Government-Owned Inventions; Availability for Licensing, 41443-41445 [E9-19691]
Download as PDF
<![CDATA[
Federal Register / Vol. 74, No. 157 / Monday, August 17, 2009 / Notices
Dated: August 10, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–19693 Filed 8–14–09; 8:45 am]
1. B Moss and PL Earl. Overview of the
vaccinia virus expression system. Curr Protoc
Mol Biol. 2002 Nov; Chapter 16: Unit16.15.
2. HL Robinson, S Sharma, J Zhao, S
Kannanganat, L Lai, L Chennareddi, T Yu,
DC Montefiori, RR Amara, LS Wyatt, B Moss.
Immunogenicity in macaques of the clinical
product for a clade B DNA/MVA HIV
vaccine: elicitation of IFN-gamma, IL–2, and
TNF-alpha coproducing CD4 and CD8 T
cells. AIDS Res Hum Retroviruses. 2007
Dec;23(12):1555–1562.
3. LS Wyatt, PL Earl, J Vogt, LA Eller, D
Chandran, J Liu, HL Robinson, B Moss.
Correlation of immunogenicities and in vitro
expression levels of recombinant modified
vaccinia virus Ankara HIV vaccines. Vaccine
2008 Jan 24;26(4):486–493.
4. M Hebben, J Brants, C Birck, JP Samama,
B Wasylyk, D Spehner, K Pradeau, A Domi,
B Moss, P Schultz, R Drillien. High level
protein expression in mammalian cells using
a safe viral vector: modified vaccinia virus
Ankara. Protein Expr Purif. 2007
Dec;56(2):269–278.
mstockstill on DSKH9S0YB1PROD with NOTICES
billion by 2012 according to some
reports.
Overall, the potential commercial
opportunity based on the subject
technology is immense.
Inventors: Bernard Moss et al.
(NIAID).
Publications: The inventor, Dr.
Bernard Moss, is an author of more than
100 publications in the area covered by
the subject patents. The following is just
a sampling of his publications in the
area:
Government-Owned Inventions;
Availability for Licensing
Patent Status: The technology is
described and claimed in the following
four (4) patents that were issued in the
U.S. in 2006 (HHS Reference E–552–
1982/2):
1. USPN 6,998,252 issued February
14, 2006, ‘‘Recombinant Poxviruses
Having Foreign DNA Expressed under
the Control of Poxvirus Regulatory
Sequences’’.
2. USPN 7,015,024 issued March 21,
2006, ‘‘Compositions Containing
Recombinant Poxviruses Having Foreign
DNA Expressed Under the Control of
Poxvirus Regulatory Sequences’’.
3. USPN 7,045,313 issued May 16,
2006, ‘‘Recombinant Vaccinia Virus
Containing Chimeric Gene Having
Foreign DNA Flanked by Vaccinia
Regulatory DNA’’.
4. USPN 7,045,136 issued May 16,
2006, ‘‘Methods of Immunization Using
Recombinant Poxviruses Having Foreign
DNA Expressed Under the Control of
Poxvirus Regulatory Sequences’’.
Licensing Status: Available for
licensing.
Licensing Contacts: Uri Reichman,
Ph.D., MBA; 301–435–4616;
ur7a@nih.gov; RC Tang, JD, LLM; 301–
435–5031; tangrc@mail.nih.gov.
VerDate Nov<24>2008
17:55 Aug 14, 2009
Jkt 217001
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
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.
Superior Method of Preparing
Dendrimers for Use as Magnetic
Resonance Imaging (MRI) Contrast
Agents
Description of Technology: There is a
need to develop more efficient
gadolinium-containing (Gd) contrast
agents for magnetic resonance imaging
(MRI) as the small molecules presently
used clinically have the disadvantage of
being rapidly cleared from circulation
and excreted by the kidneys.
Dendrimer-based macromolecular
MRI contrast agents in which numerous
chelated Gd ions are covalently attached
to a multivalent dendritic architecture
are a promising class of diagnostic
agents for medical imaging applications.
Clinical development of the dendrimerbased agents has been limited as the
current methods for synthesizing them
result in a complex mixture that
produces inconsistent imaging results.
PO 00000
Frm 00078
Fmt 4703
Sfmt 4703
41443
The present technology describes the
development of a new method of preforming the metal-ligand chelate in
alcohol prior to conjugation to the
dendrimer. Specifically, for example, a
1B4M–DTPA–Gd chelate is preformed
in methanol and purified prior to
conjugation to a PAMAM dendrimer
molecule. This results in a dendrimerbased MRI contrast agent with greatly
improved homogeneity and stability,
and possessing an unexpectedly greater
molar relaxivity that allows the use of
much less of the agent than previously
required to obtain comparable images.
