Government-Owned Inventions; Availability for Licensing, 49283-49285 [E7-16935]
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Federal Register / Vol. 72, No. 166 / Tuesday, August 28, 2007 / Notices
Dated: August 21, 2007.
John J. McGowan,
Deputy Director for Science Management,
NIAID, National Institutes of Health.
[FR Doc. E7–17012 Filed 8–27–07; 8:45 am]
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Dated: August 20, 2007.
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Director, National Institutes of Health.
[FR Doc. 07–4221 Filed 8–27–07; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
pwalker on PROD1PC71 with NOTICES
AGENCY:
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
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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.
Development of Antigenic Chimeric St.
Louis Encephalitis Virus/Dengue Virus
Type Four Recombinant Viruses (SLEV/
DEN4) as Vaccine Candidates for the
Prevention of Disease Caused by SLEV
Description of Invention: St. Louis
Encephalitis Virus (SLEV) is a
mosquito-borne flavivirus that is
endemic in the Americas and causes
sporadic outbreaks of disease in
humans. SLEV is a member of the
Japanese encephalitis virus serocomplex
and is closely related to West Nile Virus
(WNV). St. Louis encephalitis is found
throughout North, Central, and South
America, and the Caribbean, but is a
major public health problem mainly in
the United States. Prior to the outbreak
of West Nile virus in 1999, St. Louis
encephalitis was the most common
human disease caused by mosquitoes in
the United States. Since 1964, there
have been about 4,440 confirmed cases
of St. Louis encephalitis, with an
average of 130 cases per year. Up to
3,000 cases have been reported during
epidemics in some years. Many more
infections occur without symptoms and
go undiagnosed. At present, a vaccine or
FDA approved antiviral therapy is not
available.
The inventors have previously
developed a WNV/Dengue4Delta30
antigenic chimeric virus as a live
attenuated virus vaccine candidate that
contains the WNV premembrane and
envelope (prM and E) proteins on a
dengue virus type 4 (DEN4) genetic
background with a thirty nucleotide
deletion (Delta30) in the DEN4 3’-UTR.
Using a similar strategy, the inventors
have generated an antigenic chimeric
virus, SLE/DEN4Delta30. Preclinical
testing results indicate that
chimerization of SLE with DEN4Delta30
decreased neuroinvasiveness in mice,
did not affect neurovirulence in mice,
and appeared to overattenuate the virus
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for non-human primates. Modifications
of the SLE/DEN4Delta30 vaccine
candidate are underway to improve its
immunogenicity.
This application claims live
attenuated chimeric SLE/DEN4Delta30
vaccine compositions and bivalent
WNV/SLE/DEN4Delta30 vaccine
compositions. Also claimed are methods
of treating or preventing SLEV infection
in a mammalian host, methods of
producing a subunit vaccine
composition, isolated polynucleotides
comprising a nucleotide sequence
encoding a SLEV immunogen, methods
for detecting SLEV infection in a
biological sample and infectious
chimeric SLEV.
Application: Immunization against
SLEV or SLEV and WNV.
Development Status: Live attenuated
vaccine candidates are currently being
developed and preclinical studies in
mice and monkeys are in progress.
Suitable vaccine candidates will then be
evaluated in clinical studies.
Inventors: Stephen S. Whitehead,
Joseph Blaney, Alexander Pletnev, Brian
R. Murphy (NIAID).
Patent Status: U.S. Provisional
Application No. 60/934,730 filed 14 Jun
2007 (HHS Reference No. E–240–2007/
0–US–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Collaborative Research Opportunity:
The NIAID Laboratory of Infectious
Diseases is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize live attenuated virus
vaccine candidates for St. Louis
encephalitis virus. Please contact Dr.
Whitehead at 301–496–7692 for more
information.
Monoclonal Antibodies Against Dengue
and Other Viruses With Deletion in Fc
Region
Description of Invention: The four
dengue virus (DENV) serotypes (DENV–
1 to DENV–4) are the most important
arthropod-borne flaviviruses in terms of
morbidity and geographic distribution.
