Public Teleconference Regarding Licensing and Collaborative Research Opportunities for: A Double-Barreled Attack: Azatoxins, A New Hope for Treating Cancer, 18585-18586 [E9-9344]
Download as PDF
<![CDATA[
sroberts on PROD1PC70 with NOTICES
Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices
4 p.m.–5 p.m., May 13, 2009.
Place: Holiday Inn Amarillo Hotel, 1911 I–
40 East, Amarillo, TX 79102; Phone: (806)
372–8741; Fax: (806) 372–7045. Audio
Conference Call via FTS Conferencing. The
USA toll-free dial-in number is 1–866–659–
0537 with a pass code of 9933701.
Status: Open to the public, limited only by
the space available. The meeting space
accommodates approximately 100 people.
Background: The Advisory Board was
established under the Energy Employees
Occupational Illness Compensation Program
(EEOICP) Act of 2000 to advise the President
on a variety of policy and technical functions
required to implement and effectively
manage the new compensation program. Key
functions of the Advisory Board include
providing advice on the development of
probability of causation guidelines which
have been promulgated by the Department of
Health and Human Services (HHS) as a final
rule; advice on methods of dose
reconstruction which have also been
promulgated by HHS as a final rule; advice
on the scientific validity and quality of dose
estimation and reconstruction efforts being
performed for purposes of the compensation
program, and advice on petitions to add
classes of workers to the Special Exposure
Cohort (SEC).
In December 2000, the President delegated
responsibility for funding, staffing, and
operating the Advisory Board to HHS, which
subsequently delegated this authority to the
CDC. NIOSH implements this responsibility
for CDC. The charter was issued on August
3, 2001, renewed at appropriate intervals,
and will expire on August 3, 2009.
Purpose: This Advisory Board is charged
with (a) providing advice to the Secretary,
HHS, on the development of guidelines
under Executive Order 13179; (b) providing
advice to the Secretary, HHS, on the
scientific validity and quality of dose
reconstruction efforts performed for this
program; and (c) upon request by the
Secretary, HHS, advise the Secretary on
whether there is a class of employees at any
Department of Energy facility who were
exposed to radiation but for whom it is not
feasible to estimate their radiation dose, and
on whether there is reasonable likelihood
that such radiation doses may have
endangered the health of members of this
class.
Matters To Be Discussed: The agenda for
the Advisory Board meeting includes: NIOSH
Program Status Update; Department of Labor
(DOL) Update; Department of Energy (DOE)
Update; Board Security Plan; Special
Exposure Cohort (SEC) Petitions for: Linde
Ceramics Plant (Residual Period); Standard
Oil Development Company of New Jersey;
Blockson Chemical Company (radon-related
dose reconstruction); and Dow Chemical
Company (Madison, Illinois); Special
Exposure Cohort (SEC) Petition Status
Updates; Work Group reports; Reports of the
Subcommittees on Dose Reconstruction
Reviews and Procedures Reviews; and Board
Future Plans and Meetings.
The agenda is subject to change as
priorities dictate.
In the event an individual cannot attend,
written comments may be submitted
VerDate Nov<24>2008
16:59 Apr 22, 2009
Jkt 217001
according to the policy provided below. Any
written comments received will be provided
at the meeting and should be submitted to
the contact person below well in advance of
the meeting.
Policy on Redaction of Board Meeting
Transcripts (Public Comment), (1) if a person
making a comment gives his or her name, no
attempt will be made to redact that name. (2)
NIOSH will take reasonable steps to ensure
that individuals making public comment are
aware of the fact that their comments
(including their name, if provided) will
appear in a transcript of the meeting posted
on a public Web site. Such reasonable steps
include: (a) A statement read at the start of
each public comment period stating that
transcripts will be posted and names of
speakers will not be redacted; (b) A printed
copy of the statement mentioned in (a) above
will be displayed on the table where
individuals sign up to make public comment;
(c) A statement such as outlined in (a) above
will also appear with the agenda for a Board
Meeting when it is posted on the NIOSH Web
site; (d) A statement such as in (a) above will
appear in the Federal Register Notice that
announces Board and Subcommittee
meetings. (3) If an individual in making a
statement reveals personal information (e.g.,
medical information) about themselves that
information will not usually be redacted. The
NIOSH FOIA coordinator will, however,
review such revelations in accordance with
the Freedom of Information Act and the
Federal Advisory Committee Act and if
deemed appropriate, will redact such
information. (4) All disclosures of
information concerning third parties will be
redacted. (5) If it comes to the attention of the
Designated Federal Officer (DFO) that an
individual wishes to share information with
the Board but objects to doing so in a public
forum, the DFO will work with that
individual, in accordance with the Federal
Advisory Committee Act, to find a way that
the Board can hear such comments.
