Government-Owned Inventions; Availability for Licensing, 26402-26404 [E7-8893]
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26402
Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
SUMMARY: The inventions listed below
are owned by an agency 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.
sroberts on PROD1PC70 with NOTICES
Selenocysteine Mediated Hybrid
Antibody Molecules
Description of Technology: Available
for licensing is a new class of hybrid
molecules composed of an antibody, or
antibody fragment, and a small
synthetic molecule (such as a small
molecule inhibitor, or cytotoxic
compound). These biological and
chemical components are covalently
linked at an engineered selenocysteine
near the C-terminus of the antibody, or
antibody fragment. Through this
covalent linkage, the chemical and the
biological component can acquire
properties of one another. For example,
the synthetic molecule acquires
antibody properties such as circulatory
half-life, effector functions, and ability
to interfere with protein interactions
whereas the antibody, or antibody
fragment, acquires properties of the
small synthetic molecule such as
specificity, affinity, and stability to bind
to targets that are sterically inaccessible
to immunoglobulins. The technology
can also be used to equip an antibody,
or antibody fragment, with a small
synthetic molecule that enhances target
destruction or imaging capabilities
through site-selective biotinylation,
PEGylation, addition of an imaging
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agent, or addition of a cytotoxic agent
such as a chemotherapeutic drug or a
chelate for radioisotope labeling. The
hybrid antibody molecules can be
engineered with a variety of small
synthetic molecules, and the
combination of immunogenic properties
and those of the small synthetic
molecules results in compounds with
powerful target destruction or imaging
capabilities. This technology could be
applied towards the targeted delivery of
small synthetic molecules to various
cell surface receptors, and may have
applicability as a prevention, diagnosis,
or therapy for numerous disease states.
Applications: Potent novel
compositions that retains immunogenic
properties and those of small synthetic
molecules that can be produced at a
large scale; Method to prevent,
diagnose, and treat cancer, infectious
diseases and autoimmune diseases.
Market: Monoclonal antibody market
is projected to exceed $30 billion by
2010; Revenue from antibodies for
therapeutics and diagnostic uses are
expected to grow at an average annual
growth rate of 11.5%.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Christoph Rader et al.
(NCI).
Patent Status: U.S. Provisional
Application No. 60/909,665 filed 02 Apr
2007 (HHS Reference No. E–146–2007/
0–US–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Jennifer Wong;
301/435–4633; wongje@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute, Center for
Cancer Research, Experimental
Transplantation and Immunology
Branch, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize Selenocysteine Mediated
Hybrid Antibody Molecules. Please
contact Dr. Christoph Rader at (301)
451–2235 or raderc@mail.nih.gov for
more information.
chronological lifespan of yeast. These
mutations in addition to a deletion in
the sch9 allele, the yeast homolog to
human kinase AKT, can increase yeast
lifespan from 45 to 57 days,
approximately 20% longer than the
wildtype strain. These genetically
engineered yeast strains may have the
longest chronological lifespan reported
to date.
Applications: Model to study aging
and longevity factors; Model to screen
compounds that affect lifespan; A longlived yeast strain could be used to
ferment alcohol in a more efficient and
cost effective as an alternative fuel
source; Method to extend lifespan of
transgenic farm animals.
Market: Anti-aging and alternative
fuel industries are worth billions of
dollars.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Bradley T. Scroggins (NCI)
et al.
Related Publication: BT Scroggins et
al. An acetylation site in the middle
domain of Hsp90 regulates chaperone
function. Mol Cell. 2007 Jan
12;25(1):151–159.
Patent Status: U.S. Provisional
Application No. 60/848,346 filed 09 Sep
2006 (HHS Reference No. E–319–2006/
0–US–01).
Licensing Status: Available for nonexclusive licensing.
Licensing Contact: Jennifer Wong;
301/435–4633; wongje@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute’s Urologic
Oncology Branch is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize models to study aging
and longevity factors. Please contact
John D. Hewes, Ph.D. at 301–435–3121
or hewesj@mail.nih.gov for more
information.
