Government-Owned Inventions; Availability for Licensing, 57180-57182 [E9-26607]
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57180
Federal Register / Vol. 74, No. 212 / Wednesday, November 4, 2009 / Notices
comment period for the draft guidance
until January 4, 2010. The agency
believes that this extension allows
adequate time for interested persons to
submit comments without significantly
delaying finalization of this level 1
guidance.
II. Request for Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) electronic or written
comments on this document. Submit a
single copy of electronic comments or
two paper copies of any mailed
comments, except that individuals may
submit one paper copy. Comments are
to be identified with the docket number
found in brackets in the heading of this
document. Received comments may be
seen in the Division of Dockets
Management between 9 a.m. and 4 p.m.,
Monday through Friday.
Dated: October 30, 2009.
David Horowitz,
Assistant Commissioner for Policy.
[FR Doc. E9–26636 Filed 11–2–09; 11:15 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2009–D–0348]
Draft Guidance for Industry: Guide to
Minimize Microbial Food Safety
Hazards of Leafy Greens; Extension of
Comment Period
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice; extension of comment
mstockstill on DSKH9S0YB1PROD with NOTICES
period.
SUMMARY: The Food and Drug
Administration (FDA) is extending to
January 4, 2010, the comment period for
the draft guidance entitled ‘‘Guidance
for Industry: Guide to Minimize
Microbial Food Safety Hazards of Leafy
Greens’’ that appeared in the Federal
Register of August 3, 2009 (74 FR
38439), as corrected on August 21, 2009
(74 FR 42311). In the notice of
availability, FDA requested comments
by November 2, 2009. The agency is
taking this action in response to
requests for an extension to allow
interested persons additional time to
submit comments.
DATES: Submit written or electronic
comments by January 4, 2010.
ADDRESSES: Submit electronic
comments to https://www.
regulations.gov. Submit written
comments to the Division of Dockets
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16:29 Nov 03, 2009
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Management (HFA–305), Food and Drug
Administration, 5630 Fishers lane, rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Amy Green, Center for Food Safety and
Applied Nutrition (HFS–317), Food and
Drug Administration, 5100 Paint Branch
Pkwy., College Park, MD 20740 301–
436–2025.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of August 3,
2009 (74 FR 38439), as corrected on
August 21, 2009 (74 FR 42311), FDA
published a notice of availability with a
90-day comment period to request
comments on the draft guidance entitled
‘‘Guidance for Industry: Guide to
Minimize Microbial Food Safety
Hazards of Leafy Greens’’ (the draft
guidance). Comments on the draft
guidance will inform FDA’s current
thinking for finalization of this Level 1
guidance consistent with FDA’s good
guidance practices.
The agency has received requests for
an extension of the comment period for
the draft guidance. FDA has considered
the requests and is extending the
comment period for the draft guidance
until January 4, 2010. The agency
believes that this extension allows
adequate time for interested persons to
submit comments without significantly
delaying finalization of this Level 1
guidance.
II. Request for Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) electronic or written
comments on this document. Submit a
single copy of electronic comments or
two paper copies of any mailed
comments, except that individuals may
submit one paper copy. Comments are
to be identified with the docket number
found in brackets in the heading of this
document. Received comments may be
seen in the Division of Dockets
Management between 9 a.m. and 4 p.m.,
Monday through Friday.
Dated: October 30, 2009.
David Horowitz,
Assistant Commissioner for Policy.
[FR Doc. E9–26637 Filed 11–2–09; 11:15 am]
BILLING CODE 4160–01–S
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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.
Live-Attenuated Tularemia Vaccine
Description of Invention: The
invention provides compositions and
methods of use for a modified strain of
Francisella tularensis, the causative
agent of tularemia, a category A
biodefense agent (NIAID classification).
Currently, no vaccines are available, and
the only approved therapeutics for
tularemia are antibiotics that are only
effective if delivered early in the
infection. The subject invention defines
and characterizes mutations in
Francisella tularensis that result in
attenuated bacteria capable of inducing
strong protective immune responses.
Thus, these stable mutant strains could
be used as efficient live vaccines against
tularemia.
Applications: Live-attenuated
vaccines against Francisella tularensis.
Advantages:
• Live-attenuated bacteria can be
easily produced through recombinant
technologies
• Live-attenuated vaccines do no
require adjuvants
• Immune response to live-attenuated
vaccines lasts for years and does not
require booster
Development Status: In vitro and in
vivo data available.
