[Federal Register Volume 74, Number 60 (Tuesday, March 31, 2009)]
[Notices]
[Pages 14568-14569]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-7223]


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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, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency 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 any 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.

Mouse Monoclonal Antibodies to Human Tristetraprolin (TTP)

    Description of Technology: TTP has been implicated in autoimmune 
and inflammatory diseases through its role as a regulator of the 
transcripts encoding several pro-inflammatory cytokines, including 
tumor necrosis factor alpha. However, it has been difficult to study 
endogenous TTP in man and other animals because it is expressed at very 
low levels in most cells and tissues, and because of the lack of mouse 
monoclonal antibodies directed at the human protein.
    Scientists at the NIH have developed three mouse monoclonal 
antibodies (TTP-16, TTP-214 and TTP-409) that react to different 
regions of the human TTP to allow for the identification and 
localization of the TTP protein by standard protocols. Although 
validation has only been conducted at the level of western blotting to 
date, they do not appear to cross-react with other human members of the 
TTP protein family.
    Potential Applications: Mouse monoclonal antibodies to human TTP 
will be useful in both clinical and basic research on a variety of 
inflammatory diseases and studies of mRNA destabilization. They can be 
used to identify or isolate TTP in cells or tissues by Western 
blotting, immunoprecipitation, immunohistochemistry, 
immunofluorescence, flow cytometry, and RNA super-shift assays, and can 
also be used in cross-linking and immunoprecipitation protocols.
    Inventors: Elizabeth A. Kennington and Perry J. Blackshear (NIEHS).
    Patent Status: HHS Reference No. E-123-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected].

Use of Anthrax Lethal Factor To Treat Cancer and Screening Methods for 
MAPK Kinase Protease Activity

    Description of Technology: Anthrax toxin, produced by Bacillus 
anthracis, is composed of three proteins; protective antigen (PA), 
edema factor (EF), and lethal factor (LF). PA by itself has little or 
no toxic effect upon cells, but serves to bind cell surface receptors 
and mediate the entry of EF and LF into the cell. EF has been 
identified as an adenylate cyclase and together with PA forms a toxin 
(edema toxin; EdTx) which can induce edema formation when injected 
subcutaneously. LF and PA together form a toxin (lethal toxin; LeTx) 
which can cause rapid lysis of certain macrophage-derived cell lines in 
vitro as well as death when injected intravenously.
    Indirect evidence had suggested that LF was a metalloprotease. 
However, the

[[Page 14569]]

intracellular target of LF remained unknown until recently when NIH 
scientists discovered that LF proteolytically inactivates mitogen 
activated protein kinase kinase 1 and 2 (MAPKK1, 2). Using oocytes of 
the frog Xenopus laevis as well as tumor derived NIH3T3 (490) cells 
expressing an effector domain mutant form of the human V12HaRas 
oncogene these scientists demonstrated that LF induced proteolysis of 
MAPKK 1 and 2, resulting in their irreversible inactivation. MAPKK 1 
and 2 are components of the mitogen activated protein kinase (MAPK) 
signal transduction pathway, an evolutionarily conserved pathway that 
controls cell proliferation and differentiation in response to 
extracellular signals and also plays a crucial role in regulating 
oocyte meiotic maturation. Further, the MAPK pathway has been shown to 
be constitutively activated in many primary human as well as in tumor-
derived cell lines. Consistent with this, treatment of V12Ha-Ras 
transformed NIH 3T3 cells with LeTx inhibits cell proliferation and 
causes their reversion to a non-transformed phenotype.
    This invention specifically relates to in vitro and ex vivo methods 
of screening for modulators, homologues, and mimetics of LF mitogen 
activated protein kinase kinase (MAPKK) protease activity. Applications 
for this technology could be:
     A novel tool (LF) for the study of the cellular role of 
the MAPK pathway in normal or tumor cells.
     Investigation of LF for developing inhibitors for cancer 
therapy. By analyzing structural-functional relationships, additional 
compounds with improved specificity, increased potency, and reduced 
toxicity can be generated. Mimetics which block MAPKK activity or the 
determination of mechanisms of regulation of proteases that target 
MAPKK at or near the same site targeted by LF could be developed.
     A protease-based assay for LF by using a peptide to test 
for LF cleavage. There is no commercial test for anthrax. This assay 
could be used for testing soldiers for anthrax exposure. 
Characterization of the interaction between LF and MAPKK at the amino 
acid level may lead to the generation of inhibitors which may prove 
useful in treating anthrax.
    Inventors: Nicholas S. Duesbery (NCI), Craig Webb (NCI), Stephen H. 
Leppla (NIDCR), George F. Vande Woude (NCI).
    Patent Status:
    U.S. Patent 6,485,925 issued 26 Nov. 2002 (HHS Reference No. E-066-
1998/0-US-06).
    U.S. Patent 6,893,835 issued 17 May 2005 (HHS Reference No. E-066-
1998/0-US-07).
    U.S. Patent 6,911,203 issued 28 June 2005 (HHS Reference No. E-066-
1998/0-US-08).
    U.S. Patent 7,056,693 issued 06 June 2006 (HHS Reference No. E-066-
1998/0-US-10).
    U.S. Patent 7,183,071 issued 27 Feb. 2007 (HHS Reference No. E-066-
1998/0-US-11).
    International rights available.
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    This abstract updates the version published in the Federal Register 
on Friday, March 13, 2009 (74 FR 10947-10948), to correct the reference 
numbers from E-068-1998 to E-066-1998.

    Dated: March 25, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E9-7223 Filed 3-30-09; 8:45 am]
BILLING CODE 4140-01-P