Government-Owned Inventions; Availability for Licensing, 11123-11126 [E8-3837]
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Federal Register / Vol. 73, No. 41 / Friday, February 29, 2008 / Notices
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PLCO participants .............................................................................................
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Dated: February 20, 2008.
Vivian Horovitch-Kelley,
NCI Project Clearance Liaison Office,
National Institutes of Health.
[FR Doc. E8–3836 Filed 2–28–08; 8:45 am]
BILLING CODE 4140–01–P
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.
A Pharmacophore for Isatin-bThiosemicarbazone Compounds With
MDR1-Inverse Activity
Description of Technology: One of the
major hindrances to successful cancer
chemotherapy is multi-drug resistance
(MDR), which is frequently caused by
the increased expression or activity of
ABC transporter proteins. Research has
generally been directed to overcoming
MDR during cancer therapy by
inhibiting the activity of ABC
transporters. However, compounds that
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inhibit ABC transporter activity often
elicit strong and undesirable sideeffects, restricting their usefulness in
therapy.
In an alternative approach to reducing
the debilitating effects of MDR in cancer
therapy, scientists at the National
Cancer Institute identified a family of
compounds whose antiproliferative
effects were actually enhanced in cells
with MDR. These compounds included
NSC 73306, a specific compound that
increased the chemosensitivity of cells
that overexpress ABC transporters
without inhibiting ABC transporter
activity. This invention concerns new
analogs of NSC 73306 with improved
selectivity and solubility, and the use of
the analogs as therapeutics.
Applications:
Treatment of cancers associated with
multi-drug resistance, either alone or in
combination with other therapeutics.
Development of a pharmacophore for
improved effectiveness in treating
cancers associated with multi-drug
resistance.
Advantages:
The agents capitalize on one of the
most common drawbacks to cancer
therapies (MDR) by using it as an
advantage to treating cancer.
Increased specificity allows these
analogs to be tailored to treating cancers
associated with the overexpression and
hyperactivity of particular ABC
transporters.
Increased solubility allows greater
access of the agent to tumor cells,
increasing therapeutic effectiveness of
the agents.
Benefits: Cancer is the second leading
cause of death in United States and it is
estimated that there will be
approximately 600,000 deaths caused by
cancer in 2007. Improving the quality of
life and duration of life of cancer
patients will depend on chemotherapies
with increased effectiveness and
reduced toxicity, thus this technology
can contribute significantly to a social
cause. Furthermore, small molecule
cancer therapy technologies have a
potential market of more than $2 billion.
Inventors: Matthew D. Hall et al.
(NCI).
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U.S. Patent Status: Provisional U.S.
Application (HHS Reference No. E–017–
2008/0–US–01).
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute’s
Laboratory of Cell Biology is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize for the clinic,
compounds that demonstrate MDR1inverse activity. Please contact John D.
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
An Improved Non Viral System for
Tumor Specific Suicide Gene Therapy
Description of Technology: Numerous
tumor specific promoters have been
identified and developed for targeted
gene therapy. Survivin promoter activity
is upregulated in 75% of tumors,
however the activity is specific but low,
resulting in sub-optimal suicide gene
expression. Combination of survivin
promoter with Bax, a proapoptotic gene,
previously used in such therapy has
demonstrated low efficacy.
Scientists at NCI have made a plasmid
construct consisting of survivin
promoter driven mutant form of bax that
is constitutively active. This construct is
more potent than the wild type bax,
improving its efficacy several-fold,
while, retaining specificity for tumors,
as determined by in vitro and in vivo
studies.
This new technology does not use
CMV or SV–40 promoters, alleviating
the need for modifications for
commercialization.
Advantages:
Can be used with cationic liposomes
or other DNA delivery systems.
Can be incorporated into adenoviral
and lentiviral vectors.
Excludes viral promoters.
Can be modified easily to use other
promoters/suicide genes.
Applications:
Cancer therapeutics
Targeted Gene therapy
Market: In patients with advanced
solid tumors or recurrences despite
surgery, chemotherapy can provide
quality survival. However, responses are
usually partial, often disappointingly
brief and unpredictable and coupled
with side effects. These limitations of
traditional cytotoxic chemotherapy
make it necessary to explore other
therapies such as targeted gene therapy.
Viruses, while the carrier of choice in
most gene therapy studies, present a
variety of potential problems to the
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patient—toxicity, immune and
inflammatory responses, and gene
control and targeting issues. In addition,
there is a fear that the viral vector may
recover its ability to cause disease in the
patient. Our new technology addresses
some of the above issues making it a
suitable agent for cancer and gene
therapy.
Development Status: Early.
Inventors: Himanshu Garg and Robert
P. Blumenthal (NCI).
Patent Status: HHS Reference No. E–
245–2007/0—Research Tool. Patent
protection is not being sought for this
technology.
