[Federal Register Volume 63, Number 176 (Friday, September 11, 1998)]
[Notices]
[Pages 48738-48740]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24368]
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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.
LIF And Related Cytokines That Operate Through The gp130 Receptor
Pathway As A Means To Enhancing Embryo Implantation In Mammals And
As An Alternative To Using Estrogen
CL Stewart, T Shatzer, T Sullivan, JR Chen, L Hernandez (NCI)
DDHS Reference No. E-166-98/0 filed 06 Jul 98
Licensing Contact: Dennis Penn, 301/496-7056 ext. 211
The present invention is directed to the use of Leukemia Inhibitory
Factor (LIF), or certain other cytokines as a means for enhancing
successful embryo implantation. This discovery may lead to increased
success rates in normal embryonic development in human and non-human
embryos following in vitro fertilization. The present invention, tested
in LIF deficient mice, confirms that single injections of LIF lead to
implantation and the embryo's normal development to birth. LIF may be
useful as a replacement for estrogen in inducing embryo implantation.
The invention indicates that LIF can substitute for estrogen in animal
models, in regulating the receptibility of the uterus to the implanting
embryo, and results in a significant increase in successful
implantation. This technology has both human and veterinary
applications.
Protection Of Neural Cells From Catecholamine-Induced Apoptosis By
Macrophage Migration Inhibitory Factor (MIF)
G Wistow (NEI)
DDHS Reference No. E-028-98/0 filed 28 Jul 98
Licensing Contact: Stephen Finley, 301/496-7735 ext. 215
Macrophage Migration Inhibitory Factor (MIF) was shown to have
neuroprotective properties with important implications for conditions
such as Parkinson's Disease (PD). MIF is widely distributed in
mammalian tissues. However, in vivo studies show that while the levels
of MIF expression significantly decrease with age in most tissues,
including lens, liver and kidney, it is maintained at high levels in
neural tissues, brain and retina. This suggests the possibility of an
important role for MIF in aging neural tissues. It was also shown that
MIF has catalytic enzyme activity towards the toxic
quinonesdopaminechrome (DNC), epinephrinechrome (EC) and
noreprinephrine (NEC) which arises by oxidation of the catecholamine
neurotransmitters dopamine, epinephrine and norepinephrine. These
catecholamines induce cell death by apoptosis in cultured neural cells
and other cell types. It was shown that in cell culture, MIF can block
this catecholamine-induced cell death. Death of catecholaminergic
neurons is an important feature of PD in human brain. This suggests a
physiological and/or therapeutic role for MIF in protection of neural
and other cells from apoptosis induced by toxic quinones. Decreased
levels of MIF in the aging brain may be a risk factor for PD and
similar neurodegenerative disorders. MIF may also be involved in the
synthesis of neuromelanin, which is prominent in the aging human
substantia nigra, since the guinones DNC, EC and NEC are known
neuromelanin precursors.
A surprising additional property of MIF was also observed. Lens
epithelial cell cultures differentiated into neuronlike cells,
containing neuronal cell markers, axons, and processes, upon the
constitutive expression of endogenous recombinant MIF. Thus, in
addition to its neuroprotective properties, MIF has potential to
contribute to culture methods for neural cells that may be useful in
transplantation.
G-Protein Coupled Receptor Antagonists
N Tarasova, SJ Michejda (NCI)
Serial No. 60/076,105 filed 27 Feb 98
Licensing Contact: Carol Salata, 301/496-7735 ext. 232
This invention is a potentially broadly applicable method of
disrupting the functioning of G-protein coupled receptors (GPCR). GPCRs
are a large familly of receptors involved in the regulation of
physiological activities. GPCRs have seven transmembrane regions, i.e.
they cross the cell membrane seven times. The inventors have found that
if a peptide consisting of one of the transmembrane regions of a GPCR
with an added charged amino acid on the extracellular side, is brought
into contact with a cell having the same GPCR, the functioning of the
GPCR is disrupted. It is thought that the added peptide interferes with
the correct assembly of the GPCR. Cells containing
[[Page 48739]]
the CXCR4 receptor, a co-receptor with CD4 for the entry of certain
strains of HIV-1 into T-cells, are much less receptive to infection by
HIV in the presence of a particular transmembrane peptide from the
CXCR4 receptor. Therefore, this method of disrupting the functioning of
particular GPCRs could be used to treat diseases which are mediated by
functioning GPCRs, such as HIV.
Inhibition of HFG/SF Cleavage/Activation by Suramin and Other
Related Small Molecules
C Webb, ME Jeffers, G Czerwinski, CJ Michejda,
GF Vande Woude (NCI)
Serial No. 60/075,994 filed 26 Feb 98
Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284
HGF/SF, which is the ligand for the tyrosine kinase receptor
encoded by the c-Met proto-oncogene, is involved in tumor
establishment, progression and metastasis. HGF/SF is synthesized as a
90 kDa single chain precursor polypeptide (pro-HGF/SF) which is devoid
of biological activity. The critical step in HGF/SF activition is
proteolytic cleavage generating an heterodimer in which an
chain of 60 kDa and a chain of 32-36 kDa are bound
to one another by a disulfide bridge. The cleavage/activation of pro-
HGF/SF represents the initial stage of HGF/SF-met activation and
provides a possible point for interference by potential inhibitors.