Up to 100 million DENV infections
occur every year, mostly in tropical and
subtropical areas where vector
mosquitoes are abundant. Infection with
any of the DENV serotypes may be
asymptomatic or may lead to classic
dengue fever or more severe dengue
hemorrhagic fever (DHF) and dengue
shock syndrome (DSS), which are
increasingly common in the dengue
endemic areas. Immunity to the same
virus serotype (homotypic immunity) is
life-long, whereas immunity to different
serotypes (heterotypic immunity) lasts
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Federal Register / Vol. 72, No. 166 / Tuesday, August 28, 2007 / Notices
2–3 months so that infection with a
different serotype virus is possible.
DHF/DSS often occurs in patients with
second, heterotypic DENV infections or
in infants with maternally transferred
dengue immunity. Severe dengue is a
major cause of hospitalization, and
fatality rates vary from <1% to 5% in
children.
Antibody-dependent enhancement
(ADE) has been proposed as an
underlying pathogenic mechanism of
DHF/DSS. ADE occurs because
preexisting subneutralizing antibodies
and the infecting DENV form complexes
that bind to Fc receptor-bearing cells,
leading to increased virus uptake and
replication. ADE has been repeatedly
demonstrated in vitro using dengue
immune sera or monoclonal antibodies
and cells of monocytic and recently, B
lymphocytic lineages bearing Fc
receptors. ADE of DENV–2 infection has
also been demonstrated in monkeys
infused with a human dengue immune
serum.
We have identified chimpanzeehuman chimeric IgG1 mAbs capable of
neutralizing or binding to one or more
DENV serotypes. Cross-reactive IgG 1A5
neutralizes DENV–1 and DENV–2 more
efficiently than DENV–3 and DENV–4,
and type-specific IgG 5H2 neutralizes
DENV–4 at a high titer. Analysis of
antigenic variants has localized the IgG
1A5 binding site to the conserved fusion
peptide in E. Thus, IgG 1A5 shares
many characteristics with the crossreactive antibodies detected in
flavivirus infections.
This application claims a variant of an
antibody comprising a polypeptide in
the Fc region, which binds an Fc gamma
receptor (FcgammaR) with lower affinity
than the parent antibody. The variant
polypeptide comprises a deletion of
nine amino acids at the N-terminus of
the CH2 domain in the Fc region.
Introduction of the Fc variant abrogates
the antibody-mediated dengue virus
replication enhancing activity. This
invention has important implications
for the antibody-mediated prevention of
dengue virus infection.
Application: Immunization against
Dengue and/or flaviviruses.
Developmental Status: Antibody
candidates have been synthesized and
preclinical studies have been
performed.
Inventors: Ana Goncalvez, Robert
Purcell, C.J. Lai (NIAID).
Publication: AP Goncalvez et al.
Monoclonal antibody-mediated
enhancement of dengue virus infection
in vitro and in vivo and strategies for
prevention Proc Natl Acad Sci USA.
2007 May 29;104(22):9422–9427. Epub
2007 May 15.
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Patent Status:
U.S. Provisional Application No. 60/
922,282 filed 04 Apr 2007 (HHS
Reference No. E–159–2007/0–US–01).
U.S. Provisional Application No. 60/
927,755 filed 04 May 2007 (HHS
Reference No. E–159–2007/1–US–01).
U.S. Provisional Application No. 60/
928,405 filed 08 May 2007 (HHS
Reference No. E–159–2007/2–US–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Live Attenuated Virus Vaccines for La
Crosse Virus and Other Bunyaviridae
Description of Invention: La Crosse
virus (LACV), family Bunyaviridae, is a
mosquito-borne pathogen endemic in
the United States. LACV infection
results in 70–130 clinical cases a year
and is the major cause of pediatric
arboviral encephalitis in North America.
LACV was first identified as human
pathogen in 1960 after its isolation from
a 4 year-old girl from Minnesota who
suffered meningoencephalitis and later
died in La Crosse, Wisconsin. The
majority of LACV infections are mild
and never reported, however serologic
studies estimate annual infection rates
of 10–30/100,000 in endemic areas.
