[Federal Register Volume 77, Number 86 (Thursday, May 3, 2012)]
[Notices]
[Pages 26294-26300]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-10637]


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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.

FOR FURTHER INFORMATION: 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.

Mouse Monoclonal Antibody Targeting Human NOX1, a Target for Cancer and 
Inflammation

    Description of Technology: Available for licensing is a mouse 
monoclonal antibodies targeting human nicotinamide adenine dinucleotide 
phosphate-oxidase (NAPH) oxidase 1 (NOX1) enzyme. NOX mediates the 
homeostasis of reactive oxygen species, which play a critical 
regulatory role in cancer cell signal transduction and tumor cell 
differentiation. NOX1-generated hydrogen peroxide can trigger an 
``angiogenic switch'' that includes the induction of angiogenic factors 
that promote tumor cell vascularization. Additionally, NOX1 may play a 
role in inflammation.
    Investigators at the National Cancer Institute found NOX1 is 
significantly expressed more in colon and gastric cancers compared with 
adjacent normal bowel and gastric mucosa respectively. To the best of 
NIH's knowledge, this is the only monoclonal antibody that can be used 
to detect human NOX1. This antibody detects endogenous levels of the 
NOX1 protein and could potentially be used in biochemical laboratory 
studies as well as diagnostic tests that involve the functional 
significance of NOX1 in human physiology and pathophysiology, 
particularly its role in cancer and inflammation.
    Potential Commercial Applications:
     Research tool to study cancer and inflammation
     Method to diagnose colon and gastric cancer
     Treatment for cancer and inflammation
    Competitive Advantages: To the best of NIH's knowledge, this is the 
only available monoclonal antibody to detect human NOX1.
    Development Stage:
     Early-stage
     In vitro data available
    Inventors: James Doroshaw, Krishnendu Roy, Guojian Jiang, Jiamo Lu, 
and Smitha Antony (all of NCI).
    Intellectual Property: HHS Reference No. E-097-2012/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Sabarni K. Chatterjee, Ph.D.; 301-435-5587; 
[email protected].

A Non-Invasive Post-Treatment Strategy for Stroke by Intranasal 
Delivery of Cocaine- and Amphetamine-Regulated Transcript (CART)

    Description of Technology: Cocaine and amphetamine-regulated 
transcript (CART) is a neuropeptide known to protect against ischemic 
brain injury when administered before the onset of stroke in mice, both 
in vivo and in vitro. Utilizing a classic stroke model in rodents, 
middle cerebral artery occlusion (MCAo), inventors at NIDA discovered a 
novel post-stroke therapeutic approach involving the intranasal 
administration of CART. This new non-invasive treatment strategy for 
stroke patients is effective when initiated three days after stroke, 
providing a longer treatment window. Nasal delivery of CART improved 
behavioral recovery and reduced neurological scores in stroke animals. 
CART, given after stroke, modifies endogenous neural repair in stroke 
brain by facilitating neuroprogenitor cell proliferation and migration, 
enhancing reinnervation, and improving the functional recovery.
    Potential Commercial Applications: Method of treating stroke
    Competitive Advantages:
     New treatment strategy for stroke patients
     Non-invasive (nasal spray)
     Longer treatment window (3 days post-stroke)
     Current strategies aim to protect lesion site from damage, 
whereas this method helps brain repair
    Development Stage:
     Early-stage
     Pre-clinical
     In vitro data available
     In vivo data available (animal)
    Inventors: Yun Wang, Hui Shen, Seong Jin Yu, Yihong Yang (all of 
NIDA).
    Publications: Manuscript in preparation.
    Intellectual Property: HHS Reference No. E-058-2012/0--U.S. 
Provisional Application No. 61/592,761 filed 31 Jan 2012.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].

[[Page 26295]]

Chimeric Antigen Receptors That Recognize BCMA/CD269 for Treating 
Multiple Myeloma