The use of a DOTA–Gd chelate is
equally possible.
Application: An improved method for
synthesis of dendrimer-based MRI
contrast agents that is greatly suited for
clinical development.
Advantages
• Efficient preparation of stable
dendrimer-based contrast agents
suitable for medical imaging.
• Higher molar relaxivity translates
into a lower dosage needed for imaging.
• Ability to control dendrimer size
conducive for development of
compartment-specific imaging agents.
Market: Dendrimers show particular
promise for the development of cancer
imaging agents. The ability to
exquisitely control dendrimer size
enables delivering them to specific
compartments such as small tumors
allowing for early cancer detection.
Gadolinium (Gd) chelates are
extensively used as MRI contrast agents
and have proven to be safe. The
combination of gadolinium chelates
with dendrimer chemistry could greatly
enhance the versatility of MRI imaging.
Inventors: Kido Nwe and Martin W.
Brechbiel (NCI).
Publications
1. K Nwe, H Xu, CA Regino, M Bernardo, L
Ileva, L Riffle, KJ Wong, MW Brechbiel.
A new approach in the preparation of
dendrimer-based bifunctional
diethylenetriaminepentaacetic acid MR
contrast agent derivatives. Bioconjugate
Chem. 2009 Jul;20(7):1412–1418.
2. OA Gansow, MW Brechbiel, MA
Magerstadt. Complexes of functionalized
tetraazacyclododecane chelates with
bismuth, lead, yttrium, actinium, or
lanthanide metal ions. U.S. Patent
5,428,154 issued 27 Jun 1995.
Patent Status: U.S. Provisional
Application No. 61/180,327 filed 21
May 2009 (HHS Reference No. E–207–
2009/0–US–01).
Related Technology: OA Gansow, MW
Brechbiel, MA Magerstadt, ‘‘Complexes
of Functionalized
Tetraazacyclododecane Chelates with
Bismuth, Lead, Yttrium, Actinium, or
E:\FR\FM\17AUN1.SGM
17AUN1
41444
Federal Register / Vol. 74, No. 157 / Monday, August 17, 2009 / Notices
Lanthanide Metal Ions,’’ U.S. Patent
5,428,154 issued 27 Jun 1995 (HHS
Reference No. E–347–1996/0–US–22).
Licensing Status: Available for
licensing.
Licensing Contact: Sabarni Chatterjee,
Ph.D.; 301–435–5587;
chatterjeesa@mail.nih.gov.
Collaborative Research Opportunity:
The Inorganic & Radioimmune
Chemistry Section, ROB, CCR, NCI is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
macromolecular (dendrimer-based) MR
contrast agents as well as multimodality analogs. Please contact John D.
Hewes, Ph.D. at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Two Types of Dentin
Sialophosphoprotein (DSPP) Knockout
Mice
Description of Technology: Two types
of dentin sialophosphoprotein knockout
mice are available for licensing. The
technology relates to two separate
knockout mouse models of the role of
dentin sialophosphoprotein in dentin
mineralization and development of
teeth. The first knockout mouse is a
knockout of the entire DSPP gene,
which results in a phenotype similar to
human autosomal dominant
dentinogenesis imperfecta, in which
teeth have widened predentin and
irregular dentin mineralization resulting
in sporadic unmineralized areas in
dentin and frequent pulp exposures.
DSPP protein in odontoblasts is
normally proteolytically cleaved into
two products, dentin sialoprotein (DSP)
and dentin phosphoprotein (DPP). To
distinguish the role of the proteolytic
fragments, the second knockout mouse
(DPPcKO) consists of a transgene
expressing the DSP fragment in a DSPP
null background. The DPPcKO mouse
demonstrates a partial rescue of the
DSPP knockout effect and indicates DSP
and PPP have distinct roles in dentin
development.
mstockstill on DSKH9S0YB1PROD with NOTICES
Applications
• Tool for studying dentin
development.
• Tool for developing treatments for
autosomal dominant dentinogenesis
imperfecta.
