[Federal Register Volume 75, Number 51 (Wednesday, March 17, 2010)]
[Notices]
[Pages 12764-12766]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-5765]
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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.
Spontaneously Transformed Mouse Epithelial Cancer Cell Lines Serving as
Mouse Models: A New Model for Cancer Research
Description of Invention: Investigators at the NIH have created a
collection of 45 mouse epithelial cancer cell lines derived from six
organs: Bladder, cervix, colon, lung, kidney, and mammary glands. These
cells lines were obtained from spontaneously transformed primary cell
cultures without genetic, viral or chemical manipulation so they can
serve as mouse models for studying the natural process of oncogenesis.
The cell lines were characterized cytogenetically during their
transformation from normal to spontaneously immortalization and were
found to recapitulate many of the changes observed in human cancer
cells such as the deregulation of oncogenes (Myc, Mdm2) and tumor
suppressor genes (Cdnk4a/Ink4a/p16, Rb).
Carcinomas that arise from the epithelial cells lining organs lead
to the most common cancers in humans. However, research on cellular
transformation has largely relied on fibroblast cells which are not of
epithelial origin and therefore, may not reflect the changes that lead
to epithelial oncogenesis. The availability of these mouse epithelial
cancer cell lines should allow for a more accurate analysis of this
process.
Applications: These cell lines serve as ``ideal'' murine tumor
models as they show evidence of progression, permitting analysis of the
genetic and biological changes observed in the equivalent human
carcinomas and associated with tumor progression. Their tumor histology
is comparable to human cancers.
The cell lines have unique properties that make them suitable for
study of the following:
Unlimited replicative potential.
Exhibit tumorigenic potential and EMT (Epithelial
Mesencymal Transition).
Exhibit high degree of chromosome instability (chromosome
rearrangements, amplifications) in regions orthologous to those altered
in human cancers.
Use in mapping mouse genes homologous to human cancer
genes and for the study of the effects of deregulation of cancer
associated genes, through silencing or overexpression.
For use in gene expression studies of tumor progression,
comparing profiles to human cancers involving the same tissue types.
Use as experimental controls in the analysis of oncogene
signaling pathways.
Use in the studying telomerase pathway regulation (200-
fold expression difference between cell lines).
Use of mouse as model of epithelial carcinomas and
specifically cancers of the bladder, cervix, colon, lung, mammarys and
kidney cancers.
These mouse models serve as vehicles to test the efficacy
of new therapies, targeting specific targets associated with the
transformation of six different mouse epithelial tissues.
[[Page 12765]]
Use for discovering drugs that alter the tumorigenic
potential, invasiveness, and the Epithelial-Mesenchymal Transition
state.
Advantages:
Cytogenetically defined epithelial cell lines from mouse
that model human carcinomas.
Spontaneously transformed primary cell cultures were
generated from isogenic mouse strain that has a low propensity for
epithelial tumors in vivo therefore, not involving other mouse strains
potentially influencing the genetic background.
These cell lines were generated without viral, chemical or
genetic manipulation and thus can serve as mouse models for studying
the natural process of oncogenesis and as mouse models of human
cancers.
Genomically defined colon, bladder, and kidney cell lines
showing oncogene deregulation (i.e. Mdm2 and Myc overexpression).
Development Status:
Ready for use.
Pre-clinical.
Market: Cancer is the second most common cause of death in the
United States. More than half a million Americans are expected to die
of cancer. The cell lines will serve as a valuable tool for cancer
researchers.
Inventors: Hesed AM. Padilla-Nash et al. (NCI).
Publications: None currently available for this technology.
Patent Status: HHS Reference No. E-089-2010/0--Research Material.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Sabarni Chatterjee, PhD; 301-435-5587;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Cancer Genetics Branch, is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize this technology. Please contact John Hewes,
PhD at 301-435-3131 or [email protected] for more information.
Tumor Tissues Harboring Mutations in cAMP-Specific Phosphodiesterases
Useful for the Study of Endocrine Tumors
Description of Invention: Researchers at the National Institute of
Child Health and Human Development (NICHD), NIH, have made available
samples of patient-derived adrenal and heart tumors that harbor genetic
mutations that have been implicated in the predisposition of endocrine
tumors. An endocrine tumor is a growth that affects the parts of the
body that secrete hormones. Because an endocrine tumor arises from
cells that produce hormones, the tumor itself can produce hormones and
cause serious illness.
