[Federal Register Volume 75, Number 144 (Wednesday, July 28, 2010)]
[Notices]
[Pages 44267-44270]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-18487]


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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.

Software System With Applications in Clinical Prognosis, Personalized 
Medicine and Clinical Research

    Description of Invention: Available for licensing is software that 
can provide prognostic information for different diseases and in 
particular for cancer. The software can determine whether a particular 
genotype has a significant association with survival time for an

[[Page 44268]]

individual receiving treatment. For example, it can determine if a 
specific genetic pattern is associated with an increased or decreased 
time to recurrence of a particular type of cancer for patients on a 
given treatment regimen.
    Applications:
     Applications in clinical research:

--Studying relationship between genotypes and survival times.
--Evaluation of treatment regimens.

     Applications in drug discovery programs.
     Clinical prognosis.
     Personalized medicine.
    Development Status:
     The invention has been fully developed.
     The software will be readily available in executable form 
if so requested.
    Inventor: Brian T. Luke (SAIC/NCI).
    Patent Status: HHS Reference No. E-182-2010/0--Software. Patent 
protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contacts:
     Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
     Michael Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The NCI 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 301-435-3121 or 
[email protected] for more information.

Software for Accurate Segmentation of Cell Nuclei in Breast Tissue

    Description of Invention: Automatic segmentation of cell nuclei is 
critical in several high-throughput cytometry and pathology 
applications (1), such as spatial analysis of genetic loci by 
fluorescence in situ hybridization (``FISH''), whereas manual 
segmentation is laborious (2). Current automated segmentation methods 
have varying performance in the presence of distortions introduced 
during sample preparation, non-uniform illumination, clustering of the 
individual objects of interest (cells or cell nuclei), and seldom 
assess boundary accuracy.
    Researchers at the National Cancer Institute-Frederick, NIH, have 
developed an automatic algorithm to segment cell nuclei (3) and FISH 
signals from two-dimensional images of breast tissue. This automated 
system integrates a series of advanced image processing methods to 
overcome the delays inherent to current manual methods for segmenting 
(delineating) individual cell nuclei in tissue samples. The system 
automatically selects a subset of nuclei that with high likelihood are 
accurately segmented. This system has been validated using both 
simulated and actual datasets that have been accurately analyzed by 
manual methods. The system generalizes to independent analysis of many 
spatial parameters useful for studying spatial gene positioning in 
interphase nuclei, and potentially has a wide range of diagnostic 
pathology, cytological and high throughput screening applications.
    Applications:
     Investigations on genomic organization (nuclear 
architecture and non-random gene positioning) in the individual nuclei 
in tissues.
     Other pathology and cytological and high throughput 
screening applications requiring precise, quantitative analysis of a 
subset of cell nuclei in the sample.
    Advantages:
     Automatic.
     Efficient, robust and effective in extracting individual 
nuclei with FISH labels.
     Facilitates reproducible and unbiased spatial analysis of 
DNA sequences in interphase nuclei.
    Development Status:
     Early stage.
     Negotiations are underway with several companies to scale 
up development of the system and to undertake pre-clinical validation 
for gene positioning in the nuclei of breast sections as a possible 
early-stage diagnostic or prognostic test for cancer.
    Inventors: Kaustav Nandy et al. (NCI).
    Related Publications:
    1. Gudla PR, Nandy K, Collins J, Meaburn KJ, Misteli T, Lockett SJ. 
A high-throughput system for segmenting nuclei using multiscale 
techniques. Cytometry A. 2008 May;73(5):451-466. [PubMed: 18338778].
    2. Meaburn KJ, Gulda PR, Khan S, Lockett SJ, Misteli T. Disease-
specific gene repositioning in breast cancer. J Cell Biol. 2009 Dec 
14;187(6):801-812. [PubMed: 19995938].
    3. Nandy K, Gudla PR, Meaburn KJ, Misteli T, Lockett SJ. Automatic 
nuclei segmentation and spatial FISH analysis for cancer detection. 
Conf Proc IEEE Eng Med Biol Soc 2009;2009:6718-6721. [PubMed: 
19963931].
    Patent Status: HHS Reference No. E-106-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Patrick P. McCue, PhD; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The inventers, working for the 
Office of the Director, National Cancer Institute, are seeking 
statements of capability or interest from parties interested in 
collaborative research (using the Cooperative Research and Development 
Agreement (CRADA) or Material Transfer Agreement (MTA)) to further 
develop, evaluate, or commercialize the software for accurate 
segmentation of cell nuclei and FISH signals in tissue sections. 
Collaborators working in the field of quantitative and automated 
pathology may be interested. Please contact John Hewes, PhD, at 301-
435-3121 or [email protected] for more information.