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Federal Register / Vol. 74, No. 212 / Wednesday, November 4, 2009 / Notices
Inventors: Jean A. Celli and Catharine
M. Bosio (NIAID).
Relevant Publications:
1. TD Wehrly et al. Intracellular biology
and virulence determinants of
Francisella tularensis revealed by
transcriptional profiling inside
macrophages. Cell Microbiol. 2009
Jul;11(7): 1128–1150.
2. J Su et al. Genome-wide identification
of Francisella tularensis virulence
determinants. Infect Immun. 2007
Jun;75(6):3089–3101.
´
3. S Janovska et al. Identification of
immunoreactive antigens in
membrane proteins enriched
fraction from Francisella tularensis
LVS. Immunol Lett. 2007 Feb
15;108(2):151–159.
´
4. S Janovska et al. Proteomic analysis
of antibody response in a case of
laboratory-acquired infection with
Francisella tularensis subsp.
tularensis. Folia Microbiol (Praha).
2007;52(2):194–198.
Patent Status: U.S. Provisional
Application No. 61/156,173 filed 27 Feb
2009 (HHS Reference No. E–125–2009/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Sally Hu, Ph.D.;
301–435–5606; HuS@mail.nih.gov.
Collaborative Research Opportunity:
The NIAID Office of Technology
Development is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize live vaccine strains of
Francisella tularensis with defined
mutations. Please contact Rosemary
Walsh at 301–496–2644 for more
information.
mstockstill on DSKH9S0YB1PROD with NOTICES
Improved Targeting Precision of
Radiotherapy
Description of Invention: The
technology offered for licensing is in the
field of radiotherapy. The invention
provides for improvement in the
targeting precision of 4D Image-Guided
Radiation Therapy (4D IGRT). It relates
to new methods for (1) predicting the
dynamic tidal volume of a patient and
(2) predicting the motion of the
diaphragm and points of interest near
the diaphragm, by monitoring the
external volume change of a patient’s
torso, thereby improving the timeresolved computed tomography (4DCT)
and motion-compensated radiation
therapy (4DRT). The method is based on
the observation that the change in torso
volume is representative of the change
in lung air volume (expansion and
contraction) driven by diaphragm
displacement, as evidence by the high
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Jkt 220001
linear relationship between the two
with a linear coefficient of unity. A
model of lung volume expansion and
extension within a patient’s rib cage is
presented in this invention to convert
the external torso volume change (TVC)
to relative diaphragm displacement.
Applications: The method can be
integrated with Image-Guided Radiation
Therapy and related instrumentation to
provide improvement in targeting
precision and thus enhancement in
therapeutic ratio and radiotherapy
outcome.
Advantage: The invention is
advantageous to previous methods
related to tracking of internal organ
motion due to its unique observations as
follows:
• There is a highly correlated,
quantitative linear relationship between
volume changes of the external torso
and the internal lung during respiration.
• Based on this external-internal
volumetric relationship and lung
volume compensation model, a patient’s
diaphragm displacement can be
predicted with a clinically acceptable
accuracy.
A novel approach based on these
observations may therefore offer a more
accurate and reliable approach for
motion tracking during 4D IGRT, in
comparison to existing methods. In
particular, the advantages which may be
provided by this technology are as
follows:
• Minimizing the use of excessive
ionization radiation for patient imaging.
The use of x-ray based imaging
techniques can be largely avoided.
• Minimizing the use of intrusive
implanted fiducials for target
localization, a method currently used in
radiation therapy.
• Torso volume change is more
comprehensive indication of lung
volume change than the fiducial
displacement or bellows tension, which
are both indirect indicators. This
approach intrinsically eliminates the
problems due to sensitivity of marker
location, reproducibility of marker(s)
placement, complexity of data analysis,
and reliability of motion correlation in
the presence of breathing irregularity
and breathing pattern change.
• The technology may be
advantageous to the currently used
spirometry method, which requires
frequent calibration, baseline drift
calibration and inconvenience.
• The technology can be utilized by
modifying existing superficial imaging
techniques, such as optical camera
imaging (OCI) systems. Therefore it is
highly likely that the technology can be
integrated into an image guided
radiation therapy in the future.
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57181
Development Status: The core of this
invention is established. The following
2 on-going studies have been initiated:
(1) Calculating the motion of a tumor
anywhere in the lungs using a tumor
motion model and volumetric boundary
conditions, and (2) calculating the
volumes using a surface imaging system
and testing the accuracy based on
phantom and patient studies. The
implementation of this technique after
the studies should be straightforward in
an existing radiotherapy system.
