[Federal Register Volume 73, Number 129 (Thursday, July 3, 2008)]
[Notices]
[Pages 38230-38233]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-15201]


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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.

A Prophylactic and Therapeutic for Preventing and Treating Tularemia by 
Rapid Activation of Host Cells and Antigen Recognition

    Description of Technology: The invention is a composition and 
method for prophylactic and therapeutic treatment of tularemia caused 
by Francisella tularensis comprised of Cationic Liposome DNA Complexes 
(CLDC) complexed with noncoding DNA and membrane antigens isolated from 
F. tularensis strain LVS (MPF). F. tularensis is category A pathogen 
(as designated by the NIH) that was previously weaponized by both the 
former Soviet Union and the United States of America and is currently a 
potential bioweapon and bioterrorism threat. Furthermore, tularemia is 
endemic to the U.S. (majority of the cases occurring in the Midwest) 
and Europe. The prophylactic and therapeutic activities of this 
invention rely in part on rapid activation of host cells and 
recognition of bacterial antigens. In vivo studies in mice show that 
CLDC + MPF elicit protective immunity against pneumonic tularemia when 
administered shortly (days) prior to exposure to aerosols of virulent 
F. tularensis. The method can be applicable for eliciting immune 
response in other infectious diseases.
    Applications:
    Prophylactic and therapeutic for Tularemia.
    Biodefense agent.
    Method is applicable to other infectious diseases, particularly for 
pathogens that are enveloped or encapsulated (i.e. Pseudomonas 
aeruginosa, Neisseria meningiditis, Yersinia pestis and Influenza).
    Advantages:
    Rapid induction of protective immunity against F. tularensis.
    Avoids antibiotic resistance associated with current therapies.
    Development Status: In vitro and in vivo data are available.
    Market:
    Prophylactic and treatment for tularemia and other infectious 
diseases.
    Biodefense.
    Inventors: Catherine M. Bosio (NIAID).
    Publication: PowerPoint slide presentation of invention can be 
provided upon request.
    Patent Status: U.S. Provisional Application No. 61/030,984 filed 24 
Feb 2008 (HHS Reference No. E-095-2008/0-US-01).
    Licensing Status: This invention is available for exclusive or non-
exclusive licensing.
    Licensing Contact: Sally Hu, PhD.; 301-435-5606, [email protected].

A New Method for Screening of Anti-tumor Agents

    Description of Technology: Astrocytomas and glioblastoma multiforme 
are the most common forms of malignant brain cancer, and are often 
unresponsive to surgical removal and pharmacological therapy. The 5 
year survival rate of glioblastoma is 5%, thus, making it necessary for 
the identification of more effective anti-tumor agents. Individuals 
with the familial cancer syndrome neurofibromatosis type 1 are 
predisposed to developing multiple tumors including astrocytoma and 
glioblastoma.
    Scientists at NCI have discovered a new technology that will help 
screen multiple anti-tumor and anti-neurofibromatosis agents in a high 
throughput assay by using an astrocytoma cell line (KR158) that 
expresses the luciferase gene under the influence of dual promoters, 
E2F and CMV.
    This new technology distinguishes between cytostatic and cytotoxic 
compounds, thereby significantly reducing the time and cost required to 
screen anti-tumor agents.
    Advantages:
    Quantifiable.
    Can be used in high throughput assays.
    Distinguishes between cytostatic and cytotoxic activity of 
compounds.
    Applications:
    Cancer therapeutics.
    Gene therapy.
    Screening of anti-tumor agents.
    Screening of anti-neurofibromatosis agents.
    Pharmacology of drugs.
    Market: Neurofibromatoses is inherited by many affected individuals 
and occurs in 1 in 3500 individuals. In addition, between 30 and 50 
percent of new cases arise spontaneously through mutation in an 
individual's genes which can then be passed on to succeeding 
generations, leading to increased tumor risk. Astrocytomas and 
glioblastoma multiforme are the most common malignant brain tumor in 
adults with very poor prognosis.
    Development Status: Late-stage.
    Inventors: Jessica J. Hawes and Karlyne M. Reilly (NCI).
    Patent Status: HHS Reference No. E-038-2008/0--Research Tool. 
Patent protection is not being sought for this technology.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Mouse Cancer Genetics Program is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize anti-astrocytoma or anti-
neurofibromatosis therapy. Please contact John D. Hewes, PhD., at 301-
435-3121 or [email protected] for more information.

