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[Federal Register Volume 74, Number 48 (Friday, March 13, 2009)]
[Notices]
[Pages 10945-10948]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-5418]

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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.

[[Page 10946]]

Gene Signature for Predicting Hepatocellular Carcinoma Patient 
Prognosis

    Description of Technology: A progressive sequence of somatic 
mutations and epigenetic changes of oncogenes or tumor suppressor genes 
are believed to cause tumor development. However, high genomic 
instability in tumors causes the accumulation of genomic aberrations 
that do not contribute to tumor progression. Therefore it is important 
to distinguish between ``driver'' mutations which are functionally 
important and ``passenger'' mutations which do not provide a selective 
advantage to the tumor cells.
    The current invention describes a driver gene signature for 
predicting survival in patients with hepatocellular carcinoma (HCC). 
The gene signature includes ten HCC-associated genes, and the NIH 
researchers further discovered that a decrease in DNA copy number or 
mRNA expression of some genes is associated with a poor prognosis in 
HCC tumors, while a decrease in DNA copy number or mRNA expression of a 
few other genes is associated with a good prognosis.
    Available for licensing is a method of predicting the prognosis of 
a patient diagnosed with HCC by detecting expression of one of more 
HCC-associated genes, and a method of identifying an agent for use in 
treating HCC.
    Applications: Prognosis for hepatocellular carcinoma (HCC) patient 
survival; Potential new method to identify therapeutic treatment for 
HCC patients.
    Market: Hepatocellular carcinoma (HCC) is the most frequent 
malignant tumor in the liver and the third leading cause of cancer 
death worldwide. Systemic chemotherapy has been shown to be ineffective 
and tumor recurrence rate after surgical resection is high due to 
relapse and metastasis. Therefore, the development of new drugs will be 
crucial to prevent relapse and to prolong patient survival.
    Development Status: Early-stage development.
    Inventors: Xin Wei Wang and Stephanie Roessler (NCI).
    Patent Status: U.S. Provisional Application No. 61/198,813 filed 10 
Nov 2008 (HHS Reference No. E-024-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
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 
Gene Signature for Predicting Hepatocellular Carcinoma Patient 
Prognosis. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Lasonolide Compounds as Reagents for Inducing Premature Chromosome 
Condensation and Methods of Treating Cancer

    Description of Technology: Lasonolide A is a natural product 
initially isolated from an extract of the shallow water Caribbean 
marine sponge. The chemical structure of lasonolide A was identified in 
2002, and it was chemically synthesized in 2007. The current invention 
discloses the discovery that lasonolide A may be used as a new reagent 
for inducing premature chromosome condensation in non-dividing cells; 
and a novel anti-proliferative and anti-metastatic agent for cancer 
treatment. Currently, it is difficult to analyze the cytogenetic 
composition of the genome of non-dividing cells because the chromosomes 
are loosely distributed in the nucleus, lasonolide A may be useful for 
performing cytogenetic studies in cells by inducing premature 
chromosome condensation without inducing mitosis. In addition, the 
invention also reveals that lasonolide A inhibits cancer cell motility. 
As such, lasonolide A may be used as an anti-cancer agent by itself or 
in combination with other anti-cancer agents such as inhibitors of 
topoisomerases.
    Applications: A new reagent for inducing premature chromosome 
condensation in non-dividing cells; a novel anti-cancer agent.
    Market: Cancer continues to be a burden to the public health of 
Americans. After heart disease, cancer is the most common cause of 
death in the United States. For 2008, it was estimated that about 
565,650 Americans were expected to die of cancer. The incidence of 
cancer has been dropping over the years but it is estimated that over 
1.4 million Americans would be diagnosed with cancer in 2008. 
Therefore, there is a continued need for the development of new 
therapies to effectively treat this disease.
    Development Status: Early-stage development.
    Inventors: Yves G. Pommier (NCI) et al.
    Patent Status: U.S. Provisional Application No. 61/137,193 filed 28 
Jul 2008 (HHS Reference No. E-247-2008/ 0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Molecular Pharmacology, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Lasonolide Compounds as Reagents for Inducing Premature Chromosome 
Condensation and Methods of Treating Cancer. Please contact John D. 
Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

