Government-Owned Inventions; Availability for Licensing, 25697-25699 [2011-11055]
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Subcommittee topics. The first panel will
focus on the impact of Value-Based
Purchasing Demonstrations. The second
panel will focus on primary care training and
placement. The Subcommittees will then
move into breakout sessions to further
discuss these topics. After the panel
discussions, the Committee Chair will give
an overview of the site visits. This will be
followed by a call for public comment. The
Wednesday meeting will close at 4:45 p.m.
Thursday morning, at 9 a.m., the
Committee will travel to Munson Medical
Center for a briefing on its role in serving the
region. At 10 a.m. the Committee will break
into Subcommittees and depart to the site
visits. The Value-Based Purchasing
Demonstrations Subcommittee will meet at
Mercy Cadillac Hospital in Cadillac, MI. The
Primary Care Training and Placement
Subcommittee will meet at Kalkaska Rural
Health Clinic in Kalkaska, MI. The
Subcommittees will return to the Park Place
Hotel in Traverse City at 4 p.m.
Transportation to the site visits will not be
provided to the public. The Thursday
meeting will close at 4:45 p.m.
The Final session will be convened on
Friday morning at 8:45 am. The meeting will
open with a review of the Subcommittee site
visits. The Committee will draft a letter to the
Secretary or Designee and discuss the
September 2011 meeting. The meeting will
adjourn at 10:30 a.m.
For Further Information Contact: Thomas
Morris, MPA, Executive Secretary, National
Advisory Committee on Rural Health and
Human Services, Health Resources and
Services Administration, Parklawn Building,
Room 10B–45, 5600 Fishers Lane, Rockville,
MD 20857, Telephone (301) 443–0835, Fax
(301) 443–2803.
Persons interested in attending any portion
of the meeting should contact Deborah
DeMasse-Snell at the Office of Rural Health
Policy (ORHP) via Telephone at (301) 443–
0835 or by e-mail at ddemassesnell@hrsa.gov. The committee meeting
agenda will be posted on ORHP’s Web site
https://www.ruralhealth.hrsa.gov.
Dated: April 28, 2011.
Reva Harris,
Acting Director, Division of Policy and
Information Coordination.
[FR Doc. 2011–10983 Filed 5–4–11; 8:45 am]
BILLING CODE 4165–15–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
jlentini on DSKJ8SOYB1PROD with NOTICES
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
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
SUMMARY:
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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.
Improved Standard for Immune System
Recovery Assay
Description of Invention: Monitoring
an immune system that has been
depleted by infection (e.g., HIV),
chemotherapy, or progenitor cell
transplantation is vital to assessing
individual’s recovery status. This
technology provides a new plasmid
standard to be used as part of the
existing TREC assay. This new plasmid
has a shorter insert than the
commercially available one, which
means it now matches the PCR product
generated in the qPCR reaction in the
TREC assay. Additionally, the new
plasmid is easier to grow up than the
existing standard.
Applications: TREC assay for T-cell
concentration measurements.
Advantages:
• The insert of standard plasmid is
shorter and directly matches the PCR
product generated in the qPCR reaction.
• The standard plasmid is easy to
grow up.
Development Status: Fully developed.
Inventors: Daniel C. Douek, Richard
A. Koup, Brenna J. Hill (NIAID.)
Relevant Publications:
1. Douek et al. Changes in thymic
function with age and during the
treatment of HIV infection. Nature 1998
Dec 17;396(6712):690–695. [PubMed:
9872319.]
2. Douek et al. Assessment of thymic
output in adults after haematopoietic
stem-cell transplantation and prediction
of T-cell reconstitution. Lancet 2000
May 27;355(9218):1875–1881. [PubMed:
10866444.]
Patent Status: HHS Reference No. E–
067–2011/0—Research Material. Patent
protection is not being pursued for this
technology.
Licensing Status: Research tool
available for non-exclusive licensing.
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Licensing Contact: Susan Ano, Ph.D.;
301–435–5515; anos@mail.nih.gov.
