05-5081. 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 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: [phone]; fax: [phone]. 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; [e-mail].

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; [phone]; [e-mail].

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; [phone]; [e-mail].

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; [e-mail].

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.