A Novel Therapeutic Strategy for the Treatment of Hyperpigmentation and 
Melanoma

    Description of Technology: The present invention describes that the 
transcription factor SOX9 is expressed by normal human melanocytes in 
vitro and in the skin in vivo, and that over-expression of SOX9 
decreases the proliferation of mouse and human melanoma cell lines via 
several pathways. Furthermore, SOX9 (or its

[[Page 38231]]

bioactive derivatives) appears to be potentially useful in inducing 
skin pigmentation, may inhibit the proliferation of melanoma cells and 
increase their sensitivity to retinoic acid, which could be used to 
treat melanoma.
    Advantages and Applications:
    SOX9 (or its bioactive derivative) might be useful in increasing 
skin pigmentation in acquired hypopigmentary disorders such as vitiligo 
(1-2% of world population) or post-inflammatory hypopigmentation.
    A novel gene therapy based treatment for Melanoma: Experimental 
results show that cells over-expressing SOX9 do not form tumors in 
human skin reconstructs or in mice as do wild type or GFP-transduced 
melanoma cells.
    SOX-9 therapy in combination with retinoic acid can be an effective 
therapeutic strategy for treating melanoma.
    Development Status: The technology is currently in the pre-clinical 
stage of development. Animal studies have been performed and the 
inventors are currently pursuing gene therapy approaches with SOX9 
which may be useful in the treatment of melanoma.
    Inventors: Vincent J. Hearing and Thierry Passeron (NCI).
    Patent Status: U.S. Provisional Application No. 60/963,280 filed 03 
Aug 2007 (HHS Reference No. E-150-2007/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Whitney Hastings, Ph.D.; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Laboratory of Cell Biology is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the regulation of SOX9 function as 
a strategy to treat melanoma, modulate skin pigmentation and/or 
ameliorate skin pigmentary disorders. Please contact John D. Hewes, 
Ph.D. at 301-435-3121 or [email protected] for more information.

Method for Predicting and Detecting Tumor Metastasis

    Description of Technology: Detecting cancer prior to metastasis 
greatly increases the efficacy of treatment and the chances of patient 
survival. Although numerous biomarkers have been reported to identify 
aggressive tumor types and predict prognosis, each biomarker is 
specific for a particular type of cancer, and no universal marker that 
can predict metastasis in a number of cancers has been identified. In 
addition, due to a lack of reliability, several markers are typically 
required to determine the prognosis and course of therapy.
    Available for licensing are carboxypeptidase E (CPE) inhibitor 
compositions and methods to prognose and treat cancer as well as 
methods to determine the stage of cancer. The inventors discovered that 
CPE expression levels increase according to the presence of cancer and 
metastasis wherein CPE is upregulated in tumors and CPE levels are 
further increased in metastatic cancer. This data has been demonstrated 
both in vitro and in vivo experiments and in liver, breast, prostate, 
colon, and head and neck cancers. Metastatic liver cells treated with 
CPE siRNA reversed the cells from being metastatic and arrested cells 
from further metastasis. Thus, CPE as a biomarker for predicting 
metastasis and its inhibitors have an enormous potential to increase 
patient survival.
    Applications:
    Method to prognose multiple types of cancer and determine 
likelihood of metastasis.
    Compositions that inhibit CPE such as siRNA.
    Method to prevent and treat cancer with CPE inhibitors.
    Market:
    An estimated 1,437,180 new cases and 565,650 deaths from cancer are 
projected to occur in the U.S. in 2008;
    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.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Y. Peng Loh (NICHD) et al.
    Publication: Manuscript in preparation.
    Patent Status: PCT Application No. PCT/US2008/051438 filed 18 Jan 
2008, claiming priority to 19 Jan 2007 (HHS Reference No. E-096-2007/3-
PCT-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Institute for 
Child Health and Human Development, Section on Cellular Neurobiology, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize CPE as a biomarker for predicting metastasis. Please 
contact John D. Hewes, Ph.D. at 301-435-3121 or [email protected] for 
more information.

