Government-Owned Inventions; Availability for Licensing, 55799-55801 [2010-22834]
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Federal Register / Vol. 75, No. 177 / Tuesday, September 14, 2010 / Notices
Dated: September 8, 2010.
Bernadette Dunham,
Director, Center for Veterinary Medicine.
[FR Doc. 2010–22811 Filed 9–13–10; 8:45 am]
BILLING CODE 4160–01–S
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:
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.
jlentini on DSKJ8SOYB1PROD with NOTICES
SUMMARY:
Assay for Arf GTP-Binding Proteins
Description of Invention: The
worldwide laboratory research reagents
market is expected to surpass $13
billion in 2010, and the field of
biotechnology appears key to
maintaining the market’s growth.
Antibodies are becoming increasingly
significant, especially for targeting the
diseased cells and cell compounds.
Researchers at the National Cancer
Institute (NCI), NIH, have developed an
antibody-based assay that measures
levels of Arf GTP-binding proteins,
some of which have been linked to the
invasive behavior of cancer cells. The
assay is robust, can be performed both
on cell lysates and fixed cells, and can
distinguish among specific endogenous
Arf-GTP isoforms.
Applications:
• Research on Arf function in
physiology and cancer.
• Research on cancer invasion.
• Research on membrane traffic and
actin reorganization.
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Advantages:
• Ability to distinguish between the
specific isoforms (i.e., Arf1, Arf3, Arf4,
Arf5, and Arf6).
• Antibodies bind preferentially to
the GTP-bound form of Arf.
Inventor: Paul A. Randazzo (NCI).
Relevant Publications:
1. Spang A et al. Arf GAPs:
gatekeepers of vesicle generation. FEBS
Lett. 2010 Jun 18;584(12):2646–2651.
[PubMed: 20394747].
2. Campa F and Randazzo PA. Arf
GTPase-activating proteins and their
potential role in cell migration and
invasion. Cell Adh Migr. 2008 Oct;
2(4):258–262. [PubMed: 19262159].
Patent Status: HHS Reference No. E–
198–2010/0—Research Material. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing.
Licensing Contact: Patrick P. McCue,
PhD, (301) 435–5560;
mccuepat@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research,
Laboratory of Cellular and Molecular
Biology, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize this technology. Please
contact John D. Hewes, PhD at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
Sequences Encoding Two Novel Human
Polyomaviruses
Description of Invention: Researchers
at the National Cancer Institute, NIH,
have discovered two species of a
previously unknown polyomavirus
genus.
Polyomaviruses are a diverse group of
DNA-based viruses that infect humans
and various animals. At least one
human polyomavirus, the Merkel cell
polyomavirus (MCV), plays a causal role
in the development of an unusual form
of skin cancer called Merkel cell
carcinoma. The coat proteins of
polyomaviruses can spontaneously
assemble into virus-like particles (VLPs)
similar to those that have been used in
the recent vaccines against human
papillomaviruses (HPVs).
Applications:
• Development of clinical diagnostic
assays to detect linkages between the
new polyomaviruses and human
cancers.
• Development of a VLP-based
prophylactic vaccine similar to the HPV
vaccine.
Advantages: DNA sequences have
broad applications in the studies of
polyomavirus infection mechanisms
and carcinogenesis. Notably, they are:
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• Identification and purification of
the normal and mutated polyomaviral
proteins.
• Studies of antisense
oligonucleotides in polyomavirus
biology.
• Development of polyclonal and
monoclonal antibodies against
polyomaviruses.
Development Status: Pre-clinical.
Inventors: Christopher B. Buck and
Diana V. Pastrana (NCI).
Relevant Publication: Schowalter RM
et al. Merkel cell polyomavirus and two
previously unknown polyomaviruses
are chronically shed from human skin.
Cell Host Microbe Jun 25;7(6):509–515.
[PubMed: 20542254].
Patent Status: U.S. Provisional
Application No. 61/318,080 filed 26 Mar
2010 (HHS Reference No. E–051–2010/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Patrick P. McCue,
PhD; 301–435–5560;
mccuepat@mail.nih.gov.
