[Federal Register: March 18, 2003 (Volume 68, Number 52)]
[Notices]
[Page 12916-12917]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18mr03-66]
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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.
Lepirudin Adsorbed to Catheter
McDonald Horne (CC)
DHHS Reference No. E-295-02/0
Licensing Contact: Michael Shmilovich; 301/435-5018;
shmilovichm@od.nih.gov.
The invention is a method for preventing venous access device (VAD)
thrombosis by coating the VAD catheter with lepirudin, which has been
found to be readily adsorbed by the silicone rubber of the VADs, and is
expected to have good retention properties. VADs typically remain in
place for weeks or months and sometimes cause clotting (thrombosis) of
the veins. Accordingly, the simple technique of soaking a silicone
catheter in lepirudin before venous insertion is the gist of the
invention. Chronically ill patients who must be catheterized for long
periods of time will benefit particularly from this technique which
promises to reduce swelling and pain associated with VAD-induced
thrombosis.
Peptide Inhibitors of Yersinia Phosphatase (YopH) as Potential
Treatments Against Plague
Terrence Burke, Jr., et al. (NCI)
DHHS Reference No. E-263-2002
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507;
thalhamc@od.nih.gov.
This invention pertains to compounds, i.e., peptides or pro-drugs
thereof, which are useful as inhibitors of phosphotyrosine
phosphatases, and in particular, as inhibitors of the Yersinia
phosphatase (YopH). The invention also provides pharmaceutical
compositions and a method of inhibiting the YopH enzyme as well as a
method of treating plague or Black Death. The compounds may be useful
as anti-bioterrorism agents, and are potentially important for
therapeutic development because they may facilitate bioavailablility,
given the low ionic charge of the inhibitors.
The bacterium Yersinia pestis causes bubonic, pneumonic and
septicemic plague, and it is considered as a potential bioterrorism
agent. Within Yersinia is a 70 kb virulence plasmid, which encodes for
a system of secreted proteins, called ``Yops'', which act either as
intracellular effectors or as translocators. Yersinia's Yop system
represents the archetype for one of the major virulence mechanisms in
various pathogenic bacteria, referred to as type III, where
extracellular bacteria that are in close contact with a eukaryotic cell
deliver bacterial proteins into the cytosol of the cell. Other animal
pathogens with related systems include the genera Salmonella, Shigella,
Pseudomonas, Chlamydia, and Bortedella, as well as E. coli.
One such effector protein, YopH, is a protein-tyrosine phosphatase
(PTP) with a C-terminal catalytic domain that is essential to
Yersinia's virulence, playing an antiphagocytic role by
dephosphorylating focal adhesion proteins. The phosphatase activity of
YopH is required for bacterial pathogenesis. This invention relates to
the use of tripeptides as inhibitors of YopH, and therefore as
potential treatments of plague. More in particular, the inventors have
discovered that certain structural features are required to be present
on those peptides in order to be inhibitory against Yersinia's YopH.
A Varicella-Zoster Virus Vaccine Mutant That Is Markedly Impaired for
Latent Infection
Jeffrey Cohen (NIAID), Edward Cox (FDA), Lesley Pesnicak (NIAID)
DHHS Reference No. E-250-02/0 filed 05 Nov 2002
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@od.nih.gov.
Chickenpox is caused by acute infection with varicella-zoster virus
(VZV). The virus spreads throughout the body and enters cells of the
nervous system. Latent infection occurs and the virus establishes
itself in dorsal root and cranial nerve ganglia. The latent virus
subsequently can reactivate and present as zoster (shingles). The
current varicella-zoster virus vaccine (Oka strain) is highly effective
to protect against varicella (chickenpox), but establishes a latent
infection in the central nervous system and can reactivate to cause
shingles. This invention relates to a mutated form of
[[Page 12917]]
the current Oka vaccine strain that it is markedly impaired for
establishing latency. This virus may be a safer vaccine than the
currently available vaccine.
Recombinant of Respiratory Syncytial Virus (RSV) Expressing Green and/
or Red Fluorescent Protein
Mark Peeples (Rush Presbyterian-St. Luke's Medical Center) and Peter
Collins (NIAID)
DHHS Reference No. E-038-2002/0 (Research Materials)
Licensing Contact: Susan Ano; 301/435-5515; anos@od.nih.gov.
The biological materials RSV expressing green and/or red
fluorescent proteins are available for licensing as research tools for
antiviral drug screening or for studying infection and replication of
the virus in real time in cultured cells. RSV is the most important
viral respiratory pathogen in infants and thus is a major target for
development of antiviral agents. The fluorescent protein markers allow
rapid quantification of the extent of virus infection and are easily
used in conjunction with common apparatuses such as 96-well plates and
fluorescence plate readers.
These viruses are produced by the reverse genetic system as
described in U.S. patent 6,264,957 (issued July 24, 2001) to Dr. Peter
Collins of the NIAID. This reverse genetic system is also available for
licensing (DHHS Ref. E-187-1995/1), including all of the plasmids
necessary to make the recombinant viruses.
This research has been described, in part, in Hallak et al.,
Virology 271:264-275, 2000; Zhang et al., J. Virol. 76:5654-5666, 2002;
Techaarpornkul et al., Virology 294:296-304, 2002.
HIV-1 Reverse Transcriptase Expression Systems
Dr. Stephen Hughes et al. (NCI)
DHHS Reference No. E-034-91/0
Licensing Contact: Sally Hu; 301/435-5606; hus@od.nih.gov.
This invention describes a series of HIV-1 reverse transcriptase
(RT)-based products:
(a) HIV-1 RT (66 kDa) and HIV-2 RT (68 kDa) expression plasmids.
These lead to the production of homodomeric forms of these proteins.
(b) Inducible expression plasmid p66his-prot producing large
amounts of HIV-1 RT (p66) and small amounts of HIV-1 protease. This
leads to the production of a p66/p51 heterodimeric form of the protein.
A version of this plasmid is available with 6x his tail on p66 to
simplify purification of the heterodimer. Expression plasmids for wild-
type RT and for numerous mutated RT, including most of the common drug
resistant mutants, are available. Mutated RT forms: AZT-21; HIV-2
(His); L74V; P236L; L100I; K103N; V106A; E138K; V181I; M184V; Y188L.
(c) HIV-1 RT with a substitution C280S and a double mutant C38V/
C280S that are less susceptible to oxidation than the wild-type enzyme.
These mutant HIV-1 RTs have enzymatic properties that are similar to
wild-type HIV-1 RT.
Those RT expression plasmids might be used both in biological and
medical research such as to study various properties of the enzyme, to
determine which domains of the enzyme are the most promising for
directing anti-RT reagents against, and to screen RT inhibitors in
vitro. The HIV-1 Reverse Transcriptase Expression plasmids subject of
this report are available for licensing via biological material
licenses (BML).
Dated: March 11, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer,
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-6442 Filed 3-17-03; 8:45 am]
BILLING CODE 4140-01-P