The tumor samples made available herein contain deletions in the
cyclic nucleotide phosphodiesterase (PDE) PDE7A or PDE8B genes that
impair PDE function and are characterized by high sensitivity to
changes in cAMP levels. Commercially, phosphodiesterase inhibitors are
widely used in the treatment of various disorders, including asthma,
pulmonary hypertension, and erectile dysfunction, suggesting a
potential utility for these tissues in a wide range of investigations.
Applications: Useful in the investigation of the mechanisms of
phosphodiesterase inhibition.
Inventors: Constantine Stratakis et al. (NICHD).
Patent Status: HHS Reference No. E-059-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a biological
material license.
Licensing Contact: Patrick P. McCue, PhD; 301-435-5560;
[email protected].
Collaborative Research Opportunity: The National Institute of Child
Health and Human Development, Division of Intramural Research, is
seeking statements of capability or interest from parties interested in
collaborative research. Please contact Joseph Conrad, PhD at 301-435-
3107 or [email protected] for more information.
Akt-Ser473 Phosphorylation as a Marker for Predicting Taxane
Chemotherapy Outcome
Description of Invention: Over the past decades, taxanes such as
paclitaxel and docetaxel have emerged as effective chemotherapy agents
for breast cancer and other malignancies. Taxanes are effective in many
patients, however, not all patients benefit from this type of
chemotherapy. A significant need remains for a means of predicting
clinical outcome from taxane-based chemotherapy.
Akt, a serine/threonine kinase that can block apoptosis, has been
implicated in the regulation of microtubule dynamics and organization.
Akt phosphorylation and its transducing downstream events play a
central role in cell survival and cell cycle progression at the
G2/M transition. Paclitaxel or docetaxel inhibits Akt-Ser473
phosphorylation (pAkt) and induces mitotic arrest. Therefore, taxanes
may cause more damage to tumor cells that are dependent on pAkt for
survival and cell cycle progression, significantly impacting treatment
outcome.
Researchers at the National Cancer Institute, NIH, have identified
pAkt as having predictive significance for paclitaxel chemotherapy
outcome in patients with early stage breast cancer. The researchers
have developed an immunohistochemistry method for determining pAkt
status with appropriate controls for assay performance and cutoff for
pAkt positivity. They also discovered methods of correlating pAkt
expression with clinical outcome (disease-free survival and overall
survival). pAkt is a novel predictive marker of taxane chemotherapy,
and can be applied to indicate which patients should receive taxane-
based chemotherapy.
Applications: A Kit for identifying pAkt-positive tumors in
surgical tumor specimens or tumor biopsies prior to treatment
(adjuvant, neoadjuvant therapy or therapy for metastatic disease); and
methods for predicting clinical outcome from taxane chemotherapy.
Advantages: pAkt is a useful clinical predictive marker to
determine which patients should or should not receive taxane-based
chemotherapy for cancer. Determining pAkt status would allow patients
with pAkt-positive tumors to elect taxane therapy for whom are likely
to benefit, and allow patients with pAkt-negative tumors for whom are
unlikely to benefit to be spared from taxane therapy as well as
toxicity, and earlier use of other therapies that could be more
effective. The application of this invention may potentially reduce the
cost of cancer care.
Inventors: Sherry X. Yang et al. (NCI).
Related Publications:
1. Yang, SX, Costantino JP, Mamounas EP, Nguyen D, Jeong J-H,
Wolmark N, Kim C, Kidwell K, Paik S, Swain SM. Correlation of levels of
Akt phosphorylation at Ser473 with benefit from paclitaxel chemotherapy
in NSABP B-28 patients with node-positive breast cancer. J Clin Oncol.
2009 (May 20 Supplement);27(15S):537.
2. Yang SX, Costantino JP, Mamounas EP, Nguyen D, Jeong J-H,
Wolmark N, Kim C, Kidwell K, Paik S, Swain SM. Akt phosphorylation at
Ser473 predicts benefit to paclitaxel chemotherapy in node-positive
breast cancer. J Clin Oncol. 2010, In Press.
Patent Status: U.S. Provisional Application No. 61/180,558 filed 22
[[Page 12766]]
May 2009 (HHS Reference No. E-191-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, PhD; 301-496-7057;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute
is seeking statements of capability or interest from parties interested
in collaborative research to further develop, evaluate, or
commercialize the pAkt assay for use in a clinical setting. The
National Cancer Institute would be particularly interested in
discussing collaborations to provide additional clinical validation of
pAkt as a primary biomarker. Please contact John Hewes, PhD at 301-435-
3131 or [email protected] for more information.
Dated: March 10, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-5765 Filed 3-16-10; 8:45 am]
BILLING CODE 4140-01-P