Increased Image Quality for Early Colon Polyp Detection

    Description of Technology: The invention relates to a method for 
improving the specificity and sensitivity of computer tomographic 
colonoscopy (CTC) computer aided detection (CAD). Currently CTC CAD 
programs are capable of delivering high sensitivity and low false 
positive results when used to detect large polyps of 1 cm or greater in 
diameter. However, CTC CAD is not as effective at detecting medium-
sized polyps (6-9 mm in diameter) as it demonstrates lower 
sensitivities and higher false positives in this range. Since early 
polyp detection is critical to the survival of patients with colon 
cancer, the ability to accurately detect medium size polyps could be 
advantageous to the outcome of colon cancer treatment.
    The invention uses a wavelet-based analysis to distinguish true 
polyps from false positives in CTC images. The steps involved include 
generating a 2D projection image, computing features of the 2D images 
from their Haar wavelet coefficients, applying the feature selection 
algorithm, and training a classifier using the selected features to 
classify CTC CAD.
    Using this technology, it will be possible to create high quality 
images for viewing the colon surface in 3D with reduced false positives 
in the medium-sized range for colon polyps. The technology can also be 
used to locate anomalies in both medical and non-medically related 
image applications such as endoscopy, microscopy, and photography.
    Applications: High quality images for early colon polyp detection; 
Sensitive and efficient colon cancer diagnosis; Locating anomalies in 
several different image applications.
    Development Status: Early stage.

[[Page 10947]]

    Inventors: Ronald M. Summers et al. (CC)
    Publications:
    1. J Li, R Van Uitert, J Yao, N Petrick, M Franaszek, A Huang, RM 
Summers. Wavelet method for CT colonography computer-aided polyp 
detection. Med Phys. 2008 Aug;35(8):3527-3538.
    2. S Greenblum, J Li, A Huang, RM Summers. Wavelet analysis in 
virtual colonoscopy. Proc. SPIE, Vol. 6143, 614336 (March 13, 2006); 
doi:10.1117/12.655680.
    Patent Status: U.S. Patent Application No. 11/685,127 filed 12 Mar 
2007 (HHS Reference No. E-314-2006/0-US-02); No foreign rights 
available.
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey A. James, Ph.D.; 301-435-5474; 
[email protected].

Microdissection and High-Throughput Analysis of Biological Samples

    Description of Technology: A variety of techniques have been used 
to microdissect specific cells or cell populations from a histological 
sample under direct microscopic visualization. Original microdissection 
techniques involved painstaking (and sometimes clumsy) manual 
dissection using needles or other micro-manipulation devices to isolate 
individual cells based on visible, histological characteristics.
    The subject technology is a method of performing specific target 
activated transfer from a biological sample (i.e., tissue) for analysis 
using a device system that can be automated for high throughput 
analysis. The method employs a localized reagent, such as an 
absorbative stain, that specifically determines the microadhesion of 
desired cellular material in a tissue sample to a transfer surface such 
as a thermoplastic polymer film. The energy from a light or heat source 
causes the microadhesion of the target cells or cell populations to the 
thermoplastic transfer surface. Subsequent separation of the film from 
the tissue section selectively removes the adhered target from the 
tissue section. The transfer surface is activated from within the 
target to adhere the target to the transfer surface, for example by 
heating the target to adhere or to a thermoplastic transfer surface. 
Such in situ activation can be achieved by exposing the biological 
sample to an immunoreagent that specifically binds to the target (or a 
component of the target). The immunoreagent can alter the transfer 
surface directly (for example with a heat generating enzyme carried by 
the immunoreagent), or indirectly (for example by changing a 
characteristic of the target). In some embodiments, the immunoreagent 
deposits a precipitate in the target that increases its light 
absorption relative to surrounding tissue, such that the biological 
specimen can be exposed to light to selectively heat the target. 
Alternatively, the immunoreagent is an immunofluorescent agent that 
carries a fluorophore that absorbs light and emits heat.
    Applications: Microdissection of specific cells or cell populations 
from a histological sample; High throughput analysis of biological 
samples.
    Advantages: Automated system for high throughput microdissection 
and analysis; Does not require a visual detection step.
    Development Status: In vitro data can be provided upon request.
    Inventors: Michael R. Emmert-Buck (NCI), Robert F. Bonner (NICHD), 
Michael A. Tangrea (NCI), Thomas J. Pohida (CIT), Rodrigo F. Chuaqui 
(NCI).
    Patent Status:
    International Patent Application No. PCT/US03/23317 filed 23 July 
2003, which published as WO 2004/068104 on 12 Aug 2004 (HHS Reference 
No. E-113-2003/0-PCT-02),
    U.S. Patent Application No. 10/543,218 filed 22 Jul 2005 (HHS 
Reference No. E-113-2003/0-US-03),
    Canadian Patent Application No. 2513646 filed 23 Jul 2003 (HHS 
Reference No. E-113-2003/0-CA-05),
    Australian Patent Application No. 2003256803 filed 23 Jul 2003 (HHS 
Reference No. E-113-2003/0-AU-04),
    U.S. Patent Application No. 11/202,848 filed 12 Aug 2005 (HHS 
Reference No. E-113-2003/1-US-01).
    Licensing Status: Available for licensing,
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018, 
[email protected],
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Pathology, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Target Activated Microtransfer--Expression Microdissection (xMD). 
Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Use of Anthrax Lethal Factor To Treat Cancer and Screening Methods for 
MAPK Kinase Protease Activity

