[Federal Register Volume 75, Number 166 (Friday, August 27, 2010)]
[Notices]
[Pages 52758-52760]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-21349]


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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.

An XMRV Tool Box: Expression Plasmids, Genes, and Proteins for All 
Components of the Xenotropic Murine Leukemia Virus-Related Virus (XMRV)

    Description of Invention: The xenotropic murine leukemia virus-
related virus (XMRV) has been implicated as a possible causative agent 
of prostate cancer and chronic fatigue syndrome (CFS). Scientists at 
the National Institutes of Health (NIH) and Science Applications 
International Corporation in Frederick, MD (SAIC-Frederick) have 
developed sixty four (64) protein expression plasmids for components of 
XMRV. One or more

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XMRV proteins made available through these expression plasmids could 
have clinical relevance to diagnosing or treating human disease. The 
work to develop this technology was performed in the Protein Expression 
Laboratory at SAIC-Frederick in collaboration with expert 
retrovirologists from the National Cancer Institute's Frederick, MD 
campus, a site well-positioned to develop these expression plasmids 
from initial cloning to final validations. The development of these 
XMRV tools is expected to save researchers months in laboratory 
production time and thousands of dollars in labor costs.
    The XMRV strain utilized to generate these expression plasmids is a 
reference strain isolated from a human patient. Each expression plasmid 
encodes one of the ten proteins that comprise the XMRV retrovirus 
(matrix, p12, capsid, nucleocapsid, protease, reverse transcriptase, 
integrase, surface, transmembrane, and envelope). Nine of the ten XMRV 
proteins expressed by these clones have been successfully purified in 
large quantities using scale-up processes. The expression vectors were 
generated utilizing the Gateway[supreg] cloning system and consist of 
Gateway[supreg] entry clones, bacterial (Escherichia coli) expression 
clones, baculovirus expression clones, and mammalian expression clones. 
Expression of the appropriate XMRV protein from its corresponding 
expression clone has been confirmed. The entry clones have been 
validated for Gateway[supreg] subcloning and the baculovirus clones 
have been validated for baculovirus production and can be transposed 
into baculoviral genomes. The plasmids have been fully mapped and 
sequenced and contain one or more elements to facilitate laboratory 
use, such as antibiotic resistance genes, specialized promoter 
sequences, maltose-binding protein and His tags, TEV protease sites, 
Kozak-ATG sequences, signal peptides, and other elements.
    Applications:
     Research tool whose large-scale production capability can 
be utilized to develop serological assays for detecting XMRV and other 
retroviruses to possibly establish these viruses as causative agents 
for CFS, prostate cancer, and other diseases with unknown origins.
     Collection of research tools that could be utilized to 
develop a complete set of diagnostic assays for detecting each of these 
XMRV proteins in patient samples.
     Research tool to serve as a platform for developing 
therapeutic moieties, such as neutralizing antibodies and other 
biologics, for treating prostate cancer, chronic fatigue syndrome, and 
any other disease where XMRV is later identified as the causative 
agent.
     A logical starting point for generating clinical-grade 
XMRV constructs for use in clinical vaccine, immunotherapy, and gene 
therapy studies.
    Advantages:
     First complete set of plasmids available for the 
expression of each XMRV protein individually: Researchers looking to 
study XMRV can save months of time and thousands of dollars by using 
this set of XMRV tools. The plasmids have been fully-mapped and 
validated for protein expression. This plasmid portfolio offers a 
variety of vectors for expressing these XMRV proteins including 
Gateway[supreg] entry clones, bacterial vectors, baculoviral vectors, 
and mammalian expression systems.
     Clones were developed from an XMRV isolate taken from a 
patient with a confirmed XMRV infection: The proteins produced by these 
expression plasmids are anticipated to have direct clinical 
applicability to human XMRV diseases.
     Launching pad for any commercial entity desiring to 
develop diagnostics or therapeutics for XMRV: This technology is likely 
to give companies in the prostate cancer arena or the emerging chronic 
fatigue syndrome market a competitive advantage for developing anti-
XMRV products faster than competitors. The molecular targets needed as 
a starting point for therapeutic development are provided by this 
technology.
    Market: Apart from cancers of the skin, prostate cancer is the most 
common form of cancer found in men, especially in men over the age of 
65. In the United States, an estimated 200,000 men are diagnosed with 
prostate cancer each year and around 100 men die of the disease daily. 
About $5 billion dollars is spent annually on treatments for prostate 
cancer.
    The Center for Disease Control (CDC) estimates that over 1 million 
Americans are living with chronic fatigue syndrome and approximately 
80% of these individuals are undiagnosed. This debilitating disease 
likely affects over 17 million people worldwide and the cause of CFS is 
currently unknown. Those individuals diagnosed with CFS are a vocal 
patient group desiring expanded research into the cause of CFS and 
possible treatments and/or cures. In the United States alone, an 
estimated $9 billion dollars is lost annually due to CFS-induced 
decreases in worker productivity.
    Inventors: Dominic Esposito (SAIC), Alan Rein (NCI), Stuart Le 
Grice (NCI), James Hartley (SAIC), William Gillette (SAIC), Ralph 
Hopkins III (SAIC), Troy Taylor (SAIC).
    Selected Publications:
    1. VC Lombardi, et al. Detection of an infectious retrovirus, XMRV, 
in blood cells of patients with chronic fatigue syndrome. Science 2009 
Oct 23;326(5952):585-589. [PubMed: 19815723]
    2. A Urisman, et al. Identification of a novel Gammaretrovirus in 
prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS 
Pathog. 2006 Mar;2(3):e25. [PubMed: 16609730]
    Patent Status: HHS Reference No. E-155-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a Biological 
Materials License Agreement.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; bishse@mail.nih.gov.

