[Federal Register Volume 73, Number 190 (Tuesday, September 30, 2008)]
[Notices]
[Pages 56848-56850]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-22889]


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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.

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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.

Transgenic Mice With Conditionally-Enhanced Bone Morphogen Protein 
(BMP) Signaling: A Model for Human Bone Diseases

    Description of Technology: This technology relates to novel animal 
models of several human bone diseases that have been linked to enhanced 
BMP signaling. More specifically, this mouse model expresses a mutant 
receptor for BMP, known as Alk2 that is always actively signaling. This 
receptor is under the control of the Cre-loxP system, which allows 
control of expression of the mutant Alk2 in both a developmental and 
tissue-specific manner. As a result, the enhanced signaling conditions 
exhibited in multiple human bone-related diseases can be studied with 
the same animals.
    Applications: The mouse model can be applied to the study of BMP 
signaling-related human diseases such as fibrodysplasia ossificans 
progressiva, which involves the postnatal transformation of connective 
tissue into bone. Another example of BMP signaling-related disease is 
Craniosynostosis, which involves the premature closing of the sutures 
in childhood so that normal brain and skull growth are inhibited. This 
mouse model can potentially be used in other human diseases where BMP 
signaling might play a pivotal role, for example cleft lip and cleft 
palate, breast cancer, osteoarthritis, lung fibrosis, multiple myeloma, 
juvenile polyposis, cephalic neural tube closure defects, diabetes and 
other types of blood glucose control problems, and pulmonary 
hypertension.
    Development Status: Early-stage development.
    Inventors: Yuji Mishina, Manas Ray, Greg Scott (NIEHS).
    Relevant Publications:
    1. T Fukada et al. Generation of a mouse with conditionally 
activated signaling through the BMP receptor, ALK2. Genesis. 
2006;44:159-167.
    2. L Kan et al. Transgenic mice overexpressing BMP4 develop a 
fibrodysplasia ossificans progressiva (FOP)-like phenotype. Am J Path. 
2004 Oct;165(4):1107-1115.
    3. EM Shore et al. A recurrent mutation in the BMP type I receptor 
ACVR1 causes inherited and sporadic fibrodysplasia ossificans 
progressive. Nat Genet. 2006 May;38(5):525-527.
    Patent Status: HHS Reference No. E-328-2008/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Steve Standley, Ph.D.; 301-435-4074; 
[email protected].

Production of Endotoxin Free TEV Protease

    Description of Technology: This technology relates to an efficient 
method of purifying proteins. More specifically, this technology 
relates to a method of obtaining an endotoxin-free `TEV protease,' a 
common name for a 27 kDa catalytic domain of the Nuclear Inclusion a 
(NIa) protein from Tobacco Etch Virus. TEV protease is a site-specific 
protease that can be used to cleave purified fusion proteins that have 
been engineered to contain a TEV protease cleavage site. This is 
typically done to enable stable expression and purification of a 
protein of interest. The technology consists of (a) the DNA construct 
(created by Dom Esposito) to allow expression of the protein in insect 
cells, (b) the insect cell line, and (c) the purification protocol. TEV 
protease itself is expressed as a fusion to MBP (Maltose Binding 
Protein) to enhance solubility.
    Advantages: TEV protease expressed and produced in E. coli contains 
substantial amounts of endotoxin, which presents a barrier to use where 
the final purified product is required to be endotoxin-free. It is 
important to note that all proteins which are used for therapeutic 
purposes must have little or no endotoxin for safety reasons. The 
method of obtaining an endotoxin-free TEV protease is to express and 
purify TEV protease using a baculovirus/insect cell expression system, 
instead of E. coli which results in an endotoxin-free TEV protease.
    Development Status: Early stage development.
    Inventors: William K. Gillette, Dominic Esposito, and Ralph Hopkins 
(SAIC/NCI).
    Relevant Publication: RB Kapust and DS Waugh. Controlled 
intracellular processing of fusion proteins by TEV protease. Protein 
Expr Purif. 2000 Jul;19(2):312-318.
    Patent Status: HHS Reference No. E-139-2008/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Steve Standley, PhD; 301-435-4074; 
[email protected].

