[Federal Register Volume 77, Number 225 (Wednesday, November 21, 2012)]
[Notices]
[Pages 69866-69869]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-28276]


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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.

FOR FURTHER INFORMATION CONTACT: 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.

A New Class, Now in Session: the First HLA Class II Restricted T Cell 
Receptor That Recognizes the Cancer Testis Antigen, MAGE-A3, Developed 
for Cancer Immunotherapy

    Description of Technology: NIH scientists have developed T cell 
receptors (TCRs) against the melanoma antigen family A3 (MAGE-A3) tumor 
antigen in the context of major histocompatibility complex (MHC) class 
II molecule HLA-DP-beta1*04. They are the first HLA class II restricted 
MAGE-A3 TCRs developed for use in adoptive immunotherapy. Previously 
developed MAGE-A3 TCRs are HLA class I restricted and generate CD8+ T 
cell responses to mediate tumor regression in some patients with MAGE-
A3+ tumors. Other patients may not respond due to a lack of CD4+ T 
cells participation. Cancer immunotherapy with these new HLA class II 
TCRs could yield a robust and effective CD4+ T cell immune response 
that selectively targets MAGE-A3 expressing tumors without generating 
toxicity against healthy cells.
    MAGE-A3 is a cancer testis antigen expressed on many types of 
cancer cells that blocks the functions of tumor suppressor proteins to 
mediate tumor growth and spreading. MAGE-A3 is not expressed on normal 
cells other than non-MHC expressing germ cells of the testis, which do 
not generate an immune response. Thus, MAGE-A3 represents an ideal 
target for cancer immunotherapies that are predicted to generate fewer 
toxic side effects than current standard cancer treatments.
    Potential Commercial Applications:
     A personalized immunotherapy to mediate regression of many 
types of cancers using human T cells expressing a HLA class II TCR.
     An adoptive immunotherapy combining T cells engineered to 
express a HLA class I restricted TCR with HLA class II TCR-expressing T 
cells to enhance the antitumor response by eliciting CD8+ and CD4+ T 
cell immune responses in patients.
     A research tool to investigate signaling pathways in MAGE-
A3 antigen expressing cancer cells.
     An in vitro diagnostic tool to screen for cells expressing 
the MAGE-A3 tumor antigen.
    Competitive Advantages:
     Class I restricted TCRs can only treat a subset of 
patients, but since ~80% of patients express the HLA-DP-beta1*04 class 
II HLA allele, this TCR expands the population pool treatable with 
MAGE-A3 TCRs to include the majority of patients.
     MAGE-A3 is a highly expressed tumor target on many cancer 
cells, so MAGE-A3 TCR therapy should be a viable treatment option for 
many cancer cases.
     MAGE-A3 is only expressed on tumor cells and non-MHC 
expressing cells so these TCRs should target MAGE-A3 expressing tumor 
cells with little or no side effects/toxicity to normal cells.
    Development Stage:
     Early-stage.
     Pre-clinical.
     In vitro data available.

[[Page 69867]]

    Inventors: Paul Robbins, Xin Yao, Steven Rosenberg (NCI).
    Intellectual Property: HHS Reference No. E-230-2012/0 -- U.S. 
Patent Application No. 61/701,056 filed 14 Sep 2012.
    Related Technologies:
     HHS Reference No. E-236-2010/0--PCT Patent Application No. 
PCT/US2011/057272.
     HHS Reference No. E-266-2011/0--PCT Patent Application No. 
PCT/US2012/054623.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].

Novel Small Molecule Agonists of the Relaxin Receptor as Potential 
Therapy for Heart Failure and Fibrosis

