Government-Owned Inventions; Availability for Licensing, 61142-61144 [05-21010]
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61142
Federal Register / Vol. 70, No. 202 / Thursday, October 20, 2005 / Notices
Subject name
Address
Howard-Love, Kimberly .........................................................................................
Marder, Charles ....................................................................................................
Mikolinnas, Thomas ..............................................................................................
Slusher, Kevin .......................................................................................................
Zimmerman, Seth ..................................................................................................
Dated: October 6, 2005.
Katherine B. Petrowski,
Director, Exclusions Staff, Office of Inspector
General.
[FR Doc. 05–20963 Filed 10–19–05; 8:45 am]
Springfield, OH .........................................
Plano, TX ..................................................
Worcester, MA ..........................................
Shreveport, LA ..........................................
Port Washington, NY ................................
dopamine released into the extracellular
space, thereby regulating
neurotransmission. The dopamine
transporter plays a significant role in
neurotoxicity and human diseases, such
BILLING CODE 4152–01–P
as Parkinson’s disease, drug abuse
(especially cocaine addiction), Attention
Deficit Disorder/Attention Deficit
DEPARTMENT OF HEALTH AND
Hyperactivity Disorder (ADD/ADHD),
HUMAN SERVICES
and a number of other CNS disorders.
Therefore, the dopamine transporter is a
National Institutes of Health
strong target for research and the
discovery of potential therapeutics for
Government-Owned Inventions;
the treatment of these indications.
Availability for Licensing
Benztropine and its analogs bind with
AGENCY: National Institutes of Health,
high affinity to the DAT and inhibit
Public Health Service, HHS.
dopamine reuptake, but generally do not
ACTION: Notice.
produce behavioral effects comparable
SUMMARY: The inventions listed below
to those produced by cocaine. Recent
are owned by an agency of the U.S.
benztropine analogs have been shown to
Government and are available for
(1) reduce cocaine-induced stimulant
licensing in the U.S. in accordance with effects, (2) retain long-lasting actions,
35 U.S.C. 207 to achieve expeditious
and (3) lack significant abuse liability.
commercialization of results of federally These data suggest that this class of
funded research and development.
compounds may be useful medications
Foreign patent applications are filed on
for human diseases where dopamineselected inventions to extend market
related behavior is compromised,
coverage for companies and may also be
especially in situations in which an
available for licensing.
agonist treatment is indicated.
ADDRESSES: Licensing information and
Although the benztropines bind with
copies of the U.S. patent applications
listed below may be obtained by writing high affinity to the DAT without
substitution in the 2-position of the
to the indicated licensing contact at the
Office of Technology Transfer, National tropane ring, only a substituent in the Sconfiguration is tolerated at DAT, in
Institutes of Health, 6011 Executive
direct contrast to cocaine and its analogs
Boulevard, Suite 325, Rockville,
that must have the 2-position
Maryland 20852–3804; telephone: 301/
substituent in the R-configuration. In
496–7057; fax: 301/402–0220. A signed
Confidential Disclosure Agreement will this invention, substitution at the S-2be required to receive copies of the
position of 4′,4″-difluoro-or 4′,4″patent applications.
dichlorobenztropines with various
functional groups such as alkyl, aryl,
N- and 2-Substituted Benztropine
akyl, alcohol, ether, etc., as well as
Compounds and Use Thereof for
substitution at the tropane nitrogen
Treating Mental Disorders
were achieved and have demonstrated
Amy H. Newman et al. (NIDA)
high affinity and selectivity for the DAT
U.S. Provisional Application filed 24
over the other monoamine transporters
Aug 2005 (HHS Reference No. E–234– as well as muscarinic receptors, without
2005/0–US–01).
a significant cocaine-like behavioral
Licensing Contact: Marlene Shinn-Astor; profile.
301/435–4426; shinnm@mail.nih.gov.