This invention is based on the discovery that suramin and related
polysulfonated compounds inhibit cleavage of pro-HGF/SF. The invention
provides an efficient assay for identifying inhiitors of HGF/SF
activation. The invention also describes suramin-like compounds that
can be used to inhibit HGF/SF activation, thereby inhibiting tumor
growth and metastasis. These compounds are less toxic than comparable
molecules.
Vaccines For Blocking Transmission of Plasmodium vivax
DC Kaslow, T Tsuboi, M. Torii (NIAID)
Serial No. 60/067,596 filed 05 Dec 97
Licensing Contact: Carol Salata, 301/496-7735 ext. 232
This invention relates to novel methods and compositions for
blocking transmission of Plasmodium vivax which cause malaria. In
particular, Pvs25 and Pvs28 polypeptides, variants and fusion proteins
thereof, are disclosed which, when administered to a susceptible
organism, induce an immune response against a 25 kD and 28 kD protein,
respectively, on the surface of Plasmodium vivax zygotes and ookinetes.
This immune response in the susceptible organism can block transmission
of malaria.
Stromal Cell Derived Factor-1 (SDF-1) And Method of Use For
Diagnostic And Prognostic Indicator Or AIDS Pathogenesis
C. Winkler, S O' Brien (NCI)
Serial No. 60.063,832 filed 30 Oct 97
Licensing Contact: Carol Salata, 301/496-7735 ext. 232
Stromal cell derived factor-1 (SDF-1) is the principal ligand for
CXCR4 (a 7-transmembrane G/coupled receptor) which, with CD4, provides
an entry port for T-tropic HIV-1, a variety that frequently develops in
AIDS patients just prior to T-lymphocyte depletion. This invention is
based on the discovery of a correlation between the presence of a
mutation at one nucleotide position of the 3'untranslated region of the
SDF1 gene and delayed progression to AIDS and death due to HIV
infection. Based on this discovery, it is the object of the present
invention to provide diagnostic and therapeutic approaches to treating
HIV infection by diagnosing the mutation and down regulating the CXCR4
receptor with native or synthetic SDF-1.
Recominant Adenoviral Targeting Vector
SE Spence, JR Keller, JS Smith (NCI)
Serial No. 60/061,587 filed 10 Oct 97
Licensing Contact: Elaine Gese, 301/496-7056 ext. 282
The current invention embodies recombinant adenoviral vectors for
use in targeted gene transfer. The method by which these vectors are
generated involves no molecular modifications to the adenovirus genome,
and allows for the production of vectors targeted specifically to
virtually any cell line of choice. Specifically, the vectors are
generated by directly linking biotin to the capsid of advenovirus
particles. The particles are then treated with streptavidin and
subsequently incubated with a biotinylated targeting moiety which is
capable of recognizing a specific marker which is expressed on the
surface of selected cells.
The resulting adenoviral vectors would appear to be of value for
use in gene transfer, and can be targeted to virtually any cell type of
interest via incubation with a specific targeting moiety.
To date, the inventors have demonstrated that these vectors can be
specifically directed to target and infect hematopoietic cell lines
which display the c-kit receptor, and are capable of achieving high
levels of expression in these cell lines. Also, these vectors can be
specifically directed to cell surface markers such as CD34, CD 44 and
others through antibodies directly attached to the biotynilated
adenoviral vectors. Such gene transfer may represent a potential means
by which various diseases, including immunodeficiency diseases, blood
cell disorders, AIDS, and various cancers, could be treated. Therefore,
the current invention appears to represent a novel gene therapy
approach upon which the development of specific therapies against a
broad range of diseases may be based.
Recombinant Proteins of a Pakistani Strain of Hepatitis E and Their
Use in Diagnostic Methods and Vaccines
SA Tsarev, SU Emerson, RH Purcell (NIAID)
Serial No. 08/809,523 filed 28 Jun 97; PCT filed
Licensing Contact: Carol Salata, 301/496-7735, ext. 232
A strain of hepatitis E virus from Pakistan (SAR-55) implicated in
an epidemic of enterically transmitted non-A, non-B hepatitis, now
called hepatitis E, is disclosed. The invention relates to the
expression of the whole structural region of SAR-55, designated open
reading frame 2 (ORF-2), in a eukaryotic expression system. The
expressed protein is capable of forming HEV virus-like particles which
can serve as an antigen in diagnostic immunoassays and as an immunogen
or vaccine to protect against infection by hepatitis E.
