[Federal Register Volume 68, Number 52 (Tuesday, March 18, 2003)]
[Notices]
[Pages 12916-12917]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-6442]


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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; 
[email protected].

    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; 
[email protected].

    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; [email protected].

    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; [email protected].

    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; [email protected].

    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