Contact Person for More Information:
Theodore Katz, M.P.A., Executive Secretary,
NIOSH, CDC, 1600 Clifton Road, MS E–20,
Atlanta, GA 30333, Telephone (513)533–
6800, Toll Free 1(800) CDC–INFO, e-mail
ocas@cdc.gov.
The Director, Management Analysis and
Services Office, has been delegated the
authority to sign Federal Register notices
pertaining to announcements of meetings and
other committee management activities, for
both CDC and the Agency for Toxic
Substances and Disease Registry.
Dated: April 16, 2009.
Elaine L. Baker,
Director, Management Analysis and Services
Office, Centers for Disease Control and
Prevention.
[FR Doc. E9–9332 Filed 4–22–09; 8:45 am]
BILLING CODE 4163–18–P
PO 00000
Frm 00043
Fmt 4703
Sfmt 4703
18585
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding
Licensing and Collaborative Research
Opportunities for: A Double-Barreled
Attack: Azatoxins, A New Hope for
Treating Cancer
AGENCY: National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
Technology Summary
This technology describes a novel
class of Topoisomerase II (top2)
inhibitors that are useful in treating
cancer. Drugs that inhibit the top2
enzyme are among the most active
anticancer agents discovered. However,
many of the currently available
inhibitors produce toxic side effects,
have poor pharmacokinetics, or
eventually become ineffective because
malignant cells readily acquire
resistance. Therefore, there is a need for
developing new top2 inhibitor drugs
that will overcome these limitations.
Azatoxin and its derivatives, which
are derived by combining two parent
compounds etoposide and ellipticine,
are the first compounds rationally
designed as inhibitors of top2.
Azatoxins are also potent inhibitors of
tubulin polymerization. These two anticancer activities can be successfully
separated by synthesizing azatoxin
derivatives to yield compounds which
can be pharmacologically advantageous
against tumor proliferation. The
azatoxin platform represents an
unexploited class of top2 inhibitors that
could be developed into especially
potent chemotherapeutics.
Competitive Advantage of Our
Technology
Currently, several top2 inhibitors are
approved for clinical use; however, they
produce serious side effects. Etoposide,
for example, causes problems with
myelosuppression, drug resistance, and
has poor bioavailability. Moreover, it
appears to have carcinogenic properties
as it has been linked to the development
of acute myelogenous leukemia—an
effect also observed with mitoxantrone.
Anthracyclines, like doxorubicin, have
the same limitations as etoposide, but
they also possess cardiotoxic effects.
Azatoxins have the potential to be
developed into chemotherapeutics that
outperform these currently used top2
inhibitors.
Azatoxins have been substantially
characterized through years of preclinical research demonstrating that
E:\FR\FM\23APN1.SGM
23APN1
18586
Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices
sroberts on PROD1PC70 with NOTICES
they possess properties from both of its
parental compounds, etoposide and
ellipticine. They act by stabilizing the
top2–DNA cleavage complex, like
etoposide does, instead of inhibiting
top2 catalytic activity, the mechanism
by which ellipticine acts. With regard to
DNA cleavage activity, azatoxins show
similar activity to etoposide. In addition
to acting as a top2 inhibitor, azatoxin is
also a potent inhibitor of tubulin
polymerization.
The anti-cancer activity of azatoxins
has been validated by cell line
screening. The Developmental
Therapeutics Program (DTP) of the
National Cancer Institute (NCI) has
tested azatoxins in its tumor cell panel
and established their effectiveness
against disseminated leukemia and
localized tumors, such as non-small cell
lung and colon cancer. These results are
very encouraging showing that certain
azatoxin derivatives are 100 times more
active than etoposide, which is the
common top2 inhibitor used in
chemotherapy. Azatoxins are a novel
class of potent top2 and/or tubulin
inhibitors that could outperform current
chemotherapeutic agents.