Novel O-GLcNAcase Inhibitor and Fluorogenic Substrate as a Tool for 
Diagnosing Type 2 Diabetes

    Description of Technology: NIH researchers have synthesized a novel 
analogue of O-(2-acet-amido-2-deoxy-D-glycopyrano-sylidene)amino-N-
phenylcarbamate (PUGNAc), which bears an extension on the N-acetyl 
moiety. This modified PUGNAc acts as a selective inhibitor of O-
GlcNAcase; an enzyme that removes N-acetylglucosamine from nuclear and 
cytoplasmic proteins, and whose inhibition is associated with the 
development of Type 2 diabetes. The most desirable feature of this new 
compound is its ability to specifically inhibit O-GlcNAcase without 
targeting the related hexosaminidase A (HEX A) and hexoaminidase B (HEX 
B) enzymes. This unique property distinguishes it from the original 
PUGNAc and other compounds which inhibit O-GlcNAcase as well as other 
enzymes. It also has a smaller inhibitory effect on O-GlcNAcase 
compared to the original PUGNAc. These properties make the modified 
PUGNAc useful for diagnostic or therapeutic applications involving Type 
2 diabetes.
    A fluorescent derivative of the modified PUGNAc has also been 
developed. Modified PUGNAc, conjugated to a fluorescent moiety such as 
4-methylumbelliferone, can serve as a substrate for O-GlcNAcase without 
inhibiting HEX A. This allows the fluorescently labeled compound to be 
used for measuring O-GlcNAcase enzyme activity, and thus provide a 
means of diagnosing Type 2 diabetes in human blood or tissue samples. 
Previous reagents have monitored other Type 2 diabetes related enzymes, 
but with much less specificity. Recent studies that link mutations of 
the MGEA5 gene (which codes for O-GlcNAcase) to Type 2 diabetes provide 
further support for the use of the fluorescent derivative as a potent 
tool for diagnosing the disease. The fluorogenic derivative may also be 
used as a novel imaging agent for assessing O-GlcNAcase function in-
vivo.
    Applications:
    Diagnosis of type 2 diabetes.
    In vivo imaging of O-GlcNAcase enzyme function.
    Development Status: Early stage.
    Inventors: John A. Hanover et al. (NIDDK).
    Publication: Eun Ju Kim, Melissa Perreira, Craig J. Thomas, and 
John A. Hanover. An O-GlcNAcase-specific inhibitor and substrate 
engineered by the extension of the N-acetyl moiety. J. Am. Chem. Soc. 
2006 Apr 5;128(13):4234-4235.

[[Page 38232]]

    Patent Status: U.S. Patent Application No. 11/654,647 filed 18 Jan 
2007 (HHS Reference No. E-229-2006/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jasbir (Jesse) S. Kindra, J.D., M.S.; 301-435-
5170; [email protected].
    Collaborative Research Opportunity: The NIDDK Laboratory of Cell 
Biochemistry and Biology is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize modified PUGNAc for prevention or 
treatment of Type 2 diabetes. Please contact Rochelle Blaustein at 301-
451-3636 or [email protected] for more information.

Use of Human Gamma Satellite Insulator Sequences To Prevent Gene 
Silencing and Allow for Long Term Expression of Integrated Transgenes