Inhibitors of Ubiquitin E1
Description of Technology: The
present invention discloses novel
pyrazolidinyl compounds that inhibit
undesired cell proliferation. The
Mutant Alleles of Hsp90 that Modulates compounds inhibit ubiquitin E1 and can
the Lifespan of Yeast
be useful for regulating protein
Description of Technology: Heat shock ubiquitination. Specifically, the novel
pyrazolidinyl compounds can stabilize
protein 90 (Hsp90) are a class of
chaperone proteins that are up-regulated p53 and induce apoptosis in
in response to elevated temperature and mammalian cells through selective
inhibition of ubiquitin E1.
other environmental stresses. They act
Ubiquitin-mediated proteolysis is an
as chaperones to other cellular proteins
important pathway of non-lysosomal
and facilitate their proper folding and
protein degradation that controls the
repair, and aid in the refolding of
timed destruction of a number of
misfolded client proteins.
cellular regulatory proteins including
This invention identifies Hsp90
p53. The ubiquitin pathway leads to the
mutant residues that affect the
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Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Notices
covalent attachment of poly-ubiquitin
chains to target substrates which are
then degraded by a multi-catalytic
proteosome complex.
The compounds can be useful in the
treatment of solid and disseminated
cancers or other undesired cell
proliferation disease or retroviral
infections such as HIV.
Applications and Modality: Treatment
of disorders related to ubiquitin E1,
such as HIV and viral infections;
Compounds are the first general
inhibitors of Ubiquitin E1 with broader
biological effects than existing
proteosome inhibitors; The compounds
can serve as a probe to understand the
ubiquitin system.
Market: Bortezomib (marketed as
VelcadeTM by Millennium
Pharmaceuticals) is the first therapeutic
proteasome inhibitor approved by the
FDA. Severe side effects such as
peripheral neuropathy occur in 30% of
patients treated with Bortezomib. New
drugs targeting proteins in
ubiquitination pathway are needed that
will have broader efficacy and reduced
side effects.
Development Status: The technology
is in the pre-clinical stage of
development.
Inventors: Allan M. Weissman et al.
(NCI).
Related Publications:
1. A manuscript related to this
technology will be available as soon as
it is accepted for publication.
2. Y Yang et al. Small molecule
inhibitors of HDM2 ubiquitin ligase
activity stabilize and activate p53 in
cells. Cancer Cell. 2005 Jun;7(6):547–
559.
Patent Status: U.S. Provisional
Application No. 60/738,242 filed 19
Nov 2005, entitled ‘‘Inhibitors of
Ubiquitin E1’’ (HHS Reference No. E–
070–2005/0–US–01); International
Patent Application No. PCT/US2006/
0045032 filed 20 Nov 2006, entitled
‘‘Inhibitors of Ubiquitin E1’’ (HHS
Reference No. E–070–2005/0–PCT–02)
Licensing Status: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Thomas P. Clouse;
301/435–4076; clousetp@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute’s
Laboratory of Protein Dynamics and
Signaling is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize inhibitors of ubiquitin
E1. Please contact John D. Hewes, Ph.D.
at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
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Biomarkers for Tissue Status
Description of Technology: Tissue
regeneration and tumorigenesis are
complex, adaptive processes controlled
by cues from the tissue
microenvironment. There are complex
processes both characterized by cell
proliferation, migration, and
angiogenesis suggesting that wounds
and cancer share a number of
phenotypic similarities including
cellular behavior, signaling molecules,
and gene expression.
Utilizing the kidneys as a model to
compare renal regeneration and repair
(RRR) from ischemically-injured tissues
and renal cellular carcinoma (RCC), the
inventors have identified biomarkers
which are differentially expressed. The
invention relates to methods of quickly
and accurately diagnosing RCC and
monitoring renal tissue health as well as
RCC treatment.
Applications: Method to accurately
diagnose RCC; RCC biomarker inhibitors
such siRNA; Method to treat RCC;
Method to determine and monitor renal
tissue health status; Method for
improving renal ischemia recovery
without promoting RCC; Biomarkers for
immunotherapy, drug targeting and
drug screening, for targeting tumors and
not normal regenerating tissue;
Biomarkers for immunotherapy, drug
targeting and drug screening, for
targeting ischemic tissue and not
tumors.
Market: Kidney cancer is one of the
top ten most prevalent cancers in the
U.S. and it accounts for 12,200 deaths
annually; Approximately 35,000 new
cases of kidney cancer are diagnosed
annually; 50% survival rate after five
years of diagnosis; Renal cancer
accounts for 3% of all adult male
malignancies.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Joseph Riss (NCI) et al.
