[Federal Register Volume 74, Number 228 (Monday, November 30, 2009)]
[Notices]
[Pages 62578-62579]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-28538]



[[Page 62578]]

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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.

Conditional Knockout of Smad1 in Mice

    Description of Technology: NIH inventors have generated a 
conditional knockout of Smad1, a protein involved in the TGF-beta 
family signaling pathways. LoxP elements were made to flank exon 2 of 
Smad1 in one set of mice. These mice can be crossed with mice 
expressing the CRE element in a tissue-specific or inducible manner. 
These mice can be used to study the role of Smad1 under a variety of 
conditions in a variety of different paradigms.
    Applications:
     Tool for studying role of Smad1 in development in general 
or in a specific tissue.
     Tool for studying the role of Smad1 in a tissue-specific 
and/or an inducible way.
    Inventor: Dr. Shixia Huang (NCI).
    Related Publication: S Huang, B Tang, D Usoskin, RJ Lechleider, SP 
Jamin, C Li, MA Anzano, T Ebendal, C Deng, AB Roberts. Conditional 
knockout of the Smad1 gene. Genesis 2002 Feb;32(2):76-79.
    Patent Status: HHS Reference No. E-307-2009/0--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: Steve Standley, PhD; 301-435-4074; 
[email protected].

Clk and Dyrk1A Inhibitors as General Splicing Modulators and for the 
Potential Treatment of Down's Syndrome and Alzheimer's Disease

    Description of Technology: NIH investigators have discovered a 
series of potent, selective small molecule inhibitors of cdc2-like 
kinases (Clk) and dual-specificity tyrosine-regulated kinase 1A 
(Dyrk1A) with potential as modulators of gene splicing and within the 
treatment of Down's syndrome and Alzheimer's disease. Clk kinases are 
known to phosphorylate the prominent family of serine- and arginine-
rich (SR) splicing proteins. Members of the Clk family have been 
implicated in the regulation of alternative splicing of PKC[beta]II, 
TF, Tau and [beta]-globin pre-mRNA. Dyrk1A is a kinase that has been 
implicated in numerous aspects of neurological development and 
maintenance. The gene that encodes Dyrk1A is found on the Down's 
Syndrome-critical region on chromosome 21 and the over-expression of 
Dyrk1A is considered to be a primary contributor to the Down's syndrome 
phenotype. For instance, transgenic mice overexpressing Dyrk1A exhibit 
cognitive deficits, and blocking Dyrk1A in these transgenic animals has 
been shown to mitigate Down's-related deficits. Hyper-phosphorylation 
of Tau by Dyrk1A has also been directly implicated in the pathology and 
progression of Down's syndrome-associated Alzheimer's disease. 
Alzheimer's disease in general is also associated with pathological 
deposition of hyper-phosphorylated Tau. Thus, these molecules have the 
potential to treat both Down's syndrome and Alzheimer's disease.
    Applications:
     Tools for the study of alternate gene splicing.
     Potential therapeutic for Down's syndrome.
     Potential therapeutic for Alzheimer's disease.
    Development Status: Early stage.
    Market: In the United States approximately 1 in 800 births is 
associated with Down's syndrome with approximately 340,000 affected 
nationwide. Alzheimer's disease affects 1 in 68 people with 
approximately 4,000,000 affected nationwide.
    Inventors: Craig J. Thomas et al. (NHGRI).
    Publication: BT Mott et al. Evaluation of substituted 6-
arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like 
kinases (Clk). Bioorg Med Chem Lett. 2009 Dec 1;19(23):6700-6705. Epub 
ahead of print, 2009 Oct 3, doi:10.1016/j.bmcl.2009.09.121.
    Patent Status: U.S. Provisional Application No. 61/247,632 filed 01 
Oct 2009 (HHS Reference No. E-230-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Steve Standley, PhD; 301-435-4074; 
[email protected].
    Collaborative Research Opportunity: The NIH Chemical Genomics 
Center is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize appropriate lead compounds described in U.S. Provisional 
Application No. 61/247,632. Please contact Dr. Craig J. Thomas via e-
mail ([email protected]) for more information.

RORgamma (RORC) Deficient Mice Which Are Useful for the Study of Lymph 
Node Organogenesis and Immune Responses

    Description of Technology: The retinoid-related orphan receptor 
gamma (ROR[gamma]) is a member of the nuclear receptor superfamily. NIH 
investigators used homologous recombination in embryonic stem cells to 
generate mice in which the ROR[gamma] gene was disrupted. ROR[gamma] 
deficient mice lack peripheral and mesenteric lymph nodes and Peyer's 
patches indicating that ROR expression is indispensable for lymph node 
organogenesis. In addition, ROR[gamma] is required for the generation 
of Th17 cells which play a critical role in autoimmune disease.
    The ROR[gamma] deficient mice are useful to identify the 
physiological functions of the ROR[gamma]. ROR[gamma] deficient mice 
also provide an excellent tool to study the role of ROR[gamma] in 
immune responses and autoimmune disease, the study of the role of Th17 
and interleukin 17 in these processes, and the analysis.
    Inventor: Anton M. Jetten (NIEHS).
    Publication: S Kurebayashi, E Ueda, M Sakaue, DD Patel, A Medvedev, 
F Zhang, AM Jetten. Retinoid-related orphan receptor [gamma] 
(ROR[gamma]) is essential for lymphoid organogenesis and controls 
apoptosis during thymopoiesis. Proc Natl Acad Sci USA. 2000 Aug 
29;97(18):10132-10137.
    Patent Status: HHS Reference No. E-222-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a Biological 
Materials License Agreement.