Licensing Status: Available for nonexclusive licensing.
Licensing Contact: John Stansberry,
PhD; 301–435–5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute Center for
Cancer Research Nanobiology Program
is seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
tumor specific suicide gene therapy
using survivin promoter driven mutant
bax. Please contact John D. Hewes, PhD
at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Eeyarestatins: Novel Deubiquitination
Inhibitors for the Treatment of DrugResistant Cancers
Description of Technology: The
ubiquitin-proteasome system has
recently been recognized to play a
central role in tumor biology.
Bortezomib, an inhibitor of the
chymotrypsin-like activity of the
proteasome, has clinical activity in a
variety of hematologic malignancies and
is FDA approved for use in Multiple
Myeloma and Mantle Cell Lymphoma.
The present invention for the first
time describes that Eeyarestatins, a new
class of small molecules, are potential
anti-cancer agents. The compounds
inhibit the deubiquitination of proteins
by targeting the deubiquitination
enzymes in the protein degradation
pathway. More specifically, the
inventors have demonstrated that the
Eeyarestatins successfully kill different
leukemia and lymphoma cell lines as
well as leukemia cells isolated from
patients with chronic lymphocytic
leukemia by inducing the expression of
Noxa, a pro-apoptotic member of the
Bcl-2 protein family. Additionally,
Eeyarestatins are active against cells that
are resistant to Bortezomib and thus can
be effective against drug-resistant
tumors.
Applications:
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Eeyarestatins can be developed for the
treatment of deubiquitination related
disorders such as cancers and
proliferative disorders.
Eeyarestatins can potentially have
broader use against HIV and immune
related disorders considering the role of
deubiquitination in budding of
retroviruses and immune regulation.
Advantages:
Eeyarestatins are active against cells
that are resistant to Bortezomib.
In vitro data shows activity of
Eeyarestatins against primary cells from
patients with chronic lymphocytic
leukemia. Clinical trials show that
Bortezomib is inactive against patients
suffering from chronic lymphocytic
leukemia.
Market: The current cancer
chemotherapeutic market is valued at
$42 billion and expected to grow.
Additionally, this compound has
potential use in HIV and immune
related disorders.
Development Status: In vitro studies
are completed and in vivo animal model
studies are planned.
Inventors: Adrian Wiestner (NHLBI),
Yihong Ye (NIDDK), Qiuyan Wang
(NIDDK), Helena Mora-Jensen (NHLBI)
Publication: Q Wang, L Li, Y Ye.
Inhibition of p97-dependent protein
degradation by Eeyarestatin I. J Biol
Chem. 2008 Jan 16; Epub ahead of print,
doi 10.1074/jbc.M708347200.
Patent Status: U.S. Provisional
Application No. 60/961,202 filed 17 Jul
2007 (HHS Reference No. E–208–2007/
0–US–01)
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Surekha Vathyam;
301–435–4076; vathyams@mail.nih.gov.
Collaborative Research Opportunity:
The National Institutes of Health
laboratories of Dr. Adrian Wiestner
(NHLBI) and Dr. Yihong Ye (NIDDK) are
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
Eeyarestatins. Please contact Dr.
Wiestner (301–594–6855,
wiestnera@mail.nih.gov) or Dr. Ye (301–
594–0845, yihongy@mail.nih.gov) for
more information.
Synergistic Effect of TGF-Beta Blockade
and Immunogenic Agents on Tumors
Description of Technology:
Overcoming immune suppression in
cancer patients is a major challenge for
the success of cancer immunotherapy.
TGF-b and its receptors are expressed in
essentially all tissues, and they have
been found to be important in many
cellular processes including cell growth
inhibition. The inhibition of TGF-b
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signaling has been shown to have an
inhibitory effect on tumor growth.
However, TGF-b also has
immunosuppressive properties.
Cancer vaccines are one of many
therapies available for treatment and
prevention. In particular, vaccines that
elicit immune responses have been used
to treat or control tumor growth that has
evaded immunosurveillance. However,
these vaccines have demonstrated
limited success.
Available for licensing is a method for
synergistically affecting tumor growth
involving the administration of an agent
that blocks the TGF-b signaling
pathway, in combination with an
immunogenic agent. The agent that
blocks the TGF-b signaling pathway
may inhibit the immunosuppressive
effects of TGF-b, while the
immunogenic agent is believed to
enhance an immune response.
Surprisingly, the combination of such
elements produces a synergistic effect.
The administration of the 1D11.16 antiTGF-b antibody in combination with the
human papilloma virus E7(49–57)
peptide enhances tumor regression in an
animal model. The administration of the
1D11.16 anti-TGF-b antibody in
combination with irradiated CT26 cells
enhances tumor regression in another
mouse model. The investigators found
that administering the combination of
agents is more effective than the sum of
their individual effects.
