Public Teleconference Regarding Licensing and Collaborative Research Opportunities for: PDE11A as a Novel Therapeutic Target for Inherited Form of Cushing Syndrome and Endocrine Tumors; Dr. Constantine A. Stratakis et al. (NICHD), 7895-7896 [E7-2884]
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Federal Register / Vol. 72, No. 34 / Wednesday, February 21, 2007 / Notices
satisfaction with those products through
customer satisfaction surveys. By
obtaining information from customers
on the extent to which materials satisfy
their needs, OCE and NCI will be able
to systematically establish and follow a
feedback loop that provides useful
information to revise and enhance
educational programs and products so
that they attain maximum relevance,
utility, appropriateness, and impact.
Data will be collected through various
means, including telephone, mail, inperson, and web-based surveys.
Frequency of Response: On occasion.
Affected Public: Individuals or
households, organizations involved in
providing health care services.
7895
Type of Respondents: Health care
consumers of NCI educational programs
or products, including cancer patients
and families, health care professionals,
cancer control planners, and
policymakers.
The estimated annual burden hours
are as follows:
Product
Average
sample size
Frequency of
response
Average
duration
(hours)
Estimated
total burden
requested
(hours)
40 different products ........................................................................................
450
1
0.1
1800
Request for Comments: Written
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public and affected agencies are invited
on one or more of the following points:
(1) Whether the proposed collection of
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(2) The accuracy of the agency’s
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Ways to minimize the burden of the
collection of information on those who
are to respond, including the use of
appropriate automated, electronic,
mechanical, or other technological
collection techniques or other forms of
information technology.
For Further Information Contact: To
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Goodman, Senior Analyst, Office of
Communications and Education, NCI,
NIH, 6116 Executive Blvd., Suite 400,
Rockville, MD 20852, call non-toll-free
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request to: goodman@mail.nih.gov.
Comments Due Date: Comments
regarding this information collection are
best assured of having their full effect if
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rmajette on PROD1PC67 with NOTICES
Dated: February 7, 2007.
Rachelle Ragland-Greene,
NCI Project Clearance Liaison, National
Institutes of Health.
[FR Doc. E7–2886 Filed 2–20–07; 8:45 am]
BILLING CODE 4140–01–P
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Jkt 211001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding
Licensing and Collaborative Research
Opportunities for: PDE11A as a Novel
Therapeutic Target for Inherited Form
of Cushing Syndrome and Endocrine
Tumors; Dr. Constantine A. Stratakis et
al. (NICHD)
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
Technology Summary
The technology identifies a new form
of Cushing Syndrome, ‘‘isolated
micronodular adrenocortical disease’’
(iMAD), classified as a rare disease, as
well as the role of PDE11A gene in this
disease. We have identified particular
sequence variants of the PDE11A gene
causing abnormal or altered function of
this gene; these variants are present in
higher proportion in patients with
iMAD, as well as in patients with other
adrenal tumors. Additionally, we
suggest that PDE11A can be a potential
novel drug target for the treatment of
bilateral adrenal hyperplasia, and
possibly other endocrine tumors.
Technology Description
Phosphodiesterases (PDEs) are a
family of cyclic AMP (cAMP) and/or
cyclic GMP (cGMP)-hydrolyzing
enzymes that cleave 3′, 5′-cyclic
nucleotide monophosphates to 5′nucleotide monophosphates. The PDE
superfamily is large and complex,
containing 11 highly related and
structurally related gene families and
over 60 distinct isoforms. PDE family
members hydrolyze exclusively cAMP
(PDE4, PDE7, and PDE8), exclusively
cGMP (PDE5, PDE6, and PDE9), or both
cAMP and cGMP (PDE1, PDE2, PDE3,
PDE10, and PDE11). Specifically,
PO 00000
Frm 00041
Fmt 4703
Sfmt 4703
PDE11A is a dual-specificity
phosphodiesterase and is expressed in
several endocrine tissues including the
adrenal cortex. Members of the PDE
family differ in tissue distribution,
inhibitor specificity, and in mode of
regulation. The side effects of the PDE
inhibitors are contributed by the crossreactivity of the inhibitors to other
isoforms of the PDE.
