[Federal Register Volume 73, Number 250 (Tuesday, December 30, 2008)]
[Notices]
[Pages 79890-79892]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-30849]


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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.

Doxycycline-Inducible B16 Melanoma Cell Lines Expressing CXCR4 or CCR10

    Description of Technology: The chemokine receptor CXCR4 functions 
in normal cells, but has been shown to be the most common chemokine 
receptor expressed on cancer cells, including melanoma, colon, breast, 
and lung cancers. It plays roles in angiogenesis and cancer cell 
survival as well as metastasis. CCR10 has also been shown to be 
expressed by melanoma cells. Like CXCR4, expression of CCR10 can 
enhance cancer cell survival and block immune recognition of cancer 
cells. Antagonists of CXCR4 and CCR10, under various conditions, have 
decreased metastasis or prevented tumor formation after implantation of 
cancer cells in mice.
    These cell lines are based on the widely used B16 murine melanoma 
cell line. The cell lines were transduced with retroviral vectors 
encoding cDNA for either CXCR4 or CCR10 under control of a TET-
dependent promoter. Both lines achieve greater than 10 fold induction 
of the respective genes (proteins), which has been confirmed by surface 
antibody staining using flow cytometry. These cell lines are ideally 
suited for studying the effect of these chemokine receptors in tumor 
growth or metastasis. They are also useful for developing a mouse model 
for studying the effect of down-regulating these receptors specifically 
in melanoma cells. This would mimic the effect of antagonists without 
the confounding effects of systemically inhibiting CXCR4 or CCR10. By 
either adding or removing dietary administered doxycycline, receptor 
expression can be regulated to assess the role of these two receptors 
in a variety of cancer-related assays.
    Applications:
     Study the effect of chemokine receptors in tumor growth or 
metastasis
     Test CXCR4 and CCR10 antagonists in preclinical studies
     Develop B16 melanoma mouse model mimicking the effect of 
chemokine receptor antagonists
    Advantages:
     Ability to regulate in vitro and in vivo expression of the 
chemokine receptor
     Ability to investigate the in vivo role in cancer cells of 
doxycycline control of chemokine receptor expression
    Market: Cancer is the second leading cause of death in the U.S. and 
it is estimated that more than 1 million Americans develop cancer in a 
year.
    Development Status: The technology is currently in the preclinical 
stage of development.
    Inventors: Sam T. Hwang (NCI) .
    Publication: T Kakinuma, ST Hwang. Chemokines, chemokine receptors, 
and cancer metastasis. J Leukoc Biol. 2006 Apr;79(4):639-651.
    Patent Status: HHS Reference No. E-345-2008/0--Research Material. 
Patent protection is not being sought for either technology.
    Licensing Status: Available for non-exclusive licensing under a 
Biological Materials License Agreement.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
[email protected].

Monoclonal Antibodies to the Tumor-Specific Antigen, Human ROR1

    Description of Technology: B-cell chronic lymphocytic leukemia (B-
CLL) is an incurable disease developed by more than 15,000 Americans 
each year and currently, there are no therapeutic monoclonal antibodies 
(mAbs) that specifically recognize B-CLL tumor cells. Receptor tyrosine 
kinase-like orphan receptor 1 (ROR1) is a constitutively expressed 
tumor-specific cell surface antigen and an ideal target for therapeutic 
antibodies.
    Available for licensing are four mouse anti-human ROR1 mAbs 
(hybridomas designated 2A2, 2D11, 1A1, and 1A7). All four mAbs bind 
specifically to the extracellular domain of human ROR1 and have good 
potential for therapeutic development by either humanization, 
conversion to chimeric mouse/human antibodies, or conjugation to a 
radioisotope, chemical drug or bacterial toxin.
    Applications:
     Therapeutic antibodies against ROR1-expressing cancers 
like B-CLL and possibly other hematologic and solid malignancies
     Research tools for the study of ROR1 in cancer biology
    Advantages:
     Hybridomas provide a continuous source of mAb
     Target extracellular domain of ROR1
    Market:
     Currently, mAbs alemtuzumab[reg] and rituximab[reg], which 
are not tumor cell-specific, are used for treating B-CLL. 
Rituximab[reg] generated sales of 5.2 billion U.S. dollars in 2007.
     MAb market is estimated to be worth $30.3 billion in 2010 
and it is one of the fastest growing sectors of the pharmaceutical 
industry with a 48.1% growth rate between 2003 and 2004.
    Inventors: Christoph Rader and Sivasubramanian Baskar (NCI).
    Publication: S Baskar et al. Unique cell surface expression of 
receptor tyrosine kinase ROR1 in human B-cell

