[Federal Register Volume 77, Number 14 (Monday, January 23, 2012)]
[Notices]
[Pages 3273-3275]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-1264]


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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.

Enhancement of Cancer Imaging and Treatment With Somatostatin Analogs

    Description of Technology: Available for licensing is a novel 
method using short-term treatment with a glucocorticoid antagonist to 
increase the expression of somatostatin receptors in tumor cells and 
improve rates of tumor identification in patients with high cortisol 
levels.
    Tumors express up to five different receptors for somatostatin 
analogs on their surface. This enables somatostatin and its analogs to 
bind to the tumor cells. When the compound has a radioactive or 
radiopharmaceutical ``tag'' it can allow the cell to be killed (via 
radiation) or imaged (via the radiopharmaceutical). Somatostatin 
analogs have variable affinity for the five somatostatin receptors 
(types 1-5). As a result, if tumors express less of the more avid 
receptors, imaging or treatment with the analogs is less likely to be 
successful. There is a large variability in functional type 2 receptor 
expression in these tumors. High cortisol levels (such as those seen in 
Cushing's syndrome) cause the type 2 receptor level to decrease, which 
(with type 5) is the primary binding site for \111\1n-DTPA-D-Phe-
pentetreotide, which is used to image tumors (in an octreotide nuclear 
medicine scan).
    Potential Commercial Applications: Tumor imaging and 
radiopharmaceutical therapy using somatostatin analogs.
    Competitive Advantages: Allows conversion of a negative to positive 
octreotide scan in patients with active hypercortisolism.
    Development Stage: Pilot.
    Inventors: Lynnette Nieman (NICHD), et al.
    Intellectual Property: HHS Reference No. E-252-2011/0--U.S. 
Provisional Application No. 61/533,664 filed 12 Sep 2011.
    Licensing Contact: Patrick McCue, Ph.D.; (301) 435-5560; 
[email protected].

PARP Inhibitor/NO Donor Dual Prodrugs as Anticancer Agents

    Description of Technology: Scientists at NIH have developed a 
hybrid prodrug molecule with enhanced biological activity as anticancer 
agent. Novel cancer therapeutic strategies are in high demand. 
Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a 
growing class of promising anticancer agents. Poly (ADP-ribose) 
polymerase (PARP) inhibitors have also emerged as a promising class of 
therapeutic compounds for cancer. The two-component prodrug described 
in the instant invention is expected to deliver DNA damaging agent (NO 
release) along with an inhibitor of DNA repair (PARP inhibitor) 
simultaneously to a cancer cell. The prodrugs are activated by 
glutathione/glutathione S-transferase (GSH/GST) and release cytotoxic 
NO and a PARP inhibitor in the target cancer cell. The high levels of 
GSH/GST are often a feature of cancer cells. The compound is predicted 
to have strong synergy with other anticancer therapeutics.

Potential Commercial Applications

     Cancer therapeutics.
     Cancer therapeutics in combination with other anticancer 
therapies.
    Competitive Advantages: Combination of DNA damaging agent and DNA 
repair inhibitor in one molecule has advantage over both individual 
drug treatments.

Development Stage

     Prototype.
     Early-stage.
     Pre-clinical.
     In vitro data available.
    Inventors: Anna E. Maciag, Larry K. Keefer, and Joseph E. Saavedra 
(NCI).
    Publication: PARP Inhibitor/NO Donor Dual Prodrugs as Anticancer 
Agents, manuscript in preparation.
    Intellectual Property: HHS Reference No. E-220-2011/0--U.S. Patent 
Application No. 61/549,862 filed 21 Oct 2011.

Related Technologies

     HHS Reference No. E-093-1996/3--U.S. Patent No. 6,610,660 
issued 26 Aug 2003.
     HHS Reference No. E-025-2010/0--PCT Application No. PCT/
US2010/056446 filed 12 Nov 2010, which published as WO 2011/060215 on 
19 May 2011
    Licensing Contact: Betty B. Tong, Ph.D.; (301) 594-6565; 
[email protected].