Use of Cucurbitacins and Withanolides for the Treatment of Cancer

    Description of Invention: Certain members of the cucurbitacin and 
Withanolide family have been identified that can sensitize some tumor 
cell lines to cell death (apoptosis) on subsequent exposure of the 
cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL ``death 
receptors''. These PARAS include TRAIL itself, and agonist antibodies 
to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death 
receptor 5 (DR5, TRAIL-R2).
    The protein TRAIL has a very interesting characteristic that it can 
preferentially cause death of cancer cells whereas normal non-
transformed cells are unaffected. Thus use of TRAIL or agonist 
antibodies to its so-called ``death receptors'' has been a current 
focus in cancer therapy.
    Applications:
     Use of the compounds with known TRAIL or agonist 
antibodies such as Mapatumumab (currently being developed by Human 
Genome Sciences).
     Use of the compounds in combination with immunotherapeutic 
approaches for the treatment of cancer.
    Advantages: CUCURBITACINS AND WITHANOLIDES can be successfully 
developed in combination with known TRAIL agonist have the potential of 
new cancer combination therapies without major toxicities.
    Development Status: In vivo studies are ongoing.
    Inventors: Thomas J. Sayers et al. (NCI).
    Publication: NL Booth et al. A cell-based high-throughput screen to 
identify synergistic TRAIL sensitizers. Cancer Immunol Immunother. 2009 
Aug;58(8):1229-1244. [PubMed: 19089423].

[[Page 44269]]

    Patent Status: U.S. Provisional Application No. 61/287,139 filed 16 
Dec 2009 (HHS Reference No. E-050-2010/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Sabarni Chatterjee, PhD; 301-435-5587; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Experimental Immunology, Cancer Inflammation Program, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
the use of certain cucurbatacins or withanolides in combination with 
pro-apoptotic agonists of TRAIL death receptors for cancer therapy. 
Please contact John Hewes, PhD, at 301-435-3121 or [email protected] 
for more information.

Nitroxyl (HNO) Releasing Compounds and Uses Thereof in Treating 
Diseases

    Description of Invention: This technology discloses HNO releasing 
compounds and methods of treating various diseases with such compounds. 
HNO has recently emerged as a prospective pharmacological agent. 
Studies of the chemistry of HNO have led to an understanding that HNO 
is vastly different from nitric oxide (NO), the one-electron oxidation 
product of HNO. HNO displays unique cardiovascular properties and has 
been shown to have positive effects in failing hearts without changing 
heart rate. HNO has also been shown to have beneficial effects in 
ischemia reperfusion injury. In addition to the cardiovascular effects 
observed, HNO has shown initial promise in the realm of cancer therapy. 
HNO has been demonstrated to inhibit a key glycolytic enzyme. Due to 
the Warburg effect, inhibiting glycolysis is an attractive target for 
inhibiting tumor proliferation. HNO has recently been shown to inhibit 
tumor proliferation in mouse xenografts. Additionally, HNO inhibits 
tumor angiogenesis and induces cancer cell apoptosis.
    Applications:
     Potential treatment for cardiovascular disease, ischemia, 
and cancer.
     Tool to probe the role of HNO in normal physiology and 
disease states.
    Inventors: Larry K. Keefer (NCI).
    Related Publications:
    1. CH Switzer, et al. The emergence of nitroxyl (HNO) as a 
pharmacological agent. Biochim Biophys Acta 2009 Jul;1787(7):835-840. 
[PubMed: 19426703].
    2. LK Keefer. Nitric oxide (NO)- and nitroxyl (HNO)-generating 
diazeniumdiolates (NONOates): emerging commercial opportunities. Curr 
Top Med Chem. 2005;5(7):625-636. [PubMed: 16101424].
    Patent Status: U.S. Provisional Application No. 61/315,604 filed 19 
Mar 2010 (HHS Reference No. E-019-2010/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Steve Standley, PhD; 301-435-4074; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Comparative Carcinogenesis, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize agents that 
generate HNO in physiological media for therapeutic benefit. Please 
contact John Hewes, PhD, at 301-435-3121 or [email protected] for 
more information.