Market: The commercial market of
radiotherapy and related equipment is
huge. Radiotherapy alone or in
combination with chemotherapy is used
for at least 50% of cancer treatments.
According to market research the
radiation therapy market is growing
rapidly with annual cancer rates
worldwide projected to increase by fifty
percent by 2020. Extra-cranial
stereotactic body radiotherapy (SBRT)
using ablative or near ablative radiation
dose to the tumor has shown significant
improvement in local control rate,
especially in early stage of non-small
cell lung cancer (NSCLC). The
requirement for high precision motion
monitoring and tracking is critical for
SBRT procedures with clinically
tolerable toxicity to normal tissues.
Methods of calculating internal organ
motion are incorporated into
radiotherapy systems to enhance their
targeting precision and improve
therapeutic ratio. The market for these
methods is therefore vast and rapidly
growing. In particular, there is a
constant need for such improved
methods that can readily be integrated
into existing systems. The invention
described here has therefore a good
potential for commercial success.
Inventors: Guang (George) Li (NCI),
Robert W. Miller (NCI), Kevin A.
Camphausen (NCI), et al.
Patent Status: U.S. Provisional
Application No. 61/145,487 filed 16 Jan
2009 (HHS Reference No. E–151–2008/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contacts: Uri Reichman,
Ph.D., MBA; 301–435–4616;
UR7a@nih.gov; John Stansberry, Ph.D.;
301–435–5236; stansbej@mail.nih.gov.
A Novel Multimeric CD4 Fusion Protein
for Treating HIV Infection
Description of Invention: This
invention could potentially provide an
alternative to antiretroviral therapy
(ART), especially in cases where
productively-infected cells persist with
ART. This multimeric CD4 fusion
protein acts as a decoy to inhibit human
immunodeficiency virus (HIV–1) entry
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mstockstill on DSKH9S0YB1PROD with NOTICES
57182
Federal Register / Vol. 74, No. 212 / Wednesday, November 4, 2009 / Notices
into host cells. More specifically, this
multimeric CD4 inhibits the interaction
between HIV–1 gp120 and CD4 present
on the surface of CD4 T-cells, the major
HIV–1 target cell. There is strong
evidence that binding between gp120, as
part of a virion spike, and CD4 on cell
surface is the first step for HIV entry
into host cells. This multimeric CD4
provides a number of advantages over
inhibitory CD4 molecules previously
developed. First, this CD4 multimer is
capable of binding at least 10 gp120
simultaneously with high avidity.
Second, it does not enhance HIV
infection at suboptimal concentrations,
a phenomenon observed with
previously developed recombinant CD4
molecules. Third, it has been
demonstrated that this CD4 fusion
protein hyper-crosslinks CD16 on
natural killer (NK) cells and as a
consequence delivers an exceptionally
strong signal to NK cells, promoting
potent Antibody-Dependent Cellular
Cytotoxicity (ADCC) and lysis of HIVinfected cells. The inventors have
shown that this recombinant CD4
multimer efficiently neutralizes primary
isolates from different HIV subgroups.
The invention comprises an
immunoglobulin construct having up to
12 amino terminal domains of CD4
(D1D2), the epitope responsible for
HIV–1 gp120 binding activity. It also
comprises domains of a human IgG1
heavy chain, as well as the IgA tailpiece
that drives its polymerization. The two
amino terminal domains of CD4 are
fused to the CH2CH3 domains (which
bears the FC receptor recognition
epitopes) of a human IgG1 heavy chain.
Applications: HIV therapeutics and
HIV vaccine development.
Advantages: Efficient inhibition of
HIV–1 viral entry without enhancement
of infection at suboptimal
concentrations. Potent activation of
Antibody-Dependent Cellular
Cytotoxicity (ADCC) and lysis of HIVinfected cells.
Development Status: The anti-HIV
activity of this multimeric CD4 protein
has been well characterized in vitro.
Inventors: James Arthos, Claudia
Cicala, Anthony S. Fauci (NIAID).
Publications:
1. J Arthos et al. Biochemical and
biological characterization of a
dodecameric CD4–Ig fusion protein:
implications for therapeutic and
vaccine strategies. J Biol Chem.
2002 Mar 29;277(13):11456–11464.
2. PD Kwong et al. HIV–1 evades
antibody-mediated neutralization
through conformational masking of
receptor-binding sites. Nature. 2002
Dec 12;420(6916):678–682.