Glucocerebrosidase Activators as a
Treatment for Gaucher Disease
Description of Invention: This
technology is a collection of small
molecule activators of a genetically
defective version of the enzyme called
glucocerebrosidase (GCase), which
causes Gaucher disease. Gaucher
disease is a rare disease affecting 1 in
40,000 babies born. Ashkenazi Jews of
eastern European descent (about 1 in
800 live births) are at particular risk of
carrying this genetic defect. It is caused
by inherited genetic mutations in the
gene that encodes GCase, which result
in reduced activity of the enzyme. This
enzyme is normally made and then
transported to an organelle called a
lysosome, which is dedicated to the
degradation and disposal of molecules
the cell no longer needs. GCase is
responsible for the breakdown of a fatty
material called glucocerebroside (or
glucosylceramide). The accumulation of
this lipid occurs inside specific cells
called macrophages and macrophagederived cells. The disease has been
categorized into three types:
neuronopathic (types 2, 3) and nonneuronopathic (type 1) with mild to
severe symptoms that can appear at
anytime from infancy to adulthood.
Clinical manifestations can include an
enlarged spleen and liver, anemia,
decreased platelets, bone disease and
neurodegeneration, with varying
severity depending on the type of
disease and time of diagnosis. The
deficient GCase activity has been
attributed to insufficient GCase enzyme
in the lysosome. After production in the
endoplasmic reticulum (ER), defective
GCase does not fold properly and is
therefore degraded in the ER and not
transported to the lysosome where it
would hydrolyze glucocerebroside. The
small molecule activators may act by
increasing the concentration of GCase
that reaches the lysosome by facilitating
the proper folding of GCase so that it
can be released from the ER and
transported to lysosomes. Thus, these
small molecules could be acting like
‘‘chaperones,’’ because they facilitate
proper folding which results in some
active enzyme. Prior failed attempts to
use small molecule chaperones to
improve GCase folding and transport
were made with inhibitors of GCase,
which ironically properly folded active
GCase that was subsequently
transported to the lysosome, but the
molecule also inhibited the GCase co
that it could not break down
glucocerebroside. On the other hand,
these proposed small molecules were
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Federal Register / Vol. 76, No. 87 / Thursday, May 5, 2011 / Notices
jlentini on DSKJ8SOYB1PROD with NOTICES
screened for their ability to activate
defective GCase in the presence of a
fluorogenic mimic of glucocerebroside,
and their ability to facilitate
translocation of defective GCase to
lysosomes as well. This creates the
opportunity to induce proper folding,
while avoiding inhibition of enzyme
function.
Application: Treatment of Gaucher
Disease.
Development Status: Early
development.
Inventors: Juan Marugan, Noel T.
Southall, Ehud M. Goldin, Wei Zheng,
Samarjit Patnaik, Ellen Sidransky, Omid
Motabar, Wendy Westbroek (NHGRI.)
Related Publications: None.
Patent Status: U.S. Provisional
Application No. 61/420,946, filed
December 8, 2010, (HHS Reference No.
E–257–2010/0–US–01.)
Licensing Status: Available for
licensing.
Licensing Contact: Steve Standley,
PhD; 301–435–4074; sstand@od.nih.gov.
A Novel Strategy for Development of an
Effective HIV/AIDS Vaccine
Description of Invention: The
invention offered for licensing and
commercial development relates to the
field of HIV/AIDS Vaccines. More
specifically, the invention describes a
novel strategy that can be useful in
effective vaccination and treatment of
HIV/AIDS infected persons. In this
strategy (called ‘trigger-and-neutralize’
strategy) the infected subject is primed
with HIV trimeric gp 120 immunogen to
induce the production of CD4i (CD4induced) antibodies. The patient is then
treated with a compound that stabilizes
the ‘open’ conformation of the gp120 of
the HIV virus, at which conformation
the gp120 epitope is better exposed and
effectively neutralized by the CD4i
antibodies.
Applications: Vaccination and
treatment of HIV/AIDS infected
patients.
Advantages: The unique strategy of
eliciting CD4i antibodies in vivo and
ensuring their neutralizing effect by
stabilizing the gp120 open
conformation, will provide more
effective treatment compared to other
published methods that utilize
neutralizing antibodies to treat HIV/
AIDS.