Prolonging Survival in Melanoma Patients: Early Stage Diagnosis and 
Treatment by Detecting and Inhibiting NUAK2 Overexpression

    Description of Invention: Melanoma accounts for only 4% of skin 
cancers, but is responsible for over 75% of skin cancer deaths 
worldwide. There are few treatment options available for melanoma and 
all current options show limited effectiveness. Melanoma is most 
treatable in its early stages, but most cases are not identified until 
the disease has progressed to the point where treatment is less 
effective. As normal melanocytes transform into melanoma tumor cells 
and metastasize, many changes occur in their gene expression patterns. 
Identifying genes whose expression levels impact melanoma patient 
survival is a key factor in developing better early detection tests and 
more effective treatment modalities for the disease.
    NUAK2 is a stress-activated kinase and a member of the SNF-1/AMPK 
kinase family, a conserved family of serine/threonine kinases 
ubiquitous to all eukaryotes. This enzyme is normally involved in 
helping cells cope with glucose starvation, promoting cell-cell 
detachment for motility, and protecting cells from CD95-mediated 
apoptosis. SNF-1/AMPK kinases, such as NUAK2, also regulate cell cycle 
machinery by influencing the function of cyclin-dependent kinases 
(CDKs), such as CDK2. When deregulated, SNF-1/AMPK family members are 
known to contribute to cancer development and tumor progression in 
various cancers.
    Scientists at the National Institutes of Health (NIH) have 
identified the NUAK2 gene (also known as SNARK) as a factor to predict 
the clinical outcome for melanoma patients. NUAK2 was selected as a 
gene of interest through extensive analysis of over 120 primary 
melanomas using a microarray-based comparative genomic hybridization 
approach which showed that genetic aberrations in NUAK2 correlated with 
disease. The most prominent discovery was that gain at the NUAK2 locus 
and deletion at the PTEN locus strongly correlated with more severe 
acral melanoma. Overexpression of phospho-Akt (p-Akt), caused by the 
PTEN deletion, combined with the overexpression of NUAK2 were found to 
be associated with rapid disease progression, poor patient survival, 
and increased tumor thickness, especially in acral melanoma models. The 
scientists are developing diagnostic tests for NUAK2 to better detect 
melanomas at an early stage when the disease is most treatable. They 
are also developing therapeutic small hairpin RNAs (shRNAs) to inhibit 
NUAK2 gene expression and thereby reduce melanoma tumor thickness and 
prevent aggressive disease progression. The shRNAs utilized to silence 
these target genes are incorporated into lentiviral vectors, which have 
the potential to be delivered into humans. These scientists also 
observed that NUAK2 overexpression correlated with increased expression 
of various CDKs. So, they are testing the effectiveness of CDK 
inhibitors in targeting melanomas that specifically exhibit genetic 
aberrations in NUAK2 and PTEN leading to NUAK2 and p-Akt 
overexpression. These new potential diagnostics and therapeutics 
centered on NUAK2 could provide important pharmaceutical tools to 
detect and treat melanoma at various stages of disease.
    Applications:
     Diagnostic tools and kits to identify melanoma at an early 
stage of disease where treatments are more effective and the mortality 
rate is reduced. Diagnostic tests for NUAK2 expression may be most 
useful in detecting acral melanoma, which is one of the most prominent 
forms of melanoma in Hispanic, Asian, and African-American populations.
     Therapeutic nucleic acids to inhibit melanoma disease 
progression by targeting specific genes important in poor clinical 
outcomes, such as NUAK2 and PTEN.
    Advantages:
     Genetic aberrations in the NUAK2 and PTEN genes show a 
high correlation with poor clinical outcomes in

