Government-Owned Inventions; Availability for Licensing, 56848-56850 [E8-22889]
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56848
Federal Register / Vol. 73, No. 190 / Tuesday, September 30, 2008 / Notices
B. Regular Review of Compliance
Program Effectiveness
Nursing facilities should regularly
review the implementation and
execution of their compliance program
systems and structures. This review
should be conducted periodically,
typically on annual basis. The
assessment should include an
evaluation of the overall success of the
program, as well as each of the basic
elements of a compliance program
individually, which include:
• Designation of a compliance officer
and compliance committee;
• Development of compliance
policies and procedures, including
standards of conduct;
• Developing open lines of
communication;
• Appropriate training and teaching;
• Internal monitoring and auditing;
• Response to detected deficiencies;
and
• Enforcement of disciplinary
standards.
Nursing facilities seeking guidance for
establishing and evaluating their
compliance operations should review
OIG’s 2000 Nursing Facility CPG, which
explains in detail the fundamental
elements of a compliance program.133
Nursing facilities may also wish to
consult quality of care corporate
integrity agreements (CIA) entered into
between OIG and parties settling
specific matters.134 Other issues a
nursing facility may want to evaluate
are whether there has been an allocation
of adequate resources to compliance
initiatives; whether there is a reasonable
timetable for implementation of the
compliance measures; whether the
compliance officer and compliance
committee have been vested with
sufficient autonomy, authority, and
accountability to implement and enforce
appropriate compliance measures; and
whether compensation structures create
undue pressure to pursue profit over
compliance.
V. Self-Reporting
ebenthall on PROD1PC60 with NOTICES
If the compliance officer, compliance
committee, or a member of senior
management discovers credible
evidence of misconduct from any source
and, after a reasonable inquiry, believes
that the misconduct may violate
criminal, civil, or administrative law,
the nursing facility should promptly
report the existence of the misconduct
133 2000 Nursing Facility CPG, supra note 2, at
14289.
134 OIG, ‘‘HHS—OIG—Fraud Prevention &
Detection—Corporate Integrity Agreements,’’
available on our Web site at https://oig.hhs.gov/
fraud/cias.html.
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15:35 Sep 29, 2008
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to the appropriate Federal and State
authorities.135 The reporting should
occur within a reasonable period, but
not longer than 60 days,136 after
determining that there is credible
evidence of a violation.137 Prompt
voluntary reporting will demonstrate
the nursing facility’s good faith and
willingness to work with governmental
authorities to correct and remedy the
problem. In addition, prompt reporting
of misconduct will be considered a
mitigating factor by OIG in determining
administrative sanctions (e.g., penalties,
assessments, and exclusion) if the
reporting nursing facility becomes the
subject of an OIG investigation.138
To encourage providers to make
voluntary disclosures to OIG, OIG
published the Provider Self-Disclosure
Protocol.139 When reporting to the
135 Appropriate Federal and State authorities
include OIG, CMS, the Criminal and Civil Divisions
of the Department of Justice, the U.S. Attorney in
relevant districts, the Food and Drug
Administration, the Department’s Office for Civil
Rights, the Federal Trade Commission, the Drug
Enforcement Administration, the Federal Bureau of
Investigation, and the other investigative arms for
the agencies administering the affected Federal or
State health care programs, such as the State
Medicaid Fraud Control Unit, the Defense Criminal
Investigative Service, the Department of Veterans
Affairs, the Health Resources and Services
Administration, and the Office of Personnel
Management (which administers the Federal
Employee Health Benefits Program).
136 To qualify for the ‘‘not less than double
damages’’ provision of the False Claims Act, the
provider must provide the report to the Government
within 30 days after the date when the provider first
obtained the information. 31 U.S.C. 3729(a).
137 Some violations may be so serious that they
warrant immediate notification to governmental
authorities prior to, or simultaneous with,
commencing an internal investigation. By way of
example, OIG believes a provider should
immediately report misconduct that: (i) Is a clear
violation of administrative, civil, or criminal laws;
(ii) poses an imminent danger to a patient’s safety;
(iii) has a significant adverse effect on the quality
of care provided to Federal health care program
beneficiaries; or (iv) indicates evidence of a
systemic failure to comply with applicable laws or
an existing corporate integrity agreement, regardless
of the financial impact on Federal health care
programs.
138 OIG has published criteria setting forth those
factors that OIG takes into consideration in
determining whether it is appropriate to exclude an
individual or entity from program participation
pursuant to section 1128(b)(7) of the Act (42 U.S.C.
1320a–7(b)(7)) for violations of various fraud and
abuse laws. See 62 FR 67392 (December 24, 1997),
‘‘Criteria for Implementing Permissive Exclusion
Authority Under Section 1128(b)(7) of the Social
Security Act.’’
139 For details regarding the Provider SelfDisclosure Protocol, including timeframes and
required information, see 63 FR 58399 (October 30,
1998), ‘‘Publication of the OIG’s Provider SelfDisclosure Protocol,’’ available on our Web site at
https://oig.hhs.gov/authorities/docs/
selfdisclosure.pdf. See also OIG’s April 15, 2008,
Open Letter to Health Care Providers, available on
our Web site at https://oig.hhs.gov/fraud/docs/
openletters/OpenLetter4–15–08.pdf; OIG’s April 24,
2006, Open Letter to Health Care Providers,
available on our Web site at https://oig.hhs.gov/
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Sfmt 4703
Government, a nursing facility should
provide all relevant information
regarding the alleged violation of
applicable Federal or State law(s) and
the potential financial or other impact of
the alleged violation. The compliance
officer, under advice of counsel and
with guidance from governmental
authorities, may be requested to
continue to investigate the reported
violation. Once the investigation is
completed, and especially if the
investigation ultimately reveals that
criminal, civil, or administrative
violations have occurred, the
compliance officer should notify the
appropriate governmental authority of
the outcome of the investigation. This
notification should include a
description of the impact of the alleged
violation on the applicable Federal
health care programs or their
beneficiaries.