Chimeric Gag Pseudovirions
GJ Tobin, MA Gonda (NCI)
Serial No. 08/857,385 filed 15 May 97
Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264
The human immunodeficiency virus (HIV) is the causative agent of
acquired immunodeficiency syndrome (AIDS). The HIV virion basically
consists of a viral core and envelope. The core consists predominantly
of gag- and pol- encoded proteins and the viral RNA. Expression of
recombinant Gag precursor proteins can lead to assembly and budding of
virus-like particles (pseudovirions). The production of Gag-based
pseudovirions in mammalian and insect cell systems using recombinant
virus vectors provides a novel technology for engineering recombinant
protein-based particulate vaccines for HIV and other viruses. The
incorporation of additional viral or cellular, peptides and
polypeptides may be advantageous in vaccine
[[Page 48740]]
preparations, since they may contain antigenic epitopes that may play a
role in inducing protection from infection or disease.
The subject invention provides chimeric nucleic acids comprising a
retroviral gag sequence, a target nucleic acid sequence derived from a
nucleic acid encoding a fusion partner, and a frame shift site.
Expression of the chimeric gene cassette results in packaging the
fusion partner into the Gag pseudovirion. Suitable fusion partners can
be derived from any protein of interest which has a biological activity
or which elicits a cellular or humoral immune response.
Method For Measuring Mechanical Properties of the Collagen Network
in Cartilage
PJ Basser, A Maroudas (NICHD)
Serial No. 60/038,005 filed 14 Feb 97; PCT/US98/02727 filed 17 Mar 98
Licensing Contact: John Fahner-Vihtelic, 301/496-7735 ext. 270
The present application describes a methodology for assessing the
mechanical integrity of extracellular matrices such as cartilage.
Specifically, the invention teaches how to characterize the mechanical
integrity of the collagen network as well as the swelling properties of
the proteoglycans trapped within it. This is done by performing an
osmotic stress titration experiment on a tissue specimen, and
interpreting the results using a simple mathematical model. This
invention provides the necessary experimental and theoretical tools to
understand functional consequences of: (1) endogenous changes in
cartilage structure that occur normally due to growth or aging; (2)
exogenous changes in cartilage structure due to the addition of
biochemical agents or caused by genetic manipulations; and (3) inherent
differences between cartilage specimens that are obtained from
different joints within the same subject or from different subjects.
These methods can also be applied to characterize the mechanical
integrity of tissue cultured or ``tissue engineered'' cartilage.
Vectors for Delivering Viral and Oncogenic Inhibitors
SM Rybak, A Cara, GL Gusella, DL Newton (NCI)
Serial No. 60/022,052 filed 22 Jul 96; PCT/US97/12637 filed 17 Jul 97
Licensing Contact: Carol Salata, 301/496-7735, ext. 232
The invention concerns cell transduction vectors which are capable
of inhibiting viral replication in cells transduced with these vectors,
and which also are capable of inhibiting the growth of cancer cells.
Specifically, these expressions vectors produce protective genes which
interfere with viral replication. These genes are tightly regulated by
HIV-1 Tat and Rev proteins, which if produced after infection can
induce expression of the protective genes. The vectors contain either a
single gene (delta-gag), or a combination of two different genes
(delta-gag and RNAse) which interfere with HIV-1 replication at
different stages of the HIV-1 life cycle. Following transduction of
target cells, the mRNA for the protective genes is incorporated into
the newly budding virion along with the viral genomic mRNA. Following
infection of neighboring cells, the mRNA for the protective gene can be
reverse transcribed and integrated into these cells, thereby increasing
the proportion of cells containing the protective gene.
In providing protection against viral replication, the vectors
embodied in this invention could be used in gene therapy against HIV
and against other viral diseases. In addition, the vectors could be
used for introducing specific genes into neoplastic cells and thereby
be effective in treating cancer and other diseases.
Anti-Viral Pharmaceutical Compositions Containing 1,2-Dithiane
Compounds and Methods of Using Thereof
WG Rice, R Schultz, D Baker, LE Henderson (NCI)
Serial No. 60/021,665 filed 05 July 96; PCT/US97/10870 filed 03 Jul 97
Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264
Certain highly conserved structures, known as retroviral-type CCHC
zinc fingers, are found in the nucleocapsid proteins of all
retroviruses, including HIV-1 and HIV-2. It is known that these zinc
finger structures perform essential functions in viral infection and
replication.
The subject invention provides for pharmaceutical compositions
comprising dithiane dioxide compounds which are useful as antiviral
agents and are particularly effective at inhibiting the replication of
retroviruses and for treating retroviral pathologies. The 1,2-dithiane
compounds target the zinc fingers of the nucleocapsid protein. These
compositions represent potential agents for prevention and treatment of
HIV and of other retroviral diseases. The subject invention also
embodies methods for the administration of these compositions, a kit
containing these compositions, and methods for the inactivation of
contaminating retrovirus in samples of potentially infected body
fluids.
Dated: September 3, 1998.
Jack Spiegel,
Diretor, Division of Technology Development and Transfer, Office of
Technology Transfer.
[FR Doc. 98-24368 Filed 9-10-98; 8:45 am]
BILLING CODE 4140-01-M