Applications: A method of cancer
combination therapy based on
immunotherapeutics.
Development Status: The invention is
in the clinical stages of development.
Inventors: Masaki Terabe (NCI) et al.
Publications:
1. PCT patent publication WO 2006/
089251, August 24, 2006.
2. M Terabe et al. Transforming
growth factor-beta production and
myeloid cells are an effector mechanism
through which CD1d-restricted T cells
block cytotoxic T lymphocyte-mediated
tumor immunosurveillance: abrogation
prevents tumor recurrence. J Exp Med.
2003 Dec 1;198(11):1741–1752.
Patent Status: U.S. Provisional
Application No. 60/654,329 filed 17 Feb
2005 (HHS Reference No. E–019–2005/
0–US–01); PCT Application No. PCT/
US2006/005888 filed 16 Feb 2006 (HHS
Reference No. E–019–2005/0–PCT–02);
U.S. Patent Application No. 11/816,410
filed 15 Aug 2007 (HHS Reference No.
E–019–2005/0–US–06)
Licensing Status: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Jennifer Wong;
301–435–4633; wongje@mail.nih.gov.
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Biologically Active Macrolides,
Compositions and Uses Thereof
Description of Technology: The
current invention embodies the
identification of a novel class of potent
vacuolar-type (H+)-ATPase-inhibitory
compounds. Vacuolar-type (H+)ATPases are present in many tissues
and cells of the body and are involved
in the maintenance of various
physiological functions. The
modification of these functions, via
inhibition of vacuolar-type (H+)ATPases, may represent an effective
means of treating various disease states,
including Alzheimer’s disease,
glaucoma, and osteoporosis. In addition,
these inhibitors may also be of
particular value for use against cancer,
as vacuolar-type (H+)-ATPases have
been implicated in processes relating to
cellular proliferation, angiogenesis,
tumor cell invasiveness, metastasis, and
drug resistance.
Inventors: Michael R. Boyd (NCI),
Kirk R. Gustafson (NCI), et al.
Patent Status: U.S. Patent No.
7,144,918 issued 05 Dec 2006 (HHS
Reference No. E–203–2000/0–US–04);
U.S. Patent Application No. 11/435,189
filed 16 May 2006 (HHS Reference No.
E–203–2000/08–US–08)
Licensing Status: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Adaku
Nwachukwu, J.D.; 301–435–5560;
madua@mail.nih.gov.
Human p53 Mutations and a Genetic
System in Yeast for Functional
Identification of Human p53 Mutations
Description of Technology: The tumor
suppressor gene p53, a key regulator of
cellular mechanisms that maintain
genome integrity, is the most commonly
inactivated gene target associated with
neoplastic transformation. p53 is
mutated in about 50% of all human
tumors and more than 80% of these
mutations are missense, leading to
single amino acid changes. This
invention relates to human p53 mutants
and identification methods using
screening assays in the yeast
Saccharomyces cerevisiae to
functionally categorize expressed p53
mutant proteins at varying levels of
expression towards several human
target response sequences. Additionally,
the invention relates to methods of
detecting or generating novel human
p53 mutations with properties that can
include toxicity in yeast and growth
suppression in human cells, enhanced
or reduced transactivation relative to
wildtype p53, altered promoter
selectivity, and reactivation by mutation
or chemical modification of common
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tumor mutations for the transactivation
function of major p53 downstream
genes. In particular, the inventors have
discovered a V122A p53 mutation
exhibits strong cell proliferation
inhibition. This feature suggests that
p53 alleles such as V122A might be
valuable both for functional studies of
p53-regulated cellular responses and
possibly for p53 based cancer gene
therapy.
Applications:
Cancer therapeutics.
Model to screen for small molecules
or peptides that can modify p53
functions.
Pharmaceutical screen for p53 drug
modifiers.
Market:
An estimated 1,444,920 new cancer
diagnoses in the U.S. in 2007.
Cancer drug market is estimated to be
$50 billion a year in 2010.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Michael A. Resnick and
Alberto Inga (NIEHS)
Publications:
1. A Jegga, A Inga, D Menendez, BJ
Aronow, MA Resnick. Functional
evolution of the p53 regulatory network
through its target response elements.
Proc Natl Acad Sci. USA. 2008 Jan
22;105(3):944–949.
2. MM Horvath, X Wang, MA Resnick,
DA Bell. Divergent evolution of human
p53 binding sites: cell cycle versus
apoptosis. PLoS Genet. 2007
Jul;3(7):1284–1295.
3. D Menendez, A Inga, J Snipe,O
¨
Krysiak, G Schonfelder, MA Resnick. A
single-nucleotide polymorphism in a
half-binding site creates p53 and
estrogen receptor control of vascular
endothelial growth factor receptor 1.