Development Status: The subject
matter of the invention continues to be
researched. Proof-of-principle of some
of the aspects of the invention have
been demonstrated.
Market: Although there are currently
many commercial drugs available for
treatment of HIV/AIDS, there still exists
an urgent need to develop vaccines
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Jkt 223001
against the disease. This need (no
approved vaccine is available yet) is
particularly important because of the
resistance developed by many patients
to commercial drugs and thus the need
for the use of drug cocktails, as well as
the severe side effects that many of the
drugs exhibit. At present, the World
Health Organization estimates that over
30 million people are infected with HIV
and that over 25 million individuals
have died from AIDS-related illnesses.
The potential market for HIV vaccines is
therefore huge and thus this invention
may be commercially attractive for
vaccine and drug manufacturers.
Inventors: Sriram Subramaniam (NCI.)
Relevant Publications:
1. Liu J, Bartesaghi A, Borgnia MJ,
Sapiro G, Subramaniam S. Molecular
architecture of native HIV–1 gp120
trimers. Nature. 2008 Sep
4;455(7209):109–113. [PubMed:
18668044.]
2. White TA, Bartesaghi A, Borgnia
MJ, Meyerson JR, M. de la Cruz MJ, Bess
JW, Nandwani R, Hoxie JA, Lifson JD,
Milne JL, Subramaniam S. Molecular
architectures of trimeric SIV and HIV–
1 envelope glycoproteins on intact
viruses: strain dependent variation in
quaternary structure. PLoS Pathog. 2010
Dec 23;6(12):e1001249. [PubMed:
21203482.]
3. Felts RL, Narayan K, Estes JD, Shi
D, Trubey CM, Fu J, Hartnell LM, Ruthel
GT, Schneider DK, Nagashima K, Bess
JW Jr, Bavari S, Lowekamp BC, Bliss D,
Lifson JD, Subramaniam S. 3D
visualization of HIV transfer at the
virological synapse between dendritic
cells and T-cells. Proc Natl Acad Sci U
S A. 2010 Jul 27;107(30):13336–13341.
[PubMed: 20624966.]
Patent Status: U.S. Provisional
Application No. 61/356,326 filed 18 Jun
2010 (HHS Reference No. E–201–2010/
0–US–01), entitled ‘‘Immunogenic
Compositions Derived from Structural
Alteration of HIV Envelope Proteins.’’
Licensing Status: Available for
licensing and commercial development.
Licensing Contacts:
• Uri Reichman, PhD, MBA; 301–
435–4616; UR7a@nih.gov.
• John Stansberry, PhD; 301–435–
5236; js852e@nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research, NCI/
NIH is seeking statements of capability
or interest from parties interested in
collaborative research to further
develop, produce, evaluate, or
commercialize trimeric gp120
immunogens. Please contact John
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
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Epoxy-guaiane Cancer Inhibitors: New
Class of Natural Products Isolated From
the African Plant Phyllanthus englerii
Description of Invention: The present
invention involves the observation of
renal selective inhibitory activity by the
extracts of the African plant Phyllanthus
englerii. Bioassay-guided fractionation
of the purified extracts revealed a series
of novel chemical entities which are
named Englerin A–F. The englerins and
their derivatives are useful in the
treatment of a number of cancers,
particularly renal cancer. The englerins
exhibit selective and potent renal cell
inhibitory activity in vitro.
These compounds are recoverable in
reasonable yield from natural product
extracts and are considered to be
reasonably tractable for synthetic
chemistry schemes. Sufficient supply of
several analogs had been extracted from
repository samples for identification
and initial biological characterization.
Subsequent five-dose testing in the
NCI60 screening panel indicated and
confirmed impressive renal-selective
activity.
Applications: The new chemical
entities can be potential cancer
therapeutics, especially for renal cancer.
Advantages:
• There is reasonable yield and
recovery of the compounds from the
natural product extracts.
• The synthetic chemistry schemes
for synthesis of these compounds are
considered to be reasonably tractable.
Development Status: Proof of concept
in vitro studies have been completed
and further in vitro and in vivo animal
model studies are ongoing.
