[Federal Register Volume 72, Number 166 (Tuesday, August 28, 2007)]
[Notices]
[Pages 49283-49285]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-16935]


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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.

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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; 
[email protected].

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; 
[email protected].
    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; 
[email protected].
    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 [email protected] 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]
BILLING CODE 4140-01-P