[[Page 79891]]

chronic lymphocytic leukemia. Clin Cancer Res. 2008 Jan 15;14(2):396-
404.
    Patent Status: HHS Reference No. E-274-2008/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: This technology is available as a research tool 
under a Biological Materials License.
    Licensing Contact: Jennifer Wong; 301-435-4633.; 
[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 
diagnostic or therapeutic mAbs against ROR1. Please contact John D. 
Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

A Novel and Efficient Technology for Targeted Delivery of siRNA

    Description of Technology: The biological phenomenon of RNA 
interference (RNAi) has much promise for developing therapeutics to a 
variety of diseases. However, development of RNAi therapies remains 
mainly in preclinical stages largely because of difficulties in 
delivering small inhibitory RNAs (siRNA) and short hairpin RNAs (shRNA) 
into target cells. Although viral vector-based siRNA delivery systems 
have been widely used, their specificity and safety remains significant 
issue. Without a solution to this delivery problem, RNAi cannot fulfill 
its therapeutic promise.
    Investigators at the National Institutes of Health have developed 
novel compositions and methods for delivering inhibitory 
oligonucleotides to cells in a targeted and efficient manner. The 
compositions and methods are based on utilizing a cell surface receptor 
targeting ligand, such as cytokine or chemokine, and a domain that 
binds an inhibitory oligonucleotide, to efficiently deliver the 
inhibitory oligonucleotide to the cell that expresses the cell surface 
receptor targeting ligand. Chemokine receptors are differentially 
expressed on various cells, including tumors; hence this technology 
allows targeting siRNA to aberrant cells. Gene silencing can also be 
achieved in variety of immune cells by targeting cytokine receptors. 
This technology has great potential for developing into a safe and 
effective means of delivering therapeutic siRNAs.
    Applications:
     Treatment of cancers and autoimmune diseases by delivery 
of siRNA to tumor cells or various aberrantly functioning immune cells.
     This technology can be used to boost vaccine responses 
against cancers and chronic infectious diseases.
     Targeted delivery of fluorochrome-labeled RNA both in 
vitro and in vivo for diagnostic purposes, for example, to trace or 
localize various cells and to determine tumor metastasis and aberrant 
proliferation or homing of immune cells.
    Advantages:
     Simple method for linking siRNA to polypeptides to create 
non-covalent or covalent complexes.
     In vivo targeted delivery of inhibitory RNAs into cells 
rather than systemically.
     Delivery of multiple inhibitory RNAs to target multiple 
genes.
     Long term repression of target gene expression through 
RNAi phenomenon.
    Development Status: Currently animal model studies planned.
    Inventors: Arya Biragyn, Purevdorj Olkhanud and Juan Espinoza 
(NIA).
    Publications: None directly related to the invention.
    Patent Status: U.S. Provisional Application No. 61/045,088 filed 15 
Apr 2008 (HHS Reference No. E-051-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Institute on 
Aging, Immunotherapeutics Unit, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize chemokine-based siRNA/shRNA 
technology for treatment of cancers and autoimmune diseases, i.e. to 
control expression of immunomodulatory cytokines and other factors that 
facilitate tumor escape, activity of regulatory T cells or Th2 type of 
cells. This technology can be also utilized to boost vaccine responses 
against cancers and chronic infectious diseases. Please contact John D. 
Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

Method of Promoting Hematopoietic Stem Cell Engraftment by Enhancement 
of CXCR4 Activity

