic cells for
regulating gene expression such that each gene product is produced at
appropriate times and in appropriate quantities. It is well established
that a significant amount of control over gene expression can be
exerted at the level of RNA processing and RNA stability. Evidence
exists that suggests a role for antisense RNA transcripts
(countertranscripts) in RNA destabilization and nuclear sequestration
which promotes down-regulation of protein expression.
Countertranscript-RNAs are encoded by the complementary-strand of a
gene, and they are sometimes found in different tissues or
developmental stages than their corresponding sense or transcript-RNAs,
and these different expression patterns yield different gene-product
expression patterns. Therefore, transcript-countertranscript complexes
can play a critical role in the degradation and sequestration of RNAs
and thus affect protein expression. The disclosed invention provides a
means whereby defined polynucleotides can be introduced into a cell or
tissue in order to prevent transcript-countertranscript interactions
and thereby inhibit this degradation and nuclear sequestration of
transcript RNA. This methodology could enhance the expression of a
target gene-product encoded by a transcript-RNA by preventing
transcript-countertranscript association. The polynucleotides
themselves can be introduced or expression vectors can be created
containing the polynucleotide sequence in order to express the defined
polynucleotides in the cells or tissue of choice. These polynucleotides
can also be used in in vivo and ex vivo regimens. As an example, these
polynucleotides could be used to treat tumorigenic cells in such a way
as to promote the expression of known apoptotic proteins whereby the
tumorigenic cells are selectively killed. In summary, this technology
could be used in any number of applications where the promotion of the
expression of a particular gene-product is desirable.
Labeling DNA Plasmids With Triplex-Forming Oligonucleotides and
Methods for Assaying Distribution of DNA Plasmids in Vivo
IG Panyutin, RD Neumann, O Sedelnikova (CC), DHHS Reference No. E-
142-98/0 filed 26 May 98.
Monitoring the intracellular distribution of circular plasmids that
have been introduced into cells is problematic because labeling
moieties are not readily attached to covalently closed circular DNA
molecules. Monitoring the biodistribution of DNA vectors that are
introduced into a host animal, e.g., to determine the efficiency of
transfection of target tissues in developing a method for gene therapy,
[[Page 9339]]
is also problematic because commonly used assays based on detecting
marker gene expression do not provide accurate biodistribution data due
to failure to obtain a signal in those tissues in which the marker gene
is not expressed. This invention obviates these deficiencies by
disclosing the use of triplex-forming-oligonucleotides (TFO) which bind
to their target sequences in circular plasmid DNA and thereby creating
stable readily detectable triplex-complexes when introduced into living
eukaryotic cells. These fluorescent or radio-labled polypurine TFOs can
provide a noninvasive way to study the biodistribution of a plasmid of
interest in vivo using tools developed for probe detection and
radioimaging. In summary, this technology allows one to quantitatively
monitor the whole-body distribution of labeled-vectors in living
animals or patients.
Extension of a Protein-Protein Interaction Surface To Inactivate
the Function of a Cellular Protein
CR Vinson, D Krylov (NCI), DHHS Reference No. E-113-95/1 filed 29
May 96, Related cases: Serial No. 08/690,111 filed 31 Jul 96; PCT/US96/
12590 filed 31 Jul 96.
This invention uses sequence-specific DNA binding proteins as
eukaryotic transcription factors, i.e., transcription regulatory
proteins. Specifically, multimeric proteins having nucleic acid (DNA or
RNA) binding domains in which the binding domain or protein interaction
surface is engineered or modified to be acidic in nature. The acidic
nature of the protein increases the stability of heteromultimeric or
heterodimeric complexes that are formed. This type of nucleic acid
binding protein should be capable of regulating the function of a
target nucleic acid sequence or gene to which it is bound, thereby
acting as a potent dominant-negative regulator of gene transcription,
cell growth and cell proliferation. These proteins would be useful as
drugs, inhibitory molecules or growth-controlling agents that can
inhibit the expression,and thus the activity, of cellular proteins
which have harmful, deleterious and even lethal effects on cell growth
and survival. These proteins could also be used in gene therapy by
using appropriate constructs to allow expression of a regulatory
protein to treat suitable disease states. The constructs could also be
used to create transgenic animals or plants in which the dominant-
negative protein interacts with the wild-type protein to provide viable
phenotypes to evaluate and assess the in vivo effects of the protein.
In summary, this technology provides for useful tools and therapeutics
which are capable of regulating specific target gene expression and
gene-product activity.
Dated: February 16, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer.
[FR Doc. 99-4659 Filed 2-24-99; 8:45 am]
BILLING CODE 4140-01-M