Inventors: John A. Beutler et al. (NCI)
Relevant Publication: S.
Sutthivaiyakit et al. A novel 29-nor-3,4seco-friedelane triterpene and a new
guaiane sesquiterpene from the roots of
Phyllanthus oxyphyllus. Tetrahedron
2003 Dec 8; 59(50):9991–9995.
Patent Status: U.S. Patent Application
No. 12/811,245 filed 29 Jul 2010 (HHS
Reference No. E–064–2008/2–US–06)
and related international filings.
Licensing Status: Available for
licensing.
Licensing Contact: Surekha Vathyam,
PhD; 301–435–4076;
vathyams@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute Molecular
Targets Development Program is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize epoxy-guaiane cancer
inhibitors. Please contact John D.
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
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jlentini on DSKJ8SOYB1PROD with NOTICES
Federal Register / Vol. 76, No. 87 / Thursday, May 5, 2011 / Notices
Imidazoacridones With Anti-Tumor
Activity
Description of Invention: The present
invention relates to novel bifunctional
molecules with potent and selective
activity against colon, liver and
pancreatic tumors. Compounds have
low animal toxicity, excellent PK/PD
characteristics and proved to be very
effective in several preclinical animal
models of cancer. Extensive mechanistic
studies have demonstrated that
compounds inhibit tumor growth
through a novel mechanism. These
agents are composed of an
imidazoacridone moiety linked by a
nitrogen containing aliphatic chain of
various length and rigidity to another
aromatic ring system capable of
intercalation to DNA.
Previous studies on related
symmetrical bis-imidazoacridones
revealed that only one planar
imidazoacridone moiety intercalates
into DNA. The second aromatic moiety,
which is crucial for biological activity,
along with the linker resides in DNA
minor groove, and is believed to interact
with DNA-binding proteins (most likely,
transcription factors and/or repair
proteins). The symmetrical bisimidazoacridones arrest the growth of
sensitive cancers (especially colon
cancers) but do not kill the tumors. It
was hypothesized that the growth arrest
was due to the inability of the affected
tumor cells to repair DNA damage
caused by the compounds. Remarkably,
bis-imidazoacridones are very well
tolerated, are very tissue selective and
do not appear to damage normal tissues.
Since the binding of the symmetrical
bis-imidazoacridones to DNA was
unsymmetrical, the inventors have
developed unsymmetrical compounds
in which one imidazoacridone moieties
was replaced by other intercalating
groups, with the expectation that this
would enhance biological activity while
retaining the remarkable tissue
selectivity and low systemic toxicity.
The new compounds contain
intercalating moieties such as 3-chloro7-methoxyacridine or naphthalimide
along with the original
imidazoacridones.
These new compounds, especially
those containing naphthalimide moiety,
are extremely cytotoxic against a variety
of tumor cells in vitro (IC50 at low
nanomolar range) and kill tumor cells
by inducing apoptosis. In vivo, in nude
mice xenografted with human tumors,
the compounds significantly inhibited
the growth of such tumors as colon
tumor HCT116 and Colo205 as well as
pancreatic tumors (lines 6.03 and 10.05
freshly established from a patient).
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These compounds are extremely potent
agents against hepatocellular carcinoma
as evidenced by their ability to eradicate
liver cancer in an orthotopic liver
cancer model in rats. Remarkably, no
toxicity was observed at the therapeutic
doses. These are among the most potent
agents known against cancers of the GI
tract and appear to be tolerated very
well.
Inventors: Wieslaw M. Cholody et al.
(NCI)
Patent Status:
• U.S. Patent 6,664,263 issued 16 Dec
2003 (HHS Reference No. E–289–1999/
0–US–07) and related international
patents/patent applications.
• U.S. Patent 6,541,483 issued 01 Apr
2003 (HHS Reference No. E–065–1996/
2–US–25) and related international
patents/patent applications.
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
PhD; 301–594–6565;
tongb@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute, Center for
Cancer Research, is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize imidazoacridones as
therapeutic agents for cancer treatment.