The invention is the discovery that
the PDE 11A gene has statistically
significant linkage to ‘‘isolated
micronodular adrenocortical disease’’
(iMAD), an inherited form of Cushing
Syndrome. Patients suffering from the
disease have high cortisol levels and
infants with this disease may die from
related complications, e.g., malignant
hypertension or immunosuppression.
So far the inventors have identified 3
inactivating mutations of an isoform of
the PDE 11A gene, PDE11A4 linked to
this particular form of Cushing
syndrome; they have also identified
several sequence polymorphisms of this
gene that may be associated with a
variety of adrenal and other conditions.
One of these polymorphic variations of
the sequence that have been identified
leads to an alternate protein product of
the PDE11A4 isoform. Such
polymorphisms may have important
implications for drugs that depend that
depend on PDEs functions.
The invention can be separated into
three categories:
1. Clinical identification of a new
disease termed ‘‘isolated micronodular
adrenocortical disease’’ (iMAD), an
inherited form of Cushing Syndrome.
2. Identification of PDE11A gene and
sequence variants for the diagnosis of
‘‘isolated micronodular adrenocortical
disease’’ (iMAD) a form of Cushing
Syndrome and endocrine tumors, i.e. as
diagnostic genetic biomarker.
3. Identification of PDE11A as a
potential novel drug target for the
treatment of bilateral adrenal
hyperplasia and other endocrine and
E:\FR\FM\21FEN1.SGM
21FEN1
7896
Federal Register / Vol. 72, No. 34 / Wednesday, February 21, 2007 / Notices
rmajette on PROD1PC67 with NOTICES
non-endocrine tumors and
malignancies.
The inventor is continuing work on
the development and functional
characterization of the PDE11A and its
variants in relation to iMAD and other
tumors and malignancies of the
endocrine system.
Competitive Advantage of Our
Technology
Cushing Syndrome occurs in 5 to 10
per 15 million every year and 27,000
new cases of endocrine tumors are
diagnosed every year. Our technology
identifies a functional role of PDE11A in
a new form of Cushing Syndrome and
its possible role in endocrine tumors
and/or other cancers. PDE inhibitors
have been successfully used in the
treatment of erectile dysfunction.
Currently, there are three products in
the market, which inhibit the different
forms of PDEs for the treatment of
erectile dysfunction: Sildeafil (Viagra),
Vardenafil (Levitra) and Tadalafil
(Cialis) manufactured by Pfizer,
GlaxoSmithkline/Bayer/ScheringPlough and Lily Icos respectively.
Among the marketed PDE inhibitors,
Cialis targets PDE11A and PDE5A.
Most interestingly, Cialis has no
known effects on the adrenal gland and
endocrine system and no PDE gene has
ever been reported to be associated with
endocrine or other human tumor
development. Our invention of the
variants of PDE11A genes and
subsequent new protein PDE11A4 from
one of the genetic variants have opened
up the possibility of the development of
new drugs for iMAD, adrenal
hyperplasia and other endocrine tumors
and malignancies targeting these
proteins.
The three marketed PDE inhibitors
mentioned above have exceeded
individual worldwide sales figures of 1
billion dollars each in 2007 and have
been projected to grow steadily in the
next few years. Additionally, the
endocrine drug market has been
projected to grow to more than 40
billion dollars in the next 5 years. New
PDE inhibitors and the ones in the
market are all in clinical trials for
several diseases such as erectile
dysfunction, neurological diseases and
cardiovascular diseases.
Our technology suggests that drugs
that modulate PDE function can be used
in treating iMAD, a rare genetic form of
Cushing Syndrome with fatal
implications in children. The new
PDE11A gene variants that have been
identified have diagnostic and
therapeutic implications. PCR-based
diagnostic tools can be developed to
diagnose iMAD and novel antagonists
VerDate Aug<31>2005
15:09 Feb 20, 2007
Jkt 211001
targeting these PDE11A variants can be
identified and developed as drugs.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Patent Estate
National Institutes of Health
This technology consists of U.S.
Provisional Applications Serial No. 60/
761,446 entitled ‘‘PDE11A mutations in
Adrenal Diseases’’ filed January 24,
2007. A PCT application has also been
filed.
