[Federal Register Volume 77, Number 44 (Tuesday, March 6, 2012)]
[Pages 13344-13346]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-5356]



National Institutes of Health

Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.


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.

Device for Simulating Explosive Blast Trauma

    Description of Technology: NIH scientists have developed a novel 
device to simulate the effects of pressure waves resulting from 
explosions or blasts on biological tissue. This methodology allows 
real-time monitoring of tissue damage while it is occurring and can 
track the secondary effects of pressure damage after tissue insult. 
This tool is well-adapted for investigating traumatic brain injury and 
organ damage resulting from explosion pressure waves, such as in 
military combat.

    Potential Commercial Applications:
     Real-time monitoring of tissue damage from primary blast 
     Real-time monitoring of tissue damage from secondary 
effects of blast pressure, such as tissue shearing against surfaces
     Can monitor tissue through both live imaging and assaying 
cell viability
     Can measure pressure effects on various tissues
    Competitive Advantages:
     Allows differentiation of primary and secondary blast 
pressure effects on tissue damage
     Employs multiple methods to assess cell viability
     Possesses high temporal resolution
    Development Stage: Prototype.
    Inventors: Rea Ravin, Paul Blank, Alex Steinkamp, Joshua 
Zimmerberg, Sergey Bezrukov, and Kim Lee Mcafee (all of NICHD).
    Intellectual Property: HHS Reference No E-068-2012/0--U.S. 
Provisional Application No. 61/590,209 filed 24 Jan 2012.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].

Small-Molecule Inhibitors of Human Galactokinase for the Treatment of 
Galactosemia and Cancers

    Description of Technology: Lactose, found in dairy products and 
other foods, is comprised of two simple sugars, glucose and galactose. 
In galactosemia,

[[Page 13345]]

where galactose is not properly metabolized, build-up of toxic 
compounds, such as galactose-1-phosphate, can lead to liver disease, 
renal failure, cataracts, brain damage, and even death if this disorder 
is left untreated. Currently, the only treatment for galactosemia is 
elimination of lactose and galactose from the diet, but in some cases 
this is not sufficient to avoid long-term complications from the 
    This technology describes selective small-molecule inhibitors of 
human galactokinase, which inhibit the first step in galactose 
metabolism. These compounds could be used to treat galactosemia by 
eliminating the build-up of toxic metabolites in brain, liver and other 
tissues, and could form the basis for the first effective treatment for 
this disorder.
    These inhibitors are also promising candidates for the treatment of 
certain cancers, such as PTEN/AKT misregulated cancers. The inventors 
have already shown that the inhibitors are cytotoxic for several cancer 
cell lines.
    Potential Commercial Applications:
     Treatment of galactosemia
     Treatment of certain cancers, such as PTEN/AKT 
misregulated cancers
    Competitive Advantages:
     There is currently no effective treatment for classic 
galactosemia, where dietary restriction cannot prevent long-term 
complications in some cases.
     Cancer therapeutics based on these inhibitors are 
predicted to have minimal side-effects.
    Development Stage:
     In vitro data available
    Inventors: Matthew Boxer et al. (NCATS).
    Intellectual Property: HHS Reference No. E-240-2011/0 -- PCT 
Application No. PCT/US2011/053021 filed 23 Sep 2011.
    Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize Small-Molecule Inhibitors of Human 
Galactokinase for the Treatment of Galactosemia and Cancers. For 
collaboration opportunities, please contact Lili M. Portilla, MPA at 
[email protected].

The Cancer Stem Cell Finder: A Novel Reporter Construct Which Uses 
Transposition and Green Fluorescent Protein Expression To Identify 
Cancer Stem Cells