Publications:
1. Journal of Urology, May 2007, Vol.
177 No. 5, in press.
2. J Riss et al. Cancers as wounds that
do not heal: differences and similarities
between renal regeneration/repair and
renal cell carcinoma. Cancer Res. 2006
July 15;66(14):7216–7224.
Patent Status: U.S. Provisional
Application No. 60/649,208 filed 01 Feb
2005 (HHS Reference No. E–064–2005/
0–US–01); PCT Application No. PCT/
US2006/003611 filed 01 Feb 2006 (HHS
Reference No. E–064–2005/0–PCT–02).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Jennifer Wong;
301/435–4633; wongje@mail.nih.gov.
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Collaborative Research Opportunity:
The National Cancer Institute, Center for
Cancer Research, Laboratory of Cancer
Biology and Genetics, Wound Healing
and Oncogenesis (NCI/CCR/LCBG), is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
topics of invention or related to cancer
biology, metastasis, wound healing,
bioinformatics, pharmacogenomics and
therapeutic. Please contact John D.
Hewes, Ph.D. at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
New Maleiimide Anti-Phosphatase
Inhibitors
Description of Technology: The
present invention describes novel
phenyl maleiimide phosphatase
inhibitors that appear to target the
Cdc25 family of phosphatases. The new
compounds are inhibitors of several
human tumor cell lines. The
compounds have potent activity against
human liver cancer cells in vitro and in
vivo against an orthotopic liver cancer
in rats. In tumor cells, these new
inhibitors appear to target the
phosphorylation status of several cell
cycle proteins that are important for cell
survival and thus could represent a
novel class of chemotherapeutic agents
targeting cancer cells.
Applications and Modality:
Compound targets Cdc25 family of
phosphatases and inhibit growth of
several human tumor cell lines; Potent
activity in vitro against human liver
cancer cells and in vivo against
orthotopic liver cancer in rats; Targets
phosphorylation of cell cycle proteins
important for cell survival.
Market: 600,000 deaths from cancer
related diseases were estimated in 2006;
In 2006, cancer drug sales were
estimated to be $25 billion.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Christopher Michejda (NCI)
et al.
Relevant Publication: S Kar, M Wang,
W Yao, CJ Michejda, BI Carr. PM–20, A
novel inhibitor of Cdc25A, induces
extracellular signal-regulated kinase 1/2
phosphorylation and inhibits
hepatocellular carcinoma growth in
vitro and in vivo. Mol Cancer Ther.
2006 Jun;5(6):1511–1519.
Patent Status: PCT Patent Application
No. PCT/US2005/05742 filed 22 Feb
2005, which published as WO 2005/
081972 on 09 Sep 2005 (HHS Reference
No. E–110–2004/0–PCT–02); U.S. Patent
Application No. 11/508,605 filed 22
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26404
Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Notices
Aug 2006 (HHS Ref. No. E–110–2004/0–
US–06).
Licensing Status: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Adaku
Nwachukwu, J.D.; 301/435–5560;
madua@mail.nih.gov.
Leu574 of HIF–1alpha as a Molecular
Basis for Therapeutic Application
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Description of Technology: The
hypoxia-inducible factor 1 (HIF–1) is a
transcription factor that plays a pivotal
role in cellular adaptation to oxygen
availability. HIF–1alpha protein is a
subunit of HIF–1. Although the gene for
HIF–1alpha is constitutively expressed,
it is an extremely short-lived protein
under normoxic conditions and is
targeted for destruction via the
proteosome pathway by an E3 ubiquitin
ligase involving the VHL protein.
The invention relates to the discovery
that mutations or deletions of Leu574
result in a more stable and more active
form of HIF–1alpha. Therefore, the
invention relates to methods and
compositions for modulating oxygen
homeostasis for therapeutic application.
In one aspect, the inventors contemplate
the use of a more stable form of HIF–
1alpha protein for therapeutic
angiogenesis purposes such as may be
useful in ischemic vascular disease. In
another aspect, the inventors
contemplate the use of this particular
site in a screen for targeted drugs that
modulates HIF–1alpha activity. The
inventors also suggest that Leu574 could
be used for developing drugs targeted to
HIF hydroxylase binding, thereby
altering HIF–1alpha stability.