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3. N Gupta et al. Targeted lysis of HIVinfected cells by natural killer cells
armed and triggered by a
recombinant immunoglobulin
fusion protein: implications for
immunotherapy. Virology. 2005 Feb
20;332(2):491–497.
4. T Zhou et al. Structural definition of
a conserved neutralization epitope
on HIV–1 gp120. Nature. 2007 Feb
15;445(7129):732–737.
5. A Bennett et al. A Cryoelectron
tomographic analysis of an HIVneutralizing protein and its
complex with native viral gp120. J
Biol Chem. 2007 Sep
21;282(38):27754–27759.
Patent Status: HHS Reference No. E–
337–2001/0—
• U.S. Patent No. 7,368,114 issued 06
May 2008
• European Application No.
02799169.4 (recently allowed)
Licensing Status: Available for
licensing.
Licensing Contact: RC Tang, JD, LLM;
301–435–5031; tangrc@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Allergy and
Infectious Diseases, Laboratory of
Immunoregulation, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this invention. Please
contact William Ronnenberg at 301–
451–3522 or
wronnenberg@niaid.nih.gov for more
information.
Dated: October 29, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–26607 Filed 11–3–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Center for Scientific Review; Notice of
Closed Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. App.), notice is
hereby given of the following meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
PO 00000
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individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: Center for Scientific
Review Special Emphasis Panel, Member
Conflict: Development and Social
Psychology.
Date: November 12, 2009.
Time: 10 a.m. to 12 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: Lee S. Mann, PhD,
Scientific Review Officer, Center for
Scientific Review, National Institutes of
Health, 6701 Rockledge Drive, Room 3186,
MSC 7848, Bethesda, MD 20892, 301–435–
0677, mannl@csr.nih.gov.
This notice is being published less than 15
days prior to the meeting due to the timing
limitations imposed by the review and
funding cycle.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.306, Comparative Medicine;
93.333, Clinical Research, 93.306, 93.333,
93.337, 93.393–93.396, 93.837–93.844,
93.846–93.878, 93.892, 93.893, National
Institutes of Health, HHS)
Dated: October 28, 2009.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. E9–26576 Filed 11–3–09; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Cancer Institute; Notice of
Meeting
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 meeting of the
National Cancer Advisory Board.
The meeting will be open to the
public as indicated below, with
attendance limited to space available.
Individuals who plan to attend and
need special assistance, such as sign
language interpretation or other
reasonable accommodations, should
notify the Contact Person listed below
in advance of the meeting.
A portion of the meeting will be
closed to the public in accordance with
the provisions set forth in section
552b(6), as amended. The discussions
could disclose personal information
concerning NCI Staff and/or its
contractors, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
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]]>Agencies
[Federal Register Volume 74, Number 212 (Wednesday, November 4, 2009)]
[Notices]
[Pages 57180-57182]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-26607]
-----------------------------------------------------------------------
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.
Live-Attenuated Tularemia Vaccine
Description of Invention: The invention provides compositions and
methods of use for a modified strain of Francisella tularensis, the
causative agent of tularemia, a category A biodefense agent (NIAID
classification). Currently, no vaccines are available, and the only
approved therapeutics for tularemia are antibiotics that are only
effective if delivered early in the infection. The subject invention
defines and characterizes mutations in Francisella tularensis that
result in attenuated bacteria capable of inducing strong protective
immune responses. Thus, these stable mutant strains could be used as
efficient live vaccines against tularemia.
Applications: Live-attenuated vaccines against Francisella
tularensis.
Advantages:
Live-attenuated bacteria can be easily produced through
recombinant technologies
Live-attenuated vaccines do no require adjuvants
Immune response to live-attenuated vaccines lasts for
years and does not require booster
Development Status: In vitro and in vivo data available.
[[Page 57181]]
Inventors: Jean A. Celli and Catharine M. Bosio (NIAID).
Relevant Publications:
1. TD Wehrly et al. Intracellular biology and virulence determinants of
Francisella tularensis revealed by transcriptional profiling inside
macrophages. Cell Microbiol. 2009 Jul;11(7): 1128-1150.
2. J Su et al. Genome-wide identification of Francisella tularensis
virulence determinants. Infect Immun. 2007 Jun;75(6):3089-3101.
3. S Janovsk[aacute] et al. Identification of immunoreactive antigens
in membrane proteins enriched fraction from Francisella tularensis LVS.