Association of the ECHDCI/RNF146 Gene Region on Human Chromosome 6q 
With Breast Cancer Risk and Protection

    Description of Technology: The technology describes a genetic locus 
(ECHDC l/RNF146 gene region on human chromosome 6q) that may be 
predictive for risk of breast cancer in relatives of individuals 
diagnosed with breast cancer. Furthermore, the invention provides 
evidence that one or more polymorphism alleles in chromosome 6q22.33 
indicates a lower risk or increased risk of developing breast cancer in 
individuals.
    Applications:
     The invention has the potential of being developed into a 
predictive diagnostic test, for people at a risk of breast cancer, 
together with other risk factors for the disease, such as age, parity, 
and other genetic contributions especially for predicting risk of 
breast cancer in individuals free of BRCA1 and BRCA2 polymorphism.
     The invention may help to develop pharmaceuticals through 
elucidation of the contributing biochemical, etiologic pathway.
    Advantages: This study was a clinical study in a cohort of 
individuals. Thus the relevance of the data is of considerable 
significance.
    Development Status: Validation of the correlation between the 
polymorphisms and risk of breast cancer is ongoing using different 
cohorts.
    Inventors: Bert Gold et al. (NCI).
    Patent Status: U.S. Provisional Application No. 61/023,936 filed 28 
Jan 2008 (HHS Ref. No. E-065-2008/0-US-01).
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].

Novel Chemoattractant-Based Toxins to Improve Vaccine Immune Responses 
for Cancer and Infectious Diseases

    Description of Technology: Cancer is one of the leading causes of 
death in the United States and it is estimated that there will be more 
than half a million

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deaths caused by cancer in 2008. A major drawback of the current 
chemotherapy-based therapeutics is the cytotoxic side-effects 
associated with them. Thus there is a dire need to develop new 
therapeutic strategies with fewer side-effects. Immuno-therapy has 
taken a lead among the new therapeutic approaches. Enhancing the innate 
immune response of an individual has been a key approach for the 
treatment against different diseases such as cancer and infectious 
diseases.
    This technology involves the generation of novel chemoattractant 
toxins that deplete the T regulatory cells (Treg) or other 
immunosuppressive or hyperactivated cells locally. Treg controls 
activation of immune responses by suppressing the induction of adaptive 
immune responses, particularly T cell responses. Immunosuppressive 
cells such as tumor infiltrating macrophages or NKT and other cells 
down regulate antitumor immune responses. The chemoattractant toxins 
consist of a toxin moiety fused with a chemokine receptor ligand, 
chemokines and other chemoattractants that enables specific targeting 
and delivery to the Treg cells. This technology is advantageous over 
the more harmful antibodies and chemicals that are currently used for 
the systemic depletion of Treg cells. The current technology can be 
used therapeutically in a variety of ways. They can be used together 
with vaccines to increase efficacy of the vaccine for the treatment of 
cancer, and can be used to locally deplete Treg cells or other immuno 
suppressive cells to induce cytolytic cell responses at the tumor site 
or to eliminate chronic infectious diseases such as HIV and 
tuberculosis.
    Applications:
     New chemoattractant based toxins targeted towards Treg 
cells.
     New chemoattractant based toxins targeted towards 
immunosuppressive NKT, and macrophages.
     New chemoattractant based toxins targeted towards local 
depletion of hyperactivated CD4 T cells to treat autoimmune diseases.
     Chemoattractant based toxins depleting Treg cells or other 
immunosuppressive cells causing enhanced vaccine immune responses.
     Novel immunotherapy by increasing vaccine efficacy against 
cancer and infectious diseases.
    Market:
     565,650 deaths from cancer related diseases estimated in 
2008.
     The technology platform involving novel chemo-attractant 
based toxins can be used to improve vaccine immune responses. The 
cancer vaccine market is expected to increase from $135 million in 2007 
to more than $8 billion in 2012.
     The technology platform has additional market in treating 
several other clinical problems such as autoimmune diseases.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Arya Biragyn (NIA), Dolgor Bataar (NIA), et al.
    Related Publications:
    1. Copy of manuscript from this technology can be provided once 
accepted for publication.
    2. M Coscia, A Biragyn. Cancer immunotherapy with chemoattractant 
peptides. Semin Cancer Biol 2004 Jun;14(3):209-218.
    3. R Schiavo et al. Chemokine receptor targeting efficiently 
directs antigens to MHC class I pathways and elicits antigen-specific 
CD8+ T-cell responses. Blood 2006 Jun 15;107 (12):4597-4605.
    Patent Status: U.S. Patent Application filed 28 Mar 2008, claiming 
priority to 30 Sep 2005 (HHS Reference No. E-027-2005/0-US-06).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].
    Collaborative Research Opportunity: The NIA Laboratory of 
Immunology is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize novel chemoattractant-based toxins. Please contact John 
D. Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

    Dated: September 18, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-22889 Filed 9-29-08; 8:45 am]
BILLING CODE 4140-01-P