Inventor: L. Eric Huang (NCI).
Patent Status: U.S. Patent No.
7,193,053 issued 20 Mar 2007 (HHS
Reference No. E–281–2002/0–US–02).
Licensing Status: This technology is
available for licensing on an exclusive
or a non-exclusive basis.
Licensing Contact: Jesse S. Kindra,
J.D.; 301/435–5559;
kindraj@mail.nih.gov.
Dated: April 30, 3007.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer,Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E7–8893 Filed 5–8–07; 8:45 am]
BILLING CODE 4140–01–P
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Jkt 211001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
SUMMARY: The inventions listed below
are owned by an agency 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.
New Compounds and Methods for the
Treatment of Spinal Muscular Atrophy
and Other Diseases
Description of Technology: Spinal
muscular atrophy (SMA) is caused by
mutations in the SMN1 gene that result
in reduced expression of the survival
motor neuron (SMN) protein and a loss
of spinal motor neurons. An SMN2 gene
paralog that differs from SMN by a
single base pair has inadequate
expression of SMN to support motor
neuron survival. Alternative splicing
caused by the single base substitution in
the SMN2 gene results in a slightly
truncated and highly unstable SMN
protein. Drugs that allow translational
read through of the stop codons
introduced by the alternative splice
event have been shown to stabilize the
mutant protein, resulting in increased
levels of SMN.
A chemical library screen identified
indoprofen, a nonsteroidal antiinflammatory drug, as an inducer of
SMN expression in cultured cells.
However, indoprofen cannot enter the
brain in satisfactory amounts, has a
relatively low level of activity and can
cause substantial side-effects in part due
to its cyclooxygenase inhibitory activity.
NIH inventors designed indoprofen
derivatives without cyclooxygenase
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activity that can enter the CNS and
increase expression of a SMN protein
from the SMN2 gene with increased
potency and efficacy. The mechanism of
action of these indoprofen analogs
appears to be translational readthrough
of stop codons introduced by the
alternative SMN2 splicing event. In
addition to treating SMA, novel drugs
that allow read through of stop codons
could potentially treat many other
diseases caused by such mutations such
as cystic fibrosis and muscular
dystrophy.
Available for licensing are
compounds and methods useful for the
treatment of spinal muscular atrophy by
increasing SMN expression and
increasing the expression from any
nucleic acid that encodes a translational
stop codon.
Applications: Efficacious treatment
for SMA, utilizing indoprofen analogs
that increase SMN protein expression;
Treatment of any genetic disease caused
by premature termination of protein
translation.
Market: SMA is a rare genetic disease
that affects approximately 1 in 6,000
live births, and is the leading genetic
cause of death in infants and toddlers.
The projected market size for SMA is
between $250 million and $750 million.
Development Status: Clinical
candidate selection scheduled for June
2007.
Inventors: Jill Heemskerk (NINDS), et
al.
Publication: MR Lunn, DE Root, AM
Martino, SP Flaherty, BP Kelley, DD
Coovert, AH Burghes, NT Man, GE
Morris, J Zhou, EJ Androphy, CJ
Sumner, BR Stockwell. Indoprofen
upregulates the survival motor neuron
protein through a cyclooxygenaseindependent mechanism. Chem. Biol.
2004 Nov;11(11):1489–1493.
Patent Status: U.S. Provisional
Application No. 60/783,292 filed 17 Mar
2006 (HHS Reference No. E–133–2006/
0-US–01); PCT Application No. PCT/
2007/006772 filed 16 Mar 2007 (HHS
Reference No. E–133–2006/1–PCT–01)
Licensing Availability: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Norbert Pontzer,
J.D., Ph.D.; 301/435–5502;
pontzern@mail.nih.gov.
STAMP, a Novel Cofactor and Possible
Steroid Sparing Agent, Modulates
Steroid-Induced Induction or
Repression of Steroid Receptors
Description of Technology: Steroid
hormones such as androgens,
glucocorticoids, and estrogens are used
in the treatments of many diseases.
They act to regulate many physiological
responses by binding to steroid
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]]>Agencies
[Federal Register Volume 72, Number 89 (Wednesday, May 9, 2007)]
[Notices]
[Pages 26402-26404]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-8893]
[[Page 26402]]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The inventions listed below are owned by an agency 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.