Fenoterol and Fenoterol Analogues for
Treatment of Glioma, Glioblastoma,
and Astrocytoma
Description of Invention: To date
there is no effective treatment for the
brain tumors or brain cancers
indentified as gliomas, glioblastomas, or
astrocytomas.
This technology relates to the
discovery that fenoterol and related
analogues block astrocytoma and
glioblastoma cell division at low doses.
In a xenograft model utilizing the
1321N1 astrocytoma tumor implanted in
the flank of SKID mice, the (R,R)-4methoxyfenoterol analogue significantly
decreased tumor growth relative to a
control group receiving vehicle and
studies utilizing [3H]-(R,R)-4methoxyfenoterol have shown that the
compound readily passes the bloodbrain barrier. The anti-tumor effect is
associated with the ability of fenoterol
and related analogues to induce
production of cyclic adenosine
monophosphate (cAMP), which is
normally decreased in glioblastomas
and astrocytomas. Induced cAMP
production inhibits brain tumor growth
in vivo. Fenoterol and related analogues
are beta-2 adrenergic receptor (b2 AR)
agonists and the anti-tumor effect is
associated with the expression of this
receptor. Since there is a heterogeneous
expression of b2 AR in human brain
tumors, patients who will respond to
fenoterol therapy can be predetermined
leading to individualized treatment. In
addition to use in the initial treatment
of brain tumors, the systemic and CNS
bioavailability of the drug after oral
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Federal Register / Vol. 75, No. 177 / Tuesday, September 14, 2010 / Notices
jlentini on DSKJ8SOYB1PROD with NOTICES
administration and the minimal
systemic toxicity suggest that fenoterol
and it analogs can be used in the
adjuvant treatment of patients with b2
AR-positive gliomas, glioblastomas or
astrocytomas. Studies with a number of
fenoterol analogs and CNS-implanted
tumors are in progress.
The fenoterol analogues discussed in
this technology are subject to HHS Ref.
No. E–205–2006/3 (U.S. Patent
Application No. 12/376,945 and PCT
Publication No. WO/2008/022038).
Applications: Therapeutic in the front
line and adjuvant treatment of glioma,
glioblastoma and astrocytoma.
Advantages: Potential first-in-class
therapeutic for multiple types of brain
tumors.
Development Status: In vivo: tumor
models in SKID mice. In vitro: cellbased assays using human glioblastoma
and astrocytoma cell lines. Further in
vivo studies in animal models are
underway.
Market: Approximately 17,000
Americans are diagnosed with gliomas
annually (https://www.mayoclinic.org/
glioma/).
Inventors: Irving W. Wainer (NIA),
et al.
Publication: Submitted.
Patent Status: U.S. Provisional
Application No. 61/312,642 filed 10 Mar
2010 (HHS Reference No. E–013–
2010/0).
Licensing Status: Available for
licensing.
Licensing Contact: Fatima Sayyid,
M.H.P.M.; 301–435–4521;
Fatima.Sayyid@nih.hhs.gov.
Collaborative Research Opportunity:
The National Institute on Aging,
Laboratory of Clinical Investigation, is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize the
use of fenoterol and fenoterol analogs in
the front line and adjuvant treatment of
CNS tumors and other b2 AR expressing
tumors. Please contact Nicole Darack,
PhD at 301–435–3101 or
darackn@mail.nih.gov for more
information.
Chemical Attraction: Cell Lines
Expressing the CXCR1 or CXCR2
Chemokine Receptors
Description of Invention:
Chemoattractant receptors have been
identified as important factors in
regulating many innate and adaptive
immune responses. Modulation of these
receptors have implications for shifting
immune responses to create either a
dampening effect in fighting
inflammatory diseases, such as
autoimmune diseases or cardiovascular
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diseases, or a boosting effect to generate
more effective responses to infectious
agents, tumors, and promote wound
healing. Chemokine receptors are
expressed on a variety of tumor cells
and play a role in helping cancer cells
sense new microenvironments for
metastatic growth.