National Heart, Lung, and Blood
Institute; Notice of Closed Meeting
Next Step: Teleconference
There will be a teleconference where
the principal investigator 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 Mojdeh Bahar;
(301) 435–2950; baharm@mail.nih.gov.
OTT will then e-mail you the date, time
and number for the teleconference.
Dated: February 13, 2007.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E7–2884 Filed 2–20–07; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Office of the Director, National
Institutes of Health; Amended Notice
of Meeting
Notice is hereby given of a change and
additional information for the meeting
of the Advisory Committee to the
Director, NIH, February 21, 2007, 2:30 to
4 p.m., National Institutes of Health,
9000 Rockville Pike, Bethesda, MD
20892 (Telephone Conference Call)
which was published in the Federal
Register on February 8, 2007, 72 FR
5982.
The meeting will be held from 2:30
p.m. to 4:30 p.m. Also, individuals
interested in attending the meeting must
contact Dr. Penny W. Burgoon for
telephone number and pass code. The
meeting is open to the public.
Dated: February 9, 2007.
Anna Snouffer,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 07–763 Filed 2–20–07; 8:45 am]
BILLING CODE 4140–01–M
PO 00000
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
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 Heart, Lung,
and Blood Institute Special Emphasis Panel,
Research Demonstration and Dissemination
Projects (R18).
Date: March 6, 2007.
Time: 1 p.m. to 3 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: Patricia A. Haggerty, PhD,
Scientific Review Administrator, Review
Branch/DERA, National Heart, Lung, and
Blood Institute, 6701 Rockledge Drive, Room
7194, Bethesda, MD 20892–7924, 301–435–
0288, haggertp@nhibi.nih.gob.
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. 93.233, National Center for
Sleep Disorders Research; 93.837, Heart and
Vascular Diseases Research; 93.838, Lung
Diseases Research; 93.839, Blood Diseases
and Resources Research, National Institutes
of Health, HHS)
Dated: February 9, 2007.
Anna Snouffer,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 07–761 Filed 2–20–07; 8:45 am]
BILLING CODE 4140–07–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Human Genome Research
Institute; Notice of Closed Meetings
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
Frm 00042
Fmt 4703
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E:\FR\FM\21FEN1.SGM
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]]>Agencies
[Federal Register Volume 72, Number 34 (Wednesday, February 21, 2007)]
[Notices]
[Pages 7895-7896]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-2884]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding Licensing and Collaborative
Research Opportunities for: PDE11A as a Novel Therapeutic Target for
Inherited Form of Cushing Syndrome and Endocrine Tumors; Dr.
Constantine A. Stratakis et al. (NICHD)
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
Technology Summary
The technology identifies a new form of Cushing Syndrome,
``isolated micronodular adrenocortical disease'' (iMAD), classified as
a rare disease, as well as the role of PDE11A gene in this disease. We
have identified particular sequence variants of the PDE11A gene causing
abnormal or altered function of this gene; these variants are present
in higher proportion in patients with iMAD, as well as in patients with
other adrenal tumors. Additionally, we suggest that PDE11A can be a
potential novel drug target for the treatment of bilateral adrenal
hyperplasia, and possibly other endocrine tumors.
Technology Description
Phosphodiesterases (PDEs) are a family of cyclic AMP (cAMP) and/or
cyclic GMP (cGMP)-hydrolyzing enzymes that cleave 3', 5'-cyclic
nucleotide monophosphates to 5'-nucleotide monophosphates. The PDE
superfamily is large and complex, containing 11 highly related and
structurally related gene families and over 60 distinct isoforms. PDE
family members hydrolyze exclusively cAMP (PDE4, PDE7, and PDE8),
exclusively cGMP (PDE5, PDE6, and PDE9), or both cAMP and cGMP (PDE1,
PDE2, PDE3, PDE10, and PDE11). Specifically, PDE11A is a dual-
specificity phosphodiesterase and is expressed in several endocrine
tissues including the adrenal cortex. Members of the PDE family differ
in tissue distribution, inhibitor specificity, and in mode of
regulation. The side effects of the PDE inhibitors are contributed by
the cross-reactivity of the inhibitors to other isoforms of the PDE.