Inventors: Ashok Kulkarni and
Shigeki Suzuki (NIDCR)
Related Publications
1. Sreenath T, Thyagarajan T, Hall B,
Longenecker G, D’Souza R, Hong S,
Wright JT, MacDougall M, Sauk J,
Kulkarni AB. Dentin
VerDate Nov<24>2008
17:55 Aug 14, 2009
Jkt 217001
sialophosphoprotein knockout mouse
teeth display widened predentin zone
and develop defective dentin
mineralization similar to human
dentinogenesis imperfecta type III. J Biol
Chem. 2003 Jul 4;278(27):24874–24880.
2. Suzuki S, Sreenath T, Haruyama N,
Honeycutt C, Terse A, Cho A, Kohler T,
Muller R, Goldberg M, Kulkarni A.
Dentin sialoprotein and dentin
phosphoprotein have distinct roles in
dentin mineralization. Submitted, 2009.
Patent Status: HHS Reference No. E–
201–2009/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: This technology is
available as a research tool under a
Biological Materials License.
Licensing Contact: Steve Standley,
PhD; 301–435–4074; sstand@od.nih.gov.
Novel Diagnostic and Therapeutic
Biomarkers for Squamous Cell
Carcinomas
Description of Technology: Head and
neck squamous cell carcinoma (HNSCC)
includes tumors of the nasal cavities,
paranasal sinuses, oral cavity,
nasopharynx, oropharynx,
hypopharynx, and larynx. HNSCC is an
aggressive cancer with poor prognosis
after metastasis. In patients where
HNSCC is identified early, prognosis is
better and patient survival increases.
However, at present, very few if any
biomarkers are available to diagnosis
HNSCC. The overall 5-year survival rate
for patients is only 50% and has not
improved in over 30 years. New
treatments and diagnostics for early
detection are needed to improve patient
survival and quality of life for this these
types of cancers.
Scientists at the National Institutes of
Health (NIH) have discovered that the
TGF-b signaling pathway crosstalks
with the PI3K/Akt signaling pathway to
suppress squamous cell carcinomas
(SCCs). When the TGF-b pathway is
inactivated and the PI3K pathway
becomes hyperactive, HNSCC
development is accelerated. Combined
mutations in the transforming growth
factor-b receptor type 1 (TGFbR1) gene
and the phosphate and tensin homolog
(PTEN) gene directly correlate with an
individual having HNSCC or being
increasingly susceptible to HNSCC.
When tumor-associated mutations in
both biomarkers were induced in animal
subjects, spontaneous SCCs were
developed in every test subject. Given
this high correlation, this technology
could be utilized to improve diagnosis
of HNSCC at its early stages when the
malignancy is most treatable. This
technology also includes therapeutic
combinations of TGF-b and PI3K/Akt
modulators as treatments for HNSCC
PO 00000
Frm 00079
Fmt 4703
Sfmt 4703
and methods of treating patients
diagnosed with HNSCC.
Applications
• Biomarkers to diagnose patients
with HNSCC or predict patients who
have a high susceptibility for
developing HNSCC.
• Diagnostic tool to identify patients
predicted to respond to specific HNSCC
therapies as part of a personalized
treatment strategy.
• Therapeutic drug combinations of
TGF-b pathway modulators and PI3K/
Akt inhibitors to treat various head and
neck cancers, including nasal, oral,
pharyngeal, laryngeal, and cranial
tumors.
Advantages
• Complete Penetrance: All test
subjects exhibiting mutations in the
TGFbR1 and PTEN genes develop
HNSCC. A diagnostic kit that includes
assays for these mutations is predicted
to have high accuracy for identifying
HNSCC.
• Earlier diagnosis could yield more
effective treatments: This technology
could provide for a more accurate and
earlier diagnosis of SCCs to
revolutionize the treatment of this
malignancy. Current SCC therapies may
become more effective treatments and
new therapies could be developed as
better treatment options.
• Diagnostic for HNSCC susceptibility
could lead to HNSCC prevention: This
technology could identify patients
predisposed to developing HNSCC in
order to help prevent individuals from
developing head and neck cancer.
Development Status: This technology
is in the pre-clinical stage of
development. In vivo and in vitro mouse
data is available.
Market: Cancer continues to be a
medical and financial burden on U.S.
public health. The incidence of HNSCC
is over 500,000 cases worldwide and
approximately 47,000 new cases are
diagnosed each year in the United
States. Despite our increasing
knowledge of cancer treatment and
diagnosis methods, the fight against
cancer will continue to benefit from the
development of new technologies aimed
at treating individuals with disease and
diagnosing susceptible patients.
Inventors: Ashok B. Kulkarni and
Yansong Bian (NIDCR).