LACV is a member of the California
serogroup of viruses in the genus
Orthobunyavirus. The serogroup
contains members found on five
continents that include human
pathogens such as La Crosse, Snowshoe
hare, and Jamestown Canyon viruses in
North America; Guaroa virus in North
and South America; Inkoo and Tahyna
viruses in Europe; and Lumbo virus in
Africa. Children who recover from
severe La Crosse encephalitis may have
significantly lower IQ scores than
expected and a high prevalence (60% of
those tested) of attention-deficithyperactivity disorder. Seizure
disorders are also common in survivors.
LACV can also cause encephalitis in
immunosuppressed adults. Projected
lifelong economic costs associated with
neurologic sequelae range from
$48,775–3,090,398 per case. At present,
a vaccine or FDA-approved antiviral
therapy is not available.
This application principally claims
live attenuated LACV vaccine
compositions, but also includes subunit
vaccine compositions including
California encephalitis virus (CEV)
serogroup immunogens, attenuated and
inactivated CEV serogroup and chimeric
Bunyaviridae. Also claimed are methods
of treating or preventing CEV serogroup
infection in a mammalian host, methods
of producing a subunit vaccine
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composition, isolated polynucleotides
comprising a nucleotide sequence
encoding a CEV serogroup immunogen,
methods for detecting LACV infection in
a biological sample and infectious
chimeric Bunyaviridae.
Application: Immunization against
Bunyaviridae.
Developmental Status: Live
attenuated vaccine candidates are
currently being developed and
preclinical studies in mice and monkeys
are in progress. Suitable vaccine
candidates will then be evaluated in
clinical studies.
Inventors: Stephen S. Whitehead,
Richard S. Bennett, Brian R. Murphy
(NIAID).
Publication: RS Bennett et al. Genome
sequence analysis of La Crosse virus and
in vitro and in vivo phenotypes. Virol
J. 2007 May 8;4:41.
Patent Status:
U.S. Provisional Application No. 60/
920,691 filed 29 Mar 2007 (HHS
Reference No. E–158–2007/0–US–01).
U.S. Provisional Application No. 60/
928,406 filed 08 May 2007 (HHS
Reference No. E–158–2007/1–US–01).
U.S. Provisional Application filed 29
Jun 2007 (HHS Reference No. E–158–
2007/2–US–01).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity:
The NIAID Laboratory of Infectious
Diseases is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize live attenuated virus
vaccine candidates for La Crosse virus
and other Bunyaviridae. Please contact
Dr. Whitehead at 301/496–7692 for
more information.
Chlamydia Vaccine
Description of Invention: Chlamydia
trachomatis is an obligate intracellular
bacterial pathogen that colonizes and
infects oculogenital mucosal surfaces.
The organism exists as multiple
serovariants that infect millions of
people worldwide. Ocular infections
cause trachoma, a chronic follicular
conjunctivitis that results in scarring
and blindness. The World Health
Organization estimates that 300–500
million people are afflicted by
trachoma, making it the most prevalent
form of infectious preventable
blindness. Urogenital infections are the
leading cause of bacterial sexually
transmitted disease in both
industrialized and developing nations.
Moreover, sexually transmitted diseases
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are risk factors for infertility, the
transmission of HIV, and human
papilloma virus-induced cervical
neoplasia. Control of C. trachomatis
infections is an important public health
goal. Unexpectedly, however, aggressive
infection control measures based on
early detection and antibiotic treatment
have resulted in an increase in infection
rates, most likely by interfering with
natural immunity, a concept suggested
by studies performed in experimental
infection models. Effective management
of chlamydial disease will likely require
the development of an efficacious
vaccine.
This technology claims vaccine
compositions that comprise an
immunologically effective amount of
PmpD protein from C. trachomatis. Also
claimed in the application are methods
of immunizing individuals against C.
trachomatis. PmpD is an antigenically
stable pan-neutralizing target that, in
theory, would provide protection
against all human strains, thus allowing
the development of a univalent vaccine
that is efficacious against both blinding
trachoma and sexually transmitted
disease.
Application: Prophylactics against C.
trachomatis.
Developmental Status: Preclinical
studies have been performed.