Technology Description
Topoisomerase enzymes are critical
for normal cell division because they
prevent tangles and knots from forming
during DNA replication by cleaving and
religating DNA. Several compounds
have been discovered that block
topoisomerases and stop its ability to
religate DNA resulting in an increased
number of double strand DNA breaks
that kill the cell. These inhibitors are
especially effective against rapidly
dividing malignant cells that express
high levels of top2, which represents a
main reason these top2 enzymes have
become an important therapeutic target.
The problem is that currently used
drugs are limited by their toxicity,
insolubility, and their susceptibility to
induce drug resistance.
In an effort to produce top2 inhibitors
with increased therapeutic efficiency,
well established top2 inhibitors were
compared by molecular modeling to
produce a composite top2 inhibitor
pharmacophore of the diverse
inhibitors. Based on this model,
azatoxin was designed as an analogue
hybrid of etoposide and ellipticine.
Subsequently, several modifications of
azatoxin have been synthesized to
generate derivatives, such as
anilinoazatoxins, which have improved
pharmacological profiles.
Market
Despite further discoveries leading to
a greater understanding and treating of
VerDate Nov<24>2008
16:59 Apr 22, 2009
Jkt 217001
cancer, it continues to be a burden to
the public health. After heart disease,
cancer is the most common cause of
death in the United States. In 2008, it
was estimated that about 565,650
Americans were expected to die of
cancer. Although, the incidence of
cancer has been dropping over the
years, it was estimated that over 1.4
million Americans would be diagnosed
with cancer in 2008.
Cancer is not only a health burden but
also a financial burden to the country.
The NIH estimated the overall cost of
cancer in 2007 to be $219.2 billion
dollars with $89 billion attributable to
direct medical costs. It is expected that
cancer will continue to be a public
health problem for the foreseeable
future which prompts the need for the
development of new therapeutics.
Chemotherapy is still the standard
approach for treating cancers even
though there were high expectations
that targeted therapeutics would become
the preferred drugs in cancer treatment.
Current topoisomerase inhibitors have
demonstrated to be effective
chemotherapy drugs and they continue
being developed for use in combination
therapy with targeted therapeutics.
However, top2 inhibitors need to be
improved in order to overcome their
limitations. A next-generation top2
inhibitor like azatoxins has potential in
meeting this need.
Patent Estate
The National Institutes of Health
holds a substantial portfolio of patents
in U.S., Europe, Canada, and Australia
which claim compositions of azatoxin
and its derivatives, pharmaceutical
formulations, and methods of use for
chemotherapy.
The portfolio includes the following
issued patents:
I. United States Patent No. 5,622,960
entitled ‘‘Topoisomerase II inhibitors
and therapeutic uses therefor’’ issued
April 22, 1997 (HHS Ref. No. E–119–
1992/1–US–01).
II. United States Patent No. 5,747,520
entitled ‘‘Topoisomerase II inhibitors
and therapeutic uses therefor’’ issued
May 5, 1998 (HHS Ref. No. E–119–1992/
1–US–17).
III. European Patent No. 0665846
entitled ‘‘Topoisomerase II inhibitors
and therapeutic uses therefor’’ issued
July 29, 1998 (HHS Ref. No. E–119–
1992/1–EP–10) validated in Austria,
Belgium, Denmark, France, Germany,
Great Britain, Ireland, Italy,
Luxembourg, Switzerland, and The
Netherlands.
IV. Canadian Patent No. 2147608
entitled ‘‘Topoisomerase II inhibitors
and therapeutic uses therefor’’ issued
PO 00000
Frm 00044
Fmt 4703
Sfmt 4703
December 12, 2006 (HHS Ref. No. E–
119–1992/1–CA–06).
V. Australian Patent No. 676511
entitled ‘‘Topoisomerase II inhibitors
and therapeutic uses therefor’’ issued
June 13, 1997 (HHS Ref. No. E–119–
1992/1–AU–04).
Next Step: Teleconference
There will be a teleconference where
the principal investigator, Dr. Yves
Pommier, will explain this technology.
