Government-Owned Inventions; Availability for Licensing, 81628-81630 [2010-32671]
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Identification of Subjects Likely To
Benefit From Copper Treatment
Description of Technology: Menkes
disease is an infantile onset X-linked
recessive neurodegenerative disorder
caused by deficiency or dysfunction of
a copper-transporting ATPase, ATP7A.
The clinical and pathologic features of
this condition reflect decreased
activities of enzymes that require copper
as a cofactor, including dopamine-bhydrolase, cytochrome c oxidase and
lysyl oxidase. Recent studies indicate
that ATP7A normally responds to
N-methyl-D-aspartate receptor
activation in the brain, and an impaired
response probably contributes to the
neuropathology of Menkes disease.
Affected infants appear healthy at birth
and develop normally for 6 to 8 weeks.
Subsequently, hypotonia, seizures and
failure to thrive occur and death by 3
years of age is typical. Occipital horn
syndrome (OHS) is also caused by
mutations in the copper transporting
ATPase ATP7A, although its symptoms
are milder than Menkes syndrome,
including occipital horns and lax skin
and joints.
Treatment with daily copper
injections may improve the outcome in
Menkes disease if commenced within
days after birth; however, newborn
screening for this disorder is not
available and early detection is difficult
because clinical abnormalities in
affected newborns are absent or subtle.
Moreover, the usual biochemical
markers (low serum copper and
ceruloplasmin) are unreliable predictors
in the neonatal period, since levels in
healthy newborns are low and overlap
with those in infants with Menkes
disease. Although molecular diagnosis
is available, its use is complicated by
the diversity of mutation types and the
large size of ATP7A (about 140kb).
Thus, there is a need for improved
methods for early detection of infants
with Menkes disease or OHS in order to
improve outcomes.
This technology relates to methods of
identifying individuals who may benefit
from treatment with copper, particularly
those having Menkes disease or
Occipital Horn Syndrome.
Inventor: Stephen G. Kaler (NICHD).
Publication: SG Kaler, CS Holmes, DS
Goldstein, JR Tang, SC Godwin,
A Donsante, CJ Liew, S Sato, N
Patronas. Neonatal diagnosis and
treatment of Menkes disease. N Engl J
Med. 2008 Feb 7;358(6):605–614.
[PubMed: 18256395]
Patent Status: PCT Application No.
PCT/US2008/078966 filed 06 Oct 2008,
which published as WO 2010/042102
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22:37 Dec 27, 2010
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on 15 Apr 2010 (HHS Reference No.
E–186–2008/0–PCT–01).
Licensing Status: Available for
licensing.
Licensing Contact: Fatima Sayyid,
M.H.P.M.; 301–435–4521;
Fatima.Sayyid@nih.hhs.gov.
Collaborative Research Opportunity:
The National Institute of Child Health
and Human Development, Division of
Intramural Research, Molecular
Medicine Program, Unit on Pediatric
Genetics, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize population-based
newborn screening for Menkes disease
and related disorders of copper
transport in order to identify subjects
likely to benefit from copper injections
and other treatments. Please contact
Alan Hubbs, PhD at 301–594–4263 or
hubbsa@mail.nih.gov for more
information.
Dated: December 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2010–32669 Filed 12–27–10; 8:45 am]
BILLING CODE 4140–01–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:
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
SUMMARY:
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be required to receive copies of the
patent applications.
A New Class of Antibiotics: Natural
Inhibitors of Bacterial Cytoskeletal
Protein FtsZ to Fight Drug-susceptible
and Multi-drug Resistant Bacteria
Description of Technology: The risk of
infectious diseases epidemic has been
alarming in recent decades. This is not
only because of the increase incident of
so-called ‘‘super bugs,’’ but also because
of the scarce number of potential
antibiotics in the pipeline. Currently,
the need for new antibiotics is greater
than ever! The present invention by the
National Institute of Diabetes and
Digestive and Kidney Disease (NIDDK),
part of the National Institute of Health
(NIH), address this urgent need. The
invention is a new class of
chrysophaentin antibiotics that inhibit
the growth of broad-spectrum, drugsusceptible, and drug-resistant bacteria.
