[Federal Register Volume 75, Number 43 (Friday, March 5, 2010)]
[Notices]
[Pages 10286-10289]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-4757]
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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.
Methods To Increase Stability of Recombinant Vaccinia-Vectored Vaccines
and Increase Expression of a Foreign Gene Inserted in Such Vaccines
Description of Invention: The technology offered for licensing is
in the field of vaccinia-based recombinant vaccines. In particular the
invention relates to methods of stabilizing the recombinant virus, thus
resulting in efficient production of the vaccine and efficient
expression of the inserted gene. Stabilization of the recombinant virus
is achieved by the insertion of the exogenous gene into an intergenic
region (IGR) of the viral genome (i.e. Modified Vaccinia Ankara, MVA),
where the IGR is flanked by open reading frames of conserved poxvirus
genes. Furthermore, the invention relates to plasmids vectors useful to
[[Page 10287]]
insert the exogenous DNA into the genome of a vaccinia virus. Stability
can be further enhanced by incorporating silent mutations that decrease
the lengths of homopolynucleotide runs in the foreign gene.
Applications:
Efficient production of vaccinia-vectored vaccines for
infectious diseases and other diseases such as cancer.
Efficient production of therapeutic proteins from
vaccinia-vectored exogenous genes.
Advantages:
Enhancing stability of foreign genes in vaccinia-vectored
constructs.
Increasing efficiency of vaccine production and gene
expression.
Development Status: The invention is fully developed.
Market: Vaccines development based on vaccinia (e.g. MVA) vector
inserted with foreign gene of immunologic or therapeutic interest has
become one of the most promising approaches for vaccine development.
Several companies established vaccine development programs based on
this approach and many research laboratories around the world conduct
research in the area. Improvements in the production process and in
production yields, such as provided by the subject invention, are
therefore of great significance for successful accomplishments in this
area. Commercial products for veterinary use already exist. Many
applications for human use are now in various stages of clinical
trials, in particular applications for HIV, HPV in the infectious
disease area and as therapeutic vaccine in the cancer field. The market
potential for the subject technology is therefore vast.
Inventors: Bernard Moss et al. (NIAID).
Related Publication: LS Wyatt, PL Earl, W Xiao, J Americo, C
Cotter, J Vogt, B Moss. Elucidating and minimizing the loss by
recombinant vaccinia virus of human immunodeficiency virus gene
expression resulting from spontaneous mutations and positive
selections. J Virol. 2009 Jul;83(14):7176-7184. [PubMed: 19420086].
Patent Status: U.S. Provisional Application No. 61/252,326 filed
October 16, 2009, entitled ``Plasmid Shuttle Vector for Insertion of
Foreign Genes into Del III Site of Modified Vaccinia Ankara (MVA) to
Increase Stability of Foreign Gene Expression in This Site'' (HHS
Reference No. E-018-2010/0-US-01).
Related Technologies:
WO 2008/142479 A2 (PCT/IB2007/004575)--``Intergenic Sites
between Conserved Genes In The Genome of Modified Vaccinia Ankara (MVA)
Vaccinia Virus,'' Bernard Moss et al.
US Patent 6,998,252; US Patent 7,015,024; US Patent
7,045,136; US Patent 7,045,313--``Recombinant Vaccinia Virus Containing
a Chimeric Gene Having Foreign DNA Flanked by Vaccinia Regulatory
DNA,'' Bernard Moss et al.
Licensing Status: Available for licensing.
Licensing Contacts: Uri Reichman, PhD, MBA; 301-435-4616;
[email protected]; or John Stansberry, Ph.D.; 301-435-5236;
[email protected].
Compounds That Interfere With the Androgen Receptor Complex: Use in
Treating Prostate Cancer or Enlargements, Diabetes, and as
Contraceptives
Description of Invention: Investigators at the National Institutes
of Health (NIH) have discovered compounds that have potential as novel
anti-androgen therapeutics. The immunophilin protein FKBP52 is part of
a protein complex that helps fold the androgen receptor (AR) protein, a
target for treating prostate cancer, and enhances its activity.
Disruption of the FKPB52-AR interaction greatly reduces the activity of
the AR. With the goal of finding potential therapeutic compounds that
inhibit the FKBP52-mediated activation of AR, several small molecules
were tested and found to be antagonists of FKBP52 and to inhibit AR
activity in prostate cells. These compounds can serve as therapeutics
for the treatment of prostate cancer and benign prostate enlargement.
Moreover, FKBP52 is also implicated in the regulation of other hormone
receptors so these compounds could be used to treat other hormone-
dependent diseases such as diabetes or even used as contraceptives.
One of the standard treatments for prostate cancer makes use of
anti-androgens, like bicalutamide, which compete for binding with the
natural male hormones to AR and inhibit their proliferative activity.