[[Page 62579]]

    Licensing Contact: Suryanarayana (Sury) Vepa, PhD, J.D.; 301-435-
5020; [email protected].
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the ROR gamma 
mice or related laboratory research interests. Please contact Dr. 
Elizabeth Denholm at [email protected] or 919-541-0981 for more 
information.

Antibody Composition and Methods for the Prevention and Treatment of 
Lupus Nephritis

    Description of Technology: This technology identifies an antibody 
that induces a protective effect in vivo in a mouse model of lupus 
nephritis. Lupus is a chronic autoimmune disease that can damage 
various parts of the body, especially the kidneys. The lupus nephritis-
model mice that were treated with this antibody experienced a dramatic 
increase in survival, demonstrated a reduced immune complex formation 
deposition in the kidneys, and displayed low levels of proteinuria as 
compared with untreated mice. The antibody is an autospecific anti-
dsDNA IgM.
    In addition, this invention may be used as a component of a 
predictive diagnostic kit. As lupus-related kidney disease may be 
asymptomatic, significant kidney damage may occur before lupus is 
diagnosed (lupus.org). The inventors are currently investigating 
whether the ratio of protective antibodies to nonprotective or 
pathogenic antibodies in lupus nephritis models is predictive of 
disease. Currently available diagnostic methods (proteinuria, creatine 
clearance, or kidney biopsy) are not predictive and test only for 
existing kidney impairment or damage.
    Applications:
     A preventative and therapeutic for lupus nephritis.
     A component of a predictive diagnostic kit for lupus 
nephritis.
     A research tool for investigation of lupus nephritis in a 
mouse model.
    Advantages:
     Therapeutic antibodies are unlikely to elicit side effects 
in patient populations, unlike many existing therapies.
     The diagnostic would be predictive, unlike existing 
diagnostics.
    Development Status: Early stage, in vivo (mouse).
    Market:
     At least 1.5 million Americans have lupus (lupus.org).
     Up to 67% of children with lupus, and approximately 40% of 
all individuals with lupus, develop lupus-related kidney complications 
(lupus.org).
    Inventors: Marilyn Diaz, Chuancang Jiang, Ming-Lang Zhao (NIEHS).
    Publication: In preparation.
    Patent Status: U.S. Provisional Application No. 61/176,615 filed 08 
May 2009 (HHS Reference No. E-156-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Norbert Pontzer, J.D., PhD; 301-435-5502; 
[email protected].
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this technology 
or related laboratory research interests. Please contact Dr. Elizabeth 
Denholm at [email protected] or 919-541-0981 for more information.

P2Y1 Receptor Antagonists Useful for the Study of Platelet 
Aggregation and Clotting Conditions

    Description of Technology: NIH inventors have developed 
P2Y1 receptor antagonists ((N)-Methanocarba 2'-
Deoxyadenosine 3', 5'-Bisphosphate Analogues) for inhibition of 
platelet aggregation and treatment of clotting conditions. On the 
platelet surface, simultaneous activation of the P2Y1 and 
P2Y12 receptors by ADP induces aggregation. The 
P2Y1-mediated response is associated with the initial shape 
change and rapid aggregation, and the P2Y12 receptor is 
associated with amplification of the aggregation. P2Y12 
receptor antagonists are both in clinical use and under development as 
antithrombotic agents. Potent and selective P2Y1 receptor 
antagonists, such as the conformationally locked methanocarba 
nucleotide MRS2500 1 (Ki 0.79 nM), have been designed and 
shown to have promise in preclinical studies as antithrombotic agents. 
This novel drug concept is also supported by studies of mice in which 
the P2Y1 receptor has been genetically deleted, wherein the 
initiation of clotting events is markedly impaired.
    Applications: Potential new target for treating intravascular 
clotting.
    Development Status: Early-stage of development.
    Market: There is a very large potential market for P2Y1 
receptor antagonists. For instance, P2Y1 receptor 
antagonists may treat deep vein thrombosis, which occurs in 80 of 
100,000 individuals in the U.S. annually.
    Inventors: Kenneth A. Jacobson and Sonia De Castro (NIDDK)
    Patent Status:
     U.S. Provisional Application No. 61/061,309 filed 13 Jun 
2008 (HHS Reference No. E-235-2008/0-US-01).
     Patent Cooperation Treaty Application PCT/US2009/47204 
filed 12 Jun 2009 (HHS Reference No. E-235-2008/0-PCT-03)
    Licensing Status: Available for licensing.
    Licensing Contact: Steve Standley, PhD; 301-435-4074; 
[email protected].

    Dated: November 23, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-28538 Filed 11-27-09; 8:45 am]
BILLING CODE 4140-01-P