In addition to licensing, the
Dopamine is a neurotransmitter that
technology is available for further
exerts important effects on locomotor
development through collaborative
activity, motivation and reward, and
research opportunities with the
cognition. The dopamine transporter
inventors.
(DAT) is expressed on the plasma
membrane of dopamine synthesizing
neurons. It is responsible for clearing
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Novobiocin Analogues as Anticancer
Agents
Leonard M. Neckers (NCI) et al.
U.S. Provisional Application No. 60/
624,566 filed 03 Nov 2004 (HHS
Reference No. E–065–2005/0–US–01).
Licensing Contact: George Pipia; 301/
435–5560; pipiag@mail.nih.gov.
Functional Hsp90 requires C-terminal
homodimerization of two molecules of
Hsp90. Novobiocin competes with ATP
for binding to the C-terminus and
studies demonstrated that this binding
results in degradation of Hsp90 protein
through ubiquitination and ultimately
transportation to proteosome for
proteolysis. Twenty three analogs of
novobiocin were prepared and screened
for their activity against Hsp90 and the
most active derivatives were identified.
Novobiocin was previously identified as
an inhibitor of type II topoisomerases
and has been used clinically for more
than a decade for the treatment of
cancer. However recent studies have
shown that novobiocin selectively
inhibits the maturation of Hsp90
dependent proteins. In addition to its
effect on Hsp90, novobiocin has been
shown to reverse drug resistance and
increase the intracellular concentration
of topoisomerase II drugs such as
Etoposide and tubulin binding drugs,
such as Taxol, making cells more
susceptible to chemotherapeutics and
induction of apoptosis.
This research is described, in part, in:
Yu XM, Shen G, Neckers L, Blake H,
Holzbeierlein J, Cronk B and Blagg BSJ.
‘‘Hsp90 Inhibitors Identified from a
Library of Novobiocin Analogues,’’ J.
Am. Chem. Soc., in press.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Anticancer Effects of Novel Vitamin D
Receptor Antagonists
Julianna Barsony (NIDDK)
U.S. Provisional Application No. 60/
300,409 filed 22 Jun 2001 (HHS
Reference No. E–213–2001/1–US–01).
PCT Patent Application No. PCT/US02/
19774 filed 20 Jun 2002 (HHS
Reference No. E–213–2001/2–PCT–
01).
E:\FR\FM\20OCN1.SGM
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Federal Register / Vol. 70, No. 202 / Thursday, October 20, 2005 / Notices
U.S. Patent Application No. 10/481,052
filed 16 Dec 2003 (HHS Reference No.
E–213–2001/2–US–02).
Licensing Contact: Mojdeh Bahar; 301/
435–2950; baharm@mail.nih.gov.
The present invention relates to
cancer therapeutics. Specifically, this
invention relates to novel selective
vitamin D receptor modulators (SEDM),
also known as vitamin D receptor
antagonists. Methods of treatment
resulting in inhibition of cell growth,
inducement of cell differentiation,
inhibition of breast cancer growth, and
inhibition of parathyroid hormone
secretion in mice are disclosed.
Vitamin D does not have significant
biological activity. Rather, it must be
metabolized within the body to its
hormonally active form, calcitriol.
Calcitriol acts through the vitamin D
receptor (VDR) to regulate important
functions, such as calcium homeostasis,
cell proliferation and differentiation,
and immune functions. Many cancers
contain VDR and, therefore respond to
calcitriol. In such cancers, low
concentrations of calcitriol stimulate
growth and high concentrations inhibit
growth. High doses of calcitriol and
calcitriol analogues, however, cause
hypercalcemia, limiting the use of this
hormone for cancer treatment.
