Government-Owned Inventions; Availability for Licensing, 36423-36424 [2010-15476]
Download as PDF
Federal Register / Vol. 75, No. 122 / Friday, June 25, 2010 / Notices
Based on FDA’s knowledge of
supplements and annual reports to
NDAs and ANDAs, as well as the
agency’s familiarity with the time
needed to prepare supplements and
annual reports, our estimates for this
information collection are as follows:
The total number of supplements
submitted per year is estimated to be
reduced based on the recommendations
in the draft guidance. Based on the
number of CMC manufacturing
supplements received for NDAs and
ANDAs during 2008, FDA estimates that
it will receive annually approximately
800 responses under §§ 314.70 and
314.71 for NDAs and approximately
2,075 responses under § 314.97 for
ANDAs. The number of annual
frequencies per response will decrease
36423
accordingly. FDA estimates that
approximately the same number of
respondents will submit responses
under §§ 314.70, 314.71, and 314.97 and
each response will take approximately
the same amount of time to prepare as
in the information collection currently
approved under OMB Control Number
0910–0001.
TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1
21 CFR Section
No. of Respondents
Annual Frequency
per Response
Total Annual
Responses
Hours Per
Response
Total Hours
314.70 and 314.71
281 (same as
currently approved)
2.85
800
150 (same as
currently approved)
120,000
314.97
215 (same as
currently approved)
9.65
2,075
80 (same as
currently approved)
166,000
Total Hours
1 There
286,000
are no capital costs or operating and maintenance costs associated with this collection of information.
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.
Therefore, the estimated annual
reporting burden for this information
collection is 286,000 hours.
IV. Electronic Access
Persons with access to the Internet
may obtain the document at either
https://www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm or https://
www.regulations.gov.
Dated: June 21, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–15415 Filed 6–24–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
mstockstill on DSKH9S0YB1PROD with NOTICES
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
VerDate Mar<15>2010
16:23 Jun 24, 2010
Jkt 220001
A New Class of Antibiotics: Natural
Inhibitors of Bacterial Cytoskeletal
Protein FtsZ To Fight Drug-Susceptible
and Multi-Drug Resistant Bacteria
Description of Invention: 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
PO 00000
Frm 00078
Fmt 4703
Sfmt 4703
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 sittings.
• Since FtsZ is structurally similar,
but do not share sequence homology to
eukaryotic cytoskeletal protein tubulin,
these compounds may have antitumor
properties against some cancer types or
cell lines.
Advantages:
• 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:
E:\FR\FM\25JNN1.SGM
25JNN1
mstockstill on DSKH9S0YB1PROD with NOTICES
36424
Federal Register / Vol. 75, No. 122 / Friday, June 25, 2010 / Notices
• 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
VerDate Mar<15>2010
16:23 Jun 24, 2010
Jkt 220001
years has helped create 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,
PhD, MBA; 301–435–4616;
UR7a@nih.gov; or John Stansberry, PhD;
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.
hepatitis C virus (HCV). Co-infection of
HCV and HIV is associated with
increased morbidity and mortality
relative to mono-infection with either
virus. Compared to HCV mono-infected
individuals, HCV/HIV co-infected
individuals experience rapid
progression of liver disease, have higher
HCV RNA viral levels, decreased cure
rates, and increased toxic reactions to
anti-HCV therapy. Understanding how
these two viruses interact has been
difficult because a cell culture system
that supports HCV growth in the
laboratory was not available. Recently, a
continuous culture system to propagate
HCV was discovered, however these
cells do not express receptors that allow
for infection by HIV. The inventors were
able to genetically transform these cells
(liver cancer) to express HIV receptors
and successfully infect them with both
viruses. This modified cell culture
system will be useful for studying the
interactions between HCV and HIV
within the same cell and will serve as
a model to understand the pathogenesis
of HCV/HIV co-infection.
