[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]


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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, DHHS.

ACTION: Notice.

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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: 
<a href="/cdn-cgi/l/email-protection#483b273d23293b3808272c66262120662f273e"><span class="__cf_email__" data-cfemail="24574b514f455754644b400a4a4d4c0a434b52">[email protected]</span></a>
    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: 
<a href="/cdn-cgi/l/email-protection#680a0d1a03040d110c28070c46060100460f071e"><span class="__cf_email__" data-cfemail="b3d1d6c1d8dfd6cad7f3dcd79ddddadb9dd4dcc5">[email protected]</span></a>
    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: 
<a href="/cdn-cgi/l/email-protection#5a29352f313b292a1a353e74343332743d352c"><span class="__cf_email__" data-cfemail="ef9c809a848e9c9faf808bc1818687c1888099">[email protected]</span></a>
    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<INF>(7-33)</INF>). Variants t-
lemA, and s-lemA bearing an antigenic sequence immediately preceding 
lemA<INF>(7-33)</INF>, and lemS containing an immunogenic sequence 
immediately after lemA<INF>(7-33)</INF>, each induce a CD8+ T cell 
response and protect the crucial immunogenic oligopeptide from protease 
degradation. The site of antigen insertion relative to 
lemA<INF>(7-33)</INF> 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<INF>(7-33)</INF> 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<INF>(7-33)</INF> 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: 
<a href="/cdn-cgi/l/email-protection#1e6d7f727f6a7f7d5e717a3070777630797168"><span class="__cf_email__" data-cfemail="80f3e1ece1f4e1e3c0efe4aeeee9e8aee7eff6">[email protected]</span></a>
    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: 
<a href="/cdn-cgi/l/email-protection#80f3eff5ebe1f3f0c0efe4aeeee9e8aee7eff6"><span class="__cf_email__" data-cfemail="295a465c42485a5969464d07474041074e465f">[email protected]</span></a>
    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


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