[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