Publications
1. Y Bian et al. Progressive tumor formation
in mice with conditional deletion of
TGF-b signaling in head and neck
epithelia is associated with activation of
the PI3k/Akt Pathway. Manuscript in
preparation (accepted).
E:\FR\FM\17AUN1.SGM
17AUN1
Federal Register / Vol. 74, No. 157 / Monday, August 17, 2009 / Notices
2. Y Honjo et al. TGF-beta receptor I
conditional knockout mice develop
spontaneous squamous cell carcinoma.
Cell Cycle 2007 Jun 1:6(11):1360–1366.
Patent Status: U.S. Provisional
Application No. 61/176,723 filed 08
May 2009 (HHS Reference No. E–118–
2009/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Samuel E. Bish,
Ph.D.; 301–435–5282;
bishse@mail.nih.gov.
mstockstill on DSKH9S0YB1PROD with NOTICES
Antigen Mixtures for Serological
Detection of HHV–8 Infection
Description of Technology: This
invention describes a highly specific
and sensitive serological test for human
herpesvirus 8 (HHV–8) infection that
uses the Luciferase
Immunoprecipitation System (LIPS). A
mixture of four virus-specific antigens,
including K8.1, v-cyclin, ORF65 and
LANA, was shown to provide more
robust detection of HHV–8 infection
than traditional methods due its ability
to detect very low viral loads. In
addition, one of the antigens, v-cyclin,
was identified as a new serological
marker for HHV–8 infection, and its
similarity to a known human oncogene,
cyclin-D, raises the possibility of its use
as a diagnostic tool for detecting cancer.
This test is more sensitive and
amenable to a high-throughput format
than other conventional tests for HHV–
8 infection such as Immunofluorescent
Assays, Western Blots, ELISAs and PCR
based approaches. It simplifies data
collection and analysis and allows for
more rapid clinical output. Validation
tests on patient sera samples using this
4-antigen mixture has shown 100%
sensitivity and specificity compared to
94% for ELISAs.
The test can be incorporated into
routine screening panels for rapid
screening of HHV–8 infection, and may
be potentially adapted for use as a
diagnostic tool for detecting cancer. A
successful embodiment of the test can
be incorporated into routine blood
screening panels, and may lead a
reduced risk of transfusion-transmitted
HHV–8 infection in patients. It may also
be useful for detecting HHV–8 induced
cancer in HIV infected patients.
Applications
• Rapid and efficient serological
screening of HHV–8 infection.
• Cancer diagnostics.
Development Status: Early Stage.
Inventors: Peter D. Burbelo (NIDCR),
Joseph A. Kovacs (CC), Michael J.
Iadarola (NIDCR).
Publication: PD Burbelo, HP Leahy, S
Groot, LR Bishop, W Miley, MJ Iadarola,
VerDate Nov<24>2008
17:55 Aug 14, 2009
Jkt 217001
D Whitby, JA Kovacs. Four-antigen
mixture containing v-cyclin for
serological screening of human
herpesvirus 8 infection. Clin Vaccine
Immunol. 2009 May;16(5):621–627.
Patent Status: U.S. Patent Application
No. 61/152,058 filed 12 Feb 2009 (HHS
Reference No. E–063–2009/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Jeffrey A. James,
PhD; 301–435–5474;
jeffreyja@mail.nih.gov.
Oligo Microarray for Detection of All
Known Mammalian and Avian
Pathogenic Viruses
Description of Technology: The
spectrum of pathogenic viruses of
importance in human disease,
agriculture and biology is not only large
and diverse, but continually evolving.
The identification or isolation of viral
pathogens, in correlation with the
presence of specific disease phenotypes,
is of paramount importance both to
diagnosis of disease and the subsequent
management or treatment of viral
infection. The limitations of current
viral detection methods, such as PCR
and immunoassays, led to the
development of a novel microarray
system for specific detection of viruses.
The technology offered here for
licensing provides a method for highthroughput screening of known
pathogenic viruses along with
identification of ‘‘new’’ diseaseassociated viruses.
The novel method is based on a viral
microarray containing 10,000
immobilized DNA oligonucleotide
features, representing all known
mammalian and avian pathogenic
viruses (approximately 600). Software
was also developed to analyze the viral
microarray results. The oligonucleotide
features in this system are 60-mer long
and distributed across both conserved
and non-conserved regions of known
viral sequences. This design serves the
dual purpose of: (1) Facilitating
validation via redundant signals
associated with each represented virus
and (2) allowing for the discovery of
new viruses, which arise due to
recombination. In addition, positive and
negative controls against human and
mouse housekeeping genes are included
along with software for analysis of virus
microarray results.