Selenocysteine Mediated Hybrid Antibody Molecules
Description of Technology: Available for licensing is a new class
of hybrid molecules composed of an antibody, or antibody fragment, and
a small synthetic molecule (such as a small molecule inhibitor, or
cytotoxic compound). These biological and chemical components are
covalently linked at an engineered selenocysteine near the C-terminus
of the antibody, or antibody fragment. Through this covalent linkage,
the chemical and the biological component can acquire properties of one
another. For example, the synthetic molecule acquires antibody
properties such as circulatory half-life, effector functions, and
ability to interfere with protein interactions whereas the antibody, or
antibody fragment, acquires properties of the small synthetic molecule
such as specificity, affinity, and stability to bind to targets that
are sterically inaccessible to immunoglobulins. The technology can also
be used to equip an antibody, or antibody fragment, with a small
synthetic molecule that enhances target destruction or imaging
capabilities through site-selective biotinylation, PEGylation, addition
of an imaging agent, or addition of a cytotoxic agent such as a
chemotherapeutic drug or a chelate for radioisotope labeling. The
hybrid antibody molecules can be engineered with a variety of small
synthetic molecules, and the combination of immunogenic properties and
those of the small synthetic molecules results in compounds with
powerful target destruction or imaging capabilities. This technology
could be applied towards the targeted delivery of small synthetic
molecules to various cell surface receptors, and may have applicability
as a prevention, diagnosis, or therapy for numerous disease states.
Applications: Potent novel compositions that retains immunogenic
properties and those of small synthetic molecules that can be produced
at a large scale; Method to prevent, diagnose, and treat cancer,
infectious diseases and autoimmune diseases.
Market: Monoclonal antibody market is projected to exceed $30
billion by 2010; Revenue from antibodies for therapeutics and
diagnostic uses are expected to grow at an average annual growth rate
of 11.5%.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Christoph Rader et al. (NCI).
Patent Status: U.S. Provisional Application No. 60/909,665 filed 02
Apr 2007 (HHS Reference No. E-146-2007/0-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Jennifer Wong; 301/435-4633;
wongje@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Center for Cancer Research, Experimental Transplantation and Immunology
Branch, is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize Selenocysteine Mediated Hybrid Antibody Molecules. Please
contact Dr. Christoph Rader at (301) 451-2235 or raderc@mail.nih.gov
for more information.
Mutant Alleles of Hsp90 that Modulates the Lifespan of Yeast
Description of Technology: Heat shock protein 90 (Hsp90) are a
class of chaperone proteins that are up-regulated in response to
elevated temperature and other environmental stresses. They act as
chaperones to other cellular proteins and facilitate their proper
folding and repair, and aid in the refolding of misfolded client
proteins.
This invention identifies Hsp90 mutant residues that affect the
chronological lifespan of yeast. These mutations in addition to a
deletion in the sch9 allele, the yeast homolog to human kinase AKT, can
increase yeast lifespan from 45 to 57 days, approximately 20% longer
than the wildtype strain. These genetically engineered yeast strains
may have the longest chronological lifespan reported to date.
Applications: Model to study aging and longevity factors; Model to
screen compounds that affect lifespan; A long-lived yeast strain could
be used to ferment alcohol in a more efficient and cost effective as an
alternative fuel source; Method to extend lifespan of transgenic farm
animals.
Market: Anti-aging and alternative fuel industries are worth
billions of dollars.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Bradley T. Scroggins (NCI) et al.
Related Publication: BT Scroggins et al. An acetylation site in the
middle domain of Hsp90 regulates chaperone function. Mol Cell. 2007 Jan
12;25(1):151-159.
Patent Status: U.S. Provisional Application No. 60/848,346 filed 09
Sep 2006 (HHS Reference No. E-319-2006/0-US-01).
Licensing Status: Available for non-exclusive licensing.
Licensing Contact: Jennifer Wong; 301/435-4633;
wongje@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute's
Urologic Oncology Branch is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize models to study aging and longevity
factors. Please contact John D. Hewes, Ph.D. at 301-435-3121 or
hewesj@mail.nih.gov for more information.