Inventors: Harlan Caldwell and
Deborah Crane (NIAID).
Publication: DD Crane et al.
Chlamydia trachomatis polymorphic
membrane protein D is a speciescommon pan-neutralizing antigen. Proc.
Natl Acad Sci USA. 2006 Feb
7;103(6):1894–1899. Epub 2006 Jan 30.
Patent Status: PCT Patent Application
No. PCT/US2007/001213 filed 16 Jan
2007 (HHS Reference No. E–031–2006/
0–PCT–02).
Licensing Status: Available for
exclusive or non-exclusive licensing.
Licensing Contact: Peter A. Soukas,
J.D.; 301/435–4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity:
The NIAID, Laboratory of Intracellular
Parasites, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize PmpD vaccine
development. Please contact Harlan D.
Caldwell, at hcaldwell@niaid.nih.gov or
406/363–9333 for more information.
Dated: August 21, 2007.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E7–16935 Filed 8–27–07; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Clinical Center; Notice of Closed
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 a meeting of the
Board of Scientific Counselors of the
NIH Clinical Center.
The meeting will be closed to the
public as indicated below in accordance
with the provisions set forth in section
552b(c)(6), Title 5 U.S.C., as amended
for the review, discussion, and
evaluation of individual intramural
programs and projects conducted by the
Clinical Center, including consideration
of personnel qualifications and
performance, and the competence of
individual investigators, the disclosure
of which constitute a clearly
unwarranted invasion of personal
privacy.
Name of Committee: Board of Scientific
Counselors of the NIH Clinical Center.
Date: September 24–25, 2007.
Time: 8 a.m. to 12 p.m.
Agenda: To review and evaluate the
Critical Care Medicine Program.
Place: National Institutes of Health,
Building 10, 10 Center Drive, CRC Room 4–
2551, Bethesda, MD 20892.
Contact Person: David K. Henderson, MD,
Deputy Director for Clinical Care, Office of
the Director, Clinical Center, National
Institutes of Health, Building 10, Room 6–
1480, Bethesda, MD 20892, (301) 496–3515.
Dated: August 20, 2007.
Jennifer Spaeth,
Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 07–4196 Filed 8–27–07; 8:45 am]
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DEPARTMENT OF HEALTH AND
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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
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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 sections
552b(c)(4) and 552b(c)(6), 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 Cancer
Advisory Board.
Open: September 17, 2007, 8:30 a.m. to
4:15 p.m.
Agenda: Program reports and
presentations; Business of the Board.
Place: National Cancer Institute, 9000
Rockville Pike, Building 31, C Wing, 6th
Floor, Conference Room 10, Bethesda, MD
20892.
Contact Person: Dr. Paulette S. Gray,
Executive Secretary, National Cancer
Institute, National Institutes of Health, 6116
Executive Boulevard, 8th Floor, Room 8001,
Bethesda, MD 20892–8327, (301) 496–5147.
Name of Committee: National Cancer
Advisory Board.
Closed: September 17, 2007, 4:15 p.m. to
5:30 p.m.
Agenda: Review of grant applications.
Contact Person: Dr. Paulette S. Gray,
Executive Secretary, National Cancer
Institute, National Institutes of Health, 6116
Executive Boulevard, 8th Floor, Room 8001,
Bethesda, MD 20892–8327, (301) 496–5147.
Name of Committee: National Cancer
Advisory Board.
Open: September 18, 2007, 8 a.m. to 12
p.m.
Agenda: Program reports and
presentations; Business of the Board.
Contact Person: Dr. Paulette S. Gray,
Executive Secretary, National Cancer
Institute, National Institutes of Health, 6116
Executive Boulevard, 8th Floor, Room 8001,
Bethesda, MD 20892–8327, (301) 496–5147.
Any interested person may file written
comments with the committee by forwarding
the statement to the Contact Person listed on
this notice. The statement should include the
name, address, telephone number and when
applicable, the business or professional
affiliation of the interested person.