Further advantages of the viral
microarray include: (a) The use of
sample inputs as little as 10ng of either
total DNA or RNA extracted from virus
infected cells, representing as few as 20
viral particles; (b) detection of viruses of
both DNA and RNA classes; (c) a
capacity for high-throughput screening
PO 00000
Frm 00080
Fmt 4703
Sfmt 4703
41445
of various sample types including
serum, saliva and biopsy tissues; and (d)
analysis of a large number of samples in
parallel on identical arrays.
The detection of viral DNA is unique
to this technology, as other available
technologies only detect viral genomic
RNA or viral mRNA transcripts.
Additionally, the viral chip was found
to be highly specific and sensitive for
detecting different viral genomic
sequences in cell lines and multiple
viral constructs co-infection in cultured
cells.
Applications
• Detection and identification of
viruses that cause disease.
• Efficient discovery of new
pathogenic viruses.
• Diagnosis of human and animal
disease outbreaks.
• Identification of viral agents used in
bioterrorism.
Development Status
• The pre-clinical performance of the
viral microarray was evaluated by
application of four virally positive
infected cell lines (JSC–1-harboring EBV
and KSHV, BCBL–1 harboring KSHV,
HeLa- harboring HPV18, Cem X 174
harboring SIV).
• Clinical performance was tested
and validated through analysis of total
RNA from cold (swab), Japanese
Encephalitis, Dengue, Ebola and West
Nile virus samples.
Inventors: Cassio S Baptista and David
J Munroe (NCI).
Patent Status: U.S. Patent Application
No. 11/800,080 filed 02 May 2007 (HHS
Reference No. E–206–2006/0–US–03).
Licensing Status: Available for
licensing.
Licensing Contact: Jeffrey A. James
Ph.D.; 301–435–5474;
jeffreyja@mail.nih.gov.
Collaborative Research Opportunity:
The NCI Laboratory of Molecular
Technology is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize this oligo microarray for
identification and detection of all
known mammalian and avian
pathogenic viruses. Please contact John
D. Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Dated: August 10, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–19691 Filed 8–14–09; 8:45 am]
BILLING CODE 4140–01–P
E:\FR\FM\17AUN1.SGM
17AUN1
]]>Agencies
[Federal Register Volume 74, Number 157 (Monday, August 17, 2009)]
[Notices]
[Pages 41443-41445]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-19691]
-----------------------------------------------------------------------
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.
Superior Method of Preparing Dendrimers for Use as Magnetic Resonance
Imaging (MRI) Contrast Agents
Description of Technology: There is a need to develop more
efficient gadolinium-containing (Gd) contrast agents for magnetic
resonance imaging (MRI) as the small molecules presently used
clinically have the disadvantage of being rapidly cleared from
circulation and excreted by the kidneys.
Dendrimer-based macromolecular MRI contrast agents in which
numerous chelated Gd ions are covalently attached to a multivalent
dendritic architecture are a promising class of diagnostic agents for
medical imaging applications. Clinical development of the dendrimer-
based agents has been limited as the current methods for synthesizing
them result in a complex mixture that produces inconsistent imaging
results.
The present technology describes the development of a new method of
pre-forming the metal-ligand chelate in alcohol prior to conjugation to
the dendrimer. Specifically, for example, a 1B4M-DTPA-Gd chelate is
preformed in methanol and purified prior to conjugation to a PAMAM
dendrimer molecule. This results in a dendrimer-based MRI contrast
agent with greatly improved homogeneity and stability, and possessing
an unexpectedly greater molar relaxivity that allows the use of much
less of the agent than previously required to obtain comparable images.
The use of a DOTA-Gd chelate is equally possible.
Application: An improved method for synthesis of dendrimer-based
MRI contrast agents that is greatly suited for clinical development.
Advantages
Efficient preparation of stable dendrimer-based contrast
agents suitable for medical imaging.
Higher molar relaxivity translates into a lower dosage
needed for imaging.
Ability to control dendrimer size conducive for
development of compartment-specific imaging agents.
Market: Dendrimers show particular promise for the development of
cancer imaging agents. The ability to exquisitely control dendrimer
size enables delivering them to specific compartments such as small
tumors allowing for early cancer detection. Gadolinium (Gd) chelates
are extensively used as MRI contrast agents and have proven to be safe.