    Description of Technology: Available for licensing are chimeric 
antigen receptors (CARs) that specifically target B-cell maturation 
antigen (BCMA, CD269), a protein that is highly expressed on the 
surface of multiple myeloma cells. Multiple myeloma is a malignancy of 
plasma cells. It is almost always incurable.
    A CAR is a fusion protein that can recognize a specific protein on 
a tumor cell and activate an adaptive immune response to attack the 
tumor cell. When cultured with multiple myeloma cells in vitro, T-cells 
engineered to express the CARs were able to induce cell death in the 
myeloma cells. CARs currently are being evaluated in clinical trials as 
a promising new area of cancer therapy. The technology available for 
licensing includes vectors incorporating the CARs, as well as methods 
of destroying multiple myeloma cells using T-cells engineered to 
express a CAR.
    Potential Commercial Applications:
     Development of a tumor-specific T-cell treatment for 
multiple myeloma
     Development of a tumor-specific T-cell treatment for 
Hodgkin's lymphoma
     Treatment of diseases associated with increased or 
preferential expression of BCMA/CD269
    Competitive Advantages:
     Specifically targets an antigen that is highly expressed 
in tumor cells of multiple myeloma and Hodgkin's lymphoma
     Amenable for adoptive transfer approaches
     No other anti-BCMA immunotherapies are in clinical trials
     Targeted therapy decreases non-specific killing of 
healthy, essential cells, resulting in fewer non-specific side-effects 
and healthier patients
    Development Stage:
     Pre-clinical
     Clinical.
     In vitro data available.
    Inventor: James N. Kochenderfer (NCI).
    Intellectual Property: HHS Reference No. E-040-2012/0--U.S. 
Provisional Application 61/622,600 filed 11 April 2012.
    Related Technologies:
     HHS Reference No. E-205-2009/0--Treating Cancer with Anti-
angiogenic Chimeric Antigen Receptors.
     HHS Reference No. E-148-2011/0--Breakthrough Immunotherapy 
for Brain Cancer: Epidermal Growth Factor Receptor Variant III Chimeric 
Antigen Receptors.
     HHS Reference No. E-086-2006/0--Hybrid T-Cell Receptors 
for the Development of Improved Vaccines.
     HHS Reference No. E-265-2011/0--Chimeric Antigen Receptors 
to CD22 for Treating Hematological Cancers.
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Experimental Transplantation and Immunology Branch, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
chimeric antigen receptors to genetically-modify T cells to recognize 
BCMA/CD269. For collaboration opportunities, please contact John Hewes, 
Ph.D. at [email protected].

ROCK Inhibitors for the Prevention of Breast Cancer Metastasis and 
Tumor Relapse

    Description of Technology: The recent success of therapeutic 
approaches has significantly reduced breast cancer mortality, however, 
breast cancers that are diagnosed as ``triple-negative'' (lacking the 
estrogen receptors, HER2/Neu, and progesterone receptors) don't respond 
to these available therapies and some hormone receptor or NER2/Neu-
positive breast cancers have shown a resistance to these treatments. 
These breast cancers account for nearly 90% of all breast cancer 
deaths. Therefore, examining the mechanisms by which the breast cancer 
cells spread from their primary sites to distant organs is an active 
area of research. The NIH inventors have discovered that by blocking a 
key biochemical route necessary for the egress of breast cancer cells 
into circulation, the CXCR4-Galpha13-Rho signaling pathway, they can 
prevent the dissemination of breast cancer cells and thereby prevent 
breast cancer metastasis. In particular, they have discovered that ROCK 
inhibitors, such as Fasudil, can be used to treat of breast cancer 
patients after the initial clinical intervention (i.e., surgery, 
radiation, chemo-radiation, or their combination) to delay or prevent 
patient relapse due to the metastasis of any residual or prior 
undetected breast cancer cells.
    Potential Commercial Applications:
     Treatment of ``triple-negative'' breast cancers.
     Treatment of hormone receptor or NER2/Neu-positive breast 
cancers that are resistant to currently available therapies.
    Competitive Advantages: ROCK inhibitors can delay or prevent breast 
cancer metastasis in patients where there are no effective therapies 
currently available.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal)
    Inventors: Silvio Gutkind and Alfredo Molinolo (NIDCR).
    Intellectual Property: HHS Reference No. E-280-2011/0--U.S. 
Application No. 61/536,434 filed 19 Sep 2011.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected].

