[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

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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