    Description of Technology: Scientists at the National Institutes of 
Health (NIH) have designed a novel reporter construct which can be used 
to identify, monitor, and allow for the manipulation of cancer stem 
cells (CSCs). CSCs are a subset of poorly differentiated tumor cells 
expressed at low frequency within a tumor and are resistant to 
conventional chemotherapies. CSCs have high metastatic potential and 
give rise to new tumors that spread cancer throughout the body. These 
characteristics make CSCs prime targets for developing new therapeutic 
agents to eradicate cancer.
    The reporter construct is a novel expression vector composed of the 
Sleeping Beauty transposon plasmid and a Nanog promoter linked to green 
fluorescent protein (GFP). Nanog is a transcription factor that is 
overexpressed in embryonic stem (ES) cells and tumors that resemble ES 
cells. When introduced into a population of tumor cells, the Nanog-GFP-
Sleeping Beauty transposon construct is able to integrate into tumor 
cell DNA via transposition. If the transposed cell is a CSC, the Nanog 
transcription factor overexpressed in that CSC will bind to the Nanog-
promoter in the reporter construct to drive GFP expression within the 
cell. Thus, CSCs can be isolated based on their selective expression of 
the GFP label. The NIH scientists have utilized their reporter 
construct to identify small populations of CSCs in mouse and human 
breast cancer cell models.
    Potential Commercial Applications:
     Identify CSCs with high metastatic potential in patients 
to target with therapeutic intervention
     Screen therapeutic drug candidates to identify their 
effectiveness against CSCs in comparison to more highly differentiated 
tumor cells
     Investigate genes, surface proteins, and other markers 
responsible for CSC ``stem-ness'' to develop CSC diagnostics and 
identify therapeutic candidates to stop or reverse the properties 
contributing to the high metastatic potential of these cells
    Identify transcription factors/genes activated in the tumor 
microenvironment that trigger metastasis
    Competitive Advantages:
     The reporter construct is validated to identify CSCs in 
both human and mouse tumor cell populations
     Researchers and clinicians can monitor the ``stem-ness'' 
of a tumor cell population to predict the metastatic potential of a 
     CSCs are identified in vivo in somatic cells via GFP 
labeling without utilizing a virus for transfection
     CSCs can be isolated, monitored, and traced via their GFP 
label in both in vitro and in vivo experimentation
     Facilitates the generation of a large quantity of CSCs for 
further study
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Rachel L. de Kluyver (formerly NCI), Jimmy K. Stauffer 
(NCI), Thomas J. Sayers (SAIC-Frederick).
    Intellectual Property: HHS Reference No. E-215-2011/0 -- Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected]
    Collaborative Research Opportunity: The Cancer and Inflammation 
Program, NCI, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize Nanog promoter driven GFP constructs for the 
easy identification and isolation of cancer stem cells. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
[email protected].

Genes and Autoantibodies To Diagnose and Treat Sj[ouml]gren's Syndrome

    Description of Technology: Sj[ouml]gren's syndrome (SS) is a 
chronic autoimmune disease of unknown etiology that targets salivary 
and lacrimal glands and may be accompanied by multi-organ systemic 
manifestations. To date, no specific diagnostic test has been developed 
for SS and, as a result, SS is often underdiagnosed and undertreated.
    In order to further understand the immunopathology of SS and 
uncover both therapeutic and diagnostic targets, researchers at NIH 
compared gene expression profiles of salivary glands with severe 
inflammation to those with mild or no disease. Results from these 
studies identified target genes that were further characterized in 
tissues, serum and in cultured cell populations by real time PCR and 
protein analyses. Among the most highly expressed SS genes were genes 
associated with myeloid cells, including members of the mammalian 
chitinase family. In addition to genes, the researchers have also 
identified autoantibodies that have increase levels in SS patients. The 
gene expression levels and autoantibodies

[[Page 13346]]

identified in the research represent both promising means for 
diagnosing SS earlier in disease progression as well as therapeutic 
targets to treat SS.
    Potential Commercial Applications:
     Diagnosis of Sj[ouml]gren's syndrome
     Treatment of Sj[ouml]gren's syndrome
    Competitive Advantages: The genes and autoantibodies identified in 
this technology may lead to one of the first diagnostic tests for 
Sj[ouml]gren's syndrome.
    Development Stage:
     In vitro data available
    Inventors: Sharon M. Wahl (NIDCR), et al.

    1. Greenwell-Wild T, et al. Chitinases in the salivary glands 
and circulation of patients with Sj[ouml]gren's syndrome: macrophage 
harbingers of disease severity. Arthritis Rheum. 2011 
Oct;63(10):3103-3115, doi: 10.1002/art.30465. [PMID 21618203]
    2. Katsifis GE, et al. Systemic and local interleukin-17 and 
linked cytokines associated with Sj[ouml]gren's syndrome 
immunopathogenesis. Am J Pathol. 2009 Sep;175(3):1167-1177. [PMID 
    3. Moutsopoulos NM, et al. Lack of efficacy of etanercept in 
Sj[ouml]gren syndrome correlates with failed suppression of tumour 
necrosis factor alpha and systemic immune activation. Ann Rheum Dis. 
2008 Oct;67(10):1437-1443. [PMID 18198195]
    4. Mavragani CP, et al. Augmented interferon-alpha pathway 
activation in patients with Sj[ouml]gren's syndrome treated with 
etanercept. Arthritis Rheum. 2007 Dec;56(12):3995-4004. [PMID 
    5. Katsifis GE, et al. T lymphocytes in Sj[ouml]gren's syndrome: 
contributors to and regulators of pathophysiology. Clin Rev Allergy 
Immunol. 2007 Jun;32(3):252-264. [PMID 17992592]