Cell Line for Producing Furin That Can Cleave Papillomavirus L2, Toxins 
and Other Substrates

    Description of Technology: Human papillomavirus (HPV) is an 
infectious agent that is responsible for several different diseases. 
Although HPV often manifests as warts, it can also result in certain 
types of cancer. Since HPV can remain latent for long periods of time, 
the disease can be transmitted by someone who is not aware they are 
contagious. This partially explains why HPV is the most common sexually 
transmitted disease. The HPV genome consists of several genes, 
including the two late-expressed genes known as L1 and L2. The HPV L1 
and HPV L2 genes encapsulate amplified HPV genomes prior to their 
release in virions, which infect other cells. Since HPV L2 is present 
on the HPV virion when it is released from a cell, people infected with 
HPV will generate an immune response against HPV L2 to help contain the 
infection. This includes the generation of neutralizing antibodies 
against HPV L2. By examining a sample for the presence of these 
neutralizing antibodies, it can be determined whether a patient has HPV 
and is capable of spreading the disease.
    This technology describes a Chinese Hamster Ovary (CHO) cell line 
which expresses a truncated version of mouse furin which retains 
activity. Furin is an enzyme that cleaves proteins at a specific, 
defined amino acid sequence. The cleavage of HPV L2 makes it more 
susceptible to detection by neutralizing antibodies. As a result, the 
cell line can increase the sensitivity of an assay for detecting 
neutralizing antibodies to HPV L2.
    Potential Commercial Applications:
     The cell line secretes a truncated mouse furin for use in 
any assays which benefit from furin activity.
     A specific use for the cell line is testing samples for 
neutralizing antibodies to HPV L2.
     The cells can be developed into a validated assay for 
detecting

[[Page 26296]]

neutralizing antibodies to HPV L2 as a means of diagnosing HPV 
infection.
    Competitive Advantages:
     Neutralizing antibodies to HPV L2 are more readily 
detected when the protein is first cleaved by furin.
     The cell lines represent an established and efficient 
research tool for cleaving HPV L2 for more efficient detection of 
neutralizing antibodies to the protein.
     An assay for detecting HPV infection can be useful for 
detecting those who are asymptomatic, which is common with HPV 
infections.
    Development Stage: In vitro data available.
    Inventors: David FitzGerald et al. (NCI)
    Publications:
    1. Chiron MF, et al. Furin-mediated cleavage of Pseudomonas 
exotoxin-derived chimeric toxins. J Biol Chem. 1997 Dec 
12;272(50):31707-11. [PMID 9395513]
    2. Richards RM, et al. Cleavage of the papillomavirus minor capsid 
protein, L2, at a furin consensus site is necessary for infection. Proc 
Natl Acad Sci U.S.A. 2006 Jan 31;103(5):1522-7. [PMID 16432208]
    3. Day PM, Schiller JT. The role of furin in papillomavirus 
infection. Future Microbiol. 2009 Dec;4(10):1255-62. Review. [PMID 
19995186]
    Intellectual Property: HHS Reference No. E-233-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected]

Novel Reduced Toxicity Tropolone Derivative Compounds That Have Anti-
Viral Activity Through Inhibiting RNase H Activity

    Description of Technology: Several novel tropolone derivatives have 
been identified that inhibit HIV-1 RNase H function and have potential 
for anti-viral activity due to reduced cellular toxicity. Inhibiting 
RNase H function is a potential treatment for many viral infections, 
since RNase H function is essential for viral replication for many 
pathogenic retroviruses such as HIV-1 and HIV-2. Although many 
hydroxytropolone compounds are potent RNase H inhibitors biding at the 
enzymatic active site, they are limited as therapeutic candidates by 
their toxicity in mammalian cells. The toxicity thought to be a result 
of inhibition of multiple essential mammalian metalloenzymes. We 
reasoned that the potential beneficial application of tropolone RNase H 
inhibition might be of therapeutic use if the toxic effects in 
mammalian cell were eliminated. By selectively adding steric bulk to 
add new drug-enzyme contacts for the RNase H active site, a number of 
novel compounds, that have initially demonstrated reduced cytotoxicity, 
have been produced. Importantly, these novel compounds appear to retain 
antiviral activity essential for use as therapeutics.
    Potential Commercial Applications: Anti-viral therapeutic: HIV-1 
and other RNase H-dependent viral infections
    Competitive Advantages:
     Potentially reduced toxicity
     Availability of x ray crystallographic information to 
guide analog design
    Development Stage:
     Pre-clinical
     In vitro data available
    Inventors: John Beutler, Suhman Chung, Stuart F. LeGrice, Jennifer 
A. Wilson (NCI); Craig J. Thomas and Jian-kang Jiang (NCATS)
    Publications:
    1. Chung S, et al. Synthesis, activity and structural analysis of 
novel alpha-hydroxytropolone inhibitors of human immunodeficiency virus 
reverse transcriptase-associated ribonuclease H. J Med Chem 2011 Jul 
14;54(13):4462-4473. [PMID 21568335]
    2. Budihas SR, et al. Selective inhibition of HIV-1 reverse 
transcriptase-associated ribonuclease H activity by hydroxylated 
tropolones. Nucl Acids Res 2005 33 (4):1249-1256. [PMID 15741178]
    Intellectual Property: HHS Reference No. E-081-2011/0 -- U.S. 
Provisional Application No. 61/484,779 filed 11 May 2011
    Licensing Contact: Edward ``Tedd'' Fenn, J.D.; 301-435-5031; 
[email protected]
    Collaborative Research Opportunity: The Molecular Targets 
Laboratory, National Cancer Institute, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize antiviral 
tropolone derivatives developed by systematic medicinal chemistry on 
the lead series. For collaboration opportunities, please contact John 
Hewes, Ph.D. at [email protected].