Derived from the yellow algae
Chrysophaeum taylori, the inventor has
extracted 8 small molecules of natural
products and tested for antimicrobial
activity against drug resistant bacteria,
methicillin-resistant Staphylococcus
aureus (MRSA) and vancomycinresistant Enterococcus faecalis (VRE), as
well as other drug susceptible strains.
Structurally, the molecules represent a
new class of antibiotic that also likely
work through a distinct mechanism of
action from that of current antibiotics,
which is key for the further
development of antibiotics that inhibit
drug-resistant strains.
The bacterial cytoskeletal protein FtsZ
is a GTPase and has structural homology
to the eukaryotic cytoskeletal protein
tubulin, but lacks significant sequence
similarity. FtsZ is essential for bacterial
cell division. It is responsible for Z-ring
assembly in bacteria, which leads to
bacterial cell division. Experiments
show that the disclosed compounds are
competitive inhibitors of GTP binding to
FtsZ, and must bind in the GTP-binding
site of FtsZ. Inhibition of FtsZ stops
bacterial cell division and is a validated
target for new antimicrobials. FtsZ is
highly conserved among all bacteria,
making it a very attractive antimicrobial
target.
Applications:
• Therapeutic potential for curing
bacterial infections in vivo, including
for clinical and veterinary applications.
• Antiseptics in hospital settings.
• Since FtsZ is structurally similar,
but does not share sequence homology
to eukaryotic cytoskeletal protein
tubulin, these compounds may have
antitumor properties against some
cancer types or cell lines.
Advantages:
E:\FR\FM\28DEN1.SGM
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emcdonald on DSK2BSOYB1PROD with NOTICES
Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices
• Structurally distinct antimicrobial
compounds.
• Attack newly validated antibacterial
targeted protein FtsZ.
• These compounds have a unique
mechanism of action which inhibit FtsZ
by inhibiting FtsZ GTPase activity.
• Inhibit drug-susceptible and drugresistant bacteria.
Development Status:
• Initial isolation and chemical
structural characterization using NMR
spectroscopy have been conducted.
• Antimicrobial testing against
MRSA, Enterrococcus faecium, and VRE
were conducted in vitro using a
modified disk diffusion assay and
microbroth liquid dilution assays.
• MIC50 values were determined
using a microbroth dilution assay.
• Mode of action was elucidated and
Saturation Transfer Difference (STD)
NMR was conducted to map the binding
epitope of one of these compounds in
complex with recombinant FtsZ.
• Other experiments on different
areas to further characterize these
compounds and their mode of action are
currently ongoing.
Market: The market potential for the
disclosed compounds is huge due to the
very limited number of new antibiotics
developed in recent decades and the
increased epidemic of infectious
diseases. In fact, infectious diseases are
the leading cause of death worldwide.
In the United States alone, more people
die from MRSA than from HIV (Journal
of the American Medical Association,
2007) and more than 90,000 people die
each year from hospital acquired
bacterial infections (Centers for Disease
Control).
According to the recent report,
‘‘Antibiotics Resistance and Antibiotic
Technologies: Global Markets’’
published in November 2009, there has
been a revival in the antibiotics sector
over the past few years. Although some
companies are developing analogues of
existing antibiotic classes and putting
them into clinical trials, other start-up
biotechnology companies have come up
with molecules that adopt new
approaches in tackling antimicrobial
infections. The antibacterials market can
be split into two major groups: The
community market and the hospital
market. The smaller hospital market is
expanding more rapidly, driven by
rising resistant rates, a more severely ill
patient population and newer,
premium-priced injectable antibiotics.
Interestingly, several big pharmaceutical
companies have recently made strategic
decisions to expand their presence in
this sector by either acquiring other
companies or in-licensing new
compounds.
