[Federal Register Volume 63, Number 67 (Wednesday, April 8, 1998)]
[Notices]
[Pages 17189-17190]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-9177]


-----------------------------------------------------------------------

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.

A Human Cell Line Which Constitutively Expresses the Nonstructural 
(NS) Proteins of Hepatitis C Virus

G Sherman, S Feinstone (FDA)
DHHS Reference No. E-012-98/0
Licensing Contact: Carol Salata, 301/496-7735 ext. 232

    Currently there are no good animal models or tissue culture systems 
which can be used in assaying compounds directed against HCV. A cell 
line has been developed which may represent a valuable tool in the 
identification of potential therapeutic agents against hepatitis C. 
This permanent human cell line contains an expression vector which 
directs cells to synthesize 5 nonstructural (NS) hepatitis C proteins: 
NS3, NS4a, NS4b, NS5a, and NS5b. Two of these proteins provide 
enzymatic activities crucial to virus replication (NS3: protease, 
helicase; NS5b, RNA polymerase). The cell line will permit the 
evaluation of antivirals directed against these enzymes.

Plasmodium Falciparum Gene Linked to Chloroquine Resistance in 
Human Malaria

TE Wellems, X-Z Su (NIAID)
Serial No. 60/058,895 filed 15 Sep 97
Licensing Contact: Carol Salata, 301/496-7735 ext. 232

    Malaria infects over 200 million people annually worldwide, causing 
at least one million deaths yearly. Particularly affected areas of the 
world include Africa, Asia, the Indian subcontinent and South America. 
Malaria is caused by systemic infections with the parasite Plasmodium 
which infects blood and other tissues. Of the four species of 
Plasmodium that can infect humans, P. falciparum is the most deadly. 
Therapeutic and preventive approaches to control malaria include the 
use of drugs, particularly drugs that are chemically related to 
quinine, and the attempted development of vaccines that confer 
immunological resistance to infection.
    Chloroquine, once a first-line drug for control of malaria, now 
fails frequently against P. falciparum. This invention relates to 
methods and reagents for diagnosis of chloroquine-resistant malarial 
infections caused by P. falciparum, and the development of new 
antimalarial drugs against these infections. These diagnostics are 
based on a unique and heretofore unknown gene and its protein product 
linked to chloroquine resistance in P. falciparum malaria. Because of 
the worldwide incidence of chloroquine-resistant P. falciparum, there 
is a need for diagnostic methods for detecting chloroquine-resistant 
malaria, thus allowing such infected individuals to be treated with 
alternative drugs. Furthermore, there is a need to design and/or screen 
for new antimalarial agent that can take the place of chloroquine. Use 
of alternative drugs may prevent further spread of chloroquine-
resistant P. falciparum in infected individuals.

Phage Display of Intact Domains at High Copy Number

AC Steven (NIAMS)
Serial No. 08/837,301 filed 11 Apr 97
Licensing Contact: Carol Salata, 301/496-7735 ext. 232

    Filamentous phage-based display systems have found widespread use 
in molecular biology, including many immunologic applications such as 
antigen presentation and the immuno-isolation of desired recombinants 
by ``biopanning''. The present invention relates to a phage display 
system in which the molecules to be displayed (i.e., molecules of 
interest) are covalently connected to dispensable capsid polypeptides 
such as SOC (small outer capsid) and HOC (highly antigenic outer 
capsid) polypeptides that are, in turn, bound to a surface lattice 
protein, such as those on the surface of a virion or polyhead. 
Polyheads are tubular capsid variants containing much longer numbers of 
the surface lattice protein. Molecules of interest may be displayed in 
various ways. For example, a chimeric polypeptide that includes a 
dispensable polypeptide and a polypeptide of interest can be expressed 
in Esherichia coli, purified, and then bound in vitro to separately 
isolated surface lattice proteins. The surface lattice proteins can be 
those on the surface of a capsid or polyhead from which the wild type 
dispensable polypeptides have been deleted. Similarly, a chimera that 
contains a

[[Page 17190]]

dispensable polypeptide and a synthetic molecule of interest can be 
prepared in vitro and bound to surface lattice proteins. In another 
embodiment, a positive selection vector forces integration of a gene 
that encodes a dispensable polypeptide and a polypeptide of interest 
into the genome of a phage from which the wild type dispensable 
polypeptide is deleted. For example, a modified soc gene can be 
integrated into a soc-deleted T4 genome, leading to in vivo binding of 
the display molecule on progeny virions. More than one type of 
dispensable polypeptide can be used as part of the chimera for 
displaying one or more molecules of interest. For example, the surface 
lattice proteins of a phage may be bound to a chimera that contains SOC 
and a chimera that contains HOC.
    The display system has been successfully demonstrated for three 
molecules of interest that vary in their length and character: (1) a 
tetrapeptide; (2) the 43 amino acid residue V3 loop domain of gp120, 
the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein; 
and (3) poliovirus VP1 capsid protein (312 residues).