Hspa2 Knockout Mice for Study of Spermatogenesis and Male Infertility

    Description of Technology: HSPA2 is a member of the HSP70 family of 
heat-shock proteins that serve as molecular chaperones. Researchers 
discovered that HSPA2 protein is expressed in spermatogenesis during 
the meiotic phase. Spermatogenic cells lacking the HSPA2 protein arrest 
in mid-meiosis and undergo apoptosis. HSPA2 is present in the 
synaptonemal complex of wild-type mice and the chromosomes fail to 
separate in HSPA2-deficient mice (previously known as Hsp70-2-/-mice), 
suggesting that HSPA2 is required for the chromosomal events of meiosis 
such as synapsis, crossing over, or recombination.
    Researchers at NIEHS developed a knockout strain of mice in which 
the heat shock protein gene (Hspa2) is disrupted. This mouse model is 
useful in studying the process of spermatogenesis and the influence of 
various environmental toxins or drugs on sperm production and male 
infertility.
    Potential Commercial Applications:
     Mouse model to study spermatogenesis and male infertility
     Mouse model to study meiosis or the roles of heat-shock 
proteins in general
     Mouse model to evaluate effects of meiosis-disrupting 
agents on meiotic recombination and generation of mutations transmitted 
to offspring
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventor: Edward M. Eddy (NIEHS)
    Publication: Dix DJ, et al. Targeted gene disruption of Hsp70-2 
results in failed meiosis, germ cell apoptosis, and male infertility. 
Proc Natl Acad Sci USA. 1996 Apr 93(8):3264-3268. [PMID 8622925]
    Intellectual Property: HHS Reference No. E-052-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Related Technology: HHS Reference No. E-290-2011/0--Research Tool 
(Transgenic Hspa2-Cre Mice for Studying Spermatogenesis and Male 
Infertility). Patent protection is not being pursued for this 
technology.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected]
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize this mouse 
strain. For collaboration opportunities, please contact Elizabeth 
Denholm, Ph.D. at [email protected].

Transgenic Hspa2-Cre Mice for Studying Spermatogenesis and Male 
Infertility

    Description of Technology: HSPA2 is a member of the HSP70 family of 
heat-shock proteins that serve as molecular chaperones. Hspa2-cre 
expression mimics the spermatogenic cell-specific

[[Page 26297]]

expression of endogenous HSPA2 within the testis, being first observed 
in leptotene/zygotene spermatocytes. Expression of the transgene is 
also detected at restricted sites in the brain, as occurs for 
endogenous HSPA2.
    Researchers at NIEHS developed the first transgenic mouse line that 
expresses Cre-recombinase under the control of the promoter of the heat 
shock protein A2 (Hspa2) gene. Expression of the Hspa2-Cre transgene 
during meiosis in male germ cells makes these mice a useful tool for 
defining the roles of genes expressed at different times during 
spermatogenesis or expressed in spermatogenic cells.
    Potential Commercial Applications:
     New mouse model to study spermatogenesis and male 
infertility
     New mouse model to study meiosis or the roles of heat-
shock proteins in general
    Competitive Advantages: Researchers generated an Hspa2-cre line 
that expresses cre in spermatocytes to overcome the limitations of 
other transgenic lines.
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventor: Edward M. Eddy (NIEHS)
    Publication: Inselman AL, et al. Heat shock protein 2 promoter 
drives cre expression in spermatocytes of transgenic mice. Genesis. 
2010 Feb 48(2):114-120. [PMID 20027617]
    Intellectual Property: HHS Reference No. E-290-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Related Technology: HHS Reference No. E-052-2011/0--Research Tool 
(Hspa2 Knockout Mice for Study of Spermatogenesis and Male 
Infertility). Patent protection is not being pursued for this 
technology.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected]
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize this mouse 
strain. For collaboration opportunities, please contact Elizabeth 
Denholm, Ph.D. at [email protected].