    Description of Technology: The present invention is directed to 
novel small molecule agonists of the mammalian relaxin family receptor 
1 (RXFP1), including human RXFP1. Activation of RXFP1 induces: (1) 
Vasodilation due to up-regulation of the endothelin system; (2) 
extracellular matrix remodeling; (3) moderation of inflammation by 
reducing levels of inflammatory cytokines; and (4) angiogenesis. Small 
molecule agonists of RXFP1 may be useful in treating acute heart 
failure (AHF), scleroderma, fibrosis, other conditions associated with 
the biology of relaxin, and in improving reproductive health and wound 
healing. These compounds are the first and only small molecule agonists 
of RXFP1.
    Potential Commercial Applications: Therapeutics for:
     Cardiovascular diseases.
     Ischemia.
     Fibrosis.
     Inflammation.
     Acute heart failure.
     Human and animal reproductive health.
    Competitive Advantages:
     First and only small molecule agonists of RXFP1.
     Potent and highly selective.
     Bioavailable with excellent exposure.
     Easy to synthesize and scale-up.
    Development Stage:
     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Juan J. Marugan (NCATS), et al.
    Publications:
    1. Chen ZC, et al. Identification of small-molecule agonists of 
human relaxin family receptor 1 (RXFP1) by utilizing a homogeneous 
cell-based cAMP assay. J. Biomol. Screen. 2012, accepted.
    2. Additional manuscript is under revision.
    Intellectual Property: HHS Reference No. E-072-2012/0--U.S. 
Provisional Application No. 61/642,986 filed 04 May 2012.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected].
    Collaborative Research Opportunity: The National Center for 
Advancing Translational Sciences is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize small molecule agonists of RXFP1. 
For collaboration opportunities, please contact Krishna (Balki) 
Balakrishnan, Ph.D. at 301-217-2336 or [email protected].

Treatment of Tuberculosis--Adjuvant Therapies To Increase the 
Efficiency of Antibiotic Treatments

    Description of Technology: There is growing evidence that 
resistance to Mycobacterium tuberculosis infection is governed in large 
part by the regulation of host cell death. Lipid mediators called 
eicosanoids are thought to play a central role in this process. The 
subject invention is a novel method of enhancing the efficacy of 
antibiotic treatments for Mycobacterium tuberculosis infection by co-
administering an inhibitor of 5-lipoxygenase and a COX-2 dependent 
prostaglandin. Inhibition of 5-lipoxygenase and treatment with 
prostaglandin E2 results in alteration of the eicosanoid balance. The 
synergistic effects of altering the eicosanoid balance and treatment 
with antibiotics is believed to result in more efficient reduction of 
the bacterial burden and thus, the period of antibiotic administration 
and antibiotic dosage could potentially be reduced. In vivo data from 
mouse models can be provided upon request.
    Potential Commercial Applications: The subject invention can be 
used as an adjuvant therapy for existing antibiotic treatment regiments 
against tuberculosis.
    Competitive Advantages: The disclosed method can be applied to 
increase the efficacy of existing antibiotic treatments for 
tuberculosis, potentially reducing both the duration and dosage of the 
antibiotic treatment.
    Development State:
     Early-stage.
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Katrin D. Mayer, Bruno Bezerril D. Andrade, F. Alan 
Sher, and Daniel L. Barber (NIAID).
    Intellectual Property:
     HHS Reference No. E-189-2011/0--U.S. Provisional Patent 
Application No. 61/515,229 filed 04 Aug 2011.
     HHS Reference No. E-189-2011/1--U.S. Provisional Patent 
Application No. 61/515,237 filed 04 Aug 2011.
     HHS Reference No. E-189-2011/2--International Application 
No. PCT/US2012/049280 filed 02 Aug 2012.
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize adjuvant therapy for antibiotic 
treatment regiments against tuberculosis. For collaboration 
opportunities, please contact Katrin Mayer, Ph.D. at 
[email protected] or 301-594-8061.

Adeno-Associated Virus Gene Therapy for Diabetes and Obesity

    Description of Technology: This invention is directed to adeno-
associated virus (AAV) vector delivery of exendin-4 (Ex-4) to salivary 
glands as treatment for diabetes and obesity. Ex-4 is a potent and 
long-acting agonist of the receptor for glucagon-like peptide 1 (GLP-
1). Scientists at NIDCR have shown that AAV-mediated delivery of Ex-4 
resulted in improved glucose homeostasis and weight profile in two rat 
models of obesity and type 2 diabetes. Further, AAV-mediated delivery 
of Ex-4 to rat salivary glands resulted in localized and sustained 
expression of Ex-4 that was biologically active and well tolerated.
    AAV-mediated delivery of Ex-4 is superior to administering GLP-1 
analogs in that AAV-Ex-4 expression is more stable and longer acting. 
Like GLP-1 analogs, Ex-4 expression also potentially provides 
beneficial effects like reduced hypoglycemia, appetite suppression, and 
potential weight loss.
    Potential Commercial Applications: Therapy for diabetes or obesity.
    Competitive Advantages:
     Potential for potent glucose homeostasis therapy with 
longer duration than current drugs.
     More convenient than daily or weekly injections.
    Development Stage:
     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: John A. Chiorini (NIDCR), Giovanni DiPasquale (NIDCR), 
Edoardo Mannucci (Careggi Teaching Hospital).
    Publication: Di Pasquale G, et al. Sustained exendin-4 secretion 
through