The combination of gadolinium chelates with dendrimer chemistry could
greatly enhance the versatility of MRI imaging.
Inventors: Kido Nwe and Martin W. Brechbiel (NCI).
Publications
1. K Nwe, H Xu, CA Regino, M Bernardo, L Ileva, L Riffle, KJ Wong,
MW Brechbiel. A new approach in the preparation of dendrimer-based
bifunctional diethylenetriaminepentaacetic acid MR contrast agent
derivatives. Bioconjugate Chem. 2009 Jul;20(7):1412-1418.
2. OA Gansow, MW Brechbiel, MA Magerstadt. Complexes of
functionalized tetraazacyclododecane chelates with bismuth, lead,
yttrium, actinium, or lanthanide metal ions. U.S. Patent 5,428,154
issued 27 Jun 1995.
Patent Status: U.S. Provisional Application No. 61/180,327 filed 21
May 2009 (HHS Reference No. E-207-2009/0-US-01).
Related Technology: OA Gansow, MW Brechbiel, MA Magerstadt,
``Complexes of Functionalized Tetraazacyclododecane Chelates with
Bismuth, Lead, Yttrium, Actinium, or
[[Page 41444]]
Lanthanide Metal Ions,'' U.S. Patent 5,428,154 issued 27 Jun 1995 (HHS
Reference No. E-347-1996/0-US-22).
Licensing Status: Available for licensing.
Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587;
chatterjeesa@mail.nih.gov.
Collaborative Research Opportunity: The Inorganic & Radioimmune
Chemistry Section, ROB, CCR, NCI is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize macromolecular (dendrimer-based) MR
contrast agents as well as multi-modality analogs. Please contact John
D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more
information.
Two Types of Dentin Sialophosphoprotein (DSPP) Knockout Mice
Description of Technology: Two types of dentin sialophosphoprotein
knockout mice are available for licensing. The technology relates to
two separate knockout mouse models of the role of dentin
sialophosphoprotein in dentin mineralization and development of teeth.
The first knockout mouse is a knockout of the entire DSPP gene, which
results in a phenotype similar to human autosomal dominant
dentinogenesis imperfecta, in which teeth have widened predentin and
irregular dentin mineralization resulting in sporadic unmineralized
areas in dentin and frequent pulp exposures. DSPP protein in
odontoblasts is normally proteolytically cleaved into two products,
dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). To
distinguish the role of the proteolytic fragments, the second knockout
mouse (DPPcKO) consists of a transgene expressing the DSP fragment in a
DSPP null background. The DPPcKO mouse demonstrates a partial rescue of
the DSPP knockout effect and indicates DSP and PPP have distinct roles
in dentin development.
Applications
Tool for studying dentin development.
Tool for developing treatments for autosomal dominant
dentinogenesis imperfecta.
Inventors: Ashok Kulkarni and Shigeki Suzuki (NIDCR)
Related Publications
1. Sreenath T, Thyagarajan T, Hall B, Longenecker G, D'Souza R, Hong
S, Wright JT, MacDougall M, Sauk J, Kulkarni AB. Dentin
sialophosphoprotein knockout mouse teeth display widened predentin
zone and develop defective dentin mineralization similar to human
dentinogenesis imperfecta type III. J Biol Chem. 2003 Jul
4;278(27):24874-24880.
2. Suzuki S, Sreenath T, Haruyama N, Honeycutt C, Terse A, Cho A,
Kohler T, Muller R, Goldberg M, Kulkarni A. Dentin sialoprotein and
dentin phosphoprotein have distinct roles in dentin mineralization.
Submitted, 2009.
Patent Status: HHS Reference No. E-201-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: This technology is available as a research tool
under a Biological Materials License.
Licensing Contact: Steve Standley, PhD; 301-435-4074;
sstand@od.nih.gov.
Novel Diagnostic and Therapeutic Biomarkers for Squamous Cell
Carcinomas
Description of Technology: Head and neck squamous cell carcinoma
(HNSCC) includes tumors of the nasal cavities, paranasal sinuses, oral
cavity, nasopharynx, oropharynx, hypopharynx, and larynx. HNSCC is an
aggressive cancer with poor prognosis after metastasis. In patients
where HNSCC is identified early, prognosis is better and patient
survival increases. However, at present, very few if any biomarkers are
available to diagnosis HNSCC. The overall 5-year survival rate for
patients is only 50% and has not improved in over 30 years. New
treatments and diagnostics for early detection are needed to improve
patient survival and quality of life for this these types of cancers.