Diagnostic H5N1 Avian Influenza Virus Peptides

    Description of Technology: The recent spread of highly pathogenic 
H5N1 avian influenza viruses among poultry and transmission of these 
viruses to humans raises concerns of a potential influenza pandemic. 
There is a need to track the spread of these viruses both in the animal 
and human populations to avert or reduce the impact of any potential 
influenza pandemic as well as to know the actual number (accurate 
surveillance) of people infected with H5N1, including individuals with 
subclinical H5N1 infection.
    The subject technology is a specific combination of H5N1 peptides 
useful for assays to detect antibodies generated against a wide range 
of different H5N1 strains. The combination of peptides was able to 
specifically detect anti-H5N1 antibodies from serum samples of H5N1 
survivors at early and later times post infection while excluding 
antibodies generated in individuals infected with other strains of 
influenza virus. Also, the peptides did not react with sera from 
individuals vaccinated with H5N1 vaccine, in contrast to the strain-
specific detection of anti-H5N1 antibodies in sera from infected 
individuals. Immunoassays using the H5N1 peptide combination provide 
highly specific, sensitive and reproducible methods for diagnosing H5N1 
infection in humans and animals.
    Potential Commercial Applications: Diagnostics for influenza virus 
specific antibodies in humans and animals.
    Competitive Advantages: High specificity, sensitivity, and 
reproducibility
    Development Stage:
     Pre-clinical
     In vitro data available
    Inventors: Hana Golding and Surender Khurana (FDA)
    Publication: Khurana S, et al. H5N1-SeroDetect EIA and rapid test: 
a novel differential diagnostic assay for serodiagnosis of H5N1 
infections and surveillance. J Virol. 2011 Dec;85(23):12455-63. [PMID 
21957281]
    Patent Status: HHS Reference No. E-093-2010/0 -- PCT Application 
No. PCT/US2011/032555 filed 14 Apr 2011, which published as WO 2011/
130555 on 20 Oct 2011
    Related Technology: HHS Reference No. E-236-2007/3 -- U.S. Patent 
Application No. 12/664,052 filed 10 Dec 2009
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected]

Parvovirus B19 Codon Optimized Structural Proteins for Vaccine and 
Diagnostic Applications

    Description of Technology: Parvovirus B19 (B19V) is the only known 
pathogenic human parvovirus. Infection by this viral pathogen can cause 
transient aplastic crisis in individuals with high red cell turnover, 
pure red cell aplasia in immunosuppressed patients, and hydrops fetalis 
during pregnancy. In children, B19V most commonly causes erythema 
infectiosum, or fifth's disease. Infection can also cause arthropathy 
and arthralgia. The virus is very erythrotropic, targeting human 
erythroid (red blood) progenitors found in the blood, bone marrow, and 
fetal liver. Currently, there are no approved vaccines or antiviral 
drugs for the treatment or prevention of B19V infection.
    The subject technology is a series of plasmid constructs with codon 
optimized B19 viral capsid genes (VP1 and VP2) that can be expressed in 
mammalian cells. Transfection of vectors encoding these optimized VP1 
and VP2 genes into different mammalian cell lines, including 293, Cos7, 
and Hela cells produce virus-like particles (VLPs). The vectors include 
bicistronic plasmids expressing the VP1 and VP2 proteins at different 
ratios to produce B19V VLPs with optimal antigenicity for vaccine 
applications. This technology can also be used for diagnostic 
applications and development of a viral packaging system for producing 
infectious B19V virus.
    Potential Commercial Applications:
     VLPs based vaccines for the prevention and/or treatment of 
B19V infection
     DNA based vaccines for the prevention and/or treatment of 
B19V infection
     B19V diagnostics
     Viral packaging system
    Competitive Advantages:
     Codon optimized VP1 and VP2 genes for better expression in 
mammalian cell lines
     Expression of B19V VLPs from ``nonpermissive'' cell lines
    Development Stage: In vitro data available
    Inventors: Ning Zhi, Sachiko Kajigaya, and Neal S. Young (NHLBI)
    Patent Status: HHS Reference No. E-011-2010/0--PCT Application No. 
PCT/US2011/024199 filed 09 Feb 2011, which published as WO 2011/100330 
on 22 Dec 2011
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected]
    Collaborative Research Opportunity: The National Heart Lung and 
Blood Institute, Hematology Branch, is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize the subject technology. 
Please contact Cecilia Pazman, Ph.D., at [email protected] for more 
information.