Scientists at the National Institutes of
Health (NIH) have developed human
embryonic kidney (HEK) 293 cell lines
that express the CXCR1 chemokine
receptor or the CXCR2 chemokine
receptor. These two receptors are also
known as the IL-8 receptor-alpha and
IL-8 receptor-beta, respectively. They
both effectively bind IL-8, a potent
neutrophil chemoattractant, as well as
other chemokines with varying
affinities. The collection of cell lines
produced by these scientists includes
HEK 293 cells that express the wild-type
CXCR1, wild-type CXCR2, or mutant
variants of each receptor. The cell lines
were created by stably transfecting
vectors containing the cDNA for each
receptor into HEK 293 cells. HEK 293
cells transfected with the wild-type
CXCR1 or CXCR2 display strong
chemoattractant properties when placed
in the presence of their corresponding
CXC family chemokines, such as IL-8.
Application:
• Research tools for testing the
activity of potential drugs and
chemokine analogs in their ability to
block cellular responses triggered by
CXC chemokines, such as inflammatory
responses induced by IL-8
• Cell lines expressing the wild-type
CXCR1 or CXCR2 can serve as positive
controls in chemokine receptor studies
designed to identify novel
chemoattractants or agents that inhibit
chemokinetic functions.
• Research tool for screening
compounds that block these receptors as
a possible anti-cancer agent to inhibit
angiogenesis and metastasis
Advantages:
• Both wild-type and mutant cell
lines available: Wild-type CXCR1/
CXCR2 receptors or mutant receptors
with point and deletion mutations have
been cloned into HEK 293 cells. These
cell lines will have varying degrees of
potency for their chemoattractant
responses to provide a range of
functional comparisons in chemokine
studies.
• Experimental verification of
response to CXC family chemokines:
The scientists have compiled years of
data over various publications
indicating that these receptors respond
appropriately to a profile of
chemokines.
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Inventors: Joost Oppenheim, Adit
Ben-Baruch, Ji Ming Wang, David
Kelvin (all NCI).
Publications:
1. E Cohen-Hillel, et al. Cell migration
to the chemokine CXCL8: paxillin is
activated and regulates adhesion and
cell motility. Cell Mol Life Sci. 2009
Mar;66(5):884–899. [PubMed:
19151925].
2. H Attal, et al. Intracellular crosstalk between the GPCR CXCR1 and
CXCR2: role of carboxyl terminus
phosphorylation sites. Exp Cell Res.
2008 Jan 15;314(2):352–365. [PubMed:
17996233].
3. A Ben-Baruch, et al. The
differential ability of IL–8 and
neutrophil-activating peptide-2 to
induce attenuation of chemotaxis is
mediated by their divergent capabilities
to phosphorylate CXCR2 (IL–8 receptor
B). J Immunol. 1997 Jun
15;158(12):5927–5933. [PubMed:
9190946].
4. A Ben-Baruch, et al. IL–8 and NAP–
2 differ in their capacities to bind and
chemoattract 293 cells transfected with
either IL–8 receptor type A or type B.
Cytokine 1997 Jan;9(1):37–45. [PubMed:
9067094].
5. A Ben-Baruch, et al. Interleukin-8
receptor beta. The role of the carboxyl
terminus in signal transduction. J Biol
Chem. 1995 Apr 21;270(16):9121–9128.
[PubMed: 7721826].
Patent Status: HHS Reference No. E–
221–2009/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing under a Biological Materials
License Agreement.
Licensing Contact: Samuel E. Bish,
Ph.D.; 301–435–5282;
bishse@mail.nih.gov.
DLC–1 Gene Deleted in Cancers
Description of Invention:
Chromosomal regions that are
frequently deleted in cancer cells are
thought to be the loci of tumor
suppressor genes, which restrict cell
proliferation. Recurrent deletions on the
short arm of human chromosome 8 in
liver, breast, lung and prostate cancers
have raised the possibility of the
presence of tumor suppressor genes in
this location.