The problem with available anti-androgen drugs is that prostate tumors
eventually become drug resistant resulting in so-called androgen-
resistant prostate cancer. One cause of this is an increase in the
levels of AR produced by the prostate cancer cells. A solution to this
problem may lie in disrupting the protein folding of AR by interfering
with its interaction with FKBP52 using these compounds.
Applications:
Use of the compounds for treatment of prostate cancer and
benign prostate enlargement
Use of the compounds in treating insulin-independent
diabetes
Use of the compounds as male or female contraceptives
Use in screening for compounds that inhibit of FKBP52-
enhanced AR activity
Advantages:
The compounds do not compete with androgens and
specifically inhibit FKBP52-enhanced AR function
Potential for synergistic use with conventional anti-
androgens for treatment of androgen resistant prostate cancer
Development Status: Pre-clinical.
Market: Prostate cancer is the second most common type of cancer
among men in the United States and is the second leading cause of
cancer death in men. It was estimated that in 2009 there would be
192,280 new cases and 27,360 deaths from prostate cancer in the U.S.
The prevalence of benign prostate enlargement is much greater as 50%
men age 50 are affected and continues to increase with age.
Diabetes is a growing health problem in the U.S. and the world. The
most recent estimate (2007 National Diabetes Fact Sheet) in the U.S.
was that 7.8% of the population had diabetes and 1.6 million new cases
per year would be diagnosed. In the population of people over 60 the
prevalence of diabetes is even higher (23%).
Among the 64 million women of reproductive age in the U.S., the
leading contraceptive method is hormonal contraceptives. Presently,
there are no hormonal contraceptives to reversibly block fertility in
men and there is a need for safe and effective hormonal methods as
exist for women.
Inventors: Leonard M. Neckers (NCI), Marc Cox (UTEP) et al.
Relevant Publication: J Cheung-Flynn et al. Physiological role for
the cochaperone FKBP52 in androgen receptor signaling. Mol Endocrinol.
2005 Jun;19(6):1654-1666. [PubMed: 15831525].
Patent Status: U.S. Provisional Application No. 61/242,541 filed 15
Sep 2009 (HHS Reference No. E-162-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587;
[email protected].
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 antagonists of FKBP52-dependent
remodeling of the androgen
[[Page 10288]]
receptor. Please contact John D. Hewes, Ph.D. at 301-435-3121 or
[email protected] for more information.
Radioprotectants and Tumor Radiosensitizers Targeting Thrombospondin-1
and CD47
Description of Invention: Radiation therapy not only damages cancer
cells, but it also damages healthy cells and can cause serious side
effects for patients. One effort to enhance the therapeutic potential
of radiotherapy, while reducing its detrimental effects on normal
tissue and maintaining tumor sensitivity, is centered upon the
development of radioprotective agents.
NIH inventors previously discovered that when the secreted protein,
thrombospondin-1 (TSP1) binds to its receptor CD47, this signaling
pathway prevents nitric oxide from dilating blood vessels and
increasing blood flow to organs and tissues. They found that blocking
TSP1-CD47 interaction through the use of antisense morpholino
oligonucleotides, peptides or antibodies has several therapeutic
benefits; one of them being increased blood flow to ischemic tissues.
In the present technology, the inventors discovered that hindlimb
irradiated TSP1 and CD47 null mice have less hair loss, and decreased
cell death in muscle and bone marrow than untreated TSP1 and CD47 null
mice. They also discovered that when irradiated human vascular cells
are treated with antibodies towards TSP1 or CD47, viability and
proliferative capacity are preserved. Furthermore, the inventors
determined that irradiation of wild type mice following treatment with
CD47 antisense morpholino resulted in decreased apoptosis in irradiated
tissues at 24 hours, preservation of hematopoietic stem cell
proliferative capacity in irradiated bone marrow, and less alopecia,
ulceration, and desquamation at the end of eight weeks. These results
led the inventors to propose that antagonists of TSP1 and/or CD47
preserve cell viability and tissue function following radiation
treatment, and these antagonists may be useful as radioprotective
agents to reduce side effects associated with radiation therapy.
Remarkably, the same treatment dramatically enhanced the delay in
melanoma and squamous carcinoma tumor regrowth following irradiation.
Thus, these agents are radioprotective agents for normal tissue but
radiosensitizers for tumor tissue.
The present technology describes the use of morpholinos, peptides
and antibodies that block the TSP1/CD47 signaling pathway as
radioprotectants for normal tissue, radioenhancers for tumor tissue,
and methods of selectively protecting normal tissue from damage caused
by radiation exposure by contacting the tissue with these agents.
Applications:
Protect normal tissue from damage following radiation
therapy.
Enhance tumor responses to radiotherapy.