The present invention relates to
derivatives of calcitriol that have been
synthesized in a manner similar to the
principles developed to create estrogen
receptor modulators (SERM). These
vitamin D receptor modulators bind
well to VDR, inhibit their ability to
stimulate cancer cell growth and
increase their ability to induce cell
differentiation. In mice, SEDM inhibited
human breast cancer growth without
causing hypercalcemia. The technology
disclosed herein may also be used for
the prevention of breast cancer,
treatment and/or prevention of other
types of conditions or diseases, such as,
but not limited to, prostate, colorectal,
and lung cancers, leukemia, primary or
metastatic melanoma, glyoma, and
parathyroid diseases.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
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Zebularine, A Stable and Orally Active
Inhibitor of Cytosine DNA
Methyltransferase Capable of
Reactivating Dormant Tumor
Suppressor and Inhibiting Tumor
Growth
Victor E. Marquez (NCI) et al.
U.S. Provisional Application No. 60/
309,242 filed 31 Jul 2001 (HHS Ref.
No. E–081–2001/0–US–01).
U.S. Provisional Application No. 60/
311,435 filed 10 Aug 2001 (HHS Ref.
No. E–081–2001/1–US–01).
PCT Application No. PCT/US02/24223
filed 30 Jul 2002, which published as
WO 03/012051 on 13 Feb 2003 (HHS
Ref. No. E–081–2001/2–PCT–01).
U.S. Patent Application No. 10/485,438
filed 30 Jan 2004 (HHS Ref. No. E–
081–2001/2–US–06).
Licensing Contact: John Stansberry; 301/
435–5239; stansbej@mail.nih.gov.
DNA methyltransferases (also referred
to as DNA methylases) transfer methyl
groups from the universal methyl donor
S-adenosyl methionine to specific sites
on a DNA molecule. When gene
sequences contain many methylated
cytosines, they are less likely to be
expressed. Several such ‘silenced’ genes
are now known to be an important
contributing factor in many cancers
where expression of tumor suppressor
genes has been suppressed. Preventing
DNA methyltransferase production, or
inhibiting the enzyme, may allow tumor
suppressor genes that have been
silenced by hypermethylation to be reactivated. Re-activation of tumor
suppressor genes is intended to stop or
slow tumor growth by restoring growth
control mechanisms. Thus, there exists
a need for an effective and stable
inhibitor of DNA methylation.
The inventors have discovered a
potent inhibitor of DNA methylation
(Zebularine) that can specifically
reactivate silenced tumor suppressor
genes. This agent can be used to inhibit
methylation and thereby combat certain
cancers that have been linked to
hypermethylation. This agent has also
been shown in initial animal testing to
be active orally and is more stable than
some other agents in this same area of
therapy and is a suitable candidate for
further pre-clinical and clinical
development as an anti-cancer agent to
be used as monotherapy and/or as an
adjunct to existing anti-cancer
therapeutics.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
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61143
Compositions and Methods of
Specifically Targeting Tumors
Dr. Raj K. Puri (FDA) et al.
U.S. Patent No. 6,428,788 issued 06 Aug
2002 (HHS Reference No. E–266–
1994/1–US–01).
Licensing Contact: Jesse S. Kindra; 301/
594–4697; kindraj@mail.nih.gov.
A chimeric molecule that binds
specifically to IL–13 receptors has been
identified. The molecule, IL13PE38QQR, targets tumor cells with less
binding to healthy cells. The improved
specific targeting of this molecule is
premised upon the discovery that tumor
cells overexpress IL–13 receptors at
extremely high levels and that binding
of IL–13–PE38QQR can be blocked to
IL–4 receptors in normal cells. This
phenomenon permits the use of lower
dosages of chimeric molecules along
with IL–4 receptor blocker to deliver
effector molecules to targeted tumor
cells.
This invention may be useful in the
treatment of cancer. The targeting
method could be used in conjunction
with current methods, e.g.,
chemotherapy to help maintain the
healthy cells. To date, IL13–PE38QQR
has been shown to be effective against
a variety of solid tumor cancers in
animal models including
adenocarcinoma, brain cancer and AIDS
associated Kaposi’s sarcoma.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
1,2-Dihydroellipticines with Activity
Against CNS-Specific Cancer Cell Lines
Rudiger D. Haugwitz (NCI) et al.