Scientists at the National Institutes of Health (NIH) have
discovered that the TGF-[beta] signaling pathway crosstalks with the
PI3K/Akt signaling pathway to suppress squamous cell carcinomas (SCCs).
When the TGF-[beta] pathway is inactivated and the PI3K pathway becomes
hyperactive, HNSCC development is accelerated. Combined mutations in
the transforming growth factor-[beta] receptor type 1 (TGF[beta]R1)
gene and the phosphate and tensin homolog (PTEN) gene directly
correlate with an individual having HNSCC or being increasingly
susceptible to HNSCC. When tumor-associated mutations in both
biomarkers were induced in animal subjects, spontaneous SCCs were
developed in every test subject. Given this high correlation, this
technology could be utilized to improve diagnosis of HNSCC at its early
stages when the malignancy is most treatable. This technology also
includes therapeutic combinations of TGF-[beta] and PI3K/Akt modulators
as treatments for HNSCC and methods of treating patients diagnosed with
HNSCC.
Applications
Biomarkers to diagnose patients with HNSCC or predict
patients who have a high susceptibility for developing HNSCC.
Diagnostic tool to identify patients predicted to respond
to specific HNSCC therapies as part of a personalized treatment
strategy.
Therapeutic drug combinations of TGF-[beta] pathway
modulators and PI3K/Akt inhibitors to treat various head and neck
cancers, including nasal, oral, pharyngeal, laryngeal, and cranial
tumors.
Advantages
Complete Penetrance: All test subjects exhibiting
mutations in the TGF[beta]R1 and PTEN genes develop HNSCC. A diagnostic
kit that includes assays for these mutations is predicted to have high
accuracy for identifying HNSCC.
Earlier diagnosis could yield more effective treatments:
This technology could provide for a more accurate and earlier diagnosis
of SCCs to revolutionize the treatment of this malignancy. Current SCC
therapies may become more effective treatments and new therapies could
be developed as better treatment options.
Diagnostic for HNSCC susceptibility could lead to HNSCC
prevention: This technology could identify patients predisposed to
developing HNSCC in order to help prevent individuals from developing
head and neck cancer.
Development Status: This technology is in the pre-clinical stage of
development. In vivo and in vitro mouse data is available.
Market: Cancer continues to be a medical and financial burden on
U.S. public health. The incidence of HNSCC is over 500,000 cases
worldwide and approximately 47,000 new cases are diagnosed each year in
the United States. Despite our increasing knowledge of cancer treatment
and diagnosis methods, the fight against cancer will continue to
benefit from the development of new technologies aimed at treating
individuals with disease and diagnosing susceptible patients.
Inventors: Ashok B. Kulkarni and Yansong Bian (NIDCR).
Publications
1. Y Bian et al. Progressive tumor formation in mice with
conditional deletion of TGF-[beta] signaling in head and neck
epithelia is associated with activation of the PI3k/Akt Pathway.
Manuscript in preparation (accepted).
[[Page 41445]]
2. Y Honjo et al. TGF-beta receptor I conditional knockout mice
develop spontaneous squamous cell carcinoma. Cell Cycle 2007 Jun
1:6(11):1360-1366.
Patent Status: U.S. Provisional Application No. 61/176,723 filed 08
May 2009 (HHS Reference No. E-118-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
bishse@mail.nih.gov.
Antigen Mixtures for Serological Detection of HHV-8 Infection
Description of Technology: This invention describes a highly
specific and sensitive serological test for human herpesvirus 8 (HHV-8)
infection that uses the Luciferase Immunoprecipitation System (LIPS). A
mixture of four virus-specific antigens, including K8.1, v-cyclin,
ORF65 and LANA, was shown to provide more robust detection of HHV-8
infection than traditional methods due its ability to detect very low
viral loads. In addition, one of the antigens, v-cyclin, was identified
as a new serological marker for HHV-8 infection, and its similarity to
a known human oncogene, cyclin-D, raises the possibility of its use as
a diagnostic tool for detecting cancer.
This test is more sensitive and amenable to a high-throughput
format than other conventional tests for HHV-8 infection such as
Immunofluorescent Assays, Western Blots, ELISAs and PCR based
approaches. It simplifies data collection and analysis and allows for
more rapid clinical output. Validation tests on patient sera samples
using this 4-antigen mixture has shown 100% sensitivity and specificity
compared to 94% for ELISAs.