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22:37 Dec 27, 2010
Jkt 223001
While the number of such new
molecules in the approval stages is still
low, R&D pipelines are promising, and
several novel classes of antibiotics are in
their early stages of development. This
antibacterial R&D bailout that started
about 5 years ago due to tougher
regulatory conditions, restrictions on
the use of antibiotics and emergence of
resistance to newer antibiotics within 3
years has helped create a global
antimicrobial therapeutic market of $24
billion in 2008 with 14 products
recording sales of more than $1 billion.
Inventors: Carole A. Bewley et al.
(NIDDK).
Related Publications:
1. DJ Haydon et al. An inhibitor of
FtsZ with potent and selective antistaphylococcal activity. Science. 2008
Sept 19; 321(5896):1673–1675.
[PubMed: 18801997].
2. NR Stokes et al. Novel inhibitors of
bacterial cytokinesis identified by a cellbased antibiotic screening assay. J Biol
Chem. 2005 Dec 2; 280(48):39709–
39715. [PubMed: 16174771].
3. J Wang et al. Discovery of small
molecule that inhibits cell division by
blocking FtsZ, a novel therapeutic target
of antibiotics. J Biol Chem. 2003 Nov 7;
278(45):44424–44428. [PubMed:
12952956].
4. P Domadia et al. Berberine targets
assembly of Escherichia coli cell
division protein FtsZ. Biochemistry.
2008 Mar 11; 47(10):3225–3234.
[PubMed: 18275156].
5. P Domadia et al. Inhibition of
bacterial cell division protein FtsZ by
cinamaldehyde. Biochem Pharmacol.
2007 Sep 15:74(6):831–840. [PubMed:
17662960].
6. S Urgaonkar et al. Synthesis of
antimicrobial natural products targeting
FtsZ: (+/-)-dichamanetin and (+/-)-2′″hydroxy-5″-benzylisouvarinol-B. Org
Lett. 2005 Dec 8;7(25):5609–5612.
[PubMed: 16321003].
Patent Status: U.S. Provisional
Application No. 61/308,911 filed 27 Feb
2010 (HHS Reference No. E–116–2010/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contacts:
• Uri Reichman, Ph.D., MBA; 301–
435–4616; UR7a@nih.gov.
• John Stansberry, Ph.D.; 301–435–
5236; stansbej@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Diabetes and
Digestive and Kidney Diseases,
Laboratory of Bioorganic Chemistry is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize the
chrysophaentin antibiotics. Please
PO 00000
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81629
contact Cindy K. Fuchs at 301–451–
3636 or cfuchs@mail.nih.gov for more
information.
GATA–3 Reporter Plasmids for
Revealing Underlying Mechanisms in
Breast Cancer
Description of Technology: Scientists
at the National Institutes of Health (NIH)
have developed GATA–3 gene reporter
plasmids that express a green
fluorescent protein (GFP) or luciferase
reporter protein under the control of a
GATA–3 promoter. Cells expressing this
plasmid will glow fluorescent green or
emit light energy, respectively, if
GATA–3 gene expression is activated in
the cells. The reporter construct allows
cells where GATA–3 gene expression is
activated to be isolated and collected for
further analysis or be monitored in the
host environment.
GATA–3 is a transcription factor that
is highly expressed in several types of
cells and is a critical transcription factor
for the development of particular
lineages of hematopoietic cells and
normal mammary luminal epithelium.
GATA–3 plays a regulatory role in
determining the fate of cells in the
hematopoietic systems and the
mammary gland. Disruption of GATA–
3 expression leads to defects in the
development of sub-types of lymphoid
cells and luminal mammary epithelial
cells. GATA–3 expression is highly
associated with luminal sub-types of
breast cancer, whereas expression of
GATA–3 is low or undetectable in basal
subtypes of breast cancer which often
have a poor prognosis. Low or limited
GATA–3 expression is correlated with
larger tumors, increased likelihood of
tumor-positive lymph nodes, and
predicts an overall poorer clinical
outcome compared to patients with
higher mammary GATA–3 expression.