The inventors have discovered the
deletion of human DLC–1 gene in
hepatocellular cancer (HCC) cells. They
have performed in vitro experiments
demonstrating the deletion in over 40%
of human primary HCC and in 90% of
HCC cell lines. The DLC–1 gene is
located on human chromosome 8p21.3–
22, a region frequently deleted in many
types of human cancer. DLC–1 mRNA is
E:\FR\FM\14SEN1.SGM
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jlentini on DSKJ8SOYB1PROD with NOTICES
Federal Register / Vol. 75, No. 177 / Tuesday, September 14, 2010 / Notices
expressed in all normal tissues tested,
but it has either no or low expression in
a high percentage of several types of
human cancer, such as liver, breast,
lung, and prostate cancers. Through in
vitro and in vivo tumor suppression
experiments, the inventors further
demonstrated that DLC–1 acts as a new
tumor suppressor gene for different
types of human cancer.
Applications:
• Method to diagnose HCC.
• Method to treat HCC patients with
DLC–1 compositions.
• Transgenic model to study HCC and
other types of human cancer.
• DLC–1 compositions.
Market:
• Primary liver cancer accounts for
about 2% of cancers in the U.S., but up
to half of all cancers in some
undeveloped countries.
• 251,000 new cases are reported
annually.
• Post-operative five year survival
rate of HCC patients is 30–40%.
Development Status: The technology
is currently in the pre-clinical stage of
development.
Inventors: Bao-Zhu Yuan, Snorri S.
Thorgeirsson, Nicholas Popescu (NCI).
Publications:
1. BZ Yuan et al. DLC–1 operates as
a tumor suppressor gene in human nonsmall cell lung carcinomas. Oncogene.
2004 Feb 19;23(7):1405–1411. [PubMed:
14661059].
2. BZ Yuan et al. DLC–1 gene inhibits
human breast cancer cell growth and in
vitro tumorigenicity. Oncogene. 2003
Jan 23;22(3):445–450. [PubMed:
12545165].
3. BZ Yuan et al. Promoter
hypermethylation of DLC–1, a candidate
tumor suppressor gene, in several
common human cancers. Cancer Genet
Cytogenet. 2003 Jan 15;140(2):113–117.
[PubMed: 12645648].
4. BZ Yuan et al. Cloning,
characterization, and chromosomal
localization of a gene frequently deleted
in human liver cancer (DLC–1)
homologous to rat RhoGAP. Cancer Res.
1998 May 15;58(10):2196–2199.
[PubMed: 9605766].
Patent Status:
• U.S. Patent No. 6,897,018 issued 24
May 2005 (HHS Reference No. E–042–
1998/0–US–03).
• U.S. Patent No. 7,534,565 issued 19
May 2009 (HHS Reference No. E–042–
1998/0–US–05).
Licensing Status: Available for
licensing.
Licensing Contact: Jennifer Wong;
301–435–4633; wongje@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute,
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Jkt 220001
Laboratory of Experimental
Carcinogenesis, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize diagnostics based on
tumor suppressor genes. Please contact
John D. Hewes, PhD, at 301–435–3121
or hewesj@mail.nih.gov for more
information.
Dated: September 7, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2010–22834 Filed 9–13–10; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Medicare & Medicaid
Services
[CMS–1338–CN]
RIN 0938–AP87
Medicare Program; Prospective
Payment System and Consolidated
Billing for Skilled Nursing Facilities for
FY 2011; Correction
Centers for Medicare &
Medicaid Services (CMS), HHS.
ACTION: Correction notice.
AGENCY:
This document corrects
technical errors that appeared in the
notice with comment period published
in the Federal Register on July 22, 2010
entitled, ‘‘Medicare Program;
Prospective Payment System and
Consolidated Billing for Skilled Nursing
Facilities for FY 2011.’’
DATES: Effective Date: This correction is
effective October 1, 2010.
FOR FURTHER INFORMATION CONTACT: Bill
Ullman, (410) 786–5667.
SUPPLEMENTARY INFORMATION:
SUMMARY:
I. Background
In FR Doc. 2010–17628 of July 22,
2010 (75 FR 42886), there were several
technical errors that are identified and
corrected in the ‘‘Correction of Errors’’
section below. The corrections
described below are effective as if they
had been included in the document
published on July 22, 2010.
Accordingly, the corrections are
effective October 1, 2010.