The invention is the discovery that the PDE 11A gene has
statistically significant linkage to ``isolated micronodular
adrenocortical disease'' (iMAD), an inherited form of Cushing Syndrome.
Patients suffering from the disease have high cortisol levels and
infants with this disease may die from related complications, e.g.,
malignant hypertension or immunosuppression. So far the inventors have
identified 3 inactivating mutations of an isoform of the PDE 11A gene,
PDE11A4 linked to this particular form of Cushing syndrome; they have
also identified several sequence polymorphisms of this gene that may be
associated with a variety of adrenal and other conditions. One of these
polymorphic variations of the sequence that have been identified leads
to an alternate protein product of the PDE11A4 isoform. Such
polymorphisms may have important implications for drugs that depend
that depend on PDEs functions.
The invention can be separated into three categories:
1. Clinical identification of a new disease termed ``isolated
micronodular adrenocortical disease'' (iMAD), an inherited form of
Cushing Syndrome.
2. Identification of PDE11A gene and sequence variants for the
diagnosis of ``isolated micronodular adrenocortical disease'' (iMAD) a
form of Cushing Syndrome and endocrine tumors, i.e. as diagnostic
genetic biomarker.
3. Identification of PDE11A as a potential novel drug target for
the treatment of bilateral adrenal hyperplasia and other endocrine and
[[Page 7896]]
non-endocrine tumors and malignancies.
The inventor is continuing work on the development and functional
characterization of the PDE11A and its variants in relation to iMAD and
other tumors and malignancies of the endocrine system.
Competitive Advantage of Our Technology
Cushing Syndrome occurs in 5 to 10 per 15 million every year and
27,000 new cases of endocrine tumors are diagnosed every year. Our
technology identifies a functional role of PDE11A in a new form of
Cushing Syndrome and its possible role in endocrine tumors and/or other
cancers. PDE inhibitors have been successfully used in the treatment of
erectile dysfunction. Currently, there are three products in the
market, which inhibit the different forms of PDEs for the treatment of
erectile dysfunction: Sildeafil (Viagra[supreg]), Vardenafil
(Levitra[supreg]) and Tadalafil (Cialis[supreg]) manufactured by
Pfizer, GlaxoSmithkline/Bayer/Schering-Plough and Lily Icos
respectively.
Among the marketed PDE inhibitors, Cialis[supreg] targets PDE11A
and PDE5A. Most interestingly, Cialis[supreg] has no known effects on
the adrenal gland and endocrine system and no PDE gene has ever been
reported to be associated with endocrine or other human tumor
development. Our invention of the variants of PDE11A genes and
subsequent new protein PDE11A4 from one of the genetic variants have
opened up the possibility of the development of new drugs for iMAD,
adrenal hyperplasia and other endocrine tumors and malignancies
targeting these proteins.
The three marketed PDE inhibitors mentioned above have exceeded
individual worldwide sales figures of 1 billion dollars each in 2007
and have been projected to grow steadily in the next few years.
Additionally, the endocrine drug market has been projected to grow to
more than 40 billion dollars in the next 5 years. New PDE inhibitors
and the ones in the market are all in clinical trials for several
diseases such as erectile dysfunction, neurological diseases and
cardiovascular diseases.
Our technology suggests that drugs that modulate PDE function can
be used in treating iMAD, a rare genetic form of Cushing Syndrome with
fatal implications in children. The new PDE11A gene variants that have
been identified have diagnostic and therapeutic implications. PCR-based
diagnostic tools can be developed to diagnose iMAD and novel
antagonists targeting these PDE11A variants can be identified and
developed as drugs.
Patent Estate
This technology consists of U.S. Provisional Applications Serial
No. 60/761,446 entitled ``PDE11A mutations in Adrenal Diseases'' filed
January 24, 2007. A PCT application has also been filed.
Next Step: Teleconference
There will be a teleconference where the principal investigator
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 Mojdeh
Bahar; (301) 435-2950; baharm@mail.nih.gov. OTT will then e-mail you
the date, time and number for the teleconference.
Dated: February 13, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-2884 Filed 2-20-07; 8:45 am]
BILLING CODE 4140-01-P