[[Page 69868]]

gene therapy targeting salivary glands in two different rodent models 
of obesity/type 2 diabetes. PLoS One. 2012;7(7):e40074. [PMID 22808093]
    Intellectual Property: HHS Reference No. E-142-2011/0--
     U.S. Application No. 61/477,523 filed 20 May 2011.
     PCT Application No. PCT/US2012/34268 filed 19 Apr 2012.
    Licensing Contact: Lauren Nguyen-Antczak, Ph.D., J.D.; 301-435-
4074; [email protected].
    Collaborative Research Opportunity: The NIDCR is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize treatment of 
diabetes by expression NGF-extendin 4 protein. For collaboration 
opportunities, please contact David Bradley, Ph.D. at 301-402-9242 or 
[email protected].

Small Molecule MRS5474 With Anticonvulsant Activity for Treatment of 
Epilepsy

    Description of Technology: Adenosine modulates many physiological 
processes by activating specific adenosine receptors. These adenosine 
receptors play a critical role in the regulation of cellular signaling 
and are broadly distributed throughout the body. Thus, the ability to 
modulate adenosine receptor-mediated signaling is an attractive 
therapeutic strategy for a broad range of diseases. This technology 
relates to a group of compounds that display high affinity and 
specificity for the A1 adenosine receptor subtype.
    One of the compounds, MRS5474, displays anticonvulsant activity in 
the 6 Hz animal model of clonic seizures. In the minimal behavioral 
toxicity test using the rotarod, no toxicity (zero out of eight mice) 
was observed at all doses tested up to 30 mg/kg, the highest dose 
tested, which was nearly completely protective (seven out of eight 
animals) in the 6 Hz model. MRS 5474 also tested well in the corneal 
kindled mouse model to examine its effect on focal seizures.
    Potential Commercial Applications:
     Oral anticonvulsant drug.
     Provides a means to mimic A1AR mediated signaling in vitro 
and in vivo.
    Competitive Advantages:
     These small molecules display increased specificity for 
the A1 type of adenosine receptors, which may reduce unwanted side 
effects previously seen in A1AR agonist therapies.
     The physical properties of these molecules are drug-like, 
which makes them attractive for pre-clinical development.
    Development Stage:
     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventor: Kenneth A. Jacobson (NIDDK).
    Publication: Tosh DK, et al. Truncated (N)-Methanocarba Nucleosides 
as A1 Adenosine Receptor Agonists and Partial Agonists: Receptor 
Docking and Potent Anticonvulsant Activity. In preparation.
    Intellectual Property:
     HHS Reference No. E-285-2008/0--International Application 
No. PCT/US2009/52439 filed 31 Jul 2009.
     HHS Reference No. E-285-2008/1--U.S. Patent Application 
No. 13/479,973 filed 24 May 2012.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The NIDDK is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize MRS5474, A1 
adenosine receptor agonist for treatment of seizures. For collaboration 
opportunities, please contact Marguerite Miller at 
[email protected].