Immunol Lett. 2007 Feb 15;108(2):151-159.
4. S Janovsk[aacute] et al. Proteomic analysis of antibody response in
a case of laboratory-acquired infection with Francisella tularensis
subsp. tularensis. Folia Microbiol (Praha). 2007;52(2):194-198.
Patent Status: U.S. Provisional Application No. 61/156,173 filed 27
Feb 2009 (HHS Reference No. E-125-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Sally Hu, Ph.D.; 301-435-5606; HuS@mail.nih.gov.
Collaborative Research Opportunity: The NIAID Office of Technology
Development is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize live vaccine strains of Francisella
tularensis with defined mutations. Please contact Rosemary Walsh at
301-496-2644 for more information.
Improved Targeting Precision of Radiotherapy
Description of Invention: The technology offered for licensing is
in the field of radiotherapy. The invention provides for improvement in
the targeting precision of 4D Image-Guided Radiation Therapy (4D IGRT).
It relates to new methods for (1) predicting the dynamic tidal volume
of a patient and (2) predicting the motion of the diaphragm and points
of interest near the diaphragm, by monitoring the external volume
change of a patient's torso, thereby improving the time-resolved
computed tomography (4DCT) and motion-compensated radiation therapy
(4DRT). The method is based on the observation that the change in torso
volume is representative of the change in lung air volume (expansion
and contraction) driven by diaphragm displacement, as evidence by the
high linear relationship between the two with a linear coefficient of
unity. A model of lung volume expansion and extension within a
patient's rib cage is presented in this invention to convert the
external torso volume change (TVC) to relative diaphragm displacement.
Applications: The method can be integrated with Image-Guided
Radiation Therapy and related instrumentation to provide improvement in
targeting precision and thus enhancement in therapeutic ratio and
radiotherapy outcome.
Advantage: The invention is advantageous to previous methods
related to tracking of internal organ motion due to its unique
observations as follows:
There is a highly correlated, quantitative linear
relationship between volume changes of the external torso and the
internal lung during respiration.
Based on this external-internal volumetric relationship
and lung volume compensation model, a patient's diaphragm displacement
can be predicted with a clinically acceptable accuracy.
A novel approach based on these observations may therefore offer a
more accurate and reliable approach for motion tracking during 4D IGRT,
in comparison to existing methods. In particular, the advantages which
may be provided by this technology are as follows:
Minimizing the use of excessive ionization radiation for
patient imaging. The use of x-ray based imaging techniques can be
largely avoided.
Minimizing the use of intrusive implanted fiducials for
target localization, a method currently used in radiation therapy.
Torso volume change is more comprehensive indication of
lung volume change than the fiducial displacement or bellows tension,
which are both indirect indicators. This approach intrinsically
eliminates the problems due to sensitivity of marker location,
reproducibility of marker(s) placement, complexity of data analysis,
and reliability of motion correlation in the presence of breathing
irregularity and breathing pattern change.
The technology may be advantageous to the currently used
spirometry method, which requires frequent calibration, baseline drift
calibration and inconvenience.
The technology can be utilized by modifying existing
superficial imaging techniques, such as optical camera imaging (OCI)
systems. Therefore it is highly likely that the technology can be
integrated into an image guided radiation therapy in the future.
Development Status: The core of this invention is established. The
following 2 on-going studies have been initiated: (1) Calculating the
motion of a tumor anywhere in the lungs using a tumor motion model and
volumetric boundary conditions, and (2) calculating the volumes using a
surface imaging system and testing the accuracy based on phantom and
patient studies. The implementation of this technique after the studies
should be straightforward in an existing radiotherapy system.
Market: The commercial market of radiotherapy and related equipment
is huge. Radiotherapy alone or in combination with chemotherapy is used
for at least 50% of cancer treatments. According to market research the
radiation therapy market is growing rapidly with annual cancer rates
worldwide projected to increase by fifty percent by 2020. Extra-cranial
stereotactic body radiotherapy (SBRT) using ablative or near ablative
radiation dose to the tumor has shown significant improvement in local
control rate, especially in early stage of non-small cell lung cancer
(NSCLC). The requirement for high precision motion monitoring and
tracking is critical for SBRT procedures with clinically tolerable
toxicity to normal tissues.
Methods of calculating internal organ motion are incorporated into
radiotherapy systems to enhance their targeting precision and improve
therapeutic ratio. The market for these methods is therefore vast and
rapidly growing. In particular, there is a constant need for such
improved methods that can readily be integrated into existing systems.