U.S. Patent No. 5,272,146 issued 21 Dec
1993 (HHS Reference No. E–110–
1992/0–US–01).
U.S. Patent No. 5,441,941 issued 15 Aug
1995 (HHS Reference No. E–110–
1992/0–US–02).
Licensing Contact: George G. Pipia; 301/
435–5560; pipiag@mail.nih.gov.
The present invention is directed, in
general, to methods for treating human
cancers and in particular to new
compounds which cross the blood brain
barrier and retain activity against CNS
specific cancer cell lines, to
pharmaceutical formulations containing
such compounds, and to methods for
the treatment of cancer.
This research is described, in part, in
Jurayj et al., ‘‘Design and Synthesis of
Ellipticinium Salts and 1,2Dihydroellipticines with High
Selectivities against Human CNS
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61144
Federal Register / Vol. 70, No. 202 / Thursday, October 20, 2005 / Notices
Cancers in vitro,’’ J. Med. Chem.
37(4):2190–2197, 1994.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Dated: October 10, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–21010 Filed 10–19–05; 8:45 am]
National Institutes of Health
National Institutes of Health
National Heart, Lung, and Blood
Institute; Notice of Closed Meetings
National Heart, Lung, and Blood
Institute; Notice of Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meetings.
The meetings will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Heart, Lung, and Blood
Institute; Notice of Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.233, National Center for
Sleep Disorders Research; 93.937, Heart and
Vascular Diseases Research; 93.838, Lung
Diseases Research; 93.839, Blood Diseases
and Resources Research, National Institutes
of Health, HHS)
Name of Committee: National Heart, Lung,
and Blood Institute Special Emphasis Panel
Review of Research Project (Cooperative
Agreement) Applications
Date: November 15, 2005.
Time: 1 p.m. to 3 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, 6701
Rockledge Drive, Bethesda, MD 20892,
(Telephone Conference Call).
Contact Person: Shelley S. Sehnert, PhD,
Scientific Review Administrator, Review
Branch, NIH/NHLBI, 6701 Rockledge Drive,
Room 7206, Bethesda, MD 20892–7924, 301/
435–0303, ssehnert@nhlbi.nih.gov.
Name of Committee: National Heart, Lung,
and Blood Institute Special Emphasis Panel
Review of Research Project Grant
Applications (R01s)
Date: November 17, 2005.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications.
Place: Bethesda Marriott, 5151 Pooks Hill
Road, Bethesda, MD 20814.
Contact Person: YingYing Li-Smerin, PhD,
MD, Scientific Review Administrator,
Division of Extramural Affairs, Review
Branch, National Heart, Lung, and Blood
Institute, NIH, 6701 Rockledge Drive, Room
7184, Bethesda, MD 20814, 301/435–0275,
lismerin@nhlbi.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.233, National Center for
Sleep Disorders Research; 93.837, Heart and
Vascular Diseases Research; 93.838, Lung
Diseases Research; 93839, Blood Diseases
and Resources Research, National Institutes
of Health, HHS)
Dated: October 11, 2005.
Anthony M. Coelho, Jr.,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 05–21020 Filed 10–19–05; 8:45 am]
Dated: October 11, 2005.
Anthony M. Coelho, Jr.,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 05–21022 Filed 10–19–05; 8:45 am]
BILLING CODE 4140–01–M
BILLING CODE 4140–01–M
Name of Committee: National Heart, Lung,
and Blood Institute Special Emphasis Panel
Review of Conference Grants (R13s)
Date: November 8–9, 2005.
Time: 8 a.m. to 8 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, 6701
Rockledge Drive, Bethesda, MD 20892
(Telephone Conference Call)
Contact Person: Deborah P. Beebe,
Director, Division of Extramural Affairs,
National Heart, Lung, and Blood Institute,
NIH, Two Rockledge Center, Room 1700,
6701 Rockledge Drive, Bethesda, MD 20892,
301/435–0260, beebed@nhlbi.nih.gov.