[[Page 26298]]

Construct for Tetracycline Inducible Podocyte Specific Gene Expression 
in Mice

    Description of Technology: The National Institutes of Health 
announces the generation of a construct by ligating 2.5kb human podocin 
promoter sequence to gene encoding reverse tetracycline-controlled 
transcriptional activator which enables tetracycline-inducible podocyte 
specific gene of interest expression with another construct consisting 
of tetracycline responsive element, minimal CMV promoter and gene of 
interest.
    Podocytes are post-mitotic epithelial cells that are positioned on 
the exterior aspect of the glomerular capillary wall and contribute to 
the selective molecular permeability of glomeruli. Podocyte damage or 
dysfunction results in loss of the characteristic foot processes that 
normally interdigitate and form the selective permeability barriers 
composed of filtration slits bridged by slit diaphragms. Minimal damage 
causes proteinuria that in the case of minimal change disease can be 
reversed by steroid treatment. In focal segmental glomerulosclerosis, 
more severe loss of podocytes ultimately results in glomerulosclerosis. 
The podocyte-specific inducible transgene system can be used to 
identify factors that exacerbate or ameliorate podocyte injury, and can 
be used to express Cre-recombinase.
    Potential Commercial Applications: This technology can be used for 
the study of renal disease.
    Competitive Advantages: The podocyte-specific inducible transgene 
system can be used to identify factors that exacerbate or ameliorate 
podocyte injury, and can be used to express Cre-recombinase.
    Development Stage: Pre-clinical
    Inventors: Jeffrey B. Kopp et al. (NIDDK)
    Publication: Shigehara T, et al. Inducible podocyte-specific gene 
expression in transgenic mice. J Am Soc Nephrol. 2003 Aug;14(8):1998-
2003. [PMID 12874453]
    Intellectual Property: HHS Reference No. E-299-2007/0 -- Research 
Material. Patent protection has not been pursued for this technology.

    Note: The use of Tetracycline controllable expression systems is 
covered by a series of patents including US 5,464,758 and 
5,814,618 which are proprietary to TET systems GmbH & Co. KG. 
Interested parties are also advised to contact TET Systems, 
[email protected] or by electronic request at www.tetsystems.com/main_inquiry.htm]

    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected]

Parallel High Speed Single Molecule Nucleic Acid Sequencing

    Description of Technology: This invention entails a new system, 
methods, and compositions for DNA sequencing, known as Two Dye 
Sequencing (TDS). The system utilizes Forster Resonance Energy Transfer 
(FRET). The TDS method consists of the following steps:
    (1) Attaching to a microscope chamber, DNA polymerases labeled with 
a donor fluorophore.
    (2) Adding to the chamber DNA molecules annealed to a primer.
    (3) Adding four dNTPs, each labeled with a different fluorescent 
acceptor dye.
    (4) Exciting the donor fluorophore with light, causing energy 
transfer (FRET) to the acceptor fluorophore for a given dNTP, that then 
radiates light of a different wavelength.
    (5) Identifying nucleotides as they are added to the nascent 
polynucleotide by recording the FRET signals at the location of each 
DNA polymerase in the microscope field of view.
    (6) Converting the sequential signals into a DNA sequence for each 
DNA molecule in the microscope field of view.
    Potential Commercial Applications: High throughput sequencing of 
single DNA molecules on a substrate.
    Competitive Advantages:
     Detection of individual DNA molecule sequences
     Sequences multiple DNA molecules in parallel with one 
microscope
     Eliminates washing steps, because all four nucleotides are 
added at once
     Rapid, works at the speed of the DNA polymerase
    Development Stage: Early-stage
    Inventors: Thomas D. Schneider and Denise Rubins (NCI)
    Intellectual Property: HHS Reference No. E-033-1999/0 --
     US Patent No. 6,982,146 issued 03 Jan 2006
     PCT Application No. PCT/US00/23736 filed 29 Aug 2000
     US Application No. 12/886,686 filed 29 Aug 2000
    Related Technologies: HHS Reference No. E-194-2005/0 --
     US Patent No. 7,871,777 issued 18 Jan 2011
     EP Patent No. 1960550 issued 15 Sep 2010, validated in DE, 
FR, and GB
     JP Application No. 2009-545768 filed 12 Dec 2006
     US Application No. 12/980,802 filed 29 Dec 2010
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., MBA; 301-435-
4507; [email protected]