Enable use of higher therapeutic doses for radiotherapy of
cancer.
Protect personnel from radiation injuries resulting from
occupational exposure to ionizing radiation, military exposure, or
terrorist acts.
Development Status: Mouse data available. In vitro data available
in mouse, bovine, porcine, and human cells.
Inventors: Jeffery S. Isenberg, David D. Roberts, Justin B.
Maxhimer (NCI)
Related Publications:
1. JB Maxhimer, DR Soto-Pantoja, LA Ridnour, HB Shih, WG DeGraff, M
Tsokos, DA Wink, JS Isenberg, DD Roberts. Radioprotection in normal
tissue and delayed tumor growth by blockade of CD47 signaling. Sci
Transl Med. 21 October 2009; Vol 1, Issue 3, pg. 3ra7; DOI:10.1126/
scitranslmed.3000139.
2. JS Isenberg, G Martin-Manso, JB Maxhimer, DD Roberts. Regulation
of nitric oxide signaling by thrombospondin-1: implications for anti-
angiogenic therapies. Nat Rev Cancer. 2009 Mar;9(3):182-194. [PubMed:
19194382]
3. JS Isenberg, JB Maxhimer, F Hyodo, ML Pendrak, LA Ridnour, WG
DeGraff, M Tsokos, DA Wink, DD Roberts. Thrombospondin-1 and CD47 limit
cell and tissue survival of radiation injury. Am J Pathol.
2008;173(4):1100-1112. [PubMed: 18787106]
Patent Status: PCT/US2009/052902 filed 05 Aug 2009 (HHS Reference
No. E-153-2008/0-PCT-02).
Licensing Status: Available for licensing.
Licensing Contact: Charlene A. Sydnor, Ph.D.; 301-435-4689;
[email protected].
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Pathology, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize CD47-targeting agents as
radioprotectants and tumor sensitizers. Please contact John D. Hewes,
Ph.D. at 301-435-3121 or [email protected] for more information.
Mouse Lacking the Chemokine Receptor CX3CR1
Description of Invention: This mouse has been generated by targeted
gene disruption. The mouse provides a model to investigate the function
of the chemokine receptor CX3CR1, which is a proinflammatory receptor
for the leukocyte chemoattractant CX3CL1 (aka fractalkine). As an
example, the mouse is in use in the study of atherosclerosis. Further,
the mouse may serve as a model study the role of the immune system
during infection with pathogens as well as other immunologically
mediated diseases and responses to tumors.
Inventors: Philip Murphy, Christopher Combadi[egrave]re, Ji-liang
Gao (NIAID).
Related Publication: C Combadi[egrave]re et al. Decreased
atheroscelerotic lesion formation in CX3R1/ApoE double knockout mice.
Circulation 2003 Feb 25;107(7):1009-1016. [PubMed: 12600915].
Patent Status: HHS Reference No. E-216-2003/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a biological
materials license.
Licensing Contact: Susan Ano, Ph.D.; 301-435-5515;
[email protected].
Oligonucleotides Which Specifically Bind Retroviral Nucleocapsid
Proteins
Description of Invention: The human immunodeficiency virus (HIV) is
the causative agent of acquired immunodeficiency syndrome (AIDS). A
retroviral protein species, the gag polyprotein, is involved in the
assembly of retrovirus particles and capable of specific interactions
with nucleic acids. After the virion is released from the cell, the
polyprotein is cleaved by the virus-encoded protease. One of the
cleaved products, the nucleocapsid (NC) protein, then binds to genomic
RNA, forming the ribonucleoprotein core of the mature particle. The
interaction between gag and genomic RNA is known to involve the NC
domain of the polyprotein. In addition, the NC protein plays crucial
roles in both the reverse transcription and integration steps in the
viral life cycle.
The present invention relates to retroviral nucleocapsid proteins,
such as NC and the gag precursor, and their ability to bind to specific
nucleic acid sequences with high affinity. The high affinity of this
interaction has potential applications in the design of new antiviral
approaches and in sensitive detection of HIV particles. Accordingly,
the invention provides for oligonucleotides which bind to nucleocapsid
proteins with high affinity, molecular decoys for retroviral
nucleocapsid proteins which inhibit viral replication, targeted
molecules
[[Page 10289]]
comprising high affinity oligonucleotides, assays for selecting test
compounds, and related kits.
Inventors: Alan R. Rein et al. (NCI).
Patent Status: U.S. Patent No. 6,316,190 issued 13 Nov 2001 (HHS
Reference No. E-107-1996/0-US-06).
Licensing Status: Available for licensing.
Licensing Contact: Sally Hu, PhD; 301-435-5606; [email protected].
Dated: March 1, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-4757 Filed 3-4-10; 8:45 am]
BILLING CODE 4140-01-P