[Federal Register Volume 64, Number 179 (Thursday, September 16, 1999)]
[Notices]
[Pages 50292-50293]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-24125]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 contacting Richard U. 
Rodriguez, M.B.A., Technology Licensing Specialist, at the Office of 
Technology Transfer, National Institutes of Health, 6011 Executive 
Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/
496-7056 ext. 287; fax: 301/402-0220; e-mail: [email protected]. A signed 
Confidential Disclosure Agreement will be required to receive copies of 
the patent applications.

Methods for Treating Tumors Using Anti-Angiogenic Compounds

    Steven K. Libutti, Andrew L. Feldman (NCI), Serial No. 60/133,243 
filed 07 May 1999.
    Angiogenesis is the process of tumor vascularization which involves 
both positive and negative regulators. It is recognized as a critical 
process in tumor progression and is essential for the growth and 
persistence of solid tumors and their metastases. This vacularization 
is induced by a variety of pro-angiogenic factors, which are balanced 
against naturally occurring negative regulators of angiogenesis, such 
as endostatin.
    Endostatin is a protein derived from the cleavage of the precursor 
collagen XVIII. It is an endogenous inhibitor of angiogenesis and tumor 
growth that can inhibit angiogenesis and can induce dormancy or 
regression of large tumors in mice. Furthermore, endostatin does not 
induce acquired drug resistance, a problem associated with chemotherapy 
and other cytochemical therapies. However, difficulties in producing 
sufficient recombinant endostatin for widespread clinical use has 
presented significant obstacles in developing an endostatin therapy 
model.
    The present invention describes a method of delivering endostatin 
as well as other inhibitors of angiogenesis by administering an 
adenovirus vector carrying a modified endostatin gene. This method 
allows the host to produce high levels of secreted endostatin 
systemically and in the local tumor environment.
    This invention obviates the need to systemically administer 
recombinant protein and may allow for more efficient treatment 
strategies.

Methods for Identifying Modulators of GADD45 Polypeptide Activity

    Xin Wei Wang, Curtis C. Harris, Albert J. Fornace Jr., Jill D. 
Coursen. Qimin Zhan (NCI), Serial No. 60/126,069 filed 25 Mar 1999.
    A common method of treatment for cancer is to give radiation or 
chemicals to damage cancer cell's DNA so badly that the cell dies. 
However, these treatments are equally toxic to healthy cells. One 
approach to protecting normal cells from exposure to anti-cancer 
treatments would be to simultaneously treat the cells with a second 
agent which interacts preferentially with the cancer cells making them 
more susceptible to toxic radiation or chemical effective. This could 
be achieved by ``sensitizing'' the cancer to toxic treatments so the 
growing tumor cells die with a smaller amount of toxic radiation or 
chemical.
    This invention describes a method of ``sensitizing'' the DNA of a 
cancer cell making it more susceptible to conventional therapies 
including radiation. Utilizing this technology, patients could be 
exposed to radiation doses that would inactivate the cancer cell but 
spare the healthy cells. Normally, a cell with unrepaired DNA damage 
will die by apoptosis as it progresses part G2/M into mitosis. If the 
cell can ``stall'' its cell cycle long enough to repair this DNA 
damage, the self-destructive reaction may be avoided. However, if this 
stalling mechanism can be disturbed, less DNA repair time is available 
and thus relatively lesser amounts of anti-cancer agent are needed to 
kill the cell.
    One possible mediator of this stalling mechanism is GADD45, a 
ubiquitously expressed polypeptide induced by irradiation or DNA 
damaging agents. Inhibiting GADD45 prevents the cell from sufficiently 
repairing DNA damage to prevent its self-destructive passage to 
apoptosis. Thus, when a GADD45 inhibitor is co-administered with a DNA 
damaging drug, the cell is more sensitive to the irradiation or 
damaging drug.
    The present invention describes ingenious methods that have been 
embodied in a variety of ways so that, for the first time, GADD45 can 
be envisioned as a platform from which a variety of therapeutic 
interventions might be envisioned. These include but are not limited 
to, novel methods to assay for modulators of GADD45 as means to 
sensitize a proliferating cell to a DNA damaging agent by 
administration of novel inhibitors of GADD45 polypeptide activity.

Method for Detecting Radiation Exposure

    Albert J Fornace, Jr. (NCI), Sally A. Amundson (NCI), Jeffrey Trent 
(NHGRI), Serial No. 60/121,756 filed 26 Feb 1999.
    Ionizing radiation has many medical, industrial and military uses. 
Ionizing radiation is often used in the therapy of diseases such as 
cancer, however, exposure to biologically significant levels of such 
radiation can also cause genotoxic stress. In addition, many 
individuals are potentially exposed to radiation through occupational 
or accidental exposure. Such radiation can elicit a variety of cellular 
responses, ranging from cell-cycle arrest to mutation, malignant 
transformation, or cell death. The present invention describes a method 
for detecting exposure of organisms to biologically significant or 
hazardous amounts of ionizing radiation.
    This invention describes the identification of a large set of genes 
that are induced by ionizing radiation. Different patterns of gene 
induction are produced depending upon dose of radiation and time after 
treatment. Many of these genes are induced by physiological doses of 
radiation routinely used for cancer therapy. These genes sets may be 
useful as markers of exposure to hazardous radiation, or as markers to 
predict the likely response of a particular tumor to radiation therapy, 
and subsequently to track and access the response of patients to 
radiotherapy. In addition, these gene sets may also be useful in 
toxicological and epidemiological research and studies.


[[Page 50293]]


    Dated: September 7, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institute of Health.
[FR Doc. 99-24125 Filed 9-15-99; 8:45 am]
BILLING CODE 4140-01-M