Licensing and collaborative research
opportunities will also be discussed. If
you are interested in participating in
this teleconference please call or e-mail
Samuel Bish; (301) 435–5282;
bishse@mail.nih.gov. The NIH Office of
Technology Transfer (OTT) will then email you the date, time, and number for
the teleconference.
Dated: April 16, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–9344 Filed 4–22–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HOMELAND
SECURITY
U.S. Customs and Border Protection
[Docket No. USCBP–2006–0037]
Expansion of Global Entry Pilot
Program
AGENCY: U.S. Customs and Border
Protection; Department of Homeland
Security.
ACTION: General notice.
SUMMARY: U.S. Customs and Border
Protection (CBP) is currently conducting
an international trusted traveler pilot
program, referred to as Global Entry, at
seven U.S. airports. This document
announces that pursuant to an
arrangement between the United States
and the Netherlands, CBP is expanding
eligibility for participation in the Global
Entry pilot to include citizens of the
Netherlands who participate in Privium,
an expedited travel program in the
Netherlands, and who otherwise satisfy
the requirements for participation in
Global Entry. Currently, eligibility is
limited to U.S. citizens, U.S. nationals,
and U.S. lawful permanent residents
(LPRs). Pursuant to this same
arrangement, U.S. citizens who
participate in the Global Entry pilot will
have the option to also apply for
participation in Privium.
DATES: Effective Dates: Applications for
the Global Entry pilot are currently
E:\FR\FM\23APN1.SGM
23APN1
]]>Agencies
[Federal Register Volume 74, Number 77 (Thursday, April 23, 2009)]
[Notices]
[Pages 18585-18586]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-9344]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding Licensing and Collaborative
Research Opportunities for: A Double-Barreled Attack: Azatoxins, A New
Hope for Treating Cancer
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
Technology Summary
This technology describes a novel class of Topoisomerase II (top2)
inhibitors that are useful in treating cancer. Drugs that inhibit the
top2 enzyme are among the most active anticancer agents discovered.
However, many of the currently available inhibitors produce toxic side
effects, have poor pharmacokinetics, or eventually become ineffective
because malignant cells readily acquire resistance. Therefore, there is
a need for developing new top2 inhibitor drugs that will overcome these
limitations.
Azatoxin and its derivatives, which are derived by combining two
parent compounds etoposide and ellipticine, are the first compounds
rationally designed as inhibitors of top2. Azatoxins are also potent
inhibitors of tubulin polymerization. These two anti-cancer activities
can be successfully separated by synthesizing azatoxin derivatives to
yield compounds which can be pharmacologically advantageous against
tumor proliferation. The azatoxin platform represents an unexploited
class of top2 inhibitors that could be developed into especially potent
chemotherapeutics.
Competitive Advantage of Our Technology
Currently, several top2 inhibitors are approved for clinical use;
however, they produce serious side effects. Etoposide, for example,
causes problems with myelosuppression, drug resistance, and has poor
bioavailability. Moreover, it appears to have carcinogenic properties
as it has been linked to the development of acute myelogenous
leukemia--an effect also observed with mitoxantrone. Anthracyclines,
like doxorubicin, have the same limitations as etoposide, but they also
possess cardiotoxic effects. Azatoxins have the potential to be
developed into chemotherapeutics that outperform these currently used
top2 inhibitors.
Azatoxins have been substantially characterized through years of
pre-clinical research demonstrating that
[[Page 18586]]
they possess properties from both of its parental compounds, etoposide
and ellipticine. They act by stabilizing the top2-DNA cleavage complex,
like etoposide does, instead of inhibiting top2 catalytic activity, the
mechanism by which ellipticine acts. With regard to DNA cleavage
activity, azatoxins show similar activity to etoposide. In addition to
acting as a top2 inhibitor, azatoxin is also a potent inhibitor of
tubulin polymerization.
The anti-cancer activity of azatoxins has been validated by cell
line screening. The Developmental Therapeutics Program (DTP) of the
National Cancer Institute (NCI) has tested azatoxins in its tumor cell
panel and established their effectiveness against disseminated leukemia
and localized tumors, such as non-small cell lung and colon cancer.
These results are very encouraging showing that certain azatoxin
derivatives are 100 times more active than etoposide, which is the
common top2 inhibitor used in chemotherapy. Azatoxins are a novel class
of potent top2 and/or tubulin inhibitors that could outperform current
chemotherapeutic agents.
