[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.
[[Page 56849]]
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
[[Page 56850]]
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