The MedusaTM; Sequencer: A DNA or RNA Sequencing Machine the 
Size of a Molecule

    Description of Technology: Current high-throughput DNA sequencing 
methods suffer from several limitations. Many methods require multiple 
fluid handling steps, fixing of molecules on beads or a 2D surface, and 
provide very short read-lengths. The NIH inventors offer a DNA or RNA 
sequencing device that drastically simplifies the process by combining 
all elements for sequence detection in a single molecule, the 
MedusaTM; Sequencer.
    The MedusaTM; Sequencer utilizes Forster Resonance 
Energy Transfer (FRET) to read a polynucleotide sequence while 
synthesizing a complementary strand. The device consists of a DNA (or 
RNA) polymerase labeled with a FRET donor fluorophore and attached to a 
set of four flexible arms. The tip of each arm carries a distinct set 
including one nonhydrolyzable nucleotide and one FRET acceptor 
fluorophore. While a MedusaTM; Sequencer synthesizes a 
complementary polynucleotide strand, the four different arms 
continuously ``test'' the polymerase pocket creating a characteristic 
FRET signal for the correct nucleotide. The series of FRET signals 
reveals the unknown polynucleotide sequence.
    Potential Commercial Applications:
     High-throughput DNA or RNA sequencing
     Alternative to microarrays for expression analysis
     Diagnostics of genetic diseases
    Competitive Advantages:
     Single reagent for synthesis and sequencing
     Eliminates repetitive fluid handling steps
     Able to count single mRNA or DNA molecules
     Exceptionally low manufacturing cost
     Could be injected in living cells to read/count mRNA 
sequences directly
     Low error rate per base
     High speed; one microscope obtains many sequences in 
parallel
     Can be 3D-arrayed in a gel for ultra-high density
     Use with Sequence Walkers for diagnostics (http://alum.mit.edu/www/toms/g863a.html)
    Development Stage: Early-stage
    Inventors: Thomas D. Schneider, IIya G. Lyakhov, Danielle Needle 
(NCI)
    Publication: The technology is further described at http://alum.mit.edu/www/toms/patent/medusa.
    Intellectual Property: HHS Reference No. E-194-2005/0 --

[[Page 26299]]

     US Patent No. 7,871,777 issued 18 Jan 2011
     EP Patent No. 1960550 issued 15 Sep 2010, validated in DE, 
FR, and GB
     JP Application No. 2009-545768 filed 12 Dec 2006
     US Application No. 12/980,802 filed 29 Dec 2010
    Related Technologies:
    HHS Reference No. E-195-2005/0 --
     US Application No. 60/749,858 filed 12 Dec 2005
     US Application No. 11/638,160 filed 12 Dec 2006
    HHS Reference No. E-033-1999/0 --
     US Patent No. 6,982,146 issued 03 Jan 2006
     PCT Application No. PCT/US00/23736 filed 29 Aug 2000
     US Application No. 12/886,686 filed 29 Aug 2000
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., MBA; 301-435-
4507; [email protected]
    Collaborative Research Opportunity: The National Cancer Institute, 
Gene Regulation and Chromosome Biology Laboratory, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
the MedusaTM; Sequencer. For collaboration opportunities, 
please contact John Hewes, Ph.D. at [email protected].