II. Summary of Errors
We are correcting the titles and wage
index columns (along with the resulting
values) of Tables 8A and 8B, which
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55801
appeared on page 42911 of the July 22,
2010 notice with comment period.
These two tables illustrate the skilled
nursing facility (SNF) prospective
payment system (PPS) payment rate
computations for a hypothetical ‘‘XYZ’’
SNF located in Cedar Rapids, IA (Urban
CBSA 16300) under the RUG–IV and
Hybrid RUG–III (HR–III) systems,
respectively. In the title of the tables as
well as in the third column (‘‘Wage
Index’’), the wage index value for Cedar
Rapids, IA is incorrectly displayed as
0.8858. Accordingly, in section III of
this document (‘‘Correction of Errors’’),
we are revising the entries in Tables 8A
and 8B to reflect the correct wage index
value of 0.8844. We are similarly
revising the immediately preceding
portion of the preamble text, which
references the total PPS payment
amounts displayed in these two tables.
However, we note that the
corresponding entry for CBSA 16300, as
it appears in an addendum to the July
22, 2010 notice with comment period
(Table A, ‘‘FY 2011 Wage Index for
Urban Areas Based on CBSA Labor
Market Areas’’), already reflects the
correct wage index value of 0.8844 (75
FR 42923). We are also revising the
footnote that appears in Tables 8A and
8B to clarify that in these examples, all
10 of the Medicare days listed under the
‘‘CC2’’ RUG group would involve a
resident with AIDS and, thus, would
qualify for the special 128 percent
adjustment under section 511 of the
Medicare Prescription Drug,
Improvement, and Modernization Act of
2003 (MMA) (Pub. L. 108–173, enacted
on December 8, 2003).
III. Correction of Errors
In FR Doc. 2010–17628 (75 FR 42886),
make the following corrections:
1. On page 42910, third column, in
line five from the bottom of the page,
the phrase ‘‘$41,979 for RUG–IV and
$36,517 for HR–III, respectively’’ is
revised to read ‘‘$41,935 for RUG–IV and
$36,479 for HR–III, respectively’’.
2. On page 42911, Tables 8A and 8B
are revised to read as follows:
3. On page 42911, underneath Table
8A and Table 8B, we removed the
asterisk statement ‘‘*Reflects a 128
percent adjustment from section 511 of
the MMA’’ and replaced it with
‘‘*Reflects a 128 percent adjustment
from section 511 of the MMA. All CC2
days should be considered to be for a
resident with AIDS.’’
E:\FR\FM\14SEN1.SGM
14SEN1
Agencies
[Federal Register Volume 75, Number 177 (Tuesday, September 14, 2010)]
[Notices]
[Pages 55799-55801]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-22834]
-----------------------------------------------------------------------
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.
Assay for Arf GTP-Binding Proteins
Description of Invention: The worldwide laboratory research
reagents market is expected to surpass $13 billion in 2010, and the
field of biotechnology appears key to maintaining the market's growth.
Antibodies are becoming increasingly significant, especially for
targeting the diseased cells and cell compounds.
Researchers at the National Cancer Institute (NCI), NIH, have
developed an antibody-based assay that measures levels of Arf GTP-
binding proteins, some of which have been linked to the invasive
behavior of cancer cells. The assay is robust, can be performed both on
cell lysates and fixed cells, and can distinguish among specific
endogenous Arf-GTP isoforms.
Applications:
Research on Arf function in physiology and cancer.
Research on cancer invasion.
Research on membrane traffic and actin reorganization.
Advantages:
Ability to distinguish between the specific isoforms
(i.e., Arf1, Arf3, Arf4, Arf5, and Arf6).
Antibodies bind preferentially to the GTP-bound form of
Arf.
Inventor: Paul A. Randazzo (NCI).
Relevant Publications:
1. Spang A et al. Arf GAPs: gatekeepers of vesicle generation. FEBS
Lett. 2010 Jun 18;584(12):2646-2651. [PubMed: 20394747].
2. Campa F and Randazzo PA. Arf GTPase-activating proteins and
their potential role in cell migration and invasion. Cell Adh Migr.