Mol Cell Biol. 2007 Apr;27(7):2590–
2600.
4. P Monti, Y Ciribilli, J Jordan, P
Menichini, DM Umbach, MA Resnick, L
Luzzato, A Inga, G Fronza.
Transcriptional functionality of germ
line p53 mutants influences cancer
phenotype. Clin Can Res. 2006 Jul
1;13(13):3789–3795.
5. D Menendez, A Inga, J Jordan, MA
Resnick. Changing the p53 master
regulatory network: ELEMENTary, my
dear Mr. Watson. Oncogene. 2007 Apr
2;26(15):2191–2201.
6. D Menendez, A Inga, J Jordan, MA
Resnick. The biological impact of the
human master regulator p53 can be
altered by mutations that change the
spectrum and expression of its target
genes. Mol Cell Biol. 2006
Mar;26(6):2297–2308.
7. DJ Tomso, A Inga, D Menendez, G
Pittman, M Campbell, D Bell, MA
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Resnick. Functionally distinct
polymorphic sequences in the human
genome that are targets for p53
transactivation. Proc Natl Acad Sci
USA. 2005 May 3;102(18):6431–6436.
8. MA Resnick and A Inga. Functional
mutations in the sequence-specific
transcription factor p53 and
implications for master genes of
diversity. Proc Nat Acad Sci USA. 2003
Aug 19;100(17):9934–9939.
9. A Inga, F Storici, TA Darden, MA
Resnick. Differential transactivation by
the p53 transcription factor is highly
dependent on p53 level and promoter
target sequence. Mol Cell Biol. 2002
Dec;22(24):8612–8625, 2002.
Patent Status:
U.S. Patent No. 7,256,260 issued 14
Aug 2007 (HHS Reference No. E–183–
1999/0–US–07)
U.S. Patent Application No. 11/
893,037 filed 14 Aug 2007 (HHS
Reference No. E–183–1999/0–US–09)
European Patent Application No.
0094897.0 filed 28 July 2007, recently
allowed (HHS Reference No. E–183–
1999/0–EP–05)
Australian Patent No. 784293 issued
14 Aug 2007 (HHS Reference No. E–
183–1999/0–AU–03)
Australian Patent Application No.
2006202361 filed 2 Jun 2006 (HHS
Reference No. E–183–1999/0–AU–08)
Canadian Patent Application No.
2380631 filed 28 July 2000 (HHS
Reference No. E–183–1999/0–CA–04)
Japanese Patent Application No.
2001–514117 filed 28 July 2000 (HHS
Reference No. E–183–1999/0–JP–03)
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Jennifer Wong;
301–435–4633; wongje@mail.nih.gov.
Dated: February 21, 2008.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E8–3837 Filed 2–28–08; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
available. Individuals who plan to
attend and need special assistance, such
as sign language interpretation or other
reasonable accommodations, should
notify the Contact Person listed below
in advance of the meeting.
Name of Committee: Advisory Committee
on Research on Women’s Health.
Date: March 17, 2008.
Time: 8:30 a.m. to 4 p.m.
Agenda: Provide advice to the Office of
Research on Women’s Health (ORWH) on
appropriate research activities with respect to
women’s health and related studies to be
undertaken by the national research
institutes; to provide recommendations
regarding ORWH activities; to meet the
mandates of the office; and for discussion of
scientific issues.
Place: National Institutes of Health,
Building 31, 31 Center Drive, Conference
Room 6, Bethesda, MD 20892.
Contact Person: Joyce Rudick, Director,
Programs & Management, Office of Research
on Women’s Health, Office of the Director,
National Institutes of Health, Building 1,
Room 201, Bethesda, MD 20892, 301/402–
1770.
Any interested person may file written
comments with the committee by forwarding
the statement to the Contact Person listed on
this notice. The statement should include the
name, address, telephone number and when
applicable, the business or professional
affiliation of the interested person.
Information is also available on the
Institute’s/Center’s home page: https://
www.od.nih.gov/orwh/, where an agenda and
any additional information for the meeting
will be posted when available.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.14, Intramural Research
Training Award; 93.22, Clinical Research
Loan Repayment Program for Individuals
from Disadvantaged Backgrounds; 93.232,
Loan Repayment Program for Research
Generally; 93.39, Academic Research
Enhancement Award; 93.936, NIH Acquired
Immunodeficiency Syndrome Research Loan
Repayment Program; 93.187, Undergraduate
Scholarship Program for Individuals from
Disadvantaged Backgrounds, National
Institutes of Health, HHS)
Dated: February 21, 2008.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 08–888 Filed 2–28–08; 8:45 am]
BILLING CODE 4140–01–M
National Institutes of Health
rwilkins on PROD1PC63 with NOTICES
Office of the Director, National
Institutes of Health; Notice of Meeting
Pursuant to section 10(a) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of a meeting of the
Advisory Committee on Research on
Women’s Health.