[[Page 44270]]

melanoma patients. Diagnostic tests specifically directed at NUAK2 are 
anticipated to be highly predictive of the aggression level and course 
of disease in individual patients. Gaining information about melanoma 
before late-stage symptoms are observed should give clinicians more 
opportunity to treat patients before the cancer metastasizes out of 
control.
     Few therapies exist for melanoma and the treatments 
utilized by clinicians are prone to toxic side effects. Targeted 
therapies, such as shRNAs directed against NUAK2 could combine more 
effective inhibition of melanoma with fewer harsh side effects.
    Development Status: This technology is in a preclinical stage of 
development.
    Market: There remains a long-felt public health need to develop new 
therapeutics and diagnostics for treating melanoma. Melanoma is the 
most serious type of skin cancer, accounting the majority of skin 
cancer deaths, and the percentage of people who develop melanoma has 
more than doubled in the past 30 years. With the increase in Hispanic 
and Asian populations in the United States, the incidence of acral 
melanoma has risen to become a major public health problem as it 
accounts for between 30%-70% of melanoma cases in dark-skinned 
individuals. In the United States alone in 2009, it is estimated that 
68,720 new cases of melanoma were diagnosed and 8,650 people were 
expected to die of the disease. In 2005, the American Academy of 
Dermatology and the Society for Investigative Dermatology released a 
comprehensive study that quantified the estimated total direct cost 
associated with the treatment of melanoma in 2004 at $291 million in 
the United States. Currently, there are more than 200 therapeutics in 
active development to target melanoma--from early pre-clinical to 
marketed drugs. Clearly, a sizable portion of the melanoma diagnostic 
and therapeutic markets is available, since no one course of treatment 
is effective for all patients and very few diagnostic tools exist to 
identify melanoma at early stages.
    Inventors: Vincent J. Hearing (NCI) and Takeshi Namiki (formerly 
NCI).
    Publications:
    1. T Namiki, et al. Genomic alterations in primary cutaneous 
melanomas detected by metaphase comparative genomic hybridization with 
laser capture or manual microdissection: 6p gains may predict poor 
outcome. Cancer Genet Cytogenet. 2005 Feb;157(1):1-11. [PubMed: 
15676140].
    2. JH Kim, et al. SNARK, a novel downstream molecule of EBV latent 
membrane protein 1, is associated with resistance to cancer cell death. 
Leuk Lymphoma. 2008 Jul;49(7):1392-1398. [PubMed: 18452098].
    Patent Status: U.S. Provisional Application No. 61/321,136 filed 05 
April 2010 (HHS Reference No. E-281-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Samuel E. Bish, PhD; 301-435-5282; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Cell Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize Prolonging Survival in Melanoma 
Patients. Please contact John Hewes, PhD, at 301-435-3121 or 
[email protected] for more information.

Immortalized Human Bronchial Epithelial Cell Line

    Description of Invention: Normal cells can be cultured in vitro for 
a limited period of time before they exhibit a ``crisis'' or 
senescence, wherein they display abnormal cell morphology and 
significant reduction or cessation of cell proliferation. Investigators 
at the National Cancer Institute developed immortalized cell line by 
isolating bronchial epithelial cells from non-cancerous individuals and 
subsequent infection with an adenovirus 12-SV40 virus hybrid. Unlike 
normal cells, the immortalized cells be cultured continuously in vitro 
in suitable medium and retain features of normal human bronchial 
epithelial cells, including the absence of invasive behavior in vitro 
or in vivo. These cells can also be transfected with oncogenes and used 
as a model for multistage carcinogenesis, or employed to assay a 
biological or chemical agent's ability to induce differentiation and 
carcinogenesis as well as test potential chemotherapeutic agents.
    Applications:
     Model to study multistage bronchial carcinogenesis.
     Identification of potential chemotherapeutic drugs.
     Identification of carcinogenic agents.
    Advantages: Immortalized cells that retain normal human bronchial 
characteristics.
    Market:
     Global cancer market is worth more than eight percent of 
total global pharmaceutical sales.
     Cancer industry is predicted to expand to $85.3 billion by 
2010.
    Inventors: Curtis C. Harris (NCI) et al.
    Relevant Publication: RR Reddel et al. Transformation of human 
bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 
hybrid virus, or transfection via stronium phosphate coprecipitation 
with a plasmid containing SV40 early region genes. Cancer Res. 1988 Apr 
1;48(7):1904-1909. [PubMed: 2450641].
    Patent Status: HHS Reference No. E-287-1987/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Human Carcinogenesis, is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize Immortalized Human 
Bronchial Epithelial Cell Line. Please contact John Hewes, PhD, at 301-
435-3121 or [email protected] for more information.

    Dated: July 22, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-18487 Filed 7-27-10; 8:45 am]
BILLING CODE 4140-01-P