2008 Oct; 2(4):258-262. [PubMed: 19262159].
Patent Status: HHS Reference No. E-198-2010/0--Research Material.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, PhD, (301) 435-5560;
mccuepat@mail.nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Cellular and Molecular Biology, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize this
technology. Please contact John D. Hewes, PhD at 301-435-3121 or
hewesj@mail.nih.gov for more information.
Sequences Encoding Two Novel Human Polyomaviruses
Description of Invention: Researchers at the National Cancer
Institute, NIH, have discovered two species of a previously unknown
polyomavirus genus.
Polyomaviruses are a diverse group of DNA-based viruses that infect
humans and various animals. At least one human polyomavirus, the Merkel
cell polyomavirus (MCV), plays a causal role in the development of an
unusual form of skin cancer called Merkel cell carcinoma. The coat
proteins of polyomaviruses can spontaneously assemble into virus-like
particles (VLPs) similar to those that have been used in the recent
vaccines against human papillomaviruses (HPVs).
Applications:
Development of clinical diagnostic assays to detect
linkages between the new polyomaviruses and human cancers.
Development of a VLP-based prophylactic vaccine similar to
the HPV vaccine.
Advantages: DNA sequences have broad applications in the studies of
polyomavirus infection mechanisms and carcinogenesis. Notably, they
are:
Identification and purification of the normal and mutated
polyomaviral proteins.
Studies of antisense oligonucleotides in polyomavirus
biology.
Development of polyclonal and monoclonal antibodies
against polyomaviruses.
Development Status: Pre-clinical.
Inventors: Christopher B. Buck and Diana V. Pastrana (NCI).
Relevant Publication: Schowalter RM et al. Merkel cell polyomavirus
and two previously unknown polyomaviruses are chronically shed from
human skin. Cell Host Microbe Jun 25;7(6):509-515. [PubMed: 20542254].
Patent Status: U.S. Provisional Application No. 61/318,080 filed 26
Mar 2010 (HHS Reference No. E-051-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, PhD; 301-435-5560;
mccuepat@mail.nih.gov.
Fenoterol and Fenoterol Analogues for Treatment of Glioma,
Glioblastoma, and Astrocytoma
Description of Invention: To date there is no effective treatment
for the brain tumors or brain cancers indentified as gliomas,
glioblastomas, or astrocytomas.
This technology relates to the discovery that fenoterol and related
analogues block astrocytoma and glioblastoma cell division at low
doses. In a xenograft model utilizing the 1321N1 astrocytoma tumor
implanted in the flank of SKID mice, the (R,R)-4-methoxyfenoterol
analogue significantly decreased tumor growth relative to a control
group receiving vehicle and studies utilizing [\3\H]-(R,R)-4-
methoxyfenoterol have shown that the compound readily passes the blood-
brain barrier. The anti-tumor effect is associated with the ability of
fenoterol and related analogues to induce production of cyclic
adenosine monophosphate (cAMP), which is normally decreased in
glioblastomas and astrocytomas. Induced cAMP production inhibits brain
tumor growth in vivo. Fenoterol and related analogues are beta-2
adrenergic receptor ([beta]2 AR) agonists and the anti-tumor effect is
associated with the expression of this receptor. Since there is a
heterogeneous expression of [beta]2 AR in human brain tumors, patients
who will respond to fenoterol therapy can be predetermined leading to
individualized treatment. In addition to use in the initial treatment
of brain tumors, the systemic and CNS bioavailability of the drug after
oral
[[Page 55800]]
administration and the minimal systemic toxicity suggest that fenoterol
and it analogs can be used in the adjuvant treatment of patients with
[beta]2 AR-positive gliomas, glioblastomas or astrocytomas. Studies
with a number of fenoterol analogs and CNS-implanted tumors are in
progress.
The fenoterol analogues discussed in this technology are subject to
HHS Ref. No. E-205-2006/3 (U.S. Patent Application No. 12/376,945 and
PCT Publication No. WO/2008/022038).
Applications: Therapeutic in the front line and adjuvant treatment
of glioma, glioblastoma and astrocytoma.