    Description of Technology: The success of allogeneic Hematopoietic 
Stem Cell (HSC) transplant is dependent upon factors affecting 
engraftment of donor HSC. Engraftment is affected by type and intensity 
of bone marrow conditioning and immunosuppression achieved by 
chemotherapy or radiation treatments as well as the number of stem 
cells present in the graft. Factors influencing HSC trafficking, such 
as HSC chemotaxis and adhesion, modulate the ability of HSCs to engraft 
in the transplant recipient. Chemokine receptor CXCR4 (present on HSC) 
and its ligand, SDF-1, play an important role in attracting HSC to and 
retaining HSC in the bone marrow after transplantation. Studies 
indicate that with increased amounts of CXCR4 in human HSC there is a 
several fold increase in the engraftment of HSCs in a xenograft mouse 
transplant model.
    This technology is directed to compositions comprising HSCs and 
methods for promoting CXCR4 expression in a HSC by inhibiting GRK3 or 
GRK6 (G-protein coupled receptor kinase (GRK) regulators of CXCR4) with 
an antisense compound.
    Application: Treatment of donor HSC for enhancement of engrafting 
in the recipient.
    Market: More than 45,000 HSC transplants are performed every year 
worldwide. Despite significant progress over the past half century, the 
overall five-year survival rate is below 55%. This technology, directed 
to enhancing HSC engrafting can help increase the survival rate after 
HSC transplant.
    Development Status: Preclinical.
    Inventor: Harry L. Malech (NIAID).
    Patent Status: U.S. Provisional Application No. 61/085,689 filed 01 
Aug 2008 (HHS Reference No. E-007-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Host Defenses, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize a 
method to improve hematopoietic stem cell transplantation through the 
enhancement of CXCR4 activity. Please contact Rosemary C. Walsh, PhD. 
at 301-451-3528 or [email protected] for more information.

AFMAnalyze: Software Automation and Analysis of Atomic Force Microscopy 
(AFM) Data

    Description of Technology: AFMAnalyze is a software package that is 
designed to significantly enhance the analysis and application of 
Atomic Force Microscopy (AFM) data. This software automates AFM data 
collection and analysis, and is equipped with a Graphical User 
Interface (GUI)-intensive

[[Page 79892]]

computational tool that is capable of replacing the manual or 
algorithmic methods for reconstructing, analyzing and interpreting 
large AFM data sets. AFMAnalyze provides a more robust, objective, and 
automated method for collecting and interpreting AFM results. A user, 
for example, can compute the Young's modulus of a sample at the press 
of a button located on the software interface.
    The software also enables ``reverse fitting'' of the data in order 
to calibrate AFM cantilevers using materials (such as reference gels) 
with known properties. This ability can significantly enhance the 
sensitivity, interpretation, and use of AFM measurements which depend 
on accurate determinations of cantilever properties. In a demonstration 
of the capabilities of AFMAnalyze, the software was successfully used 
to map the elasticity of the tectoral membrane (TM) by incorporating 
the analysis of over 500 force-distance curves. Generating such a map 
without automation would be prohibitively expensive and time consuming.
    AFMAnalyze is also flexibly designed for expansion, and 
incorporates modular programs for additional data analysis. Further 
modifications to the software could enable the analysis of force-volume 
data. This type of data has been, so far, difficult to analyze, but has 
significant use as a tool for distinguishing the different mechanical 
properties of materials including metals, polymers, semiconductors, 
ceramics, and biological specimens on the sub-nanometer scale.
    Applications:
     Automated, objective, and efficient AFM measurements of 
the nano-scale properties of materials.
     Efficient AFM cantilever calibration.
     Potential for AFM force-volume measurements.
    Development Status: Late stage.
    Inventor: Brett D. Shoelson (NIDCD).
    Publication: B Shoelson, EK Dimitriadis, H Cai, B Kachar, RS 
Chadwick. Evidence and implications of inhomogeneity in tectorial 
membrane elasticity. Biophys J. 2004 Oct;87(4):2768-2777.
    Patent Status: U.S. Patent No. 6,993,959 issued 07 Feb 2006 (HHS 
Reference No. E-003-2004/0-US-01); No foreign rights available.
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jeffrey A. James, Ph.D.; 301-435-5474; 
[email protected].