The meeting will be open to the
public, with attendance limited to space
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Substance Abuse and Mental Health
Services Administration
Agency Information Collection
Activities: Proposed Collection;
Comment Request
In compliance with section
3506(c)(2)(A) of the Paperwork
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Reduction Act of 1995 concerning
opportunity for public comment on
proposed collections of information, the
Substance Abuse and Mental Health
Services Administration will publish
periodic summaries of proposed
projects. To request more information
on the proposed projects or to obtain a
copy of the information collection
plans, call the SAMHSA Reports
Clearance Officer on (240) 276–1243.
Comments are invited on: (a) Whether
the proposed collections of information
are necessary for the proper
performance of the functions of the
agency, including whether the
information shall have practical utility;
(b) the accuracy of the agency’s estimate
of the burden of the proposed collection
of information; (c) ways to enhance the
quality, utility, and clarity of the
information to be collected; and (d)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques or
other forms of information technology.
Proposed Project: Data Toolkit Protocol
for the Crisis Counseling Assistance
and Training Program (CCP) (OMB No.
0930–0270)—Revision
The Substance Abuse and Mental
Health Services Administration’s
(SAMHSA) Center for Mental Health
Services (CMHS) will create a toolkit to
be used for the purposes of collecting
data on the Crisis Counseling Assistance
and Training Program (CCP). The CCP
provides supplemental funding to states
and territories for individual and
community crisis intervention services
during a federal declared disaster in
accordance with section 416, Robert T.
Stafford Disaster Relief and Emergency
Assistance Act (Pub. L. 93–288, as
amended).
The CCP has provided disaster mental
health services to millions of disaster
survivors since its inception and, as a
result of 30 years of accumulated
expertise, it has become an important
model for Federal response to a variety
of catastrophic events. State CCPs, such
as Project HOPE (after Hurricane Floyd
in North Carolina), Project Heartland (in
Oklahoma City after the Murrah Federal
Building bombing), Project Liberty (in
New York after 9/11), and Project
Outreach for Recovery (after the Rhode
Island nightclub fire), gulf coast States
affected by the 2005 hurricanes, and
recent 2007 southern California
wildfires have primarily addressed the
short-term mental and behavioral health
needs of communities through (a)
outreach and public education, (b)
individual and group counseling, and
(c) referral. Disaster victims are
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]]>Agencies
[Federal Register Volume 73, Number 41 (Friday, February 29, 2008)]
[Notices]
[Pages 11123-11126]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-3837]
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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, HHS.
ACTION: Notice.
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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.
A Pharmacophore for Isatin-[beta]-Thiosemicarbazone Compounds With
MDR1-Inverse Activity
Description of Technology: One of the major hindrances to
successful cancer chemotherapy is multi-drug resistance (MDR), which is
frequently caused by the increased expression or activity of ABC
transporter proteins. Research has generally been directed to
overcoming MDR during cancer therapy by inhibiting the activity of ABC
transporters. However, compounds that inhibit ABC transporter activity
often elicit strong and undesirable side-effects, restricting their
usefulness in therapy.
In an alternative approach to reducing the debilitating effects of
MDR in cancer therapy, scientists at the National Cancer Institute
identified a family of compounds whose antiproliferative effects were
actually enhanced in cells with MDR. These compounds included NSC
73306, a specific compound that increased the chemosensitivity of cells
that overexpress ABC transporters without inhibiting ABC transporter
activity. This invention concerns new analogs of NSC 73306 with
improved selectivity and solubility, and the use of the analogs as
therapeutics.
Applications:
Treatment of cancers associated with multi-drug resistance, either
alone or in combination with other therapeutics.
Development of a pharmacophore for improved effectiveness in
treating cancers associated with multi-drug resistance.
Advantages:
The agents capitalize on one of the most common drawbacks to cancer
therapies (MDR) by using it as an advantage to treating cancer.
Increased specificity allows these analogs to be tailored to
treating cancers associated with the overexpression and hyperactivity
of particular ABC transporters.
Increased solubility allows greater access of the agent to tumor
cells, increasing therapeutic effectiveness of the agents.
Benefits: Cancer is the second leading cause of death in United
States and it is estimated that there will be approximately 600,000
deaths caused by cancer in 2007. Improving the quality of life and
duration of life of cancer patients will depend on chemotherapies with
increased effectiveness and reduced toxicity, thus this technology can
contribute significantly to a social cause. Furthermore, small molecule
cancer therapy technologies have a potential market of more than $2
billion.
Inventors: Matthew D. Hall et al. (NCI).
[[Page 11124]]
U.S. Patent Status: Provisional U.S. Application (HHS Reference No.