Researchers believe that a better
understanding of GATA–3 function and
its dysregulation during the onset and
progression of breast cancer will lead to
new strategies in diagnosing and
treating the disease.
Applications:
• Research tool to help identify
factors that modify GATA–3 expression
that may serve as potential therapeutic
targets for developing drugs to treat
breast cancer or hematologic
malignancies.
• Research tool that could be utilized
as an important component of a breast
cancer diagnostic kit or platform to
better understand the most effective
treatment options for individual breast
cancer patients.
• Molecular tool to better understand
the mechanisms that contribute to
hematopoietic and mammary cell/gland
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emcdonald on DSK2BSOYB1PROD with NOTICES
81630
Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices
development and differentiation in
order to identify the critical stages
where dysfunction can lead to the onset
of breast cancer.
• Molecular biology laboratory tool
for sorting breast cancer positive and
negative cells so that further
comparative experiments can be
performed to understand the cellular
properties of the two sets of cells.
Advantages:
• Useful for in vitro and in vivo
assays: Using the GFP or luciferase
expression of these reporter plasmids,
researchers can identify cells expressing
various levels of GATA–3 and isolate
these different subsets in vitro. These
reporter constructs can also be
transfected into cells to measure
GATA–3 expression levels in vivo in
real time from hematopoietic and breast
cancer models.
• Possible identification of new
targets for breast cancer therapy: The
reporter plasmids could be utilized to
identify factors that serve to activate
GATA–3 in normal mammary cells or
inhibit GATA–3 expression in breast
cancer cells. Such factors could serve as
targets for novel breast cancer therapies.
Inventors: Hosein Kouros-Mehr
(formerly NCI) and Jeffrey E. Green
(NCI)
Selected Publications:
1. H. Kouros-Mehr, et al. GATA–3 and
the regulation of the mammary luminal
cell fate. Curr Opin Cell Biol. 2008
Apr;20(2):164–170. [PubMed: 18358709]
2. H. Kouros-Mehr, et al. GATA–3
links tumor differentiation and
dissemination in the luminal breast
cancer model. Cancer Cell 2008
Feb;13(2):141–152. [PubMed: 18242514]
3. H. Kouros-Mehr, et al. GATA–3
maintains the differentiation of the
luminal cell fate in the mammary gland.
Cell 2006 Dec 1;127(5):1041–1055.
[PubMed: 17129787]
Patent Status: HHS Reference No. E–
128–2009/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing under a Biological Materials
License Agreement.
Licensing Contact: Samuel E. Bish,
Ph.D.; 301–435–5282;
bishse@mail.nih.gov.
Dated: December 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2010–32671 Filed 12–27–10; 8:45 am]
BILLING CODE 4140–01–P
VerDate Mar<15>2010
22:37 Dec 27, 2010
Jkt 223001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Biomedical
Imaging and Bioengineering; Notice of
Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the following meeting.
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
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 Institute of
Biomedical Imaging and Bioengineering
Special Emphasis Panel.
Date: March 16–18, 2011.
Time: 6 p.m. to 3 p.m.
Agenda: To review and evaluate grant
applications.
Place: Sheraton Fisherman’s Wharf Hotel,
2500 Mason Street, San Francisco, CA 94133.
Contact Person: Ruth Grossman, DDS,
Scientific Review Officer, National Institute
of Biomedical Imaging and Bioengineering,
National Institutes of Health, 6707
Democracy Boulevard, Room 960, Bethesda,
MD 20892, 301–496–8775,
grossmanrs@mail.nih.gov.
Dated: December 16, 2010.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 2010–32645 Filed 12–27–10; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Center for Scientific Review; Notice of
Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the following meeting.
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
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
PO 00000
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Fmt 4703
Sfmt 9990
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: Center for Scientific
Review Special Emphasis Panel; Member
Conflict: Cardiac Development.
Date: January 4, 2011.
Time: 3 p.m. to 4 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health, 6701
Rockledge Drive, Bethesda, MD 20892.
(Telephone Conference Call).
