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: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Methylation Inhibitor Compounds

Victor Marquez et al. (NCI).

U.S. Provisional Application No. 60/547,902

Filed 25 Feb 2004

(DHHS Reference No. E-074-2004/0-US-01).

Licensing Contact: Jeff Walenta; 301/435-4633; walentaj@mail.nih.gov.

Aberrant de novo DNA methylation is commonly associated with cancer. Several studies have shown that de novo methylation of tumor suppressor genes can lead to silencing of these genes and abnormal growth of cancer cells. Therefore, DNA methylation inhibitors may be used in cancer therapy to modulate hypermethylation of genes and to reactivate anti-proliferative, apoptotic and differentiation-inducing genes in cancer cells. Although some compounds have been proposed for use as DNA methylation inhibitors, these compounds are chemically instable, have weak potency and can generate toxic metabolites, thus preventing them being used as therapeutic agents.

The present invention relates to compositions and compounds that are useful as DNA methylation inhibitor compounds. The invention also relates to a method, using these compositions and compounds, of treating various cancers having a silenced tumor suppressor gene, and a method of treating a DNA-methylation-mediated disease. These compounds are generally chemically stable, non-toxic and may be administered orally or by injection. A method of making a compound is described.

These compounds seem to have a better therapeutic profile than another published DNA methylation inhibitor, Zebularine.

A Combined Immunosuppressive Therapy Consisting of Glucocorticoid and rIL-2

Xin Chen et al. (NCI).

U.S. Provisional Application No. 60/515,217

Filed 27 Oct 2003

(DHHS Reference No. E-211-2003/0-US-01).

Licensing Contact: Mojdeh Bahar; 301/435-2950; baharm@mail.nih.gov.

The invention is a combination immunosuppressive therapeutic regimen consisting of a glucocorticoid and rIL-2. The combination minimizes the side effects associated with glucocorticoid treatment, and is useful in inhibiting or treating inflammation, immune-mediated disorders, and transplant rejection. The treatment regimen at once promotes cell death of CD4+CD25- T effector cells, including cytotoxic T cells, and expansion of inhibitory Foxp3+CD4-CD25+ T regulatory (T_reg) cells. This regimen involves application of both glucocorticoid and IL-2, and is based on the surprising observation that IL-2 selectively protects T_reg cells from glucocorticoid-induced cell death. As T_reg cells inhibit CD4+CD25- T cells, the effect of combined glucocorticoid/IL-2 therapy is to enhance the immunosuppressive effect of the glucocorticoids. In this context, glucocorticoids and IL-2 act synergistically to suppress cellular immune responses.

Production of Adeno-Associated Viruses in Insect Cells

Robert M. Kotin et al. (NHLBI).

U.S. Patent No. 6,723,551

Issued 20 April 2004

(DHHS Reference No. E-325-2001/1-US-01).

Licensing Contact: Jeff Walenta; 301/435-4633; walentaj@mail.nih.gov.

Adeno-associated virus (AAV) is being developed for gene therapy applications. This virus type presents several advantages over alternate vectors for therapeutic gene delivery. AAV is not considered pathogenic and transduces stably dividing and non-dividing cells. AAV also shows good serotype specificity to various cell types for targeted gene delivery.

The present invention describes a highly scalable adeno-associated virus (AAV) vector production method in insect cells. The system for producing recombinant AAV (rAAV) uses the AAV Rep protein and an AAV ITR. This production method produces virus particles much more efficiently than the standard mammalian cell culture system. Yields of rAAV produced in Sf9 cells exceed 10e15 per liter for some constructs. The improvement in production efficiency translates into lower production costs and potential for commercial scale manufacturing. In addition, all serotypes of AAV can be produced, with the respective AAV serotype vectors available for the immediate scale up of AAV production.

This technology will give a company producing large quantities of AAV a significant competitive advantage over traditional AAV production methods.

B-Homoestra-1,3,5(10)-trienes as Modulators of Tubulin Polymerization

Ernest Hamel et al. (NCI).

U.S. Patent No. 6,696,436

Issued 24 Feb 2004

(DHHS Reference No. E-230-1999/0-US-03).

Licensing Contact: Jeff Walenta; 301/435-4633; walentaj@mail.nih.gov.

This invention relates to the general field of steroid chemistry, particularly to estrone derivatives. Specifically, this invention provides B-ring expanded estra-1,3,5(10)-triene compounds of general formula which modulate the polymerization of tubulin and/or the depolymerization of microtubules. Successful cell division, as a step of cell mitosis, depends on the proper polymerization of tubulin and the proper depolymerization of microtubules. This invention also relates to methods of using the compounds as anti-mitotic, anti-angiogenic and anti-tumor therapeutics for the treatment of cancer or other mammalian diseases characterized by undesirable angiogenesis. Additionally, the invention provides methods of preparing the compounds. The compounds of the invention are also expected to have utility as research tools.

This invention was published in: Verdier-Pinard et al., “A Steroid Derivative With Paclitaxel-Like Effects on Tubulin Polymerization,” Mol. Pharmacol. 2000 Mar, 57(3):568-575; Wang et al., “Synthesis of B-ring Homologated Estradiol Analogues that Modulate Tubulin Polymerization and Microtubule Stability,” J. Med. Chem. 2000 Jun 15, 43(12):2419-2429.

Methods and Compositions for Transforming Dendritic Cells and Activating T Cells

Patrick Hwu et al. (NCI).

U.S. Patent No. 6,734,014

Issued 11 May 2004

(DHHS Reference No. E-040-1996/0-US-07).

Licensing Contact: Jeff Walenta; 301/435-4633; walentaj@mail.nih.gov.

T cells mediate most forms of cellular immunity. Typically T cells do not respond to free antigenic peptides, but instead T cells interact with a specialized set of cell surface proteins, which are the class I and class II major histocompatibility complexes, or MHC. Specialized antigen-presenting cells, such as macrophage and dendritic cells, present antigenic peptides on the surface cells in conjunction with the MHC molecules, and induce cytotoxic T cells to proliferate. T cells are induced by these antigen-presenting cells to recognize corresponding antigens expressed on MHC antigens on the surface of target cells, and destroy these target cells.

This invention describes a novel method for making transformed dendritic cells with any recombinant nucleic acid, which have been difficult to transduce using existing methods. Recombinant dendritic cells are made by transforming a stem cell and differentiating the stem cell into a dendritic cell. The resulting dendritic cell is an antigen-presenting cell that activates T cells against MHC class I-antigen targets. The present invention provides a valuable tool for the treatment of cancer, and viral and parasitic infections using the recombinant dendritic cells. The invention also provides therapeutic compositions and pharmaceutical compositions.

This research is described in Reeves et al., “Retroviral Transduction of Human Dendritic Cells with a Tumor-Associated Antigen Gene,” Cancer Res. 1996 Dec15, 56(24):5672-5677.