In the interest of security, NIH has
instituted stringent procedures for entrance
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including taxicabs, hotel, and airport shuttles
will be inspected before being allowed on
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Information is also available on the
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[Federal Register Volume 72, Number 166 (Tuesday, August 28, 2007)]
[Notices]
[Pages 49283-49285]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-16935]
-----------------------------------------------------------------------
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.
Development of Antigenic Chimeric St. Louis Encephalitis Virus/Dengue
Virus Type Four Recombinant Viruses (SLEV/DEN4) as Vaccine Candidates
for the Prevention of Disease Caused by SLEV
Description of Invention: St. Louis Encephalitis Virus (SLEV) is a
mosquito-borne flavivirus that is endemic in the Americas and causes
sporadic outbreaks of disease in humans. SLEV is a member of the
Japanese encephalitis virus serocomplex and is closely related to West
Nile Virus (WNV). St. Louis encephalitis is found throughout North,
Central, and South America, and the Caribbean, but is a major public
health problem mainly in the United States. Prior to the outbreak of
West Nile virus in 1999, St. Louis encephalitis was the most common
human disease caused by mosquitoes in the United States. Since 1964,
there have been about 4,440 confirmed cases of St. Louis encephalitis,
with an average of 130 cases per year. Up to 3,000 cases have been
reported during epidemics in some years. Many more infections occur
without symptoms and go undiagnosed. At present, a vaccine or FDA
approved antiviral therapy is not available.
The inventors have previously developed a WNV/Dengue4Delta30
antigenic chimeric virus as a live attenuated virus vaccine candidate
that contains the WNV premembrane and envelope (prM and E) proteins on
a dengue virus type 4 (DEN4) genetic background with a thirty
nucleotide deletion (Delta30) in the DEN4 3'-UTR. Using a similar
strategy, the inventors have generated an antigenic chimeric virus,
SLE/DEN4Delta30. Preclinical testing results indicate that
chimerization of SLE with DEN4Delta30 decreased neuroinvasiveness in
mice, did not affect neurovirulence in mice, and appeared to
overattenuate the virus for non-human primates. Modifications of the
SLE/DEN4Delta30 vaccine candidate are underway to improve its
immunogenicity.
This application claims live attenuated chimeric SLE/DEN4Delta30
vaccine compositions and bivalent WNV/SLE/DEN4Delta30 vaccine
compositions. Also claimed are methods of treating or preventing SLEV
infection in a mammalian host, methods of producing a subunit vaccine
composition, isolated polynucleotides comprising a nucleotide sequence
encoding a SLEV immunogen, methods for detecting SLEV infection in a
biological sample and infectious chimeric SLEV.
Application: Immunization against SLEV or SLEV and WNV.
Development Status: Live attenuated vaccine candidates are
currently being developed and preclinical studies in mice and monkeys
are in progress. Suitable vaccine candidates will then be evaluated in
clinical studies.
Inventors: Stephen S. Whitehead, Joseph Blaney, Alexander Pletnev,
Brian R. Murphy (NIAID).
Patent Status: U.S. Provisional Application No. 60/934,730 filed 14
Jun 2007 (HHS Reference No. E-240-2007/0-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Collaborative Research Opportunity: The NIAID Laboratory of
Infectious Diseases is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize live attenuated virus vaccine candidates for
St. Louis encephalitis virus. Please contact Dr. Whitehead at 301-496-
7692 for more information.
Monoclonal Antibodies Against Dengue and Other Viruses With Deletion in
Fc Region
Description of Invention: The four dengue virus (DENV) serotypes
(DENV-1 to DENV-4) are the most important arthropod-borne flaviviruses
in terms of morbidity and geographic distribution. Up to 100 million
DENV infections occur every year, mostly in tropical and subtropical
areas where vector mosquitoes are abundant. Infection with any of the
DENV serotypes may be asymptomatic or may lead to classic dengue fever
or more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome
(DSS), which are increasingly common in the dengue endemic areas.
Immunity to the same virus serotype (homotypic immunity) is life-long,
whereas immunity to different serotypes (heterotypic immunity) lasts
[[Page 49284]]
2-3 months so that infection with a different serotype virus is
possible. DHF/DSS often occurs in patients with second, heterotypic
DENV infections or in infants with maternally transferred dengue
immunity. Severe dengue is a major cause of hospitalization, and
fatality rates vary from <1% to 5% in children.