    Description of Technology: The lack of stable expression of 
transgenes in target cell lines remains a serious problem for gene 
therapy and cellular reprogramming approaches. Once integrated into 
chromosomes, the expression of these transgenes may be regulated by 
epigenetic effects of the surrounding chromatin. These position 
effects, which include transgene silencing and expression variegation, 
are often associated with changes in the chromatin structure, and are 
capable of inhibiting gene expression and neutralizing the intended 
effect of the inserted transgene.
    Experimental results suggest that gene position effects can be 
partially overcome by flanking the transgene with regulatory elements 
called chromatin insulators which work by establishing defined domains 
of transcriptional activity within the eukaryotic genome. These 
insulators can partially overcome position effects by shielding the 
promoters from the influence of neighboring regulatory elements, or by 
preventing the spread of heterochromatin which can lead to subsequent 
gene silencing.
    This invention discloses the use of gamma satellite DNA, residing 
in the pericentromeric region of human chromosomes, as highly efficient 
chromatin insulators. These insulators have a remarkable ability to 
overcome position effects and prevent the silencing of transgenes. When 
human chromosome 8 gamma satellite sequences were used as flanking DNA 
for eGFP (enhanced green fluorescent protein) gene expression in mouse 
erythroleukemia (MEL) cells, stable transgene expression was recorded 
for well over eight months. Until recently, no chromatin insulator 
sequences were known to completely prevent gene silencing on a long 
term basis in transfected cells. The human gamma-satellite sequences 
demonstrate a higher efficiency than any known chromatin insulator 
identified so far in intergenic regions, and may have invaluable 
applications in the fields of gene therapy, protein expression, and 
cellular reprogramming where adequate expression of the transgene is 
essential for long term therapeutic or developmental success.
    Applications:
    Gene therapy.
    Protein expression.
    Cellular reprogramming.
    Development Status: Prolonged transgene expression attained in 
mouse erythroleukemia (MEL) cells.
    Inventors: Vladimir L. Larionov, Jung-Hyun Kim, Tom Ebersole (NCI).
    Publications:
    1. G Felsenfeld, B Burgess-Beusse, C Farrell, M Gaszner, R 
Ghirlando, S Huang, C Jin, M Litt, F Magdinier, V Mutskov, Y Nakatani, 
H Tagami, A West, T Yusufzai. Chromatin boundaries and chromatin 
domains. Cold Spring Harb Symp Quant Biol. 2004;69:245-250.
    2. T Ebersole, Y Okamoto, VN Noskov, N Kouprina, JH Kim, SH Leem, 
JC Barrett, H Masumoto, V Larionov. Rapid generation of long synthetic 
tandem repeats and its application for analysis in human artificial 
chromosome formation. Nucleic Acids Res. 2005 Sep 1;33(15):e130, 
doi:10.1093/nar/gni129.
    Patent Status:
    U.S. Provisional Application No. 60/890,176 filed 15 Feb 2007 (HHS 
Reference No. E-154-2006/0-US-01).
    PCT Application No. PCT/US2008/054170 filed 15 Feb 2008 (HHS 
Reference No. E-154-2006/0-PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jasbir (Jesse) S. Kindra, J.D., M.S.; 301-435-
5170; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Laboratory of Molecular Pharmacology is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize gamma-satellite 
DNA insulators for stable transgene expression in ectopic chromosomal 
sites and in Human Artificial Chromosomes (HACs). Please contact John 
D. Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

Single Nucleotide Polymorphism Detection by DNA Melting Analysis

    Description of Technology: A Single Nucleotide Polymorphism (SNP) 
is defined as a single base pair difference occurring between members 
of the same species, or between paired chromosomes in an individual. 
Some SNPs have been associated with disease traits, and may predispose 
an individual to a disease or may influence that individual's response 
to therapeutic agents. There are several high-throughput methods that 
can detect SNPs of moderate to high abundance, where the polymorphism 
frequency is greater than ten percent. However, SNPs that alter gene 
expression or affect the structure of a gene product are often of much 
lower abundance, with allele frequency of around one percent. Thus, 
there is a need to devise high-throughput, inexpensive and efficient 
methods for their detection.
    The patent discloses methods for accurately detecting nucleotide 
sequence variations, such as polymorphisms, deletions, insertions or 
inversions, by comparison of DNA melting profiles. Methods of detecting 
single nucleotide sequence variations within arrays are also disclosed, 
as are methods of detecting mutations correlated with genetic disease.
    Applications:
    Detection of SNPs and small insertions, deletions, and inversions 
in a DNA sequence.
    Prediction of the etiology or prognosis of certain diseases, or 
determination of disease traits among individuals.
    Advantages:
    Useful for detecting rarely-occurring SNPs.
    High throughput, simple method that measures DNA melting 
efficiently, without using intervening steps such as gels, columns etc.
    Inventors: Robert H. Lipsky et al. (NIAAA)
    Patent Status: U.S. Patent No. 7,273,699 issued 25 Sep 2007 (HHS 
Reference No. E-251-2001/0 US-02).
    Licensing Status: Available for exclusive, co-exclusive, or non-
exclusive licensing.
    Licensing Contact: Jasbir (Jesse) S. Kindra, J.D., M.S.; 301-435-
5170; [email protected].
    Collaborative Research Opportunity: The National Institute on 
Alcohol Abuse and Alcoholism Section on Molecular Genetics is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
single nucleotide polymorphism detection by melting

[[Page 38233]]

analysis. Please contact Dr. Robert Lipsky at 301/402-5591 or 
[email protected] for more information.

    Dated: June 26, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-15201 Filed 7-2-08; 8:45 am]
BILLING CODE 4140-01-P