    Description of Technology: Anthrax toxin, produced by Bacillus 
anthracis, is composed of three proteins: Protective antigen (PA), 
edema factor (EF), and lethal factor (LF). PA by itself has little or 
no toxic effect upon cells, but serves to bind cell surface receptors 
and mediate the entry of EF and LF into the cell. EF has been 
identified as an adenylate cyclase and together with PA forms a toxin 
(edema toxin; EdTx) which can induce edema formation when injected 
subcutaneously. LF and PA together form a toxin (lethal toxin; LeTx) 
which can cause rapid lysis of certain macrophage-derived cell lines in 
vitro as well as death when injected intravenously.
    Indirect evidence had suggested that LF was a metalloprotease. 
However, the intracellular target of LF remained unknown until recently 
when NIH scientists discovered that LF proteolytically inactivates 
mitogen activated protein kinase kinase 1 and 2 (MAPKK1, 2). Using 
oocytes of the frog Xenopus laevis as well as tumor derived NIH3T3 
(490) cells expressing an effector domain mutant form of the human 
V12HaRas oncogene these scientists demonstrated that LF induced 
proteolysis of MAPKK 1 and 2, resulting in their irreversible 
inactivation. MAPKK 1 and 2 are components of the mitogen activated 
protein kinase (MAPK) signal transduction pathway, an evolutionarily 
conserved pathway that controls cell proliferation and differentiation 
in response to extracellular signals and also plays a crucial role in 
regulating oocyte meiotic maturation. Further, the MAPK pathway has 
been shown to be constitutively activated in many primary human as well 
as in tumor-derived cell lines. Consistent with this, treatment of 
V12Ha-Ras transformed NIH 3T3 cells with LeTx inhibits cell 
proliferation and causes their reversion to a non-transformed 
phenotype.
    This invention specifically relates to in vitro and ex vivo methods 
of screening for modulators, homologues, and mimetics of LF mitogen 
activated protein kinase kinase (MAPKK) protease activity. Applications 
for this technology could be:
     A novel tool (LF) for the study of the cellular role of 
the MAPK pathway in normal or tumor cells.
     Investigation of LF for developing inhibitors for cancer 
therapy. By analyzing structural-functional relationships, additional 
compounds with improved specificity, increased potency, and reduced 
toxicity can be generated. Mimetics which block MAPKK activity or the 
determination of mechanisms of regulation of proteases that target 
MAPKK at or near the same site targeted by LF could be developed.
     A protease-based assay for LF by using a peptide to test 
for LF cleavage.

[[Page 10948]]

There is no commercial test for anthrax. This assay could be used for 
testing soldiers for anthrax exposure. Characterization of the 
interaction between LF and MAPKK at the amino acid level may lead to 
the generation of inhibitors which may prove useful in treating 
anthrax.
    Inventors: Nicholas S. Duesbery (NCI), Craig Webb (NCI), Stephen H. 
Leppla (NIDCR), George F. Vande Woude (NCI).
    Patent Status:
    U.S. Patent 6,485,925 issued 26 Nov 2002 (HHS Reference No. E-068-
1998/0-US-06).
    U.S. Patent 6,893,835 issued 17 May 2005 (HHS Reference No. E-068-
1998/0-US-07).
    U.S. Patent 6,911,203 issued 28 Jun 2005 (HHS Reference No. E-068-
1998/0-US-08).
    U.S. Patent 7,056,693 issued 06 Jun 2006 (HHS Reference No. E-068-
1998/0-US-10).
    U.S. Patent 7,183,071 issued 27 Feb 2007 (HHS Reference No. E-068-
1998/0-US-11).
    International rights available.
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076; 
[email protected].

    Dated: March 5, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E9-5418 Filed 3-12-09; 8:45 am]
BILLING CODE 4140-01-P
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