Small Molecule Drugs for Treatment of Ataxia Telangiectasia or DNA 
Damage

    Description of Technology: Ataxia telangiectasia (A-T) is a rare 
neurodegenerative disease that is caused by mutations in the Ataxia 
Telangiectasia Mutated (ATM) gene, which is the chief activator of the 
cellular response to double stranded DNA breaks. Defects in this gene 
can lead to abnormal cell death, particularly in the brain and in the 
immune system, and the disease is also characterized by 
hypersensitivity to radiation and other DNA-damaging agents, as well as 
a predisposition to lymphoma. There is currently no effective treatment 
for this disease.
    Investigators at the National Human Genome Research Institute 
(NHGRI) have shown that ATM-null cells treated with rottlerin, a small 
molecule protein kinase inhibitor, respond to double stranded DNA 
breaks by activating an

[[Page 3274]]

alternate DNA repair pathway. Similarly, ATM-null mice demonstrate 
increased protection from radiation when treated with this compound. 
Thus, rottlerin or related compounds may be an effective treatment for 
A-T or other diseases resulting from DNA damage.
    Potential Commercial Applications: Therapy for ataxia 
telangiectasia or other diseases resulting from DNA damage.

Competitive Advantages

     There is currently no therapy for ataxia telangiectasia.
     Rottlerin is a readily-obtained, small molecule compound.

Development Stage

     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Wei Zheng et al. (NCTT).
    Intellectual Property: HHS Reference No. E-038-2011/0--U.S. 
Provisional Application No. 61/524,177 filed 16 Aug 2011.
    Licensing Contact: Tara L. Kirby, Ph.D.; (301) 435-4426; 
[email protected].

Transgenic Human Interleukin-21 Mouse Model

    Description of Technology: Available for licensing is a mouse model 
that constitutively expresses human interleukin-21 (IL-21). 
Traditionally, human IL-21 transgenic mouse models are difficult to 
produce as those with high IL-21 levels exhibit growth retardation and 
die before sexual maturity. The investigators generated transgenic mice 
that express human IL-21, which can stimulate murine cells in vitro 
thereby providing an accurate model to elucidate IL-21's role in 
immunity, immune disorders, and cancer.
    IL-21 is a type I cytokine whose receptor is expressed on T, B, and 
natural killer cells. IL-21 has pleiotropic actions ranging from 
augmenting the proliferation of T cells to driving the differentiation 
of B cells into memory cells and terminally differentiated plasma 
cells. Moreover, IL-21 has anti-tumor activity by augmenting natural 
killer cell activity. This mouse model allows studying human IL-21 in 
vivo and its role in a variety of diseases such as autoimmunity, 
immunodeficiency, allergy, and cancer.

Potential Commercial Applications

     Model to study human IL-21 in vivo.
     Research tool to elucidate IL-21's role in T, B, and 
natural killer cell function and regulating antibody production.
     Model to study IL-21's pathology in autoimmunity, 
immunodeficiency, allergy, and cancer.
    Competitive Advantages: Mouse model that constitutively expresses 
human IL-21, without the negative side effects of growth retardation 
and high toxicity present in other human IL-21 transgenic mice.

Development Stage

     Pre-clinical.
     In vivo data available (animal).
    Inventors: Warren Leonard and Katsutoshi Ozaki (NHLBI).
    Publication: Ozaki K, et al. Regulation of B cell differentiation 
and plasma cell generation by IL-21, a novel inducer of Blimp-1 and 
Bcl-6. J Immunol. 2004 Nov 1;173(9):5361-5371. [PMID 15494482].
    Intellectual Property: HHS Reference No. E-231-2010/0--Research 
Tool. Patent protection is not being pursued for this technology.

Related Technologies

     HHS Reference No. E-211-2002/1--U.S. Patent 7,332,645 
issued 19 Feb 2008; U.S. Patent Application No. 11/958,540 filed 18 Dec 
2007.
     HHS Reference No. E-120-2003/1--U.S. Patent 7,993,919 
issued 09 Aug 2011.
     HHS Reference No. E-120-2003/2--U.S. Patent 7,378,276 
issued 27 May 2008; U.S. Patent Application No. 12/126,166 filed 23 May 
2008.
     HHS Reference No. E-137-2002/0--U.S. Patent Application 
No. 10/508,978 filed 19 Nov 2004; U.S. Patent Application No. 12/
651,858 filed 04 Jan 2010.
    Licensing Contact: Jennifer Wong; (301) 435-4633; 
[email protected].