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Name of Committee: Heart, Lung, and
Blood Initial Review Group.Heart, Lung, and
Blood Program Project Review Committee.
Date: December 1, 2005.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications.
Place: Holiday Inn Chevy Chase, 5520
Wisconsin Avenue, Chevy Chase, MD 20815.
Contact Person: Jeffrey H. Hurst, PhD,
Review Branch, Division of Extramural
Affairs, National Heart, Lung, and Blood
Institute/NIH, 6701 Rockledge Drive, RM
7208, Bethesda, MD 20892, (301) 435–0303,
hurstj@nhlbi.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.233, National Center for
Sleep Disorders Research; 93.837, Heart and
Vascular Diseases Research; 93.838, Lung
Diseases Research; 93.839, Blood Diseases
and Resources Research, National Institutes
of Health, HHS)
Dated: October 11, 2005.
Anthony M. Coelho, Jr.,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 05–21024 Filed 10–19–05; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Diabetes and
Digestive and Kidney Diseases; Notice
of Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meetings.
E:\FR\FM\20OCN1.SGM
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]]>Agencies
[Federal Register Volume 70, Number 202 (Thursday, October 20, 2005)]
[Notices]
[Pages 61142-61144]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-21010]
-----------------------------------------------------------------------
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.
N- and 2-Substituted Benztropine Compounds and Use Thereof for Treating
Mental Disorders
Amy H. Newman et al. (NIDA)
U.S. Provisional Application filed 24 Aug 2005 (HHS Reference No. E-
234-2005/0-US-01).
Licensing Contact: Marlene Shinn-Astor; 301/435-4426;
shinnm@mail.nih.gov.
Dopamine is a neurotransmitter that exerts important effects on
locomotor activity, motivation and reward, and cognition. The dopamine
transporter (DAT) is expressed on the plasma membrane of dopamine
synthesizing neurons. It is responsible for clearing dopamine released
into the extracellular space, thereby regulating neurotransmission. The
dopamine transporter plays a significant role in neurotoxicity and
human diseases, such as Parkinson's disease, drug abuse (especially
cocaine addiction), Attention Deficit Disorder/Attention Deficit
Hyperactivity Disorder (ADD/ADHD), and a number of other CNS disorders.
Therefore, the dopamine transporter is a strong target for research and
the discovery of potential therapeutics for the treatment of these
indications.
Benztropine and its analogs bind with high affinity to the DAT and
inhibit dopamine reuptake, but generally do not produce behavioral
effects comparable to those produced by cocaine. Recent benztropine
analogs have been shown to (1) reduce cocaine-induced stimulant
effects, (2) retain long-lasting actions, and (3) lack significant
abuse liability. These data suggest that this class of compounds may be
useful medications for human diseases where dopamine-related behavior
is compromised, especially in situations in which an agonist treatment
is indicated.
Although the benztropines bind with high affinity to the DAT
without substitution in the 2-position of the tropane ring, only a
substituent in the S-configuration is tolerated at DAT, in direct
contrast to cocaine and its analogs that must have the 2-position
substituent in the R-configuration. In this invention, substitution at
the S-2-position of 4',4''-difluoro-or 4',4''-dichlorobenztropines with
various functional groups such as alkyl, aryl, akyl, alcohol, ether,
etc., as well as substitution at the tropane nitrogen were achieved and
have demonstrated high affinity and selectivity for the DAT over the
other monoamine transporters as well as muscarinic receptors, without a
significant cocaine-like behavioral profile.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Novobiocin Analogues as Anticancer Agents
Leonard M. Neckers (NCI) et al.
U.S. Provisional Application No. 60/624,566 filed 03 Nov 2004 (HHS
Reference No. E-065-2005/0-US-01).
Licensing Contact: George Pipia; 301/435-5560; pipiag@mail.nih.gov.
