03-28788. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent application.

Methods of Diagnosis of Colorectal Cancer, Compositions and Methods of Screening for Modulators of Colorectal Cancer

Thomas Ried and Madhvi Upender (NCI).

U.S. Provisional Application No. 60/340,124 filed 13 Dec 2001 (DHHS Reference No. E-206-2003/0-US-01); U.S. Patent Application No. 10/318,578 filed 12 Dec 2002 (DHHS Reference No. E-206-2003/0-US-02).

Licensing Contact: Catherine Joyce; [phone]; [e-mail].

Oncogene activation by gene amplification is a major pathogenetic mechanism in human cancer. Comparative genomic hybridization and DNA microarray expression profiling was used to examine the expression of over 2000 genes that were identified as residing on chromosome arms that were amplified in metastatic colon cancer cancers i.e. 7p, 8q, 13q, and 20q. The results indicated that amplified genes that also demonstrate increased expression levels are quite rare. However, the results also identified 93 genes, which reside on the chromosome arms in question, which showed an increased expression level concomitant with amplification. Some of these genes could provide targets for therapy.

As a result of the above findings, the inventors contemplate methods of diagnosing colon cancer through detection of the increased expression of one or more of the identified 93 genes. Aspects of this work have been published as follows: Platzer et al., 2002, Silence of Chromosomal Amplifications in Colon Cancer, Cancer Research 62:1134-1138.

This technology is available for licensing on an exclusive or a non-exclusive basis.

Compositions and Methods for Detecting Abnormal Cell Proliferation

Lance Liotta et al. (NCI).

U.S. Provisional Application No. 60/466,154 filed 28 Apr 2003 (DHHS Reference No. E-253-2002/0-US-01).

Licensing Contact: Catherine Joyce; [phone]; [e-mail].

The invention relates to the discovery that class 5 semaphorins are linked to cancer. A Drosophila model system was used to identify genes that functionally alter tumorigenicity or metastasis. Deletion of Drosophila lethal giant larvae (l(2)gl) leads to highly invasive and widely metastatic tumors on transplantation into adult flies. Random homozygous P element insertions were screened for the ability to modulate the l(2)gl phenotype. Analysis of metastasis patterns of the lines containing P element insertions and lacking wild-type l(2)gl expression identified Semaphorin 5c (Sema 5c) as being required for tumorigenicity.

Semaphorin 5c, is a transmembrane protein with a large extracellular domain that contains seven thrombospondin type I (Tsp I) repeats. The semaphorin 5c gene belongs to the class 5 group of semaphorins, which are transmembrane proteins with short cytoplasmic (C-terminal) tails and extracellular domains containing seven thrombospondin type I repeats, a plexin domain, and a semaphorin domain sequences. Class 3 semaphorins, previously linked to cancer, are structurally different from class 5, lacking the thrombospondin repeats present in the transmembrane class 5 semaphorins.

The invention is a screening method using Drosophila to (a) screen for functional important genes associated with cancer growth, invasion and metastasis, and (b) screen for the effects of an anti-cancer targeted therapy by administering the therapy to the drosophila host bearing the tumor. In addition the invention covers a specific gene Semaphorin 5c which is a potential therapeutic target acting in the TGFbeta pathway.

As part of the invention, the inventors contemplate the following:

(i) a method of detecting an increased risk for abnormal cellular proliferation in a subject via detection of overexpression of the Sema 5 gene product;

(ii) methods and compositions for treating abnormal cellular proliferation in a subject by administering a molecule that decreases or prevents expression of a Sema 5 gene product or a molecule that binds to Sema 5 antigen on the surface of the cell and targets the cell for destruction.

This technology is available for licensing on an exclusive or a non-exclusive basis.

Novel Antisense Oligonucleotides Targeting Folate Receptor Alpha

Mona S. Jhaveri, Patrick C. Elwood, Koong-Nah Chung (NCI).

U.S. Provisional Application No. 60/274,249 filed 09 Mar 2001 (DHHS Reference No. E-321-2000/0-US-01).

Licensing Contact: Catherine Joyce; 301/435-5034; [e-mail].

Ovarian cancer is the fifth leading cause of cancer death for women in the United States. Drug resistance of ovarian tumors to chemotherapy is a common problem resulting in only 20 to 30 percent overall 5-year survival rates. Folate is a vitamin that is absolutely necessary for cell survival. Some cancer cells, including ovarian carcinomas, have an abundance of a folate-binding protein termed the human alpha folate receptor (ahFR). It is believed that the elevated levels of ahFR contribute to the cells' cancerous state by mediating increased folate uptake or by generating positive regulatory growth signals. This invention comprises a genetic therapy that diminishes the levels of ahFR using antisense oligonucleotides that block the transcription of the gene. Studies have shown that this invention significantly decreases proliferation of cultured cancer cells and sensitizes these cells to treatment with chemotherapeutic drugs. Further development of receptor-targeted antisense oligonucleotides and related compounds have potential therapeutic value for a range of difficult-to-treat cancers including cancers of the ovary, cervix, uterus, and brain.

Dated: November 10, 2003.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.