Contact Person: Joseph Thomas Peterson,
PhD, Scientific Review Officer, Center for
Scientific Review, National Institutes of
Health, 6701 Rockledge Drive, Room 4118,
MSC 7814, Bethesda, MD 20892. 301–443–
8130.
This notice is being published less than 15
days prior to the meeting due to the timing
limitations imposed by the review and
funding cycle.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.306, Comparative Medicine;
93.333, Clinical Research, 93.306, 93.333,
93.337, 93.393–93.396, 93.837–93.844,
93.846–93.878, 93.892, 93.893, National
Institutes of Health, HHS)
Dated: December 21, 2010.
Jennifer S. Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 2010–32639 Filed 12–27–10; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Center for Scientific Review; Amended
Notice of Meeting
Notice is hereby given of a change in
the meeting of the Center for Scientific
Review Special Emphasis Panel, January
6, 2011, 1 p.m. to January 6, 2011, 3:30
p.m., National Institutes of Health, 6701
Rockledge Drive, Bethesda, MD 20892
which was published in the Federal
Register on December 16, 2010, 75 FR
78719–78720.
The meeting has been changed to an
Internet Assisted Meeting (IAM). The
meeting will be two days January 6,
2011, 9 a.m. to January 7, 2011, 5 p.m.
The meeting is closed to the public.
Dated: December 21, 2010.
Jennifer S. Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 2010–32638 Filed 12–27–10; 8:45 am]
BILLING CODE 4140–01–P
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]]>Agencies
[Federal Register Volume 75, Number 248 (Tuesday, December 28, 2010)]
[Notices]
[Pages 81628-81630]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-32671]
-----------------------------------------------------------------------
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.
A New Class of Antibiotics: Natural Inhibitors of Bacterial
Cytoskeletal Protein FtsZ to Fight Drug-susceptible and Multi-drug
Resistant Bacteria
Description of Technology: The risk of infectious diseases epidemic
has been alarming in recent decades. This is not only because of the
increase incident of so-called ``super bugs,'' but also because of the
scarce number of potential antibiotics in the pipeline. Currently, the
need for new antibiotics is greater than ever! The present invention by
the National Institute of Diabetes and Digestive and Kidney Disease
(NIDDK), part of the National Institute of Health (NIH), address this
urgent need. The invention is a new class of chrysophaentin antibiotics
that inhibit the growth of broad-spectrum, drug-susceptible, and drug-
resistant bacteria.
Derived from the yellow algae Chrysophaeum taylori, the inventor
has extracted 8 small molecules of natural products and tested for
antimicrobial activity against drug resistant bacteria, methicillin-
resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
Enterococcus faecalis (VRE), as well as other drug susceptible strains.
Structurally, the molecules represent a new class of antibiotic that
also likely work through a distinct mechanism of action from that of
current antibiotics, which is key for the further development of
antibiotics that inhibit drug-resistant strains.
The bacterial cytoskeletal protein FtsZ is a GTPase and has
structural homology to the eukaryotic cytoskeletal protein tubulin, but
lacks significant sequence similarity. FtsZ is essential for bacterial
cell division. It is responsible for Z-ring assembly in bacteria, which
leads to bacterial cell division. Experiments show that the disclosed
compounds are competitive inhibitors of GTP binding to FtsZ, and must
bind in the GTP-binding site of FtsZ. Inhibition of FtsZ stops
bacterial cell division and is a validated target for new
antimicrobials. FtsZ is highly conserved among all bacteria, making it
a very attractive antimicrobial target.
Applications:
Therapeutic potential for curing bacterial infections in
vivo, including for clinical and veterinary applications.
Antiseptics in hospital settings.
Since FtsZ is structurally similar, but does not share
sequence homology to eukaryotic cytoskeletal protein tubulin, these
compounds may have antitumor properties against some cancer types or
cell lines.
Advantages:
[[Page 81629]]
Structurally distinct antimicrobial compounds.
Attack newly validated antibacterial targeted protein
FtsZ.
These compounds have a unique mechanism of action which
inhibit FtsZ by inhibiting FtsZ GTPase activity.