E-017-2008/0-US-01).
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute's
Laboratory of Cell Biology is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize for the clinic, compounds that
demonstrate MDR1-inverse activity. Please contact John D. Hewes, PhD at
301-435-3121 or hewesj@mail.nih.gov for more information.
An Improved Non Viral System for Tumor Specific Suicide Gene Therapy
Description of Technology: Numerous tumor specific promoters have
been identified and developed for targeted gene therapy. Survivin
promoter activity is upregulated in 75% of tumors, however the activity
is specific but low, resulting in sub-optimal suicide gene expression.
Combination of survivin promoter with Bax, a proapoptotic gene,
previously used in such therapy has demonstrated low efficacy.
Scientists at NCI have made a plasmid construct consisting of
survivin promoter driven mutant form of bax that is constitutively
active. This construct is more potent than the wild type bax, improving
its efficacy several-fold, while, retaining specificity for tumors, as
determined by in vitro and in vivo studies.
This new technology does not use CMV or SV-40 promoters,
alleviating the need for modifications for commercialization.
Advantages:
Can be used with cationic liposomes or other DNA delivery systems.
Can be incorporated into adenoviral and lentiviral vectors.
Excludes viral promoters.
Can be modified easily to use other promoters/suicide genes.
Applications:
Cancer therapeutics
Targeted Gene therapy
Market: In patients with advanced solid tumors or recurrences
despite surgery, chemotherapy can provide quality survival. However,
responses are usually partial, often disappointingly brief and
unpredictable and coupled with side effects. These limitations of
traditional cytotoxic chemotherapy make it necessary to explore other
therapies such as targeted gene therapy. Viruses, while the carrier of
choice in most gene therapy studies, present a variety of potential
problems to the patient--toxicity, immune and inflammatory responses,
and gene control and targeting issues. In addition, there is a fear
that the viral vector may recover its ability to cause disease in the
patient. Our new technology addresses some of the above issues making
it a suitable agent for cancer and gene therapy.
Development Status: Early.
Inventors: Himanshu Garg and Robert P. Blumenthal (NCI).
Patent Status: HHS Reference No. E-245-2007/0--Research Tool.
Patent protection is not being sought for this technology.
Licensing Status: Available for non-exclusive licensing.
Licensing Contact: John Stansberry, PhD; 301-435-5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute
Center for Cancer Research Nanobiology Program is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize tumor specific
suicide gene therapy using survivin promoter driven mutant bax. Please
contact John D. Hewes, PhD at 301-435-3121 or hewesj@mail.nih.gov for
more information.
Eeyarestatins: Novel Deubiquitination Inhibitors for the Treatment of
Drug-Resistant Cancers
Description of Technology: The ubiquitin-proteasome system has
recently been recognized to play a central role in tumor biology.
Bortezomib, an inhibitor of the chymotrypsin-like activity of the
proteasome, has clinical activity in a variety of hematologic
malignancies and is FDA approved for use in Multiple Myeloma and Mantle
Cell Lymphoma.
The present invention for the first time describes that
Eeyarestatins, a new class of small molecules, are potential anti-
cancer agents. The compounds inhibit the deubiquitination of proteins
by targeting the deubiquitination enzymes in the protein degradation
pathway. More specifically, the inventors have demonstrated that the
Eeyarestatins successfully kill different leukemia and lymphoma cell
lines as well as leukemia cells isolated from patients with chronic
lymphocytic leukemia by inducing the expression of Noxa, a pro-
apoptotic member of the Bcl-2 protein family. Additionally,
Eeyarestatins are active against cells that are resistant to Bortezomib
and thus can be effective against drug-resistant tumors.
Applications:
Eeyarestatins can be developed for the treatment of
deubiquitination related disorders such as cancers and proliferative
disorders.
Eeyarestatins can potentially have broader use against HIV and
immune related disorders considering the role of deubiquitination in
budding of retroviruses and immune regulation.
Advantages:
Eeyarestatins are active against cells that are resistant to
Bortezomib.
In vitro data shows activity of Eeyarestatins against primary cells
from patients with chronic lymphocytic leukemia. Clinical trials show
that Bortezomib is inactive against patients suffering from chronic
lymphocytic leukemia.
Market: The current cancer chemotherapeutic market is valued at $42
billion and expected to grow. Additionally, this compound has potential
use in HIV and immune related disorders.
Development Status: In vitro studies are completed and in vivo
animal model studies are planned.
Inventors: Adrian Wiestner (NHLBI), Yihong Ye (NIDDK), Qiuyan Wang
(NIDDK), Helena Mora-Jensen (NHLBI)
Publication: Q Wang, L Li, Y Ye. Inhibition of p97-dependent
protein degradation by Eeyarestatin I. J Biol Chem. 2008 Jan 16; Epub
ahead of print, doi 10.1074/jbc.M708347200.