Functional Hsp90 requires C-terminal homodimerization of two
molecules of Hsp90. Novobiocin competes with ATP for binding to the C-
terminus and studies demonstrated that this binding results in
degradation of Hsp90 protein through ubiquitination and ultimately
transportation to proteosome for proteolysis. Twenty three analogs of
novobiocin were prepared and screened for their activity against Hsp90
and the most active derivatives were identified. Novobiocin was
previously identified as an inhibitor of type II topoisomerases and has
been used clinically for more than a decade for the treatment of
cancer. However recent studies have shown that novobiocin selectively
inhibits the maturation of Hsp90 dependent proteins. In addition to its
effect on Hsp90, novobiocin has been shown to reverse drug resistance
and increase the intracellular concentration of topoisomerase II drugs
such as Etoposide and tubulin binding drugs, such as Taxol, making
cells more susceptible to chemotherapeutics and induction of apoptosis.
This research is described, in part, in: Yu XM, Shen G, Neckers L,
Blake H, Holzbeierlein J, Cronk B and Blagg BSJ. ``Hsp90 Inhibitors
Identified from a Library of Novobiocin Analogues,'' J. Am. Chem. Soc.,
in press.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Anticancer Effects of Novel Vitamin D Receptor Antagonists
Julianna Barsony (NIDDK)
U.S. Provisional Application No. 60/300,409 filed 22 Jun 2001 (HHS
Reference No. E-213-2001/1-US-01).
PCT Patent Application No. PCT/US02/19774 filed 20 Jun 2002 (HHS
Reference No. E-213-2001/2-PCT-01).
[[Page 61143]]
U.S. Patent Application No. 10/481,052 filed 16 Dec 2003 (HHS Reference
No. E-213-2001/2-US-02).
Licensing Contact: Mojdeh Bahar; 301/435-2950; baharm@mail.nih.gov.
The present invention relates to cancer therapeutics. Specifically,
this invention relates to novel selective vitamin D receptor modulators
(SEDM), also known as vitamin D receptor antagonists. Methods of
treatment resulting in inhibition of cell growth, inducement of cell
differentiation, inhibition of breast cancer growth, and inhibition of
parathyroid hormone secretion in mice are disclosed.
Vitamin D does not have significant biological activity. Rather, it
must be metabolized within the body to its hormonally active form,
calcitriol. Calcitriol acts through the vitamin D receptor (VDR) to
regulate important functions, such as calcium homeostasis, cell
proliferation and differentiation, and immune functions. Many cancers
contain VDR and, therefore respond to calcitriol. In such cancers, low
concentrations of calcitriol stimulate growth and high concentrations
inhibit growth. High doses of calcitriol and calcitriol analogues,
however, cause hypercalcemia, limiting the use of this hormone for
cancer treatment.
The present invention relates to derivatives of calcitriol that
have been synthesized in a manner similar to the principles developed
to create estrogen receptor modulators (SERM). These vitamin D receptor
modulators bind well to VDR, inhibit their ability to stimulate cancer
cell growth and increase their ability to induce cell differentiation.
In mice, SEDM inhibited human breast cancer growth without causing
hypercalcemia. The technology disclosed herein may also be used for the
prevention of breast cancer, treatment and/or prevention of other types
of conditions or diseases, such as, but not limited to, prostate,
colorectal, and lung cancers, leukemia, primary or metastatic melanoma,
glyoma, and parathyroid diseases.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Zebularine, A Stable and Orally Active Inhibitor of Cytosine DNA
Methyltransferase Capable of Reactivating Dormant Tumor Suppressor and
Inhibiting Tumor Growth
Victor E. Marquez (NCI) et al.
U.S. Provisional Application No. 60/309,242 filed 31 Jul 2001 (HHS Ref.
No. E-081-2001/0-US-01).
U.S. Provisional Application No. 60/311,435 filed 10 Aug 2001 (HHS Ref.
No. E-081-2001/1-US-01).
