[Federal Register Volume 65, Number 201 (Tuesday, October 17, 2000)]
[Notices]
[Pages 61343-61345]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-26585]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, DHHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The inventions listed below are owned by agencies 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.
Virus-Like Particles as Unlinked Adjuvants
John Schiller, Bryce Chackerian, Joseph Lee, Douglas Lowy (NCI), DHHS
Reference No. E-231-00/0 filed 20 Jul 2000.
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; e-mail:
[email protected]
This invention claims immunostimulating or vaccine compositions in
which non-infectious virus-like particles (VLPs) serve as unlinked
adjuvants. Co-administration of VLPs with an antigen enhances induction
of high titer IgG antibodies to self or foreign antigens and promotes T
cell responses to foreign antigens. The
[[Page 61344]]
VLP-target antigen combination can be administered alone or with a
traditional adjuvant. The VLPs of the current invention are
contemplated to comprise capsid protein(s) of a virus assembled into a
shell resembling a virion, but not containing pathogenic viral DNA or
RNA. The VLPs are unlinked, rather than physically linked to the
antigen because this may reduce the manufacturing complexity of the
vaccine. Unlinked VLP adjuvants, for example papillomavirus VLPs, of
the invention have a number of advantages: (1) They are non-
inflammatory in humans, (2) are potent at amplifying IgG antibody
responses to self antigens, (3) induce a pronounced Th1 type of T cell
response, and (4) may provide two-fold protection, against the virus
corresponding to the VLP type, as well as against the disease
associated with the other component in the VLP-target antigen
combination.
System and Method for Representing Knowledge in a Distributed
System
Stephen J. Shaw (NCI), Serial No. 09/470,684 filed 23 Dec 1999.
Licensing Contact: Dale Berkley; 301/496-7735 ext. 223; e-mail:
[email protected]
This invention relates to a knowledge base (KB) system for storing
data in a computer system. More specifically, this invention relates to
systems and methods for representing, manipulating, and displaying
knowledge consisting of categories, entities and relationships stored
in a plurality of databases. The invention contemplates providing a
user-friendly computer-based distributed system of databases which
enables its users to create, use and share a knowledge base of
information consisting of diverse entities related to each other by
semantically meaningful links. The system generates a knowledge base
that allows individuals to store information on a virtually unlimited
range of entities. Due to its design as a distributed system, it is
well suited to preserve the autonomy and portability of data belonging
to each individual and workgroup, while maintaining links of that data
to publicly available data elsewhere in the system and even links to
information on entities external to the system. Diverse strategies are
employed to simplify the implementation and use of the system. Some
unique features of this software-based invention are: (1) The ability
to handle any number of conceptually distinct categories of items (such
as people, events, institutions, tasks, concepts, processes, document
types); (2) tools for creating relationships between any two or more
objects, with the ability to categorize types of relationships and
decide which categories they apply to; (3) use of parent-child
relationships to organize, view and navigate information; (4)
flexibility in adding diverse categories of objects and relationships,
while maintaining a simple underlying data structure and programming
environment; and (5) the ability to view complex relationships in
flexible and informative ways; (6) tools for managing names which are
indispensable for finding the relevant objects; and (7) efficient ways
to search information and filter retrievals to limit to relevant
information.
Peptides that Stabilize Protein Antigens and Enhance Presentation
to CD8+ T Cells
Roger Kurlander, Elizabeth Chao, Janet Fields (CC), DHHS Reference No.
E-172-99/0 filed 06 Dec 1999.
Licensing Contact: Peter Soukas; 301/496-7056, ext. 268; e-mail:
[email protected]
This invention relates to compositions and methods for stabilizing
an antigen against proteolytic degradation and enhancing its
presentation to CD8+ cells. The invention claims ``fusion agents,''
isolated molecules comprising a hydrophobic peptide joined to an
epitope to which a CD8+ T cell response is desired. Also claimed in the
invention are the nucleic acid sequences that encode the fusion agents.
Recently, there has been great interest in developing vaccines to
induce protective CD8+ T cell responses, however, there are practical
obstacles to this goal. Although purified antigenic peptides are
effectively presented in vitro, introduced in a purified form they
often do not stimulate effective T cell responses in vivo because the
antigens are insufficiently immunogenic and too easily degraded.