VI. Conclusion
In today’s environment of increased
scrutiny of corporate conduct and
increasingly large expenditures for
health care, it is imperative for nursing
facilities to establish and maintain
effective compliance programs. These
programs should foster a culture of
compliance and a commitment to
delivery of quality health care that
begins at the highest levels and extends
throughout the organization. This
supplemental CPG is intended as a
resource for nursing facilities to help
them operate effective compliance
programs that decrease errors, fraud,
and abuse and increase quality of care
and compliance with Federal health
care program requirements for the
benefit of the nursing facilities and their
residents.
Dated: September 24, 2008.
Daniel R. Levinson,
Inspector General.
[FR Doc. E8–22796 Filed 9–29–08; 8:45 am]
BILLING CODE 4152–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
fraud/docs/openletters/
Open%20Letter%20to%20Providers%202006.pdf.
E:\FR\FM\30SEN1.SGM
30SEN1
Federal Register / Vol. 73, No. 190 / Tuesday, September 30, 2008 / Notices
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.
ebenthall on PROD1PC60 with NOTICES
Transgenic Mice With ConditionallyEnhanced 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:
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15:35 Sep 29, 2008
Jkt 214001
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 nonexclusive licensing.
Licensing Contact: Steve Standley,
Ph.D.; 301–435–4074;
sstand@mail.nih.gov.
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 sitespecific 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).
PO 00000
Frm 00059
Fmt 4703
Sfmt 4703
56849
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 nonexclusive licensing.
Licensing Contact: Steve Standley,
PhD; 301–435–4074;
sstand@mail.nih.gov.
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;
vathyams@mail.nih.gov.
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
E:\FR\FM\30SEN1.SGM
30SEN1
ebenthall on PROD1PC60 with NOTICES
56850
Federal Register / Vol. 73, No. 190 / Tuesday, September 30, 2008 / Notices
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
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Jkt 214001
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 nonexclusive or exclusive licensing.
Licensing Contact: Jennifer Wong;
301–435–4633; wongje@mail.nih.gov.
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 hewesj@mail.nih.gov
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Cancer Institute; Notice of
Closed Meetings
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meetings.
The meetings will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
PO 00000
Frm 00060
Fmt 4703
Sfmt 4703
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Cancer
Institute Special Emphasis Panel; Review of
Education and Career Development Award
Applications.
Date: October 24, 2008.
Time: 10 a.m. to 1 p.m.
Agenda: To review and evaluate grant
applications.
Place: Sheraton Sand Key Resort, 1160
Gulf Boulevard, Clearwater, FL 33767.
Contact Person: Robert Bird, PhD,
Scientific Review Officer, Resources and
Training Review Branch, Division of
Extramural Activities, National Cancer
Institute, 6116 Executive Boulevard, Room
8113, Bethesda, MD 20892–8328, 301–496–
7978, birdr@mail.nih.gov.
Name of Committee: National Cancer
Institute Special Emphasis Panel; Cancer
Prevention Research Small Grant Program
(R03).
Date: October 30–31, 2008.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications.
Place: Renaissance M Street Hotel, Marriot,
1143 New Hampshire Avenue NW.,
Washington, DC 20037.
Contact Person: Irina Gordienko, PhD,
Scientific Review Officer, Scientific Review
and Logistics Branch, Division of Extramural
Activities, National Cancer Institute, NIH,
6116 Executive Blvd., Rm. 7073, Bethesda,
MD 20892, 301–594–1566,
gordienkoiv@mail.nih.gov.
Name of Committee: National Cancer
Institute Special Emphasis Panel;
Community Clinical Oncology Program
(CCOP).
Date: November 5, 2008.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications.
Place: Bethesda Marriott, 5151 Pooks Hill
Road, Bethesda, MD 20814.
Contact Person: Gerald G. Lovinger, PhD,
Scientific Review Administrator, Special
Review and Logistics Branch, Division of
Extramural Activities, National Cancer
Institute, 6116 Executive Blvd., Room 8101,
Bethesda, MD 20892–8329, 301–496–7987,
lovingeg@mail.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.392, Cancer Construction;
93.393, Cancer Cause and Prevention
Research; 93.394, Cancer Detection and
Diagnosis Research; 93.395, Cancer
Treatment Research; 93.396, Cancer Biology
Research; 93.397, Cancer Centers Support;
93.398, Cancer Research Manpower; 93.399,
Cancer Control, National Institutes of Health,
HHS)
E:\FR\FM\30SEN1.SGM
30SEN1
]]>Agencies
[Federal Register Volume 73, Number 190 (Tuesday, September 30, 2008)]
[Notices]
[Pages 56848-56850]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-22889]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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;
sstand@mail.nih.gov.
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;
sstand@mail.nih.gov.
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;
vathyams@mail.nih.gov.
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;
wongje@mail.nih.gov.
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 hewesj@mail.nih.gov 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