Antibody-dependent enhancement (ADE) has been proposed as an
underlying pathogenic mechanism of DHF/DSS. ADE occurs because
preexisting subneutralizing antibodies and the infecting DENV form
complexes that bind to Fc receptor-bearing cells, leading to increased
virus uptake and replication. ADE has been repeatedly demonstrated in
vitro using dengue immune sera or monoclonal antibodies and cells of
monocytic and recently, B lymphocytic lineages bearing Fc receptors.
ADE of DENV-2 infection has also been demonstrated in monkeys infused
with a human dengue immune serum.
We have identified chimpanzee-human chimeric IgG1 mAbs capable of
neutralizing or binding to one or more DENV serotypes. Cross-reactive
IgG 1A5 neutralizes DENV-1 and DENV-2 more efficiently than DENV-3 and
DENV-4, and type-specific IgG 5H2 neutralizes DENV-4 at a high titer.
Analysis of antigenic variants has localized the IgG 1A5 binding site
to the conserved fusion peptide in E. Thus, IgG 1A5 shares many
characteristics with the cross-reactive antibodies detected in
flavivirus infections.
This application claims a variant of an antibody comprising a
polypeptide in the Fc region, which binds an Fc gamma receptor
(FcgammaR) with lower affinity than the parent antibody. The variant
polypeptide comprises a deletion of nine amino acids at the N-terminus
of the CH2 domain in the Fc region. Introduction of the Fc
variant abrogates the antibody-mediated dengue virus replication
enhancing activity. This invention has important implications for the
antibody-mediated prevention of dengue virus infection.
Application: Immunization against Dengue and/or flaviviruses.
Developmental Status: Antibody candidates have been synthesized and
preclinical studies have been performed.
Inventors: Ana Goncalvez, Robert Purcell, C.J. Lai (NIAID).
Publication: AP Goncalvez et al. Monoclonal antibody-mediated
enhancement of dengue virus infection in vitro and in vivo and
strategies for prevention Proc Natl Acad Sci USA. 2007 May
29;104(22):9422-9427. Epub 2007 May 15.
Patent Status:
U.S. Provisional Application No. 60/922,282 filed 04 Apr 2007 (HHS
Reference No. E-159-2007/0-US-01).
U.S. Provisional Application No. 60/927,755 filed 04 May 2007 (HHS
Reference No. E-159-2007/1-US-01).
U.S. Provisional Application No. 60/928,405 filed 08 May 2007 (HHS
Reference No. E-159-2007/2-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Live Attenuated Virus Vaccines for La Crosse Virus and Other
Bunyaviridae
Description of Invention: La Crosse virus (LACV), family
Bunyaviridae, is a mosquito-borne pathogen endemic in the United
States. LACV infection results in 70-130 clinical cases a year and is
the major cause of pediatric arboviral encephalitis in North America.
LACV was first identified as human pathogen in 1960 after its isolation
from a 4 year-old girl from Minnesota who suffered meningoencephalitis
and later died in La Crosse, Wisconsin. The majority of LACV infections
are mild and never reported, however serologic studies estimate annual
infection rates of 10-30/100,000 in endemic areas. LACV is a member of
the California serogroup of viruses in the genus Orthobunyavirus. The
serogroup contains members found on five continents that include human
pathogens such as La Crosse, Snowshoe hare, and Jamestown Canyon
viruses in North America; Guaroa virus in North and South America;
Inkoo and Tahyna viruses in Europe; and Lumbo virus in Africa. Children
who recover from severe La Crosse encephalitis may have significantly
lower IQ scores than expected and a high prevalence (60% of those
tested) of attention-deficit-hyperactivity disorder. Seizure disorders
are also common in survivors. LACV can also cause encephalitis in
immunosuppressed adults. Projected lifelong economic costs associated
with neurologic sequelae range from $48,775-3,090,398 per case. At
present, a vaccine or FDA-approved antiviral therapy is not available.