Please contact John Hewes, PhD at 301–
435–3121 or hewesj@mail.nih.gov for
more information.
Dated: April 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–11055 Filed 5–4–11; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Eunice Kennedy Shriver National
Institute of Child Health & Human
Development; Notice of Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of a meeting of the
National Advisory Child Health and
Human Development Council.
The meeting will be open to the
public, with attendance limited to space
available. Individuals who plan to
attend and need special assistance, such
as sign language interpretation or other
reasonable accommodations, should
notify the Contact Person listed below
in advance of the meeting.
PO 00000
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25699
The meeting 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.,
as amended. The grant applications
and/or contract proposals 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 and/or contract proposals,
the disclosure of which would
constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Advisory
Child Health and Human Development
Council.
Date: June 2, 2011.
Open: 8 a.m. to 12:20 p.m.
Agenda: (1) A report by the Director,
NICHD; (2) Report of the Subcommittee on
Planning and Policy; (3) NICHD Scientific
Visioning update; and other business of the
Council.
Place: National Institutes of Health,
Building 31, 31 Center Drive, C-Wing,
Conference Room 6, Bethesda, MD 20892.
Closed: 12:20 p.m. to 5 p.m.
Agenda: To review and evaluate grant
applications and/or proposals.
Place: National Institutes of Health,
Building 31, 31 Center Drive, C-Wing,
Conference Room 6, Bethesda, MD 20892.
Contact Person: Yvonne T. Maddox, PhD,
Deputy Director, National Institute of Child
Health, and Human Development, NIH, 9000
Rockville Pike MSC 7510, Building 31, Room
2A03, Bethesda, MD 20892, (301) 496–1848.
Any interested person may file written
comments with the committee by forwarding
the statement to the Contact Person listed on
this notice. The statement should include the
name, address, telephone number and when
applicable, the business or professional
affiliation of the interested person.
In the interest of security, NIH has
instituted stringent procedures for entrance
onto the NIH campus. All visitor vehicles,
including taxis, hotel, and airport shuttles
will be inspected before being allowed on
campus. Visitors will be asked to show one
form of identification (for example, a
government-issued photo ID, driver’s license,
or passport) and to state the purpose of their
visit.
Information is also available on the
Institute’s/Center’s home page: https://
ww.nichd.nih.gov/about/nachhd.htm, where
an agenda and any additional information for
the meeting will be posted when available.
In order to facilitate public attendance at
the open session of Council, reserve seating
will be made available to the first five
individuals reserving seats in the main
meeting room, Conference Room 6. Please
contact Ms. Lisa Kaeser, Program and Public
Liaison Office, NICHD, at 301–496–0536 to
make your reservation. Additional seating
will be available in the meeting overflow
rooms, Conference Rooms 7 and 8.
Individuals will also be able to view the
meeting via NIH Videocast. Please go to the
following link for Videocast access
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]]>Agencies
[Federal Register Volume 76, Number 87 (Thursday, May 5, 2011)]
[Notices]
[Pages 25697-25699]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-11055]
-----------------------------------------------------------------------
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.
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.
Improved Standard for Immune System Recovery Assay
Description of Invention: Monitoring an immune system that has been
depleted by infection (e.g., HIV), chemotherapy, or progenitor cell
transplantation is vital to assessing individual's recovery status.
This technology provides a new plasmid standard to be used as part of
the existing TREC assay. This new plasmid has a shorter insert than the
commercially available one, which means it now matches the PCR product
generated in the qPCR reaction in the TREC assay. Additionally, the new
plasmid is easier to grow up than the existing standard.
Applications: TREC assay for T-cell concentration measurements.
Advantages:
The insert of standard plasmid is shorter and directly
matches the PCR product generated in the qPCR reaction.
The standard plasmid is easy to grow up.
Development Status: Fully developed.
Inventors: Daniel C. Douek, Richard A. Koup, Brenna J. Hill
(NIAID.)
Relevant Publications:
1. Douek et al. Changes in thymic function with age and during the
treatment of HIV infection. Nature 1998 Dec 17;396(6712):690-695.
[PubMed: 9872319.]