The test can be incorporated into routine screening panels for
rapid screening of HHV-8 infection, and may be potentially adapted for
use as a diagnostic tool for detecting cancer. A successful embodiment
of the test can be incorporated into routine blood screening panels,
and may lead a reduced risk of transfusion-transmitted HHV-8 infection
in patients. It may also be useful for detecting HHV-8 induced cancer
in HIV infected patients.
Applications
Rapid and efficient serological screening of HHV-8
infection.
Cancer diagnostics.
Development Status: Early Stage.
Inventors: Peter D. Burbelo (NIDCR), Joseph A. Kovacs (CC), Michael
J. Iadarola (NIDCR).
Publication: PD Burbelo, HP Leahy, S Groot, LR Bishop, W Miley, MJ
Iadarola, D Whitby, JA Kovacs. Four-antigen mixture containing v-cyclin
for serological screening of human herpesvirus 8 infection. Clin
Vaccine Immunol. 2009 May;16(5):621-627.
Patent Status: U.S. Patent Application No. 61/152,058 filed 12 Feb
2009 (HHS Reference No. E-063-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Jeffrey A. James, PhD; 301-435-5474;
jeffreyja@mail.nih.gov.
Oligo Microarray for Detection of All Known Mammalian and Avian
Pathogenic Viruses
Description of Technology: The spectrum of pathogenic viruses of
importance in human disease, agriculture and biology is not only large
and diverse, but continually evolving. The identification or isolation
of viral pathogens, in correlation with the presence of specific
disease phenotypes, is of paramount importance both to diagnosis of
disease and the subsequent management or treatment of viral infection.
The limitations of current viral detection methods, such as PCR and
immunoassays, led to the development of a novel microarray system for
specific detection of viruses. The technology offered here for
licensing provides a method for high-throughput screening of known
pathogenic viruses along with identification of ``new'' disease-
associated viruses.
The novel method is based on a viral microarray containing 10,000
immobilized DNA oligonucleotide features, representing all known
mammalian and avian pathogenic viruses (approximately 600). Software
was also developed to analyze the viral microarray results. The
oligonucleotide features in this system are 60-mer long and distributed
across both conserved and non-conserved regions of known viral
sequences. This design serves the dual purpose of: (1) Facilitating
validation via redundant signals associated with each represented virus
and (2) allowing for the discovery of new viruses, which arise due to
recombination. In addition, positive and negative controls against
human and mouse housekeeping genes are included along with software for
analysis of virus microarray results.
Further advantages of the viral microarray include: (a) The use of
sample inputs as little as 10ng of either total DNA or RNA extracted
from virus infected cells, representing as few as 20 viral particles;
(b) detection of viruses of both DNA and RNA classes; (c) a capacity
for high-throughput screening of various sample types including serum,
saliva and biopsy tissues; and (d) analysis of a large number of
samples in parallel on identical arrays.
The detection of viral DNA is unique to this technology, as other
available technologies only detect viral genomic RNA or viral mRNA
transcripts. Additionally, the viral chip was found to be highly
specific and sensitive for detecting different viral genomic sequences
in cell lines and multiple viral constructs co-infection in cultured
cells.
Applications
Detection and identification of viruses that cause
disease.
Efficient discovery of new pathogenic viruses.
Diagnosis of human and animal disease outbreaks.
Identification of viral agents used in bioterrorism.
Development Status
The pre-clinical performance of the viral microarray was
evaluated by application of four virally positive infected cell lines
(JSC-1-harboring EBV and KSHV, BCBL-1 harboring KSHV, HeLa- harboring
HPV18, Cem X 174 harboring SIV).
Clinical performance was tested and validated through
analysis of total RNA from cold (swab), Japanese Encephalitis, Dengue,
Ebola and West Nile virus samples.
Inventors: Cassio S Baptista and David J Munroe (NCI).
Patent Status: U.S. Patent Application No. 11/800,080 filed 02 May
2007 (HHS Reference No. E-206-2006/0-US-03).
Licensing Status: Available for licensing.
Licensing Contact: Jeffrey A. James Ph.D.; 301-435-5474;
jeffreyja@mail.nih.gov.
Collaborative Research Opportunity: The NCI Laboratory of Molecular
Technology is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize this oligo microarray for identification and detection of
all known mammalian and avian pathogenic viruses. Please contact John
D. Hewes, PhD at 301-435-3121 or hewesj@mail.nih.gov for more
information.
Dated: August 10, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-19691 Filed 8-14-09; 8:45 am]
BILLING CODE 4140-01-P