The invention described here has therefore a good potential for
commercial success.
Inventors: Guang (George) Li (NCI), Robert W. Miller (NCI), Kevin
A. Camphausen (NCI), et al.
Patent Status: U.S. Provisional Application No. 61/145,487 filed 16
Jan 2009 (HHS Reference No. E-151-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contacts: Uri Reichman, Ph.D., MBA; 301-435-4616;
UR7a@nih.gov; John Stansberry, Ph.D.; 301-435-5236;
stansbej@mail.nih.gov.
A Novel Multimeric CD4 Fusion Protein for Treating HIV Infection
Description of Invention: This invention could potentially provide
an alternative to antiretroviral therapy (ART), especially in cases
where productively-infected cells persist with ART. This multimeric CD4
fusion protein acts as a decoy to inhibit human immunodeficiency virus
(HIV-1) entry
[[Page 57182]]
into host cells. More specifically, this multimeric CD4 inhibits the
interaction between HIV-1 gp120 and CD4 present on the surface of CD4
T-cells, the major HIV-1 target cell. There is strong evidence that
binding between gp120, as part of a virion spike, and CD4 on cell
surface is the first step for HIV entry into host cells. This
multimeric CD4 provides a number of advantages over inhibitory CD4
molecules previously developed. First, this CD4 multimer is capable of
binding at least 10 gp120 simultaneously with high avidity. Second, it
does not enhance HIV infection at suboptimal concentrations, a
phenomenon observed with previously developed recombinant CD4
molecules. Third, it has been demonstrated that this CD4 fusion protein
hyper-crosslinks CD16 on natural killer (NK) cells and as a consequence
delivers an exceptionally strong signal to NK cells, promoting potent
Antibody-Dependent Cellular Cytotoxicity (ADCC) and lysis of HIV-
infected cells. The inventors have shown that this recombinant CD4
multimer efficiently neutralizes primary isolates from different HIV
subgroups.
The invention comprises an immunoglobulin construct having up to 12
amino terminal domains of CD4 (D1D2), the epitope responsible for HIV-1
gp120 binding activity. It also comprises domains of a human IgG1 heavy
chain, as well as the IgA tailpiece that drives its polymerization. The
two amino terminal domains of CD4 are fused to the CH2CH3 domains
(which bears the FC receptor recognition epitopes) of a human IgG1
heavy chain.
Applications: HIV therapeutics and HIV vaccine development.
Advantages: Efficient inhibition of HIV-1 viral entry without
enhancement of infection at suboptimal concentrations. Potent
activation of Antibody-Dependent Cellular Cytotoxicity (ADCC) and lysis
of HIV-infected cells.
Development Status: The anti-HIV activity of this multimeric CD4
protein has been well characterized in vitro.
Inventors: James Arthos, Claudia Cicala, Anthony S. Fauci (NIAID).
Publications:
1. J Arthos et al. Biochemical and biological characterization of a
dodecameric CD4-Ig fusion protein: implications for therapeutic and
vaccine strategies. J Biol Chem. 2002 Mar 29;277(13):11456-11464.
2. PD Kwong et al. HIV-1 evades antibody-mediated neutralization
through conformational masking of receptor-binding sites. Nature. 2002
Dec 12;420(6916):678-682.
3. N Gupta et al. Targeted lysis of HIV-infected cells by natural
killer cells armed and triggered by a recombinant immunoglobulin fusion
protein: implications for immunotherapy. Virology. 2005 Feb
20;332(2):491-497.
4. T Zhou et al. Structural definition of a conserved neutralization
epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-737.
5. A Bennett et al. A Cryoelectron tomographic analysis of an HIV-
neutralizing protein and its complex with native viral gp120. J Biol
Chem. 2007 Sep 21;282(38):27754-27759.
Patent Status: HHS Reference No. E-337-2001/0--
U.S. Patent No. 7,368,114 issued 06 May 2008
European Application No. 02799169.4 (recently allowed)
Licensing Status: Available for licensing.
Licensing Contact: RC Tang, JD, LLM; 301-435-5031;
tangrc@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases, Laboratory of Immunoregulation, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
this invention. Please contact William Ronnenberg at 301-451-3522 or
wronnenberg@niaid.nih.gov for more information.
Dated: October 29, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-26607 Filed 11-3-09; 8:45 am]
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