PCT Application No. PCT/US02/24223 filed 30 Jul 2002, which published
as WO 03/012051 on 13 Feb 2003 (HHS Ref. No. E-081-2001/2-PCT-01).
U.S. Patent Application No. 10/485,438 filed 30 Jan 2004 (HHS Ref. No.
E-081-2001/2-US-06).
Licensing Contact: John Stansberry; 301/435-5239;
stansbej@mail.nih.gov.
DNA methyltransferases (also referred to as DNA methylases)
transfer methyl groups from the universal methyl donor S-adenosyl
methionine to specific sites on a DNA molecule. When gene sequences
contain many methylated cytosines, they are less likely to be
expressed. Several such `silenced' genes are now known to be an
important contributing factor in many cancers where expression of tumor
suppressor genes has been suppressed. Preventing DNA methyltransferase
production, or inhibiting the enzyme, may allow tumor suppressor genes
that have been silenced by hypermethylation to be re-activated. Re-
activation of tumor suppressor genes is intended to stop or slow tumor
growth by restoring growth control mechanisms. Thus, there exists a
need for an effective and stable inhibitor of DNA methylation.
The inventors have discovered a potent inhibitor of DNA methylation
(Zebularine) that can specifically reactivate silenced tumor suppressor
genes. This agent can be used to inhibit methylation and thereby combat
certain cancers that have been linked to hypermethylation. This agent
has also been shown in initial animal testing to be active orally and
is more stable than some other agents in this same area of therapy and
is a suitable candidate for further pre-clinical and clinical
development as an anti-cancer agent to be used as monotherapy and/or as
an adjunct to existing anti-cancer therapeutics.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Compositions and Methods of Specifically Targeting Tumors
Dr. Raj K. Puri (FDA) et al.
U.S. Patent No. 6,428,788 issued 06 Aug 2002 (HHS Reference No. E-266-
1994/1-US-01).
Licensing Contact: Jesse S. Kindra; 301/594-4697; kindraj@mail.nih.gov.
A chimeric molecule that binds specifically to IL-13 receptors has
been identified. The molecule, IL13-PE38QQR, targets tumor cells with
less binding to healthy cells. The improved specific targeting of this
molecule is premised upon the discovery that tumor cells overexpress
IL-13 receptors at extremely high levels and that binding of IL-13-
PE38QQR can be blocked to IL-4 receptors in normal cells. This
phenomenon permits the use of lower dosages of chimeric molecules along
with IL-4 receptor blocker to deliver effector molecules to targeted
tumor cells.
This invention may be useful in the treatment of cancer. The
targeting method could be used in conjunction with current methods,
e.g., chemotherapy to help maintain the healthy cells. To date, IL13-
PE38QQR has been shown to be effective against a variety of solid tumor
cancers in animal models including adenocarcinoma, brain cancer and
AIDS associated Kaposi's sarcoma.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
1,2-Dihydroellipticines with Activity Against CNS-Specific Cancer Cell
Lines
Rudiger D. Haugwitz (NCI) et al.
U.S. Patent No. 5,272,146 issued 21 Dec 1993 (HHS Reference No. E-110-
1992/0-US-01).
U.S. Patent No. 5,441,941 issued 15 Aug 1995 (HHS Reference No. E-110-
1992/0-US-02).
Licensing Contact: George G. Pipia; 301/435-5560; pipiag@mail.nih.gov.
The present invention is directed, in general, to methods for
treating human cancers and in particular to new compounds which cross
the blood brain barrier and retain activity against CNS specific cancer
cell lines, to pharmaceutical formulations containing such compounds,
and to methods for the treatment of cancer.
This research is described, in part, in Jurayj et al., ``Design and
Synthesis of Ellipticinium Salts and 1,2-Dihydroellipticines with High
Selectivities against Human CNS
[[Page 61144]]
Cancers in vitro,'' J. Med. Chem. 37(4):2190-2197, 1994.
Dated: October 10, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 05-21010 Filed 10-19-05; 8:45 am]
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