Glucocorticoid-Induced TNFR Family-Related Receptor Ligand (GITRL) 
Antibodies for Diagnosis and Treatment of Immune System Disorders

    Description of Technology: This technology provides novel 
antibodies and methods for diagnostics and treatment of disorders 
arising from dysregulation of the immune system using antibodies 
directed against glucocorticoid-induced tumor necrosis factor receptor 
family-related receptor ligand (GITRL). Also available are hybridomas 
producing anti-mouse GITRL monoclonal antibodies (clone 5F1).
    Glucocorticoid-induced TNFR family-related receptor (GITR, also 
known as TNFRSF18) is expressed on the surface of responder T cells 
(CD4+CD25- or CD8+CD25- T cells). Upon activation of the immune 
response, GITR is up-regulated and binds to its ligand, GITRL (also 
known as TNFSF18), which enhances the immune response. The inventors 
have developed anti-GITRL monoclonal antibodies that block the 
interaction between GITR and GITRL, and have demonstrated in in vitro 
experiments that administration of these blocking antibodies can 
suppress the immune response. These antibodies may be useful for 
treatment of immune system disorders such as multiple sclerosis, 
rheumatoid arthritis, and other inflammatory diseases.
    Potential Commercial Applications:
     Development of therapeutic agents for autoimmune diseases, 
including autoimmune and inflammatory diseases, allergy and transplant 
rejection.
     Tool for investigating the role of GITRL in enhancement of 
the T-cell mediated immune response.
    Competitive Advantages: The GITR/GITRL pathway is a novel target 
for the treatment of autoimmune diseases.
    Development Stage:
     In vitro data available.
     In vivo data available (animal).
    Inventors: Ethan Shevach et al. (NIAID).
    Publication: Stephens GL, et al. Engagement of glucocorticoid-
induced TNFR family-related receptor on effector T cells by its ligand 
mediates resistance to suppression by CD4+CD25+ T cells. J Immunol. 
2004 Oct 15;173(8):5008-20. [PMID 15470044].
    Intellectual Property: HHS Reference No. E-229-2003/2--
     U.S. Patent No. 7,618,632 issued 17 Nov 2009.
     JP Patent No. 4638876 issued 03 Dec 2010.
    Licensing Contact: Tara L. Kirby. Ph.D.; 301-435-4426; 
[email protected].

Treatment for Ichthyosiform Skin Diseases

    Description of Technology: A synthetic composition that contains 
the transglutaminase 1 (TGase I) enzyme and a lipid vesicle, which can 
be used to provide ameliorative therapy for inherited autosomal 
recessive ichthyoses (ARI). Icthyoses are rare inherited skin disorders 
that result in extensive scaling of the skin. Because this abnormality 
can affect heat and fluid transfer through the skin, individuals with 
this disease may have an increased risk for dehydration and skin 
infections. Each year, more than 16,000 babies are born with some form 
of ichthyosis. Ichthyosis affects people of all ages, races and gender. 
Currently, there is no cure for this disease and the only treatments 
available alleviate symptoms without affecting the disease itself. ARI 
are often caused by defects in lipid barrier function in the skin and 
are the result of genetic errors of either protein or lipid synthesis. 
One such disease, termed lamellar ichthyosis, is caused by genetic 
inactivation of the (TGase I) gene. The TGase I enzyme is essential for 
maintaining proper skin cornification, which protects skin cells 
against water loss and infection. Rather than simply treating the 
disease symptoms superficially, this technology provides a platform for 
treating the

[[Page 69869]]

underlying cause of disease, namely the absence of TGase I function.
    Potential Commercial Applications:
     Treatment for ichthyosiform skin diseases.
     Method for correcting defects in skin cell cornification.
    Competitive Advantages: Targets underlying cause of skin disorder 
rather than just treating the resulting symptoms.
    Development Stage:
     Early-stage.
     In vitro data available.
    Inventors: Peter M Steinert, Nemes Zoltan, Lyuben N Marckov 
(NIAMS).
    Publications:
    1. Candi E, et al. Transglutaminase 1 mutations in lamellar 
ichthyosis. Loss of activity due to failure of activation by 
proteolytic processing. J Biol Chem. 1998 May 29;273(22):13693-702. 
[PMID 9593710]
    2. Yang YM, et al. Novel mutations of the transglutaminase 1 gene 
in lamellar ichthyosis. J Invest Dermatol. 2001 Aug;117(2):214-8. [PMID 
11511296]
    Intellectual Property: HHS Reference No. E-149-1999/0--U.S. Patent 
No. 6,852,686 issued 08 Feb 2005.
    Licensing Contact: Suryanarayana Vepa, Ph.D., J.D.; 301-435-5020; 
[email protected].

    Dated: November 16, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-28276 Filed 11-20-12; 8:45 am]
BILLING CODE 4140-01-P