Patent Status: U.S. Provisional Application No. 60/961,202 filed 17
Jul 2007 (HHS Reference No. E-208-2007/0-US-01)
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Surekha Vathyam; 301-435-4076;
vathyams@mail.nih.gov.
Collaborative Research Opportunity: The National Institutes of
Health laboratories of Dr. Adrian Wiestner (NHLBI) and Dr. Yihong Ye
(NIDDK) are seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize Eeyarestatins. Please contact Dr. Wiestner (301-594-6855,
wiestnera@mail.nih.gov) or Dr. Ye (301-594-0845, yihongy@mail.nih.gov)
for more information.
Synergistic Effect of TGF-Beta Blockade and Immunogenic Agents on
Tumors
Description of Technology: Overcoming immune suppression in cancer
patients is a major challenge for the success of cancer immunotherapy.
TGF-[beta] and its receptors are expressed in essentially all tissues,
and they have been found to be important in many cellular processes
including cell growth inhibition. The inhibition of TGF-[beta]
[[Page 11125]]
signaling has been shown to have an inhibitory effect on tumor growth.
However, TGF-[beta] also has immunosuppressive properties.
Cancer vaccines are one of many therapies available for treatment
and prevention. In particular, vaccines that elicit immune responses
have been used to treat or control tumor growth that has evaded
immunosurveillance. However, these vaccines have demonstrated limited
success.
Available for licensing is a method for synergistically affecting
tumor growth involving the administration of an agent that blocks the
TGF-[beta] signaling pathway, in combination with an immunogenic agent.
The agent that blocks the TGF-[beta] signaling pathway may inhibit the
immunosuppressive effects of TGF-[beta], while the immunogenic agent is
believed to enhance an immune response. Surprisingly, the combination
of such elements produces a synergistic effect. The administration of
the 1D11.16 anti-TGF-[beta] antibody in combination with the human
papilloma virus E7(49-57) peptide enhances tumor regression in an
animal model. The administration of the 1D11.16 anti-TGF-[beta]
antibody in combination with irradiated CT26 cells enhances tumor
regression in another mouse model. The investigators found that
administering the combination of agents is more effective than the sum
of their individual effects.
Applications: A method of cancer combination therapy based on
immunotherapeutics.
Development Status: The invention is in the clinical stages of
development.
Inventors: Masaki Terabe (NCI) et al.
Publications:
1. PCT patent publication WO 2006/089251, August 24, 2006.
2. M Terabe et al. Transforming growth factor-beta production and
myeloid cells are an effector mechanism through which CD1d-restricted T
cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance:
abrogation prevents tumor recurrence. J Exp Med. 2003 Dec
1;198(11):1741-1752.
Patent Status: U.S. Provisional Application No. 60/654,329 filed 17
Feb 2005 (HHS Reference No. E-019-2005/0-US-01); PCT Application No.
PCT/US2006/005888 filed 16 Feb 2006 (HHS Reference No. E-019-2005/0-
PCT-02); U.S. Patent Application No. 11/816,410 filed 15 Aug 2007 (HHS
Reference No. E-019-2005/0-US-06)
Licensing Status: Available for exclusive and non-exclusive
licensing.
Licensing Contact: Jennifer Wong; 301-435-4633;
wongje@mail.nih.gov.
Biologically Active Macrolides, Compositions and Uses Thereof
Description of Technology: The current invention embodies the
identification of a novel class of potent vacuolar-type (H+)-ATPase-
inhibitory compounds. Vacuolar-type (H+)-ATPases are present in many
tissues and cells of the body and are involved in the maintenance of
various physiological functions. The modification of these functions,
via inhibition of vacuolar-type (H+)-ATPases, may represent an
effective means of treating various disease states, including
Alzheimer's disease, glaucoma, and osteoporosis. In addition, these
inhibitors may also be of particular value for use against cancer, as
vacuolar-type (H+)-ATPases have been implicated in processes relating
to cellular proliferation, angiogenesis, tumor cell invasiveness,
metastasis, and drug resistance.
Inventors: Michael R. Boyd (NCI), Kirk R. Gustafson (NCI), et al.
Patent Status: U.S. Patent No. 7,144,918 issued 05 Dec 2006 (HHS
Reference No. E-203-2000/0-US-04); U.S. Patent Application No. 11/
435,189 filed 16 May 2006 (HHS Reference No. E-203-2000/08-US-08)
Licensing Status: Available for exclusive and non-exclusive
licensing.
Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560;
madua@mail.nih.gov.