Advantages: Potential first-in-class therapeutic for multiple types
of brain tumors.
Development Status: In vivo: tumor models in SKID mice. In vitro:
cell-based assays using human glioblastoma and astrocytoma cell lines.
Further in vivo studies in animal models are underway.
Market: Approximately 17,000 Americans are diagnosed with gliomas
annually (https://www.mayoclinic.org/glioma/).
Inventors: Irving W. Wainer (NIA), et al.
Publication: Submitted.
Patent Status: U.S. Provisional Application No. 61/312,642 filed 10
Mar 2010 (HHS Reference No. E-013- 2010/0).
Licensing Status: Available for licensing.
Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521;
Fatima.Sayyid@nih.hhs.gov.
Collaborative Research Opportunity: The National Institute on
Aging, Laboratory of Clinical Investigation, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize the use of
fenoterol and fenoterol analogs in the front line and adjuvant
treatment of CNS tumors and other [beta]2 AR expressing tumors. Please
contact Nicole Darack, PhD at 301-435-3101 or darackn@mail.nih.gov for
more information.
Chemical Attraction: Cell Lines Expressing the CXCR1 or CXCR2 Chemokine
Receptors
Description of Invention: Chemoattractant receptors have been
identified as important factors in regulating many innate and adaptive
immune responses. Modulation of these receptors have implications for
shifting immune responses to create either a dampening effect in
fighting inflammatory diseases, such as autoimmune diseases or
cardiovascular diseases, or a boosting effect to generate more
effective responses to infectious agents, tumors, and promote wound
healing. Chemokine receptors are expressed on a variety of tumor cells
and play a role in helping cancer cells sense new microenvironments for
metastatic growth.
Scientists at the National Institutes of Health (NIH) have
developed human embryonic kidney (HEK) 293 cell lines that express the
CXCR1 chemokine receptor or the CXCR2 chemokine receptor. These two
receptors are also known as the IL-8 receptor-alpha and IL-8 receptor-
beta, respectively. They both effectively bind IL-8, a potent
neutrophil chemoattractant, as well as other chemokines with varying
affinities. The collection of cell lines produced by these scientists
includes HEK 293 cells that express the wild-type CXCR1, wild-type
CXCR2, or mutant variants of each receptor. The cell lines were created
by stably transfecting vectors containing the cDNA for each receptor
into HEK 293 cells. HEK 293 cells transfected with the wild-type CXCR1
or CXCR2 display strong chemoattractant properties when placed in the
presence of their corresponding CXC family chemokines, such as IL-8.
Application:
Research tools for testing the activity of potential drugs
and chemokine analogs in their ability to block cellular responses
triggered by CXC chemokines, such as inflammatory responses induced by
IL-8
Cell lines expressing the wild-type CXCR1 or CXCR2 can
serve as positive controls in chemokine receptor studies designed to
identify novel chemoattractants or agents that inhibit chemokinetic
functions.
Research tool for screening compounds that block these
receptors as a possible anti-cancer agent to inhibit angiogenesis and
metastasis
Advantages:
Both wild-type and mutant cell lines available: Wild-type
CXCR1/CXCR2 receptors or mutant receptors with point and deletion
mutations have been cloned into HEK 293 cells. These cell lines will
have varying degrees of potency for their chemoattractant responses to
provide a range of functional comparisons in chemokine studies.
Experimental verification of response to CXC family
chemokines: The scientists have compiled years of data over various
publications indicating that these receptors respond appropriately to a
profile of chemokines.
Inventors: Joost Oppenheim, Adit Ben-Baruch, Ji Ming Wang, David
Kelvin (all NCI).
Publications:
1. E Cohen-Hillel, et al. Cell migration to the chemokine CXCL8:
paxillin is activated and regulates adhesion and cell motility. Cell
Mol Life Sci. 2009 Mar;66(5):884-899. [PubMed: 19151925].
2. H Attal, et al. Intracellular cross-talk between the GPCR CXCR1
and CXCR2: role of carboxyl terminus phosphorylation sites. Exp Cell
Res. 2008 Jan 15;314(2):352-365. [PubMed: 17996233].