Inhibitors of Ubiquitin E1
Description of Technology: The present invention discloses novel
pyrazolidinyl compounds that inhibit undesired cell proliferation. The
compounds inhibit ubiquitin E1 and can be useful for regulating protein
ubiquitination. Specifically, the novel pyrazolidinyl compounds can
stabilize p53 and induce apoptosis in mammalian cells through selective
inhibition of ubiquitin E1.
Ubiquitin-mediated proteolysis is an important pathway of non-
lysosomal protein degradation that controls the timed destruction of a
number of cellular regulatory proteins including p53. The ubiquitin
pathway leads to the
[[Page 26403]]
covalent attachment of poly-ubiquitin chains to target substrates which
are then degraded by a multi-catalytic proteosome complex.
The compounds can be useful in the treatment of solid and
disseminated cancers or other undesired cell proliferation disease or
retroviral infections such as HIV.
Applications and Modality: Treatment of disorders related to
ubiquitin E1, such as HIV and viral infections; Compounds are the first
general inhibitors of Ubiquitin E1 with broader biological effects than
existing proteosome inhibitors; The compounds can serve as a probe to
understand the ubiquitin system.
Market: Bortezomib (marketed as VelcadeTM by Millennium
Pharmaceuticals) is the first therapeutic proteasome inhibitor approved
by the FDA. Severe side effects such as peripheral neuropathy occur in
30% of patients treated with Bortezomib. New drugs targeting proteins
in ubiquitination pathway are needed that will have broader efficacy
and reduced side effects.
Development Status: The technology is in the pre-clinical stage of
development.
Inventors: Allan M. Weissman et al. (NCI).
Related Publications:
1. A manuscript related to this technology will be available as
soon as it is accepted for publication.
2. Y Yang et al. Small molecule inhibitors of HDM2 ubiquitin ligase
activity stabilize and activate p53 in cells. Cancer Cell. 2005
Jun;7(6):547-559.
Patent Status: U.S. Provisional Application No. 60/738,242 filed 19
Nov 2005, entitled ``Inhibitors of Ubiquitin E1'' (HHS Reference No. E-
070-2005/0-US-01); International Patent Application No. PCT/US2006/
0045032 filed 20 Nov 2006, entitled ``Inhibitors of Ubiquitin E1'' (HHS
Reference No. E-070-2005/0-PCT-02)
Licensing Status: Available for exclusive and non-exclusive
licensing.
Licensing Contact: Thomas P. Clouse; 301/435-4076;
clousetp@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute's
Laboratory of Protein Dynamics and Signaling is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize inhibitors of
ubiquitin E1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or
hewesj@mail.nih.gov for more information.
Biomarkers for Tissue Status
Description of Technology: Tissue regeneration and tumorigenesis
are complex, adaptive processes controlled by cues from the tissue
microenvironment. There are complex processes both characterized by
cell proliferation, migration, and angiogenesis suggesting that wounds
and cancer share a number of phenotypic similarities including cellular
behavior, signaling molecules, and gene expression.
Utilizing the kidneys as a model to compare renal regeneration and
repair (RRR) from ischemically-injured tissues and renal cellular
carcinoma (RCC), the inventors have identified biomarkers which are
differentially expressed. The invention relates to methods of quickly
and accurately diagnosing RCC and monitoring renal tissue health as
well as RCC treatment.
Applications: Method to accurately diagnose RCC; RCC biomarker
inhibitors such siRNA; Method to treat RCC; Method to determine and
monitor renal tissue health status; Method for improving renal ischemia
recovery without promoting RCC; Biomarkers for immunotherapy, drug
targeting and drug screening, for targeting tumors and not normal
regenerating tissue; Biomarkers for immunotherapy, drug targeting and
drug screening, for targeting ischemic tissue and not tumors.
Market: Kidney cancer is one of the top ten most prevalent cancers
in the U.S. and it accounts for 12,200 deaths annually; Approximately
35,000 new cases of kidney cancer are diagnosed annually; 50% survival
rate after five years of diagnosis; Renal cancer accounts for 3% of all
adult male malignancies.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Joseph Riss (NCI) et al.
Publications:
1. Journal of Urology, May 2007, Vol. 177 No. 5, in press.
2. J Riss et al. Cancers as wounds that do not heal: differences
and similarities between renal regeneration/repair and renal cell
carcinoma. Cancer Res. 2006 July 15;66(14):7216-7224.