Inhibit drug-susceptible and drug-resistant bacteria.
Development Status:
Initial isolation and chemical structural characterization
using NMR spectroscopy have been conducted.
Antimicrobial testing against MRSA, Enterrococcus faecium,
and VRE were conducted in vitro using a modified disk diffusion assay
and microbroth liquid dilution assays.
MIC50 values were determined using a microbroth
dilution assay.
Mode of action was elucidated and Saturation Transfer
Difference (STD) NMR was conducted to map the binding epitope of one of
these compounds in complex with recombinant FtsZ.
Other experiments on different areas to further
characterize these compounds and their mode of action are currently
ongoing.
Market: The market potential for the disclosed compounds is huge
due to the very limited number of new antibiotics developed in recent
decades and the increased epidemic of infectious diseases. In fact,
infectious diseases are the leading cause of death worldwide. In the
United States alone, more people die from MRSA than from HIV (Journal
of the American Medical Association, 2007) and more than 90,000 people
die each year from hospital acquired bacterial infections (Centers for
Disease Control).
According to the recent report, ``Antibiotics Resistance and
Antibiotic Technologies: Global Markets'' published in November 2009,
there has been a revival in the antibiotics sector over the past few
years. Although some companies are developing analogues of existing
antibiotic classes and putting them into clinical trials, other start-
up biotechnology companies have come up with molecules that adopt new
approaches in tackling antimicrobial infections. The antibacterials
market can be split into two major groups: The community market and the
hospital market. The smaller hospital market is expanding more rapidly,
driven by rising resistant rates, a more severely ill patient
population and newer, premium-priced injectable antibiotics.
Interestingly, several big pharmaceutical companies have recently made
strategic decisions to expand their presence in this sector by either
acquiring other companies or in-licensing new compounds.
While the number of such new molecules in the approval stages is
still low, R&D pipelines are promising, and several novel classes of
antibiotics are in their early stages of development. This
antibacterial R&D bailout that started about 5 years ago due to tougher
regulatory conditions, restrictions on the use of antibiotics and
emergence of resistance to newer antibiotics within 3 years has helped
create a global antimicrobial therapeutic market of $24 billion in 2008
with 14 products recording sales of more than $1 billion.
Inventors: Carole A. Bewley et al. (NIDDK).
Related Publications:
1. DJ Haydon et al. An inhibitor of FtsZ with potent and selective
anti-staphylococcal activity. Science. 2008 Sept 19; 321(5896):1673-
1675. [PubMed: 18801997].
2. NR Stokes et al. Novel inhibitors of bacterial cytokinesis
identified by a cell-based antibiotic screening assay. J Biol Chem.
2005 Dec 2; 280(48):39709-39715. [PubMed: 16174771].
3. J Wang et al. Discovery of small molecule that inhibits cell
division by blocking FtsZ, a novel therapeutic target of antibiotics. J
Biol Chem. 2003 Nov 7; 278(45):44424-44428. [PubMed: 12952956].
4. P Domadia et al. Berberine targets assembly of Escherichia coli
cell division protein FtsZ. Biochemistry. 2008 Mar 11; 47(10):3225-
3234. [PubMed: 18275156].
5. P Domadia et al. Inhibition of bacterial cell division protein
FtsZ by cinamaldehyde. Biochem Pharmacol. 2007 Sep 15:74(6):831-840.
[PubMed: 17662960].
6. S Urgaonkar et al. Synthesis of antimicrobial natural products
targeting FtsZ: (+/-)-dichamanetin and (+/-)-2'''-hydroxy-5''-
benzylisouvarinol-B. Org Lett. 2005 Dec 8;7(25):5609-5612. [PubMed:
16321003].
Patent Status: U.S. Provisional Application No. 61/308,911 filed 27
Feb 2010 (HHS Reference No. E-116-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contacts:
Uri Reichman, Ph.D., MBA; 301-435-4616; UR7a@nih.gov.