Methods and Compositions for Selectively Enriching Microbes

    Description of Technology: The described technology provides 
markedly improved enrichment of E. coli O157:H7, Shiga toxin-producing 
E. coli (STEC) and Shigella. This improved enrichment can be 
complimentary to, and enhance performance of, existing nucleic acid or 
antibody based detection methods. In addition, the improved enrichment 
method facilitates isolation of pathogens following positive results by 
any nucleic acid or antibody based test. Such isolation by cultural 
methods is essential for epidemiology, antibiotic sensitivity testing 
and other biochemical characterization.
    Current enrichment protocols are often inadequate as they allow 
large numbers of interfering bacteria to grow. This makes it necessary 
for microbiologists to screen hundreds of presumptive colonies to 
achieve successful isolation (A Khan et al., Emerg Infect Dis. 2002 
Jan; 8:54-62). The new technology is a simple two step process. The 
sample is first placed in a low pH solution for a brief period and then 
transferred to a medium permitting maximal growth of target bacteria. 
With this new technology there is no risk of false negative results due 
to inadvertent inhibition of target bacteria by novobiocin, tellurite, 
cefixime, or other additives commonly used in existing enrichment 
procedures.
    This new technology has been shown to be effective with food, 
water, environmental and clinical samples. Its components are 
inexpensive and microbiologists are not required to impede their 
workflow by adding separate selective agents at specified intervals 
such as four or six hours.
    Applications: Improved detection of E. coli O157:H7, STEC and 
Shigella in:
     Clinical samples
     Food
     Beverages
     Dairy
     Water
     Wastewater
     Environmental
     Veterinary Samples
    Advantages:
     Simple
     Inexpensive
     Requires no addition of antibiotic or other inhibitor 
solutions
     Reduces interfering bacterial competitors and makes 
detection of target pathogens easier
    Market: Manufacturers of Microbiological Media and Tests for use 
in:
     Hospitals
     Clinics
     Food and Beverage Manufacturers
     Testing Laboratories
     Dairies
     Veterinary Clinics
     Water Testing Laboratories
     Water and Wastewater Facilities
    Inventor: Michael A. Grant (FDA).
    Publications:
    1. MA Grant. Comparison of Escherichia coli O157:H7 enrichment in 
spiked produce samples. J Food Prot. 2008 Jan;71(1):139-145.
    2. MA Grant. Comparison of a new enrichment procedure for Shiga 
toxin-producing Escherichia coli with five standard methods. J Food 
Prot. 2005 Aug;68(8):1593-1599.
    3. MA Grant. Improved laboratory enrichment for enterohemorrhagic 
Escherichia coli by exposure to extremely acidic conditions. Appl 
Environ Microbiol. 2004 Feb;70(2):1226-1230.
    4. Submitted for publication--two papers demonstrating 
effectiveness of new enrichment procedure with clinical and 
environmental samples.
    Patent Status:
     U.S. Provisional Application No. 60/435,639 filed 20 Dec 
2002 (HHS Reference No. E-228-2002/0-US-01).
     International Application No. PCT/US03/40806 filed 19 Dec 
2003, which published as WO 2004/111180 on 23 Dec 2004 (HHS Reference 
No. E-228-2002/0-PCT-02).
     U.S. Patent Application No. 10/539,765 filed 20 Jun 2005 
(HHS Reference No. E-228-2002/0-US-04).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Rung C. (RC) Tang, JD LLM; 301-435-5031; 
[email protected].
    Collaborative Research Opportunity: The FDA is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize methods for 
detecting pathogenic bacteria, especially E. coli O157:H7, Shiga toxin-
producing E. coli (STEC) and Shigella. Please contact Alice Welch at 
[email protected] for more information.

    Dated: December 18, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-30849 Filed 12-29-08; 8:45 am]
BILLING CODE 4140-01-P