Nanoprobes for Detection or Modification of Molecules

    Description of Technology: This invention describes ``Rod-tether 
Nanoprobes'', devices consisting of a rigid molecular rod with a 
flexible molecular tether attached at both ends that can detect and/or 
modify molecules. Each tether tip has a functional group, such as an 
antibody or oligonucleotide that recognizes a target molecule. In 
addition, one tip carries a donor fluorophore and the other carries an 
acceptor fluorophore. The fluorophores form a pair for Forster 
Resonance Energy Transfer (FRET). In the absence of the target 
molecule, the rod keeps the tether arms apart, while in the presence of 
the target molecule, both recognizers bind to the target. This binding 
holds the donor and acceptor fluorophores close together, allowing a 
FRET signal. By reducing an ELISA-like assay entirely to the molecular 
level, complex macroscopic or microfluidic washing and pumping systems 
can be eliminated. Rod-tether Nanoprobes can detect a wide variety of 
clinical and biowarfare reagents. The nanoprobes can also rapidly and 
simply detect, modify, and/or destroy endogenous molecules (e.g., 
proteins, mRNA) involved in a broad range of diseases. The simplest 
ssDNA-detecting nanoprobe has been created.
    Potential Commercial Applications:
     Instantly detect molecules of interest (e.g., proteins, 
mRNA) in multiple settings:
--Clinical
--Scientific research
--Biowarfare
     An improved substitute for ELISA assays
     Modify or destroy target molecules, while detecting them
     Detect genetic diseases in the clinic from patient blood 
samples
    Competitive Advantages:
     Only one reagent required for detection
     Entire reaction contained in a single molecule
     Eliminates washing steps
     Complicated and expensive microfluidic chips are 
eliminated
     High speed
     Exceptionally low cost
    Development Stage: Early-stage
    Inventors: Thomas D. Schneider, IIya G. Lyakhov, Danielle Needle 
(NCI)
    Publication: The technology is further described at http://alum.mit.edu/www/toms/patent/nanoprobe/.
    Intellectual Property: HHS Reference No. E-195-2005/0--
     US Application No. 60/749,858 filed 12 Dec 2005
     US Application No. 11/638,160 filed 12 Dec 2006
    Related Technologies: HHS Reference No. E-194-2005/0--
     US Patent No. 7,871,777 issued 18 Jan 2011
     EP Patent No. 1960550 issued 15 Sep 2010, validated in DE, 
FR, and GB
     JP Application No. 2009-545768 filed 12 Dec 2006
     US Application No. 12/980,802 filed 29 Dec 2010
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., MBA; 301-435-
4507; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Gene Regulation and Chromosome Biology Laboratory, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
Rod-Tether Nanoprobes. For collaboration opportunities, please contact 
John Hewes, Ph.D. at [email protected].

Immunogenic Peptides (Vaccines) for the Treatment of Prostate and 
Breast Cancer

    Description of Technology: Collectively, cancer is the second 
leading cause of death in the United States. Current treatments of 
cancer often involve non-specific strategies (such as chemotherapy) 
which attack healthy cells as well as diseased cells, leading to 
harmful side-effects. As a result, the development of more targeted 
means of treating cancer are highly sought. One option for a targeted 
treatment is the creation of a vaccine that induces an immune response 
only against cancer cells. In this sense, vaccination involves the 
introduction of a peptide into a patient that causes the formation of T 
cells that recognize the peptide. If those recognize a peptide found in 
a protein found selectively on cancer cells, those T cells can trigger 
the death of those cancer cells without harming non-cancer cells. This 
can result in fewer side effects for the patient. TARP (T cell receptor 
gamma alternate reading frame protein) is a protein that is selectively 
expressed on the cells of certain types of prostate and breast cancer. 
This invention concerns the identification of immunogenic peptides 
within TARP, and their use to create an anti-cancer immune response in 
patients. By introducing these peptides into a patient, an immune 
response against these cancer cells can be initiated by the peptides, 
resulting in treatment of the cancer. A phase I clinical trial in stage 
D0 prostate cancer patients is nearing completion. Initial results 
indicate a statistically significant decrease in the slope of PSA for 
48 weeks after vaccination.
    Potential Commercial Applications:
     Peptides can be used as cancer vaccines.
     Treatment of any cancer associated with increased or 
preferential expression of TARP.
     Specific diseases include breast cancer and prostate 
cancer.
    Competitive Advantages: Targeted therapy decreases non-specific 
killing of healthy, essential cells, resulting in fewer non-specific 
side-effects and healthier patients.
    Development Stage:
     Pre-clinical
     Clinical
     In vivo data available (animal)
     In vivo data available (human)
    Publications:
    1. Epel M, et al. Targeting TARP, a novel breast and prostate 
tumor-associated antigen, with T cell receptor-like human recombinant 
antibodies. Eur J Immunol. 2008 Jun;38(6):1706-1720. [PMID 18446790]
    2. Oh S, et al. Human CTLs to wild-type and enhanced epitopes of a 
novel prostate and breast tumor-associated protein, TARP, lyse human 
breast cancer cells. Cancer Res. 2004 Apr 1;64(7):2610-2618. [PMID 
15059918]

[[Page 26300]]

    Intellectual Property: HHS Reference No. E-116-2003/0--
     US Patent 7,541,035 issued 02 Jun 2009
     US Patent 8,043,623 issued 25 Oct 2011
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Vaccine Branch, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize a prostate cancer vaccine targeting the TARP 
antigen currently completing phase I clinical trials. For collaboration 
opportunities, please contact John Hewes, Ph.D. at [email protected].

    Dated: April 27, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-10637 Filed 5-2-12; 8:45 am]
BILLING CODE 4140-01-P