2. Douek et al. Assessment of thymic output in adults after
haematopoietic stem-cell transplantation and prediction of T-cell
reconstitution. Lancet 2000 May 27;355(9218):1875-1881. [PubMed:
10866444.]
Patent Status: HHS Reference No. E-067-2011/0--Research Material.
Patent protection is not being pursued for this technology.
Licensing Status: Research tool available for non-exclusive
licensing.
Licensing Contact: Susan Ano, Ph.D.; 301-435-5515;
anos@mail.nih.gov.
Glucocerebrosidase Activators as a Treatment for Gaucher Disease
Description of Invention: This technology is a collection of small
molecule activators of a genetically defective version of the enzyme
called glucocerebrosidase (GCase), which causes Gaucher disease.
Gaucher disease is a rare disease affecting 1 in 40,000 babies born.
Ashkenazi Jews of eastern European descent (about 1 in 800 live births)
are at particular risk of carrying this genetic defect. It is caused by
inherited genetic mutations in the gene that encodes GCase, which
result in reduced activity of the enzyme. This enzyme is normally made
and then transported to an organelle called a lysosome, which is
dedicated to the degradation and disposal of molecules the cell no
longer needs. GCase is responsible for the breakdown of a fatty
material called glucocerebroside (or glucosylceramide). The
accumulation of this lipid occurs inside specific cells called
macrophages and macrophage-derived cells. The disease has been
categorized into three types: neuronopathic (types 2, 3) and non-
neuronopathic (type 1) with mild to severe symptoms that can appear at
anytime from infancy to adulthood. Clinical manifestations can include
an enlarged spleen and liver, anemia, decreased platelets, bone disease
and neurodegeneration, with varying severity depending on the type of
disease and time of diagnosis. The deficient GCase activity has been
attributed to insufficient GCase enzyme in the lysosome. After
production in the endoplasmic reticulum (ER), defective GCase does not
fold properly and is therefore degraded in the ER and not transported
to the lysosome where it would hydrolyze glucocerebroside. The small
molecule activators may act by increasing the concentration of GCase
that reaches the lysosome by facilitating the proper folding of GCase
so that it can be released from the ER and transported to lysosomes.
Thus, these small molecules could be acting like ``chaperones,''
because they facilitate proper folding which results in some active
enzyme. Prior failed attempts to use small molecule chaperones to
improve GCase folding and transport were made with inhibitors of GCase,
which ironically properly folded active GCase that was subsequently
transported to the lysosome, but the molecule also inhibited the GCase
co that it could not break down glucocerebroside. On the other hand,
these proposed small molecules were
[[Page 25698]]
screened for their ability to activate defective GCase in the presence
of a fluorogenic mimic of glucocerebroside, and their ability to
facilitate translocation of defective GCase to lysosomes as well. This
creates the opportunity to induce proper folding, while avoiding
inhibition of enzyme function.
Application: Treatment of Gaucher Disease.
Development Status: Early development.
Inventors: Juan Marugan, Noel T. Southall, Ehud M. Goldin, Wei
Zheng, Samarjit Patnaik, Ellen Sidransky, Omid Motabar, Wendy Westbroek
(NHGRI.)
Related Publications: None.
Patent Status: U.S. Provisional Application No. 61/420,946, filed
December 8, 2010, (HHS Reference No. E-257-2010/0-US-01.)
Licensing Status: Available for licensing.
Licensing Contact: Steve Standley, PhD; 301-435-4074;
sstand@od.nih.gov.
A Novel Strategy for Development of an Effective HIV/AIDS Vaccine
Description of Invention: The invention offered for licensing and
commercial development relates to the field of HIV/AIDS Vaccines. More
specifically, the invention describes a novel strategy that can be
useful in effective vaccination and treatment of HIV/AIDS infected
persons. In this strategy (called `trigger-and-neutralize' strategy)
the infected subject is primed with HIV trimeric gp 120 immunogen to
induce the production of CD4i (CD4-induced) antibodies. The patient is
then treated with a compound that stabilizes the `open' conformation of
the gp120 of the HIV virus, at which conformation the gp120 epitope is
better exposed and effectively neutralized by the CD4i antibodies.