Adjuvants or infectious ``carriers'' often can enhance these immune
responses, however, these added agents can cause unacceptable local or
systemic side effects. The present invention increases antigen
stability and promotes in vivo responses in the absence of an adjuvant
or active infection.
The invention describes three variants of lemA, an antigen
recognized by CD8+ cells in mice infected with Listeria monocytogenes.
The antigenic and stabilizing properties of lemA can be accounted for
by the covalent association of the immunogenic aminoterminal
hexapeptide with the protease resistant scaffolding provided by amino
acids 7 to 33 of the lemA sequence (lemA(7-33)). Variants t-
lemA, and s-lemA bearing an antigenic sequence immediately preceding
lemA(7-33), and lemS containing an immunogenic sequence
immediately after lemA(7-33), each induce a CD8+ T cell
response and protect the crucial immunogenic oligopeptide from protease
degradation. The site of antigen insertion relative to
lemA(7-33) can influence antigen processing by
preferentially promoting processing either in the cytoplasm or
endosomal compartment. Therefore, several embodiments of the invention
involve the construction of antigen processing protein molecules and
their methods of use. Alternatively, a DNA sequence coding
lemA(7-33) may be inserted at an appropriate site to enhance
the immunogenicity of the antigenic element coded by a DNA vaccine. In
sum, this invention is an attractive, nontoxic alternative to protein/
adjuvant combinations in eliciting CD8 responses in vivo and a useful
element for enhancing the efficiency with which products coded by DNA
vaccines are processed and presented in vivo. Because
lemA(7-33) is particularly effective in protecting
oligopeptides from proteases, this invention may have particular
usefulness in enhancing local T cell at sites such as mucosal surfaces
where there may be high proteolytic activity.
For more specific information about the invention or to request a
copy of the patent application, please contact Peter Soukas at the
telephone number or e-mail listed above. Additionally, please see a
related article published in the Journal of Immunology at:
1999;163:6741-6747.
Major Neutralization Site of Hepatitis E Virus and Use of this
Neutralization Site in Methods of Vaccination
Darren Schofield, Suzanne U. Emerson, Robert H. Purcell (NIAID), DHHS
Reference No. E-043-00/0 filed 01 Dec 1999.
Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail:
[email protected]
Hepatitis E is endemic in many countries throughout the developing
world, in particular on the continents of Africa and Asia. The disease
generally affects young adults and has a very high mortality rate, up
to 20%, in pregnant women. This invention relates to the identification
of a neutralization site of hepatitis E virus (HEV) and neutralizing
antibodies that react with it. The neutralization site is located on a
polypeptide from the ORF2 gene (capsid gene) of HEV. This
neutralization site was identified using a panel of chimpanzee
monoclonal antibodies that are virtually identical to human antibodies.
Since this neutralization site
[[Page 61345]]
is conserved among genetically divergent strains of HEV, the
neutralizing monoclonal antibodies may be useful in the diagnosis,
treatment and/or prevention of hepatitis E. Furthermore, immunogens
that encompass this neutralization site may be used in vaccination to
effectively prevent, and/or reduce the incidence of HEV infection.
Polypeptides containing this neutralization site may be useful in
evaluating vaccine candidates for the production of neutralizing
antibodies to HEV.
Viral Glycoprotein Subunit Vaccine
Richard Compans, Ranjit Ray, U.S. Patent 4,790,987 issued 13 Dec 1988.
Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; e-mail:
[email protected]
The present invention relates to a vaccine composition useful in
the prevention of virus-caused disease comprising as its active agent
at least one immunogenically effective amount of immunogenic viral
envelope glycoprotein complexed with a lipid. These subunit vaccine
compositions are useful for the prevention of viral infections
including influenza virus, parainfluenza virus, herpes virus,
paramyxoviruses, rabies virus, and human T-cell lymphotrophic viruses.
The patent also discloses a method for preparing the vaccine
compositions. A novel feature of the invention is the utilization of a
dialyzable detergent for solubilization of the active component, which
allows a relatively simple purification process on a large scale. Thus,
these vaccines are easier to prepare than other glycoprotein subunit
vaccines and retain their antigenicity to a greater extent than
formalin-inactivated subunit vaccines.
Dated: October 5, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 00-26585 Filed 10-16-00; 8:45 am]
BILLING CODE 4140-01-P