Patent Status: U.S. Provisional Application No. 60/649,208 filed 01
Feb 2005 (HHS Reference No. E-064-2005/0-US-01); PCT Application No.
PCT/US2006/003611 filed 01 Feb 2006 (HHS Reference No. E-064-2005/0-
PCT-02).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Jennifer Wong; 301/435-4633;
wongje@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Center for Cancer Research, Laboratory of Cancer Biology and Genetics,
Wound Healing and Oncogenesis (NCI/CCR/LCBG), is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize topics of
invention or related to cancer biology, metastasis, wound healing,
bioinformatics, pharmacogenomics and therapeutic. Please contact John
D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more
information.
New Maleiimide Anti-Phosphatase Inhibitors
Description of Technology: The present invention describes novel
phenyl maleiimide phosphatase inhibitors that appear to target the
Cdc25 family of phosphatases. The new compounds are inhibitors of
several human tumor cell lines. The compounds have potent activity
against human liver cancer cells in vitro and in vivo against an
orthotopic liver cancer in rats. In tumor cells, these new inhibitors
appear to target the phosphorylation status of several cell cycle
proteins that are important for cell survival and thus could represent
a novel class of chemotherapeutic agents targeting cancer cells.
Applications and Modality: Compound targets Cdc25 family of
phosphatases and inhibit growth of several human tumor cell lines;
Potent activity in vitro against human liver cancer cells and in vivo
against orthotopic liver cancer in rats; Targets phosphorylation of
cell cycle proteins important for cell survival.
Market: 600,000 deaths from cancer related diseases were estimated
in 2006; In 2006, cancer drug sales were estimated to be $25 billion.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Christopher Michejda (NCI) et al.
Relevant Publication: S Kar, M Wang, W Yao, CJ Michejda, BI Carr.
PM-20, A novel inhibitor of Cdc25A, induces extracellular signal-
regulated kinase 1/2 phosphorylation and inhibits hepatocellular
carcinoma growth in vitro and in vivo. Mol Cancer Ther. 2006
Jun;5(6):1511-1519.
Patent Status: PCT Patent Application No. PCT/US2005/05742 filed 22
Feb 2005, which published as WO 2005/081972 on 09 Sep 2005 (HHS
Reference No. E-110-2004/0-PCT-02); U.S. Patent Application No. 11/
508,605 filed 22
[[Page 26404]]
Aug 2006 (HHS Ref. No. E-110-2004/0-US-06).
Licensing Status: Available for exclusive and non-exclusive
licensing.
Licensing Contact: Adaku Nwachukwu, J.D.; 301/435-5560;
madua@mail.nih.gov.
Leu574 of HIF-1alpha as a Molecular Basis for Therapeutic Application
Description of Technology: The hypoxia-inducible factor 1 (HIF-1)
is a transcription factor that plays a pivotal role in cellular
adaptation to oxygen availability. HIF-1alpha protein is a subunit of
HIF-1. Although the gene for HIF-1alpha is constitutively expressed, it
is an extremely short-lived protein under normoxic conditions and is
targeted for destruction via the proteosome pathway by an E3 ubiquitin
ligase involving the VHL protein.
The invention relates to the discovery that mutations or deletions
of Leu574 result in a more stable and more active form of HIF-1alpha.
Therefore, the invention relates to methods and compositions for
modulating oxygen homeostasis for therapeutic application. In one
aspect, the inventors contemplate the use of a more stable form of HIF-
1alpha protein for therapeutic angiogenesis purposes such as may be
useful in ischemic vascular disease. In another aspect, the inventors
contemplate the use of this particular site in a screen for targeted
drugs that modulates HIF-1alpha activity. The inventors also suggest
that Leu574 could be used for developing drugs targeted to HIF
hydroxylase binding, thereby altering HIF-1alpha stability.
Inventor: L. Eric Huang (NCI).
Patent Status: U.S. Patent No. 7,193,053 issued 20 Mar 2007 (HHS
Reference No. E-281-2002/0-US-02).
Licensing Status: This technology is available for licensing on an
exclusive or a non-exclusive basis.
Licensing Contact: Jesse S. Kindra, J.D.; 301/435-5559;
kindraj@mail.nih.gov.
Dated: April 30, 3007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer,Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-8893 Filed 5-8-07; 8:45 am]
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