Human p53 Mutations and a Genetic System in Yeast for Functional
Identification of Human p53 Mutations
Description of Technology: The tumor suppressor gene p53, a key
regulator of cellular mechanisms that maintain genome integrity, is the
most commonly inactivated gene target associated with neoplastic
transformation. p53 is mutated in about 50% of all human tumors and
more than 80% of these mutations are missense, leading to single amino
acid changes. This invention relates to human p53 mutants and
identification methods using screening assays in the yeast
Saccharomyces cerevisiae to functionally categorize expressed p53
mutant proteins at varying levels of expression towards several human
target response sequences. Additionally, the invention relates to
methods of detecting or generating novel human p53 mutations with
properties that can include toxicity in yeast and growth suppression in
human cells, enhanced or reduced transactivation relative to wildtype
p53, altered promoter selectivity, and reactivation by mutation or
chemical modification of common tumor mutations for the transactivation
function of major p53 downstream genes. In particular, the inventors
have discovered a V122A p53 mutation exhibits strong cell proliferation
inhibition. This feature suggests that p53 alleles such as V122A might
be valuable both for functional studies of p53-regulated cellular
responses and possibly for p53 based cancer gene therapy.
Applications:
Cancer therapeutics.
Model to screen for small molecules or peptides that can modify p53
functions.
Pharmaceutical screen for p53 drug modifiers.
Market:
An estimated 1,444,920 new cancer diagnoses in the U.S. in 2007.
Cancer drug market is estimated to be $50 billion a year in 2010.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Michael A. Resnick and Alberto Inga (NIEHS)
Publications:
1. A Jegga, A Inga, D Menendez, BJ Aronow, MA Resnick. Functional
evolution of the p53 regulatory network through its target response
elements. Proc Natl Acad Sci. USA. 2008 Jan 22;105(3):944-949.
2. MM Horvath, X Wang, MA Resnick, DA Bell. Divergent evolution of
human p53 binding sites: cell cycle versus apoptosis. PLoS Genet. 2007
Jul;3(7):1284-1295.
3. D Menendez, A Inga, J Snipe,O Krysiak, G Sch[ouml]nfelder, MA
Resnick. A single-nucleotide polymorphism in a half-binding site
creates p53 and estrogen receptor control of vascular endothelial
growth factor receptor 1. Mol Cell Biol. 2007 Apr;27(7):2590-2600.
4. P Monti, Y Ciribilli, J Jordan, P Menichini, DM Umbach, MA
Resnick, L Luzzato, A Inga, G Fronza. Transcriptional functionality of
germ line p53 mutants influences cancer phenotype. Clin Can Res. 2006
Jul 1;13(13):3789-3795.
5. D Menendez, A Inga, J Jordan, MA Resnick. Changing the p53
master regulatory network: ELEMENTary, my dear Mr. Watson. Oncogene.
2007 Apr 2;26(15):2191-2201.
6. D Menendez, A Inga, J Jordan, MA Resnick. The biological impact
of the human master regulator p53 can be altered by mutations that
change the spectrum and expression of its target genes. Mol Cell Biol.
2006 Mar;26(6):2297-2308.
7. DJ Tomso, A Inga, D Menendez, G Pittman, M Campbell, D Bell, MA
[[Page 11126]]
Resnick. Functionally distinct polymorphic sequences in the human
genome that are targets for p53 transactivation. Proc Natl Acad Sci
USA. 2005 May 3;102(18):6431-6436.
8. MA Resnick and A Inga. Functional mutations in the sequence-
specific transcription factor p53 and implications for master genes of
diversity. Proc Nat Acad Sci USA. 2003 Aug 19;100(17):9934-9939.
9. A Inga, F Storici, TA Darden, MA Resnick. Differential
transactivation by the p53 transcription factor is highly dependent on
p53 level and promoter target sequence. Mol Cell Biol. 2002
Dec;22(24):8612-8625, 2002.
Patent Status:
U.S. Patent No. 7,256,260 issued 14 Aug 2007 (HHS Reference No. E-
183-1999/0-US-07)
U.S. Patent Application No. 11/893,037 filed 14 Aug 2007 (HHS
Reference No. E-183-1999/0-US-09)
European Patent Application No. 0094897.0 filed 28 July 2007,
recently allowed (HHS Reference No. E-183-1999/0-EP-05)
Australian Patent No. 784293 issued 14 Aug 2007 (HHS Reference No.
E-183-1999/0-AU-03)
Australian Patent Application No. 2006202361 filed 2 Jun 2006 (HHS
Reference No. E-183-1999/0-AU-08)
Canadian Patent Application No. 2380631 filed 28 July 2000 (HHS
Reference No. E-183-1999/0-CA-04)
Japanese Patent Application No. 2001-514117 filed 28 July 2000 (HHS
Reference No. E-183-1999/0-JP-03)
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Jennifer Wong; 301-435-4633;
wongje@mail.nih.gov.
Dated: February 21, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-3837 Filed 2-28-08; 8:45 am]
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