This application principally claims live attenuated LACV vaccine
compositions, but also includes subunit vaccine compositions including
California encephalitis virus (CEV) serogroup immunogens, attenuated
and inactivated CEV serogroup and chimeric Bunyaviridae. Also claimed
are methods of treating or preventing CEV serogroup infection in a
mammalian host, methods of producing a subunit vaccine composition,
isolated polynucleotides comprising a nucleotide sequence encoding a
CEV serogroup immunogen, methods for detecting LACV infection in a
biological sample and infectious chimeric Bunyaviridae.
Application: Immunization against Bunyaviridae.
Developmental Status: Live attenuated vaccine candidates are
currently being developed and preclinical studies in mice and monkeys
are in progress. Suitable vaccine candidates will then be evaluated in
clinical studies.
Inventors: Stephen S. Whitehead, Richard S. Bennett, Brian R.
Murphy (NIAID).
Publication: RS Bennett et al. Genome sequence analysis of La
Crosse virus and in vitro and in vivo phenotypes. Virol J. 2007 May
8;4:41.
Patent Status:
U.S. Provisional Application No. 60/920,691 filed 29 Mar 2007 (HHS
Reference No. E-158-2007/0-US-01).
U.S. Provisional Application No. 60/928,406 filed 08 May 2007 (HHS
Reference No. E-158-2007/1-US-01).
U.S. Provisional Application filed 29 Jun 2007 (HHS Reference No.
E-158-2007/2-US-01).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The NIAID Laboratory of
Infectious Diseases is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize live attenuated virus vaccine candidates for
La Crosse virus and other Bunyaviridae. Please contact Dr. Whitehead at
301/496-7692 for more information.
Chlamydia Vaccine
Description of Invention: Chlamydia trachomatis is an obligate
intracellular bacterial pathogen that colonizes and infects
oculogenital mucosal surfaces. The organism exists as multiple
serovariants that infect millions of people worldwide. Ocular
infections cause trachoma, a chronic follicular conjunctivitis that
results in scarring and blindness. The World Health Organization
estimates that 300-500 million people are afflicted by trachoma, making
it the most prevalent form of infectious preventable blindness.
Urogenital infections are the leading cause of bacterial sexually
transmitted disease in both industrialized and developing nations.
Moreover, sexually transmitted diseases
[[Page 49285]]
are risk factors for infertility, the transmission of HIV, and human
papilloma virus-induced cervical neoplasia. Control of C. trachomatis
infections is an important public health goal. Unexpectedly, however,
aggressive infection control measures based on early detection and
antibiotic treatment have resulted in an increase in infection rates,
most likely by interfering with natural immunity, a concept suggested
by studies performed in experimental infection models. Effective
management of chlamydial disease will likely require the development of
an efficacious vaccine.
This technology claims vaccine compositions that comprise an
immunologically effective amount of PmpD protein from C. trachomatis.
Also claimed in the application are methods of immunizing individuals
against C. trachomatis. PmpD is an antigenically stable pan-
neutralizing target that, in theory, would provide protection against
all human strains, thus allowing the development of a univalent vaccine
that is efficacious against both blinding trachoma and sexually
transmitted disease.
Application: Prophylactics against C. trachomatis.
Developmental Status: Preclinical studies have been performed.
Inventors: Harlan Caldwell and Deborah Crane (NIAID).
Publication: DD Crane et al. Chlamydia trachomatis polymorphic
membrane protein D is a species-common pan-neutralizing antigen. Proc.
Natl Acad Sci USA. 2006 Feb 7;103(6):1894-1899. Epub 2006 Jan 30.
Patent Status: PCT Patent Application No. PCT/US2007/001213 filed
16 Jan 2007 (HHS Reference No. E-031-2006/0-PCT-02).
Licensing Status: Available for exclusive or non-exclusive
licensing.
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The NIAID, Laboratory of
Intracellular Parasites, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize PmpD vaccine development. Please
contact Harlan D. Caldwell, at hcaldwell@niaid.nih.gov or 406/363-9333
for more information.
Dated: August 21, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-16935 Filed 8-27-07; 8:45 am]
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