[Federal Register Volume 70, Number 49 (Tuesday, March 15, 2005)]
[Notices]
[Pages 12700-12701]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5081]


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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 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.

Karyotypic Complexity as a Determinant of Anti-Cancer Drug Activity

    Ilan R. Kirsch and Anna V. Roschke (NCI).
U.S. Provisional Patent Application filed 04 Feb 2005 (DHHS Reference 
No. E-101-2005/0-US-01).
Licensing Contact: Michelle A. Booden; 301/451-7337; 
[email protected].


[[Page 12701]]


    The recent clinical introduction of small molecule inhibitors that 
target single molecules as effective anticancer therapies underscores 
the potential of patient specific therapeutic interventions. However, 
the definition of a cancer specific target need not be a single 
transforming or survival-related gene or gene product. Another 
targetable and relatively irreversible cellular state might be the 
complexity and instability of the chromosomal complement of cancer 
cells. Structural and numerical chromosomal alterations are present in 
most neoplasms and karyotypic complexity is associated with a poor 
clinical prognosis as well as aggressive and distinctive 
histopathologic features.
    The present invention describes methods for the selecting candidate 
compounds for evaluation for the treatment of cancer by defining the 
karyotypic complexity and heterogeneity in human cancer cells based on 
three components of genomic anatomy: ploidy, numerical chromosome 
changes, and structural chromosome rearrangements. Measures of 
complexity include the number of chromosomal rearrangements present in 
a cell line (structural complexity, SC ) and the number of chromosome 
deviations from the ploidy level (numerical complexity, NC). Measures 
of cell-to-cell chromosomal variability, which reflect the degree of 
ongoing instability, include numerical heterogeneity (NH) and 
structural heterogeneity (SH). Utilizing the methods claimed in the 
this application, a number of chemical compounds were identified and 
later determined to have increased cytotoxicity toward cancer cell 
lines with a specific karyotypic complexity.
    The positive correlations between drug sensitivity and karyotypic 
complexity and heterogeneity found in this analysis (122 statistically 
significant positive correlations) provide a distinct opportunity to 
identify agents that are more active against karyotypically complex and 
chromosomally unstable cancer cells. Such cells would typically be 
found in the epithelial cancers, which cause so much therapeutic 
concern and frustration.

Inhibition of Human Papillomavirus Type 16 and 18 E6 and E7 Oncogene 
Expression by E6 and E7-Specific siRNAs

Zhi-Ming Zheng (NCI).
DHHS Reference No. E-079-2005/0-US-01.
Licensing Contact: Michelle A. Booden; (301) 451-7337; 
[email protected].
    Cervical infection with human papillomaviruses (HPVs), such as 
HPV16 and HPV18, is strongly associated with development of cervical 
cancer. Integration of the viral genomes into the cervical cell genome 
is characteristic of infection with these HPVs. Thus, the majority of 
cervical cancer cells isolated from patients carry these viral genomes 
and express two viral oncoproteins, E6 and E7, which induce p53 and pRb 
degradation. Importantly, expression of both E6 and E7 oncogenes is 
essential for survival of cervical cancer cells.
    Small interfering RNA (siRNA) is emerging as a powerful tool for 
gene silencing and has much potential for anticancer and antiviral 
applications. The present invention describes a method employing novel 
siRNA sequences for inhibiting expression of the E6 and E7 viral 
oncoproteins of HPV 16 and 18, which are required for development and 
progression of HPV mediated cervical cancer.
    Since HPV 16 and HPV 18 are the most prevalent HPV types inducing 
cervical cancer in women, this discovery may have a significant impact 
on cervical cancer therapy. This technology could also have additional 
implications in variety of HPV-associated indications, such as 
anogenital warts, bladder, and head and neck carcinomas.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Biomarkers for Osteoarthritis

Shari M. Ling et al. (NIA).
U.S. Provisional Application No. 60/602,334 filed 18 Aug 2004 (DHHS 
Reference No. E-354-2004/0-US-01).
Licensing Contact: Marlene Shinn-Astor; (301) 435-4426; 
[email protected].
    Osteoarthritis is chronic, often progressive and substantially 
disabling condition that becomes more common with advanced age. 
Osteoarthritis commonly involves the knees, hands, hips, neck and back 
resulting in pain and limitations of movement.
    Unfortunately clinically available tests are neither capable of 
detecting osteoarthritis early in its development, nor sensitive enough 
to adequately assess disease progression. A better means of diagnosing 
early osteoarthritis and its progression that can be used to assess the 
response to therapeutic treatments is needed. The currently available 
laboratory techniques are highly sensitive but either lack specificity 
or require large volumes of sample. Rolling Circle Amplification (RCA) 
is new technology that precisely localizes unique signals arising from 
single reporter molecules. RCA has been incorporated into antibody-
based microarray system protein chips that enable testing with high 
sensitivity and specificity for hundreds of proteins simultaneously, 
using small sample volumes.
    This invention describes a method of using RCA technology for 
detecting the expression of serum proteins that are perturbed in 
osteoarthritis patients. The results of this testing can be used to 
identify proteins associated with osteoarthritis presence, prediction 
of osteoarthritis development and prognosis, predict response to 
osteoarthritis treatment and potentially also identify future anti-
osteoarthritic drugs.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Water-Soluble, Antineoplastic Derivatives of Taxol

Rudiger D. Haugwitz et al. (NCI).
U.S. Patent 4,942,184 issued 17 Jul 1990 (DHHS Reference No. E-090-
1987/0-US-01).
Licensing Contact: John Stansberry; 301/435-5236; 
[email protected].
    A new class of taxol derivatives offer an improved method for 
treating certain cancers. The use of taxol as an antineoplastic agent 
has been limited due to poor solubility in aqueous solutions. These new 
taxol derivatives have improved water solubility while retaining the 
cytotoxic properties of the parent compounds. Their method of synthesis 
and use in treating cancer patients are provided.

    Dated: March 7, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-5081 Filed 3-14-05; 8:45 am]
BILLING CODE 4140-01-P