[Federal Register Volume 71, Number 42 (Friday, March 3, 2006)]
[Notices]
[Pages 10980-10981]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-3013]


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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 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.

Use of Replicators in Gene Therapy

Mirit Aladjem, Cindy Tseng, Haiqing Fu and Lixin Wang (NCI).
U.S. Provisional Application No. 60/715,113 filed 07 Sep 2005 (HHS 
Reference No. E-309-2005/0-US-01).
Licensing Contact: Susan Carson, D. Phil.; 301/435-5020; 
[email protected].

    There remains a need for a gene therapy vector capable of 
delivering a stably maintained, appropriately-regulated therapeutic 
transgene without adverse side effects. Lack of expression of a 
therapeutic transgene is still a major obstacle for gene therapy and 
the extent of transcriptional silencing of gene therapy vectors depends 
on their chromosomal location and on the presence of nearby 
heterochromatin. Most active genes replicate early during S phase, 
while transcriptional silencing correlates with late replication. The 
location of DNA replication initiation events on chromatin is affected 
by DNA sequences termed replicators, which interact with distal 
sequences to establish an epigenetic permissive state that directs the 
replication machinery to the replicator at a specific time during S 
phase. NIH researchers at the National Cancer Institute have now shown 
that inclusion of functional replicators in transgenes are able to 
prevent gene silencing, suggesting that replicator sequences have an 
important role in stabilizing gene expression patterns. The ideal gene 
delivery vector system would include functional elements that permit 
stable maintenance and long-term regulated transgene expression and the 
inclusion of replicators may be key

[[Page 10981]]

in the prevention of gene silencing and replication delay.
    Claims are directed to specific constructs and methods of using 
replicators and transgene constructs to inhibit, delay or prevent gene 
silencing and are available for licensing. The addition of these 
sequences to non-replicating or self-replicating gene delivery systems 
may be key in the development of effective gene delivery vectors.
    Related portfolios available for licensing include: (1) the 
Mammalian Artificial Chromosome Portfolio [HHS Ref. No. E-128-2005/0-
US-01, U.S. Provisional Patent Application No. 60/669,589 filed 08 Apr 
2005 and HHS Ref. No. E-253-2000/0-US-03, U.S. Patent Application 
Publication No. U.S. 2004/0245317 filed 08 Apr 2002) and (2) the TAR 
Cloning Portfolio (HHS Ref. No. E-121-1996/0-US-06 and HHS Ref. No. E-
158-2001/0-US-02, U.S. Patent Application Publication No. U.S. 2004/
0248289 filed 04 Oct 2002].
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

TNF-alpha Converting Enzyme Inhibitory Agents and Stimulatory Agents

Stewart J. Levine et al. (NHLBI).
U.S. Provisional Application No. 60/505,394 filed 24 Sep 2003 (HHS 
Reference No. E-208-2003/0-US-01); PCT Application No. PCT/US2004/
031608 filed 24 Sep 2004, which published as WO 2005/030798 on 07 Apr 
2005 (HHS Reference No. E-208-2003/0-PCT-02).
Licensing Contact: Marlene Astor; 301/435-4426; [email protected].

    The action of Tumor Necrosis Factor alpha (TNF-alpha) has been 
implicated in such diseases as arthritis, sepsis, ulcerative colitis, 
multiple sclerosis, Crohn's disease, septic shock, graft rejection, 
cachexia, insulin resistance, post-ischemic reperfusion injury, tumor 
metastasis, tissue ulceration, abnormal wound healing, periodontal 
disease, bone disease, proteinuria, aneurismal aortic disease, 
degenerative cartilage loss, demyelinating diseases of the nervous 
system, and HIV infection. TNF-alpha converting enzyme (TACE) or ADAM 
17 (A Disintegrin And Metalloprotease) is a member of a family of zinc 
metalloproteases, and is an important regulator of inflammation, immune 
regulation, and cellular proliferation as a consequence of its ability 
to catalyze the activation of TNF-alpha from a membrane bound to a 
soluble form.
    The NIH announces the identification of a protein, corresponding to 
the amino-terminus of the TACE prodomain, that possesses a TACE 
inhibitory activity that is independent of a cysteine-switch mechanism. 
This TACE inhibitory protein could be used as a new therapeutic agent 
against chronic inflammatory diseases that are mediated by TNF-alpha.

    Dated: January 21, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E6-3013 Filed 3-2-06; 8:45 am]
BILLING CODE 4167-01-P