Applications: Vaccination and treatment of HIV/AIDS infected
patients.
Advantages: The unique strategy of eliciting CD4i antibodies in
vivo and ensuring their neutralizing effect by stabilizing the gp120
open conformation, will provide more effective treatment compared to
other published methods that utilize neutralizing antibodies to treat
HIV/AIDS.
Development Status: The subject matter of the invention continues
to be researched. Proof-of-principle of some of the aspects of the
invention have been demonstrated.
Market: Although there are currently many commercial drugs
available for treatment of HIV/AIDS, there still exists an urgent need
to develop vaccines against the disease. This need (no approved vaccine
is available yet) is particularly important because of the resistance
developed by many patients to commercial drugs and thus the need for
the use of drug cocktails, as well as the severe side effects that many
of the drugs exhibit. At present, the World Health Organization
estimates that over 30 million people are infected with HIV and that
over 25 million individuals have died from AIDS-related illnesses. The
potential market for HIV vaccines is therefore huge and thus this
invention may be commercially attractive for vaccine and drug
manufacturers.
Inventors: Sriram Subramaniam (NCI.)
Relevant Publications:
1. Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S.
Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008 Sep
4;455(7209):109-113. [PubMed: 18668044.]
2. White TA, Bartesaghi A, Borgnia MJ, Meyerson JR, M. de la Cruz
MJ, Bess JW, Nandwani R, Hoxie JA, Lifson JD, Milne JL, Subramaniam S.
Molecular architectures of trimeric SIV and HIV-1 envelope
glycoproteins on intact viruses: strain dependent variation in
quaternary structure. PLoS Pathog. 2010 Dec 23;6(12):e1001249. [PubMed:
21203482.]
3. Felts RL, Narayan K, Estes JD, Shi D, Trubey CM, Fu J, Hartnell
LM, Ruthel GT, Schneider DK, Nagashima K, Bess JW Jr, Bavari S,
Lowekamp BC, Bliss D, Lifson JD, Subramaniam S. 3D visualization of HIV
transfer at the virological synapse between dendritic cells and T-
cells. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13336-13341.
[PubMed: 20624966.]
Patent Status: U.S. Provisional Application No. 61/356,326 filed 18
Jun 2010 (HHS Reference No. E-201-2010/0-US-01), entitled ``Immunogenic
Compositions Derived from Structural Alteration of HIV Envelope
Proteins.''
Licensing Status: Available for licensing and commercial
development.
Licensing Contacts:
Uri Reichman, PhD, MBA; 301-435-4616; UR7a@nih.gov.
John Stansberry, PhD; 301-435-5236; js852e@nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
NCI/NIH is seeking statements of capability or interest from parties
interested in collaborative research to further develop, produce,
evaluate, or commercialize trimeric gp120 immunogens. Please contact
John Hewes, PhD at 301-435-3121 or hewesj@mail.nih.gov for more
information.
Epoxy-guaiane Cancer Inhibitors: New Class of Natural Products Isolated
From the African Plant Phyllanthus englerii
Description of Invention: The present invention involves the
observation of renal selective inhibitory activity by the extracts of
the African plant Phyllanthus englerii. Bioassay-guided fractionation
of the purified extracts revealed a series of novel chemical entities
which are named Englerin A-F. The englerins and their derivatives are
useful in the treatment of a number of cancers, particularly renal
cancer. The englerins exhibit selective and potent renal cell
inhibitory activity in vitro.
These compounds are recoverable in reasonable yield from natural
product extracts and are considered to be reasonably tractable for
synthetic chemistry schemes. Sufficient supply of several analogs had
been extracted from repository samples for identification and initial
biological characterization. Subsequent five-dose testing in the NCI60
screening panel indicated and confirmed impressive renal-selective
activity.
Applications: The new chemical entities can be potential cancer
therapeutics, especially for renal cancer.
Advantages:
There is reasonable yield and recovery of the compounds
from the natural product extracts.
The synthetic chemistry schemes for synthesis of these
compounds are considered to be reasonably tractable.
Development Status: Proof of concept in vitro studies have been
completed and further in vitro and in vivo animal model studies are
ongoing.
