[Federal Register Volume 66, Number 30 (Tuesday, February 13, 2001)]
[Notices]
[Pages 10026-10028]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-3605]


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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

[[Page 10027]]

Confidential Disclosure Agreement will be required to receive copies of 
the patent applications.

Benzoylalkylindolepyridinium Compounds and Pharmaceutical 
Compositions Comprising Such Compounds

William G. Rice, Mingjun Huang, Robert W. Buckheit, Jr., David G, 
Covell, Grzegorz Czerwinski, Christopher Michejda, and Vadim Makarov 
(NCI)
DHHS Reference No. E-278-98/0 filed 18 Dec 2000

    Licensing Contact: Sally Hu; 301/496-7056 ext. 265; e-mail: 
[email protected].
    The present invention provides novel antiviral compounds active 
against HIV. These compounds, referred to as 
benzoylalkylindolepyridinium compounds (BAIPs) are effective against 
HIV isolates that have developed mutations rendering conventional drugs 
ineffective. BAIPs apparently do not require intracellular 
phosphorylation nor bind to the reverse transcriptase (RT) active site, 
which distinguishes their mechanism of action from the 
dideoxynucleoside (ddN) and acyclic nucleoside phosphonate (ANP) 
nucleoside analog drugs. ddN and ANP have proven clinically effective 
against limiting human immunodeficiency virus (HIV) infection, but 
resistance rapidly emerges due to mutations in and around the RT active 
site. The BAIPs also may be distinguished from non-nucleoside reverse 
transcriptase inhibitors (NNRTIs), in part because the BAIPs bind to a 
different site on the RT enzyme. The usage of NNRTIs is limited by the 
rapid emergence of resistant strains also. Moreover, unlike the NNRTIs, 
BAIPs of the present invention have been shown to be effective against 
HIV-1, HIV-2 and simian immunodeficiency virus (SIV) proliferation. 
Thus, BAIPs are broadly antiviral, non-nucleoside reverse transcriptase 
inhibitors (BANNRTIs).

Monoclonal Antibodies Specific for the E2 Glycoprotein of Hepatitis 
C Virus and Their Use in the Diagnosis, Treatment and Prevention of 
Hepatitis C

Darren Schofield, Suzanne U. Emerson, Robert H. Purcell, Harvey J. 
Alter (NIAID)
DHHS Reference No. E-017-01/0 filed 01 Dec 2000

    Licensing Contact: Carol Salata; 301/496-7735 ext. 232; 
[email protected].
    Hepatitis C virus is an enveloped, single stranded RNA virus, 
approximately 50 nm in diameter, that has been classified as a separate 
genus in the Flaviviridae family. Most persons infected with hepatitis 
C virus develop chronic infection. These chronically infected 
individuals have a relatively high risk of developing chronic 
hepatitis, liver cirrhosis and hepatocellular carcinoma. There is 
currently no vaccine to prevent hepatitis C virus infection. The 
present invention relates to human monoclonal antibodies which exhibit 
immunological binding affinity for the hepatitis C virus E2 
glycoprotein and are cross-reactive against different hepatitis C virus 
strains. These antibodies may be used in passive immunoprophylaxis for 
the prevention of hepatitis C virus infection and/or in passive 
immunotherapy for the treatment of hepatitis C.

Cell-Free Assembly of Lentiviral Capsids

Campbell et al. (NCI)
DHHS Reference No. E-287-00/0 filed 01 Dec 2000

    Licensing Contact: Carol Salata; 301/496-7735 ext. 232; e-mail: 
[email protected].
    Dr. Campbell and his colleagues have discovered a novel method of 
assembling HIV immature capsids from recombinant purified Gag proteins 
in vitro. Specifically, the discovery is that the presence of certain 
phosphates is required for assembly of full-sized HIV capsids in vitro. 
Therefore, compounds which interfere with the effect of these 
phosphates on virus assembly or that deplete cellular pools of these 
phosphates, could be effective antiviral agents. This discovery then 
provides an in vitro screening method of identifying such potential 
antiviral agents. It also provides techniques for producing full-size 
virus-like particles in vitro. In fact, Dr. Campbell is the first to 
report the assembly of authentic viral capsids from full length Gag 
proteins in a completely defined system. Such proteins could be 
potentially useful as safe HIV vaccines or for delivery of nucleic 
acids or pharmacological agents in patients.

Sample Delivery System With Laminar Mixing for Microvolume 
Biosensing

Peter Schuck (ORS)
DHHS Reference No. E-143-00/0 filed 06 Nov 2000

    Licensing Contact: Dale Berkley; 301/496-7735 ext. 223; e-mail: 
[email protected].
    The invention is a sample delivery system that comprises at least 
two microchannels in fluid communication with a sample chamber 
containing a biosensor. Biosensing for studying molecular recognition 
has become an important biophysical tool for biomedical research. The 
system aspirates a small sample volume into the system's microfluidic 
channels and applies a periodic oscillatory flow pattern to the sample. 
This prevents sample depletion in the stagnant layer across the sensor 
surface and results in efficient mixing of the sample during the 
biosensor measurement. Because the oscillatory flow pattern does not 
produce a net transport of the sample with time, there is a very long 
incubation time of the sensor surfaces with a very small sample volume. 
The new sample delivery system uses sample volumes of only 3 to 8 
microliters, compared to the 25 to 200 microliter volumes of 
conventional systems, which use cuvette principles or continuous flow 
microfluidics. The present invention is substantially better than 
existing systems with respect to biosensor contact time and required 
sample volume.