Ultrasound-Hall Effect Imaging System and Method

H Wen (NHLBI)
DHHS Reference No. E-067-96/0; PCT/US97/11272 filed 03 Jul 97 Licensing 
Contact: John Fahner-Vihtelic, 301/496-7735 ext. 270

    The present application provides for a new ultrasound-based imaging 
modality that is based on the interaction among a static magnetic field 
and conductive moieties in the imaged sample under electrical 
excitation. The application also provides a new ultrasound-based 
imaging modality that provides a contrast mechanism which reflects the 
conductivity distribution of the medium being imaged. The disclosed 
methods and system are advantageous over other ultrasonic imaging 
systems in the following aspects: it provides a method which is not 
limited to contrast based solely on acoustic properties; it dispenses 
with acoustic beam excitation, and therefore is suitable for fast 2D 
and 3D image formation with wide angle signal reception. A working 
prototype system is in testing and the present invention is suitable 
for development into commercial computed imaging products for 
biomedical imaging and industrial non-destructive testing.

Multideterminant Peptide Antigens That Stimulate Helper T 
Lymphocyte Response to HIV in a Range of Human Subjects

JA Berzofsky, JD Ahlers, PL Nara, M Shirai, CD Pendleton (NCI) Serial 
No. 08/060,988 filed 14 May 93; PCT/US94/05142 filed 13 May 94
Licensing Contact: Robert Benson, 301/496-7056 ext. 267

    A vaccine for the prevention and/or treatment of HIV infection 
would ideally elicit a response in a broad range of the population. It 
would also have the capability of inducing high titered neutralizing 
antibodies, cytotoxic T lymphocytes, and helper T cells specific for 
HIV-1 gp 160 envelope protein. A vaccine based on synthetic or 
recombinant peptides has been developed which elicits these responses 
while avoiding the potential safety risks of live or killed viruses. 
Unlike previously developed vaccines this invention avoids those 
regions of gp 160 which may contribute to acceleration of infection or 
the development of immune deficiency. This invention provides peptides 
up to 44 amino acid residues long that stimulate helper T-cell response 
to HIV in a range of human subjects. Six multideterminant regions have 
been identified in which overlapping peptides are recognized by mice of 
either three or all four MHC types. Four of the six regions have 
sequences relatively conserved among HIV-I isolates. These 
multideterminant cluster peptides are recognized by T cells from humans 
of multiple HLA types, and have been found in a phase I clinical trial 
to elicit neutralizing antibodies, cytotoxic T cells, and helper T 
cells in at least some of the human subjects.

Mucosal Cytotoxic T Lymphocyte Responses

J. Berzofsky, I Belyakov, M Derby, B Kelsall, W Strober (NCI)
DHHS Reference No. E-268-97/1 (incorporating USSN 60/058,523) filed 17 
Feb 98 (priority to 11 July 97)
Licensing Contact: Robert Benson, 301-496-7056 ext. 267

    This invention is the discovery that intrarectal (IR) 
administration of a peptide antigen can induce an antigen-specific, 
protective CTL response in the mucosal and systemic immune system. The 
CTL response is much greater than occurs with intranasal 
administration. The CTL response is enhanced by co-administration of a 
mucosal adjuvant such as cholera toxin, and is further enhanced by IR 
administration of interleukin 12 (IL-12). IR administration of an HIV-1 
peptide vaccine protected mice against an IR challenge with a 
recombinant vaccinia virus expressing HIV gp160. This invention 
provides an approach to the use of peptide vaccines that protect 
against mucosal infection, especially for HIV. The invention is further 
described in Proc. Natl. Acad. Sci. USA, Vol. 95, pp. 1709-1714, 1998.

    Dated: March 31, 1998.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 98-9177 Filed 4-7-98; 8:45 am]
BILLING CODE 4140-01-M