Inventors: John A. Beutler et al. (NCI)
Relevant Publication: S. Sutthivaiyakit et al. A novel 29-nor-3,4-
seco-friedelane triterpene and a new guaiane sesquiterpene from the
roots of Phyllanthus oxyphyllus. Tetrahedron 2003 Dec 8; 59(50):9991-
9995.
Patent Status: U.S. Patent Application No. 12/811,245 filed 29 Jul
2010 (HHS Reference No. E-064-2008/2-US-06) and related international
filings.
Licensing Status: Available for licensing.
Licensing Contact: Surekha Vathyam, PhD; 301-435-4076;
vathyams@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute
Molecular Targets Development Program is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize epoxy-guaiane
cancer inhibitors. Please contact John D. Hewes, PhD at 301-435-3121 or
hewesj@mail.nih.gov for more information.
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Imidazoacridones With Anti-Tumor Activity
Description of Invention: The present invention relates to novel
bifunctional molecules with potent and selective activity against
colon, liver and pancreatic tumors. Compounds have low animal toxicity,
excellent PK/PD characteristics and proved to be very effective in
several preclinical animal models of cancer. Extensive mechanistic
studies have demonstrated that compounds inhibit tumor growth through a
novel mechanism. These agents are composed of an imidazoacridone moiety
linked by a nitrogen containing aliphatic chain of various length and
rigidity to another aromatic ring system capable of intercalation to
DNA.
Previous studies on related symmetrical bis-imidazoacridones
revealed that only one planar imidazoacridone moiety intercalates into
DNA. The second aromatic moiety, which is crucial for biological
activity, along with the linker resides in DNA minor groove, and is
believed to interact with DNA-binding proteins (most likely,
transcription factors and/or repair proteins). The symmetrical bis-
imidazoacridones arrest the growth of sensitive cancers (especially
colon cancers) but do not kill the tumors. It was hypothesized that the
growth arrest was due to the inability of the affected tumor cells to
repair DNA damage caused by the compounds. Remarkably, bis-
imidazoacridones are very well tolerated, are very tissue selective and
do not appear to damage normal tissues.
Since the binding of the symmetrical bis-imidazoacridones to DNA
was unsymmetrical, the inventors have developed unsymmetrical compounds
in which one imidazoacridone moieties was replaced by other
intercalating groups, with the expectation that this would enhance
biological activity while retaining the remarkable tissue selectivity
and low systemic toxicity. The new compounds contain intercalating
moieties such as 3-chloro-7-methoxyacridine or naphthalimide along with
the original imidazoacridones.
These new compounds, especially those containing naphthalimide
moiety, are extremely cytotoxic against a variety of tumor cells in
vitro (IC50 at low nanomolar range) and kill tumor cells by inducing
apoptosis. In vivo, in nude mice xenografted with human tumors, the
compounds significantly inhibited the growth of such tumors as colon
tumor HCT116 and Colo205 as well as pancreatic tumors (lines 6.03 and
10.05 freshly established from a patient). These compounds are
extremely potent agents against hepatocellular carcinoma as evidenced
by their ability to eradicate liver cancer in an orthotopic liver
cancer model in rats. Remarkably, no toxicity was observed at the
therapeutic doses. These are among the most potent agents known against
cancers of the GI tract and appear to be tolerated very well.
Inventors: Wieslaw M. Cholody et al. (NCI)
Patent Status:
U.S. Patent 6,664,263 issued 16 Dec 2003 (HHS Reference
No. E-289-1999/0-US-07) and related international patents/patent
applications.
U.S. Patent 6,541,483 issued 01 Apr 2003 (HHS Reference
No. E-065-1996/2-US-25) and related international patents/patent
applications.
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, PhD; 301-594-6565;
tongb@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Center for Cancer Research, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize imidazoacridones as therapeutic
agents for cancer treatment. Please contact John Hewes, PhD at 301-435-
3121 or hewesj@mail.nih.gov for more information.
Dated: April 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-11055 Filed 5-4-11; 8:45 am]
BILLING CODE 4140-01-P