In Vivo DNA Engineering Using the Recombination System (red) of 
Bacteriophage Lambda

Donald Court, Daiguan Yu, E-Chiang Lee, Nancy Jenkins, Neal Copeland 
(NCI)
DHHS Reference No. E-170-99/0

    Licensing Contact: Peter Soukas; 301-496-7056 ext. 268; e-mail: 
[email protected].
    Available for licensing through a Biological Materials License 
Agreement are several E. coli strains developed through a novel 
recombination system that allows for efficient chromosome engineering 
in E. coli using electroporated linear DNA. This technique provides for 
a much greater degree of accuracy and efficiency compared to current 
restriction endonuclease techniques for DNA engineering. The inventors' 
system is based on the recombination function designated red in 
bacteriophage lambda (). High recombination efficiency is 
obtained using a PCR-amplified donor DNA fragment with two flanking 30-
40 base pairs of DNA homologous to the targeted DNA. In vivo cloning is 
accomplished by introducing linear plasmid vectors and linear DNA to be 
cloned with the segment to be cloned flanked by short homologies to the 
vector. The linear vector can also be used to subclone DNA segments 
directly from the bacterial chromosome or genomic BAC (PAC) clones by 
short homology mediated gap repair. The inventors have shown that when 
the red function is turned on for fifteen minutes, donor DNA can be 
recombined with a frequency 104-105 times higher than in a red off-
control kept at 32 degrees C. The system is further described in Yu et 
al., ``An efficient

[[Page 10028]]

recombination system for chromosome engineering in Escherichia coli,'' 
P.N.A.S. 97(11):5978-5983 (2000).

Simian-Human HAV Chimeras Encoding a Hepatitis A Virus Having a 
Chimeric 2C Protein

G Raychaudhuri, SU Emerson, RH Purcell (NIAID)
Serial No. 60/015,642 filed 19 Apr 1996; PCT/US97/06506 filed 18 Apr 
1997; Serial No. 09/171,387 filed 24 Mar 1999

    Licensing Contact: Carol Salata, 301/496-7735 ext. 232; e-mail: 
[email protected].

    The claimed invention provides nucleic acid sequences which encode 
hepatitis A viruses having a chimeric 2C protein. The chimeric 2C gene 
consists of sequences from both the human strain and the simian AGM-27 
strain. The chimeric virus is a promising candidate for an attenuated 
hepatitis A virus vaccine which may be more economical than an 
inactivated vaccine, especially in underdeveloped countries where 
hepatitis A in endemic. Additional information on the chimeras may be 
found in Rayachaudhuri et al., ``Utilization of chimeras between 
human(HM175) and simian(AGM27) strains of hepatitis A virus to study 
the molecular basis of virulence,'' J. Virol. 72:7467-7474(1998).

Novel Antimalarial Compounds, Methods of Synthesis Thereof, 
Pharmaceutical Compositions Comprising Same, and Methods of Using 
Same for Treatment and Prevention of Malaria

Michael R. Boyd (NCI), Gerhard Bringmann (EM), Sven Harmsen (EM) Roland 
Gotz (EM), T. Ross Kelly (EM), Matthias Wenzel (EM), Guido Francois 
(EM), J. D. Phillipson (EM), Laurent A. Assi (EM), Christopher 
Schneider (EM) Serial No. 08/195,547, filed 02/14/1994, now U.S. Patent 
5,639,761; Serial No. 08/843,582, filed 04/16/1997; Serial No. 08/
279,261, filed 07/22/1994, now U.S. Patent 5,552,550; Serial No. 08/
674,362, filed 07/01/1996, now U.S. Patent 5,763,613; Serial No. 09/
001,801, filed 12/31/1997, now U.S. Patent 6,140,339; Serial No. 09/
527,002, filed 03/16/2000; Serial No. 08/279,339, filed 07/22/1994, now 
U.S. Patent 5,571,919; Serial No. 08/363,684, filed 12/23/1994, now 
U.S. Patent 5,578,729; Serial No. 08/674,359, filed 07/01/1996, now 
U.S. Patent 5,789,594; Serial No. 08/721,084, filed 09/24/1996, now 
U.S. Patent 5,786,482

    Licensing Contact: Peter Soukas; 301/496-7056 ext. 268; e-mail: 
[email protected].
    According to data recently reported by the World Health 
Organization (WHO), the death rate from malaria exceeds one million 
individuals per year. The Public Health Service seeks exclusive or non-
exclusive licensee(s) to develop and commercialize the technology 
claimed within the portfolio of U.S. patents issued and pending, and 
corresponding international patents issued and pending. These patents 
and pending applications claim an exceptionally broad universe of novel 
naphthylisoquinoline alkaloid compounds, and methods of total synthesis 
thereof. Representative examples of these compounds have been shown to 
have potent in vitro activity against malaria parasites, including 
parasites that are highly resistant to available antimalarial drugs. 
Representative examples have also been shown to have potent in vivo 
activity against malaria parasites in animal models. Pharmaceutical 
compositions comprising these compounds, as well as methods of using 
the compounds to treat or prevent a malarial infection of a host, are 
claimed. The relative structural simplicity of this class of compounds, 
and the ready synthetic access thereto, provide unprecedented 
opportunities for structure-activity relationship (SAR), lead-
optimization and antimalarial drug development. The technology is 
further described in the following publications: J. Nat Prod. 1997 
Jul.;60(7):677-83 and Bioorg. Med. Chem. Lett. 1998 Jul.;8(13): 1729-
34.

    Dated: February 2, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-3605 Filed 2-12-01; 8:45 am]
BILLING CODE 4140-01-P