Technology Description
Topoisomerase enzymes are critical for normal cell division because
they prevent tangles and knots from forming during DNA replication by
cleaving and religating DNA. Several compounds have been discovered
that block topoisomerases and stop its ability to religate DNA
resulting in an increased number of double strand DNA breaks that kill
the cell. These inhibitors are especially effective against rapidly
dividing malignant cells that express high levels of top2, which
represents a main reason these top2 enzymes have become an important
therapeutic target. The problem is that currently used drugs are
limited by their toxicity, insolubility, and their susceptibility to
induce drug resistance.
In an effort to produce top2 inhibitors with increased therapeutic
efficiency, well established top2 inhibitors were compared by molecular
modeling to produce a composite top2 inhibitor pharmacophore of the
diverse inhibitors. Based on this model, azatoxin was designed as an
analogue hybrid of etoposide and ellipticine. Subsequently, several
modifications of azatoxin have been synthesized to generate
derivatives, such as anilinoazatoxins, which have improved
pharmacological profiles.
Market
Despite further discoveries leading to a greater understanding and
treating of cancer, it continues to be a burden to the public health.
After heart disease, cancer is the most common cause of death in the
United States. In 2008, it was estimated that about 565,650 Americans
were expected to die of cancer. Although, the incidence of cancer has
been dropping over the years, it was estimated that over 1.4 million
Americans would be diagnosed with cancer in 2008.
Cancer is not only a health burden but also a financial burden to
the country. The NIH estimated the overall cost of cancer in 2007 to be
$219.2 billion dollars with $89 billion attributable to direct medical
costs. It is expected that cancer will continue to be a public health
problem for the foreseeable future which prompts the need for the
development of new therapeutics.
Chemotherapy is still the standard approach for treating cancers
even though there were high expectations that targeted therapeutics
would become the preferred drugs in cancer treatment. Current
topoisomerase inhibitors have demonstrated to be effective chemotherapy
drugs and they continue being developed for use in combination therapy
with targeted therapeutics. However, top2 inhibitors need to be
improved in order to overcome their limitations. A next-generation top2
inhibitor like azatoxins has potential in meeting this need.
Patent Estate
The National Institutes of Health holds a substantial portfolio of
patents in U.S., Europe, Canada, and Australia which claim compositions
of azatoxin and its derivatives, pharmaceutical formulations, and
methods of use for chemotherapy.
The portfolio includes the following issued patents:
I. United States Patent No. 5,622,960 entitled ``Topoisomerase II
inhibitors and therapeutic uses therefor'' issued April 22, 1997 (HHS
Ref. No. E-119-1992/1-US-01).
II. United States Patent No. 5,747,520 entitled ``Topoisomerase II
inhibitors and therapeutic uses therefor'' issued May 5, 1998 (HHS Ref.
No. E-119-1992/1-US-17).
III. European Patent No. 0665846 entitled ``Topoisomerase II
inhibitors and therapeutic uses therefor'' issued July 29, 1998 (HHS
Ref. No. E-119-1992/1-EP-10) validated in Austria, Belgium, Denmark,
France, Germany, Great Britain, Ireland, Italy, Luxembourg,
Switzerland, and The Netherlands.
IV. Canadian Patent No. 2147608 entitled ``Topoisomerase II
inhibitors and therapeutic uses therefor'' issued December 12, 2006
(HHS Ref. No. E-119-1992/1-CA-06).
V. Australian Patent No. 676511 entitled ``Topoisomerase II
inhibitors and therapeutic uses therefor'' issued June 13, 1997 (HHS
Ref. No. E-119-1992/1-AU-04).
Next Step: Teleconference
There will be a teleconference where the principal investigator,
Dr. Yves Pommier, will explain this technology. Licensing and
collaborative research opportunities will also be discussed. If you are
interested in participating in this teleconference please call or e-
mail Samuel Bish; (301) 435-5282; bishse@mail.nih.gov. The NIH Office
of Technology Transfer (OTT) will then e-mail you the date, time, and
number for the teleconference.
Dated: April 16, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-9344 Filed 4-22-09; 8:45 am]
BILLING CODE 4140-01-P
