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###### Department of Health and Human Services

###### National Institutes of Health 

# 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 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. 

## Plasmids Expressing START Domains of StAR and MLN64 

Dr. Yosuke Tsujishita and Dr. James Hurley (NIDDK) 

DHHS Reference No. E-020-01/0 

*Licensing Contact:*                        Marlene Shinn; 301/496-7056 ext. 285; e-mail: shinnm@od.nih.gov
      ( print page 11595)    
Steroidogenic acute regulatory protein (StAR) manages acute steroidogenesis in the adrenal cortex and gonads by promoting the translocation of cholesterol to the mitochondrial inner membrane where initial steroid biosynthesis is catalyzed. Within StAR are StAR related lipid transfer (START) domains which are 200-210 amino acid motifs that occur in a remarkably wide range of proteins involved in diverse cell functions such as lipid transport and metabolism, signal transduction and transcription regulation. The closest homolog to StAR is MLN64, with 35% sequence identity between their START domains. 

The technology embodied in this invention encompasses plasmids expressing START domains of StAR and MLN64. These fragments enable expression of proteins for many biochemical studies and specifically towards cholesterol transfer in acute steroidegenesis. Possible commercial applications include targets for cancer treatment to known over expressed MLN64 in breast carcinoma. 

## Macromolecular Enzyme Substrates 

Glen L. Hortin (CC) 

DHHS Reference No. E-233-99/0 filed 31 Jul 2000 

*Licensing Contact:*                        Dennis Penn; 301/496-7056 ext. 211; e-mail: pennd@od.nih.gov

This invention discloses a new class of reagents used to measure the activity of enzymes. The inventor discovered that connecting a small reagent molecule onto a polymer that serves as a large carrier molecule confers advantages in the measurement of enzyme activity. Advantages of the new class of reagents are: (1) Better modeling of the size of natural targets (substrates) of many biologically important enzymes, (2) improved specificity of measurements, (3) ability to measure the influence of substrates size on enzyme activity (carrier group size can be varied over a wide range), (4) improved substrate solubility, and (5) the potential for easier methods of synthesis and purification of some enzyme substrates. Reagents of this class can be used to measure the activity of components forming and breaking down blood clots, of digestive components, of components of the complement system, and of many other components with essential biological functions. 

## Efficient Generation of Midbrain Neurons From Mouse Embryonic Stem Cells 

Sang-Hun Lee, Nadya Lumelsky, Lorenz Studer and Ronald McKay (NINDS) 

DHHS Reference No. E-291-99/0 filed May 1, 2000 

*Licensing Contact:*                        Norbert Pontzer; 301/496-7735, ext. 284; e-mail: pontzern@od.nih.gov

Parkinson's disease is a progressive neurological disorder affecting an estimated one million patients in the United States. Parkinson's disease occurs when dopamine producing cells in the central nervous system degenerate. Currently patients receive medications to treat the symptoms, but not cure or stop the progression of the disease. As the disease progresses the medications usually become less effective. One encouraging new form of therapy replaces the lost dopamine producing neurons with transplanted cells. A major obstacle to cell replacement therapy has been obtaining sufficient dopamine producing cells. Therapeutic or ethical problems exit for all presently available sources of cells for transplantation. 

This invention provides a method for efficiently generating dopaminergic neurons from embryonic stem cells. Embryonic cells are totipotent cells which can proliferate indefinitely in the undifferentiated state. A method of generating specific differentiated cells from embryonic stem cells thus provides a potentially unlimited source of those cells. A sequence of culturing steps involving exposure to specific neurotrophic factors and other agents produces a high percentage of cultured dopaminergic neurons. An unlimited supply of dopaminergic neurons which may be suitable for transplantation is thus provided. Details of some aspects of this invention can be found in Nature Biotechnology Vol. 18, pages 675-679, June 2000. 

## Methods for Delivering Biologically Active Molecules Into Cells 

Jeffrey L. Miller, Urszula Wojda, Paul K. Goldsmith (NIDDK) 

DHHS Reference Nos. E-174-98/0 filed 15 Jan 1999 and E-174-98/1 filed 14 Jan 2000 

*Licensing Contact:*                        Dennis Penn; 301/496-7056 ext. 211; e-mail: pennd@od.nih.gov

The appropriate gene therapy delivery system depends greatly on the cells being targeted and the means by which delivery is anticipated. Numerous clinical trials are currently ongoing for gene therapy, each typically usually a different mode of delivery. It is still too early to determine which mode will be approved and which will be the most effective. The polyethylenimineDNA (PEI-DNA) complex is known to be an effective system for delivery of DNA. In vitro models of a new delivery system based on the cationic properties of PEI have found that the cellular incorporation is significantly enhanced using an Avidin-PEI-DNA complex. Experiments have shown that there is, at a minimum, a 3x to 10x increase in the cellular uptake of the DNA. It is believed that this gene delivery system can be targeted to any cell of interest. It was demonstrated that the transfection can be targeted to native and biotinylated cells. For cells, with a known surface phenotype, biotinylated monoclonal antibodies can be attached to specific sites and the Avidin-PEI-DNA complex then binds and enters the cell via endocytosis. 

Alternatively, cells without a known surface phenotype, biotin can be covalently attached to the cell surface and the Avidin-PEI-DNA complex is then able to bind and carry the DNA into the cells. This system appears to be not only applicable to gene therapy, but to the diagnostic market and to the delivery of other anionic materials into cells. This Avidin-PEI-DNA system may find a niche market or it may become utilitarian, such that it can be effectively utilized in more than one gene therapy treatment. This technology is available for immediate licensing and independent commercialization and/or a Cooperative and Development Research Agreement can be considered. 

Dated: February 15, 2001. 

Jack Spiegel, 

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

[FR Doc. 01-4617 Filed 2-23-01; 8:45 am] 

BILLING CODE 4140-01-P