    Intellectual Property:
     HHS Reference No. E-140-2011/0 -- U.S. Provisional 
Application No. 61/476,192 filed 15 April 2011
     HHS Reference No. E-140-2011/1 -- U.S. Provisional 
Application No. 61/556,729 filed 07 November 2011
    Licensing Contact: Jaime M. Greene, M.S.; 301-435-5559; 
[email protected].

Bacterially Expressed Influenza Virus Recombinant HA Proteins for 
Vaccine and Diagnostic Applications

    Description of Technology: Pandemic H1N1 influenza virus is a 
recently emergent strain of influenza virus that the World Health 
Organization (WHO) estimates has killed at least 14,711 people 
worldwide. Avian influenza viruses are emerging health threats with 
pandemic potential. Due to their global health implications, there has 
been a massive international effort to produce protective vaccines 
against these influenza virus strains. Currently, influenza virus 
vaccines are produced in chicken eggs, a production method that is 
disadvantaged by lengthy vaccine production times and by inability to 
meet large-scale, global demands.
    The subject technologies are specific recombinant HA proteins from 
H1N1, H5N1, and other strains of influenza virus produced in bacteria. 
The HA proteins properly fold, form oligomers, bind fetuin, agglutinate 
red blood cells and induce strong neutralizing antibody titers in 
several in vivo animal models. The key advantages of this technology 
are that expression of these proteins in bacteria reduces the vaccine 
production time and offers the ease of scalability for global usage, an 
issue with current production methods. The recombinant HA proteins can 
also be used for diagnostic applications.
    Potential Commercial Applications:
     Vaccines for the prevention of influenza infection
     Diagnostics for influenza virus specific antibodies
    Competitive Advantages:
     Novel vaccine candidates
     Rapid production time
     Ease of scalability
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Hana Golding and Surender Khurana (FDA).
    Publication: Khurana S, et al. Recombinant HA1 produced in E. coli 
forms functional oligomers and generates strain-specific SRID potency 
antibodies for pandemic influenza vaccines. Vaccine. 2011 Aug 
5;29(34):5657-5665. [PMID 21704111].
    Intellectual Property: HHS Reference No. E-032-2010/1--PCT 
Application No. PCT/US2010/055166 filed 02 Nov 2010.
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected].

Potent, Easy To Use Targeted Toxins as Anti-Tumor Agents

    Description of Technology: The invention discloses synthesis and 
use of novel derivatives of 2-[2'-(2-aminoethyl)-2-methyl-ethyl]-l,2-
dihydro-6-methoxy-3H-dibenz-[de,h]isoquinoline-l,3-dione as targeted 
anti-tumor agents. The use of targeted toxin conjugates with anti-
cancer antibodies, such as herceptin, is increasing. Based on a 
comparison with the structurally complex toxins, such as DM1, available 
in the market, these novel toxins are more stable in circulation, thus 
making the toxin-conjugates more tumor-selective and less toxic. As 
such, these compounds are superior alternatives to the existing toxins.
    The invention describes a potent and easy to synthesize toxin that 
can be used for generating a variety of prodrugs. These compounds can 
be attached to a ligand that recognizes a receptor on cancer cells, or 
to a peptide that is cleaved by tumor-specific proteases. The compounds 
are topoisomerase inhibitors and are mechanistically different from DM1 
that targets tubulin.
    The structure of the toxin allows it to be modified with a peptide 
linker that is stable, but rapidly cleaved in lysosomes after the 
compound is specifically taken up by cancer cells.
    Potential Commercial Applications: The compounds can be used for 
preparation of a variety of potent anti-cancer agents with low systemic 
    Competitive Advantages:
     Easy to prepare
     Structural features make these compounds more stable in 
     Toxin conjugates are more tumor-selective and less toxic
    Development Status:
     In vitro data available
     In vivo data available (animal)
    Inventors: Nadya Tarasova, et al. (NCI).
    Intellectual Property: HHS Reference No. E-160-2006/0--U.S. Patent 
No. 8,008,316 issued 30 Aug 2011.
    Licensing Contact: Jennifer Wong; 301-465-4633; 
[email protected].

    Dated: February 29, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-5356 Filed 3-5-12; 8:45 am]