Tempol: A Commercially Available Nitroxide as Cancer Therapeutics

    Description of Invention: The invention is the discovery that a 
commercially available stable nitroxide, namely TEMPOL can effectively 
reduce the level of hypoxia-inducible transcription factor (HIF)-
2[alpha]. Elevated HIF-2[alpha] is associated with clear cell kidney 
cancer characterized by mutation of the VHL tumor suppressor gene and 
with many other cancers. Therefore, TEMPOL can potentially be developed 
into a cancer drug to treat patients with elevated HIF-2[alpha], 
whether due to compromised VHL function or not.
    Applications: Known compound (TEMPOL) found to be effective in 
treating several cancers.
    Advantages: Animal data confirms effectiveness of TEMPOL against 
cancer support.
    Development Status: Pre-clinical, In vivo animal data available.
    Target Market: The potential drug will target a population that 
suffers from genetic diseases such as inherited von Hippel-Lindau (VHL) 
disease, which is associated with elevated expression of HIF-2[alpha] 
and patients with kidney and other cancers characterized by elevation 
of HIF-2[alpha]. Inherited VHL disease is a cancer syndrome caused by 
germ line mutations of the VHL tumor suppressor gene. VHL is 
characterized by angiomas and hemangioblastomas of the brain, spinal 
cord, and retina. These can lead to cysts and/or tumors of the kidney, 
pancreas, and adrenal glands (e.g.,

[[Page 52760]]

pheochromocytoma and endolymphatic sac tumors).
    Renal clear cell carcinoma (RCC) develops in approximately 75% of 
VHL patients by age 60 and is a leading cause of death in this 
population. Inactivation (mutation or methylation) of the VHL gene is 
associated with greater than 90% of all clear cell RCC (including 
sporadic cases) (Nickerson et al. Clin Cancer Res 2008;14:4726-34). 
Thus, subjects with compromised VHL function represent a significant 
population that has or is at risk for developing cancer, including RCC. 
There is data that HIF-2[alpha] may be important in all or most cancers 
(Franovic et al. Proc Natl Acad Sci U S A 2009;106:21306-11).
    Inventors: W. Marston Linehan (NCI), Tracey A. Rouault (NICHD), 
James B. Mitchell (NCI), Murali K. Cherukuri (NCI).
    Patent Status: U.S. Provisional Application No. 61/265,194 filed 30 
Nov 2009 (HHS Reference No. E-133-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587; 
chatterjeesa@mail.nih.gov.
    Collaborative Research Opportunity: The Center for Cancer Research, 
Urologic Oncology Branch, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the use of Tempol to target HIF-
2[alpha] in cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

Chimeric Anti-human ROR1 Monoclonal Antibodies

    Description of Invention: Available for licensing are mouse anti-
human receptor tyrosine kinase-like orphan receptor 1 (ROR1) monoclonal 
antibodies (mAbs). ROR1 is a signature cell surface antigen for B-cell 
chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) 
cells, two incurable B-cell malignancies that are newly diagnosed in 
approximately 15,000 and 3,500 patients per year, respectively, in the 
United States. Currently, there are no therapeutic mAbs that 
specifically target B-CLL or MCL cells. Anti-ROR1 mAbs may be linked to 
chemical drugs or biological toxins thus providing cytotoxic delivery 
to malignant B-cells and not normal cells. Additionally, these 
antibodies can be fused to radioisotopes and can be used to diagnose B-
CLL and MCL malignancies.
    Applications:
     B-CLL and MCL antibody therapeutics.
     Method to diagnose B-CLL and MCL.
    Advantages: Selective targeting to malignant B-CLL and MCL cells.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market:
     The monoclonal antibody market is one of the fastest 
growing sectors of the pharmaceutical industry with a 48.1% growth 
between 2003 and 2004 and the potential to reach $30.3 billion in 2010. 
This growth rate is driven by the evolution of chimeric and humanized 
to fully humanized antibody therapeutics.
     Approximately 18,500 patients with ROR1-expressing B-cell 
malignancies are newly diagnosed annually in the United States.
    Inventors: Christoph Rader and Sivasubramanian Baskar (NCI).
    Related Publications:
    1. S Baskar et al. Unique cell surface expression of receptor 
tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia. Clin 
Cancer Res. 2008 Jan 15;14(2):396-404. [PubMed: 18223214]
    2. M Hudecek et al. The B-cell tumor associated antigen ROR1 can be 
targeted with T-cells modified to express a ROR1-specific chimeric 
antigen receptor. Blood. 2010 Aug 11; Epub ahead of print. [PubMed: 
20702778]
    Patent Status:
     U.S. Provisional Application No. 61/172,099 filed 23 Apr 
2009 (HHS Reference No. E-097-2009/0-US-01).
     PCT Application No. PCT/US10/32208 filed 23 Apr 2010 (HHS 
Reference No. E-097-2009/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
wongje@mail.nih.gov.
    Collaborative Research Opportunity: The Center for Cancer Research, 
Experimental Transplantation and Immunology Branch is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
anti-ROR1 mAbs, antibody-drug conjugates, radioimmunoconjugates, 
bispecific antibodies, and other therapeutic or diagnostic modalities. 
Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

    Dated: August 23, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-21349 Filed 8-26-10; 8:45 am]
BILLING CODE 4140-01-P