[Federal Register Volume 72, Number 149 (Friday, August 3, 2007)]
[Notices]
[Pages 43284-43285]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-15054]


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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; 
[email protected]
    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 
[email protected] 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; 
[email protected].
    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 
[email protected] 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; 
[email protected].
    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 
[email protected] 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