Method for Producing Significant Amounts of B19 Virus for Development 
of Killed or Attenuated Vaccines

    Description of Technology: Human parvovirus B19 (B19) is a common 
infection of children and adults and is the cause of fifth disease. B19 
selectively infects erythroid progenitor cells of bone marrow, fetal 
liver and a small number of specialized cell lines. These specific cell 
lines demonstrate limited infectibility and commonly produce little or 
no virus following initial inoculation with B19. Current methods for 
producing infectious B19 require phlebotomy of infrequently available 
infected donors. The available technology describes a method of 
producing pure populations of human erythroid progenitor cells that are 
fully permissive to B19 infection. The ability to efficiently generate 
significant amounts of infectious B19V in cells is useful for the 
development of killed or attenuated vaccines, therapeutics and 
efficient diagnostic tools for prevention and treatment of B19V.

Potential Commercial Applications

     Human parvovirus B19 diagnostic.
     Vaccine manufacture.
     Research and development of anti-parvovirus agents.
    Competitive Advantages: Method produces pure populations of human 
erythroid progenitor cells that are fully permissive of B19 infection.

Development Stage

     Pre-clinical.
     In vitro data available.
    Inventors: Susan Wong and Neal S. Young (NHLBI).

Publications

    1. Giarratana MC, et al. Ex vivo generation of fully mature human 
red blood cells from hematopoietic stem cells. Nat Biotechnol. 2005 
Jan; 23(1):69-74. [PMID 15619619].
    2. Freyssinier JM, et al. Purification, amplification and 
characterization of a population of human erythroid progenitors. Br J 
Haematol. 1999 Sep; 106(4):912-922. [PMID 10519992].
    Intellectual Property: HHS Reference No. E-188-2006/0--U.S. Patent 
Application No. 12/301,960 filed 21 Nov 2008.
    Licensing Contact: Kevin W. Chang, Ph.D.; (301) 435-5018; 
[email protected].
    Collaborative Research Opportunity: The NHLBI Hematology Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
novel methods to produce parvovirus B19 and use as diagnostic or 
vaccine. For collaboration opportunities, please contact Dr. Neal Young 
at (301) 496-5093 or [email protected].

HIV Therapeutics Utilizing Peptide Secreting Commensal Bacteria

    Description of Technology: Available for licensing and commercial 
development is a patent estate covering genetically engineered 
commensal bacteria compositions and their methods of use that secrete 
HIV infectivity interfering peptides with the aid of co-expressed 
translocation mediators such as HylB, HylD or tolC gene products. The 
bacteria can be, for example, Escherichia coli, and are preferably 
those that colonize the gastrointestinal or genitourinary tracts. The 
secreted anti-HIV peptide can be a

[[Page 3275]]

functional inhibitory fragment from the C-terminus of HIV, SHIV or SIV, 
or an inhibitory peptide derived from the N-terminus receptor-binding 
domain of SIV gp41, HIV-1 gp41, or HIV-2 gp41. The secreted anti-HIV 
peptide can also be a peptide from the allosteric domain of gp120, an 
extracellular loop of CCR5, an anti-CD4 immunoglobulin, a mimetic of 
CD4, an alpha-defensin or theta-defensin, a CD38 fragment homologous to 
the V3 loop of gp120, polphemusin II (a CXCR4 antagonist), a RANTES 
peptide that binds to CCR5 or an HIV surface binding peptide such as 
cyanovirin.
    Potential Commercial Applications: HIV therapeutics.
    Competitive Advantages: Utilizes naturally occurring commensal 
bacteria.

Development Stage

     Pre-clinical.
     In vivo data available (animal).
    Inventor: Dean H. Hamer (NCI).

Publications

    1. Lagenaur LA, et al. Prevention of vaginal SHIV transmission in 
macaques by a live recombinant Lactobacillus. Mucosal Immunol. 2011 
Nov;4(6):648-657. [PMID 21734653].
    2. Rao S, et al. Toward a live microbial microbicide for HIV: 
commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl 
Acad Sci U S A. 2005 Aug 23;102(34):11993-11998. [PMID 16040799].

Intellectual Property

    HHS Reference No. E-233-2004/0--
     U.S. Patent Application No. 11/710,512 filed 26 Feb 2007.
     Various international issued patents.
    Licensing Contact: Michael Shmilovich, Esq.; (301) 435-5019; 
[email protected].

    Dated: January 17, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-1264 Filed 1-20-12; 8:45 am]
BILLING CODE 4140-01-P