[Federal Register Volume 68, Number 222 (Tuesday, November 18, 2003)]
[Notices]
[Pages 65078-65079]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-28789]


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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 invention listed below is owned by an agency of the U.S. 
Government and is 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 
application 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 application.

Compositions and Methods for Enhancing Differential Gene Expression

    I Horikawa, JC Barrett (NCI).
    DHHS Reference No. E-008-2001/0-US-01 filed 05 Jun 2003.
    Licensing Contact: Susan S. Rucker; 301/435-4478; 
[email protected].
    This application describes compositions and methods useful in 
enhancing the differential expression of heterologous nucleic acids. In 
particular, the application claims inventions that encompass artificial 
promoters derived from the human telomerase reverse transcriptase 
promoter (hTERT) and their use. More particularly, this application 
describes artificial hTERT promoters that minimize the expression of a 
heterologous nucleic acid sequences operably linked thereto in normal 
cells while providing for high levels of expression of the heterologous 
nucleic acid in cancer cells. The heterologous nucleic acid sequence 
preferentially encodes a product that will have cytotoxic activity upon 
expression in the cell.
    The hTERT promoter has been characterized and research has 
demonstrated that small portions thereof are responsible for the 
cancer-specific expression of the hTERT gene. The cancer-specific 
nature of hTERT promoter activity suggests that it is a target for the 
development of specific anti-cancer therapeutics and other strategies 
for cancer treatment.
    In order to improve therapeutic strategies for delivering cytotoxic 
nucleic acid sequences that are expressed in cancer cells artificial 
hTERT promoters have been constructed that, when operably linked to the 
cytotoxic nucleic acid sequence, minimize expression of the cytotoxic 
nucleic acid sequence in normal cells while maintaining high levels of 
expression of the cytotoxic nucleic acid sequence in cancer cells. This 
differential regulatory control is accomplished by operably linking 
particular E-box nucleic acid sequences in cis with the regulatory 
elements of the hTERT promoter associated with gene expression in 
cancer cells and a nucleic acid sequence encoding a product that is 
cytotoxic upon expression. Cytotoxic substances include, for example, 
Pseudomonas exotoxin (polypeptide toxin), HSV thymidine kinase (pro-
drug converting) or bax (apoptosis inducing).
    Experimental work related to this invention has been published at 
Horikawa, I et al., Mol Biol Cell 13(8): 2585-97 (Aug 2002).

Leukoregulin, An Antitumor Lymphokine, and Its Therapeutic Uses

    JH Ransom (NCI), RP McCabe, M Haspel, N Pomato.
    U.S. Patent Application No. 06/906,353 filed 11 Sep 1986, which 
issued as U.S. Patent 4,849,506 on 18 Jul 1989 (DHHS Reference No. E-
537-1983/2-US-01); U.S. Patent Application No. 07/350,879 filed 11 May 
1989, which issued as U.S. Patent 5,082,657 on 21 Jan 1992 (DHHS 
Reference No. E-970-1997/0-US-01).
    Licensing Contact: Susan S. Rucker; (301) 435-4478; 
[email protected].
    These patents claim compositions and methods for using the 
lymphokine/cytokine known as leukoregulin. In particular, leukoregulin 
is useful in methods of treating cancer. The NIH is the exclusive 
licensee of these patents.
    Leukoregulin, a cytokine derived from T lymphocytes, is a 
glycoprotein hormone. Leukoregulin interacts with target cells to 
regulate cellular activity with its effects being pleiotrophic and 
dependent on the type of target cell. Among other roles, leukoregulin 
has been demonstrated to influence the synthesis of collagenase, 
stromelysin-1, collagen, and hyaluronan in human fibroblasts. These 
properties make it important in maintaining the

[[Page 65079]]

extracellular matrix. Leukoregulin can be used alone or in combination 
with chemotherapeutic agents. Experimental evidence suggests that 
leukoregulin in combination with chemotherapeutic agents will improve 
the activity of the chemotherapeutic agent without additional toxicity.
    This work has been published at Ransom, JH et al. Cancer Res 45(2): 
851-62 (Feb 1985) and Ransom JH, et al. Adv Exp Med Biol 184: 281-7 
(1985).

    Dated: November 10, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-28789 Filed 11-17-03; 8:45 am]
BILLING CODE 4140-01-P