John Stansberry, Ph.D.; 301-435-5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic
Chemistry is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize the chrysophaentin antibiotics. Please contact Cindy K.
Fuchs at 301-451-3636 or cfuchs@mail.nih.gov for more information.
GATA-3 Reporter Plasmids for Revealing Underlying Mechanisms in Breast
Cancer
Description of Technology: Scientists at the National Institutes of
Health (NIH) have developed GATA-3 gene reporter plasmids that express
a green fluorescent protein (GFP) or luciferase reporter protein under
the control of a GATA-3 promoter. Cells expressing this plasmid will
glow fluorescent green or emit light energy, respectively, if GATA-3
gene expression is activated in the cells. The reporter construct
allows cells where GATA-3 gene expression is activated to be isolated
and collected for further analysis or be monitored in the host
environment.
GATA-3 is a transcription factor that is highly expressed in
several types of cells and is a critical transcription factor for the
development of particular lineages of hematopoietic cells and normal
mammary luminal epithelium. GATA-3 plays a regulatory role in
determining the fate of cells in the hematopoietic systems and the
mammary gland. Disruption of GATA-3 expression leads to defects in the
development of sub-types of lymphoid cells and luminal mammary
epithelial cells. GATA-3 expression is highly associated with luminal
sub-types of breast cancer, whereas expression of GATA-3 is low or
undetectable in basal subtypes of breast cancer which often have a poor
prognosis. Low or limited GATA-3 expression is correlated with larger
tumors, increased likelihood of tumor-positive lymph nodes, and
predicts an overall poorer clinical outcome compared to patients with
higher mammary GATA-3 expression. Researchers believe that a better
understanding of GATA-3 function and its dysregulation during the onset
and progression of breast cancer will lead to new strategies in
diagnosing and treating the disease.
Applications:
Research tool to help identify factors that modify GATA-3
expression that may serve as potential therapeutic targets for
developing drugs to treat breast cancer or hematologic malignancies.
Research tool that could be utilized as an important
component of a breast cancer diagnostic kit or platform to better
understand the most effective treatment options for individual breast
cancer patients.
Molecular tool to better understand the mechanisms that
contribute to hematopoietic and mammary cell/gland
[[Page 81630]]
development and differentiation in order to identify the critical
stages where dysfunction can lead to the onset of breast cancer.
Molecular biology laboratory tool for sorting breast
cancer positive and negative cells so that further comparative
experiments can be performed to understand the cellular properties of
the two sets of cells.
Advantages:
Useful for in vitro and in vivo assays: Using the GFP or
luciferase expression of these reporter plasmids, researchers can
identify cells expressing various levels of GATA-3 and isolate these
different subsets in vitro. These reporter constructs can also be
transfected into cells to measure GATA-3 expression levels in vivo in
real time from hematopoietic and breast cancer models.
Possible identification of new targets for breast cancer
therapy: The reporter plasmids could be utilized to identify factors
that serve to activate GATA-3 in normal mammary cells or inhibit GATA-3
expression in breast cancer cells. Such factors could serve as targets
for novel breast cancer therapies.
Inventors: Hosein Kouros-Mehr (formerly NCI) and Jeffrey E. Green
(NCI)
Selected Publications:
1. H. Kouros-Mehr, et al. GATA-3 and the regulation of the mammary
luminal cell fate. Curr Opin Cell Biol. 2008 Apr;20(2):164-170.
[PubMed: 18358709]
2. H. Kouros-Mehr, et al. GATA-3 links tumor differentiation and
dissemination in the luminal breast cancer model. Cancer Cell 2008
Feb;13(2):141-152. [PubMed: 18242514]
3. H. Kouros-Mehr, et al. GATA-3 maintains the differentiation of
the luminal cell fate in the mammary gland. Cell 2006 Dec
1;127(5):1041-1055. [PubMed: 17129787]
Patent Status: HHS Reference No. E-128-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
bishse@mail.nih.gov.
Dated: December 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-32671 Filed 12-27-10; 8:45 am]
BILLING CODE 4140-01-P
