[Federal Register: August 3, 2007 (Volume 72, Number 149)]
[Notices]
[Page 43284-43285]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03au07-81]
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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 Dengue Virus Type 3 Vaccine Candidates Containing Either
1) Nucleotide Deletions in the 3'-UTR of the Genome Consisting of More
Than 30 Contiguous Nucleotides in One or Multiple Regions, or 2) a 3'-
UTR Derived From DEN4 and Containing the A30 Nucleotide Deletion
Description of Technology: The disease burden associated with
dengue virus infection has increased over the past several decades in
the tropical and semi-tropical regions of the world, where over 2
billion people live at risk of dengue infection. Annually, there are an
estimated fifty (50) to one hundred (100) million cases of dengue
fever, making development of an effective vaccine a priority. In
addition, there is a need for a ``travelers vaccine'' to protect those
visiting dengue virus endemic areas, similar in scope to other
currently available ``travelers vaccines'', such as hepatitis A
vaccine.
The previously identified [Delta]30 attenuating mutation, created
in each dengue virus serotype by the removal of 30 homologous
nucleotides from the 3'-UTR, is capable of attenuating wild-type
strains of dengue virus type 1 (DEN1), type 4 (DEN4) and to a limited
extent type 2 (DEN2). These DEN1[Delta]30 and
[[Page 43285]]
DEN4[Delta]30 viruses have been shown to be both safe and immunogenic
in humans. However, the [Delta]30 mutation failed to have an
attenuating effect on dengue virus type 3 (DEN3). To generate DEN3
vaccine candidates with a clearly attenuated phenotype, viruses were
produced containing 3'-UTR deletions consisting of extensions of the
original [Delta]30 mutation or additional mutations which remove stem-
loop structures similar to those removed by [Delta]30. In addition, the
entire 3'-UTR of DEN3 was replaced with the 3'-UTR derived from DEN4
and containing the [Delta]30 mutation. Studies in monkeys demonstrated
that these newly developed viruses are highly attenuated, yet
sufficiently immunogenic to warrant their further development for use
as live attenuated vaccine candidates. Such viruses are anticipated to
become the DEN3 component of a tetravalent vaccine formulation designed
to immunize against all four dengue virus serotypes.
Application: Immunization against all four serotypes of Dengue
Virus.
Developmental Status: Vaccine candidates have been synthesized and
preclinical studies have been performed. The vaccine candidates of this
invention are slated to enter Phase I clinical trials in the next year.
Inventors: Stephen S. Whitehead, Joseph E. Blaney, Brian R. Murphy
(NIAID).
Patent Status: U.S. Provisional Application No. 60/837,723 filed 15
Aug. 2006 (HHS Reference No. E-139-2006/0-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 National Institute of
Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or
bm25f@nih.gov for more information.
Dengue Tetravalent Vaccine Containing a Common 30-Nucleotide Deletion
in the 3'-UTR of Dengue Types 1, 2, 3, and 4
Description of Technology: The invention relates to a dengue virus
tetravalent vaccine containing a common 30-nucleotide deletion
([Delta]30) in the 3'-untranslated region (UTR) of the genome of dengue
virus serotypes 1, 2, 3, and 4. The previously identified [Delta]30
attenuating mutation, created in dengue virus type 4 (DEN4) by the
removal of 30 nucleotides from the 3'-UTR, is also capable of
attenuating a wild-type strain of dengue virus type 1 (DEN1). Removal
of 30 nucleotides from the DEN1 3'-UTR in a highly conserved region
homologous to the DEN4 region encompassing the [Delta]30 mutation
yielded a recombinant virus attenuated in rhesus monkeys to a level
similar to recombinant virus DEN4[Delta]30. This established the
transportability of the [Delta]30 mutation and its attenuation
phenotype to a dengue virus type other than DEN4. The effective
transferability of the [Delta]30 mutation establishes the usefulness of
the [Delta]30 mutation to attenuate and improve the safety of
commercializable dengue virus vaccines of any serotype.
A tetravalent dengue virus vaccine containing dengue virus types 1,
2, 3, and 4 each attenuated by the [Delta]30 mutation is being
developed. The presence of the [Delta]30 attenuating mutation in each
virus component precludes the reversion to a wild-type virus by
intertypic recombination. In addition, because of the inherent genetic
stability of deletion mutations, the [Delta]30 mutation represents an
excellent alternative for use as a common mutation shared among each
component of a tetravalent vaccine.
Inventors: Stephen S. Whitehead (NIAID), Brian R. Murphy (NIAID),
Lewis Markoff (FDA), Barry Falgout (FDA), Kathryn A. Hanley (NIAID),
Joseph E. Blaney (NIAID).
Patent Status: U.S. Patent Application No. 10/970,640 filed 21 Oct.
2004, claiming priority to 03 May 2002 (HHS Reference No. E-089-2002/1-
US-02).
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or
bm25f@nih.gov for more information.
Development of Mutations Useful for Attenuating Dengue Viruses and
Chimeric Dengue Viruses
Description of Technology: Although flaviviruses cause a great deal
of human suffering and economic loss, there is a shortage of effective
vaccines. This invention relates to dengue virus mutations that may
contribute to the development of improved dengue vaccines. Site
directed and random mutagenesis techniques were used to introduce
mutations into the dengue virus genome and to assemble a collection of
useful mutations for incorporation in recombinant live attenuated
dengue virus vaccines. The resulting mutant viruses were screened for
several valuable phenotypes, including temperature sensitivity in Vero
cells or human liver cells, host cell restriction in mosquito cells or
human liver cells, host cell adaptation for improved replication in
Vero cells, and attenuation in mice or in mosquitoes. The genetic basis
for each observed phenotype was determined by direct sequence analysis
of the genome of the mutant virus. Mutations identified through these
sequencing efforts have been further evaluated by re-introduction of
the identified mutations, singly, or in combination, into recombinant
dengue virus and characterization of the resulting recombinant virus
for phenotypes. In this manner, a menu of attenuating and growth
promoting mutations was developed that is useful in fine-tuning the
attenuation and growth characteristics of dengue virus vaccine
candidates. The mutations promoting growth in Vero cells have
usefulness for the production of live or inactivated dengue virus
vaccines.
Inventors: Stephen S. Whitehead, Brian R. Murphy, Kathryn A.
Hanley, Joseph E. Blaney (NIAID).
Patent Status: U.S. Patent No. 7,226,602 issued 05 Jun 2007 (HHS
Reference No. E-120-2001/0-US-04); U.S. Patent Application No. 11/
446,050 filed 02 Jun 2006 (HHS Reference No. E-120-2001/0-US-10).
Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646;
soukasp@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is
seeking statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or
bm25f@nih.gov for more information.
Dated: July 27, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-15054 Filed 8-2-07; 8:45 am]
BILLING CODE 4140-01-P