Applications:
• Use for clinical research to study
the pathogenesis of HCV/HIV coinfection.
• Use in development of drugs to
control both HIV and HCV infections.
Development Status:
• The cell line has been fully
generated.
• Materials will be readily available if
so requested.
Inventors: Shyam Kottilil, Xiaozhen
Zhang, and Marybeth E. Daucher
(NIAID).
Relevant Publication: Matthews GV
and Dore GJ. HIV and hepatitis C
coinfection. J Gastroenterol Hepatol.
2008 Jul;23(7 Pt 1):1000–1008.
[PubMed: 18707597].
Patent Status: HHS Reference No. E–
107–2009/0—Research Material. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing.
Licensing Contacts: Uri Reichman,
PhD, MBA; 301–435–4616;
UR7a@nih.gov; or John Stansberry, PhD;
301–435–5236; js852e@nih.gov.
Hepatoma Cell Line That Can Be
Infected With Both Hepatitis C and
Human Immunodeficiency (HIV–1)
Viruses
Description of Invention: It is
estimated that 250,000 HIV patients in
the U.S. are chronically infected with
Dated: June 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
PO 00000
Frm 00079
Fmt 4703
Sfmt 9990
[FR Doc. 2010–15476 Filed 6–24–10; 8:45 am]
BILLING CODE 4140–01–P
E:\FR\FM\25JNN1.SGM
25JNN1
Agencies
[Federal Register Volume 75, Number 122 (Friday, June 25, 2010)]
[Notices]
[Pages 36423-36424]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-15476]
-----------------------------------------------------------------------
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 Invention: 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 sittings.
Since FtsZ is structurally similar, but do not share
sequence homology to eukaryotic cytoskeletal protein tubulin, these
compounds may have antitumor properties against some cancer types or
cell lines.
Advantages:
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:
[[Page 36424]]
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 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, PhD, MBA; 301-435-4616;
UR7a@nih.gov; or John Stansberry, PhD; 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.
Hepatoma Cell Line That Can Be Infected With Both Hepatitis C and Human
Immunodeficiency (HIV-1) Viruses
Description of Invention: It is estimated that 250,000 HIV patients
in the U.S. are chronically infected with hepatitis C virus (HCV). Co-
infection of HCV and HIV is associated with increased morbidity and
mortality relative to mono-infection with either virus. Compared to HCV
mono-infected individuals, HCV/HIV co-infected individuals experience
rapid progression of liver disease, have higher HCV RNA viral levels,
decreased cure rates, and increased toxic reactions to anti-HCV
therapy. Understanding how these two viruses interact has been
difficult because a cell culture system that supports HCV growth in the
laboratory was not available. Recently, a continuous culture system to
propagate HCV was discovered, however these cells do not express
receptors that allow for infection by HIV. The inventors were able to
genetically transform these cells (liver cancer) to express HIV
receptors and successfully infect them with both viruses. This modified
cell culture system will be useful for studying the interactions
between HCV and HIV within the same cell and will serve as a model to
understand the pathogenesis of HCV/HIV co-infection.
Applications:
Use for clinical research to study the pathogenesis of
HCV/HIV co-infection.
Use in development of drugs to control both HIV and HCV
infections.
Development Status:
The cell line has been fully generated.
Materials will be readily available if so requested.
Inventors: Shyam Kottilil, Xiaozhen Zhang, and Marybeth E. Daucher
(NIAID).
Relevant Publication: Matthews GV and Dore GJ. HIV and hepatitis C
coinfection. J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 1):1000-1008.
[PubMed: 18707597].
Patent Status: HHS Reference No. E-107-2009/0--Research Material.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contacts: Uri Reichman, PhD, MBA; 301-435-4616;
UR7a@nih.gov; or John Stansberry, PhD; 301-435-5236; js852e@nih.gov.
Dated: June 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-15476 Filed 6-24-10; 8:45 am]
BILLING CODE 4140-01-P