3. A Ben-Baruch, et al. The differential ability of IL-8 and
neutrophil-activating peptide-2 to induce attenuation of chemotaxis is
mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8
receptor B). J Immunol. 1997 Jun 15;158(12):5927-5933. [PubMed:
9190946].
4. A Ben-Baruch, et al. IL-8 and NAP-2 differ in their capacities
to bind and chemoattract 293 cells transfected with either IL-8
receptor type A or type B. Cytokine 1997 Jan;9(1):37-45. [PubMed:
9067094].
5. A Ben-Baruch, et al. Interleukin-8 receptor beta. The role of
the carboxyl terminus in signal transduction. J Biol Chem. 1995 Apr
21;270(16):9121-9128. [PubMed: 7721826].
Patent Status: HHS Reference No. E-221-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
bishse@mail.nih.gov.
DLC-1 Gene Deleted in Cancers
Description of Invention: Chromosomal regions that are frequently
deleted in cancer cells are thought to be the loci of tumor suppressor
genes, which restrict cell proliferation. Recurrent deletions on the
short arm of human chromosome 8 in liver, breast, lung and prostate
cancers have raised the possibility of the presence of tumor suppressor
genes in this location.
The inventors have discovered the deletion of human DLC-1 gene in
hepatocellular cancer (HCC) cells. They have performed in vitro
experiments demonstrating the deletion in over 40% of human primary HCC
and in 90% of HCC cell lines. The DLC-1 gene is located on human
chromosome 8p21.3-22, a region frequently deleted in many types of
human cancer. DLC-1 mRNA is
[[Page 55801]]
expressed in all normal tissues tested, but it has either no or low
expression in a high percentage of several types of human cancer, such
as liver, breast, lung, and prostate cancers. Through in vitro and in
vivo tumor suppression experiments, the inventors further demonstrated
that DLC-1 acts as a new tumor suppressor gene for different types of
human cancer.
Applications:
Method to diagnose HCC.
Method to treat HCC patients with DLC-1 compositions.
Transgenic model to study HCC and other types of human
cancer.
DLC-1 compositions.
Market:
Primary liver cancer accounts for about 2% of cancers in
the U.S., but up to half of all cancers in some undeveloped countries.
251,000 new cases are reported annually.
Post-operative five year survival rate of HCC patients is
30-40%.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Bao-Zhu Yuan, Snorri S. Thorgeirsson, Nicholas Popescu
(NCI).
Publications:
1. BZ Yuan et al. DLC-1 operates as a tumor suppressor gene in
human non-small cell lung carcinomas. Oncogene. 2004 Feb 19;23(7):1405-
1411. [PubMed: 14661059].
2. BZ Yuan et al. DLC-1 gene inhibits human breast cancer cell
growth and in vitro tumorigenicity. Oncogene. 2003 Jan 23;22(3):445-
450. [PubMed: 12545165].
3. BZ Yuan et al. Promoter hypermethylation of DLC-1, a candidate
tumor suppressor gene, in several common human cancers. Cancer Genet
Cytogenet. 2003 Jan 15;140(2):113-117. [PubMed: 12645648].
4. BZ Yuan et al. Cloning, characterization, and chromosomal
localization of a gene frequently deleted in human liver cancer (DLC-1)
homologous to rat RhoGAP. Cancer Res. 1998 May 15;58(10):2196-2199.
[PubMed: 9605766].
Patent Status:
U.S. Patent No. 6,897,018 issued 24 May 2005 (HHS
Reference No. E-042-1998/0-US-03).
U.S. Patent No. 7,534,565 issued 19 May 2009 (HHS
Reference No. E-042-1998/0-US-05).
Licensing Status: Available for licensing.
Licensing Contact: Jennifer Wong; 301-435-4633;
wongje@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Laboratory of Experimental Carcinogenesis, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize diagnostics
based on tumor suppressor genes. Please contact John D. Hewes, PhD, at
301-435-3121 or hewesj@mail.nih.gov for more information.
Dated: September 7, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-22834 Filed 9-13-10; 8:45 am]
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