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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. 

## Ocular Therapeutic Agent Delivery Devices And Methods 

Michael R. Robinson (NEI), Karl G. Csaky (NEI), Peng Yuan (NEI), Cynthia Sung (EM), Robert B. Nussenblatt (NEI), Janine A. Smith (NEI) 

Serial No. 09/808,149, filed Mar. 15, 2001 

*Licensing Contact*: Dale Berkley; 301/496-7735 ext. 223; e-mail: berkleyd@od.nih.gov

                    The invention is directed to ocular implant devices for the delivery of therapeutic agents to the eye in a controlled and sustained manner. Implants suitable for either subconjunctival or intravitreal placement are the subject of the invention. These implants permit                           ( print page 29154)                        continuous release of therapeutic agents into the eye over specified periods of time, which can be weeks, months or years. In one aspect of the invention a therapeutic agent is included in both an inner core or pellet and an exterior composite matrix layer to provide a dual mode release of the therapeutic agent. That is, a loading dose is initially delivered to the eye by the matrix layer followed by a transition in release rate to a relatively steady maintenance dosage that is sustained over a prolonged period of time. In another aspect of the invention, methods for making and using the implants are described. The time-dependent delivery of one or more drugs to the eye by this invention makes it possible to maximize the pharmacological and physiological effects of the eye treatment for human and veterinary applications.                 

## Vessel Surface Reconstruction with a Tubular Deformable Model 

Yim et al. (CC) 

DHHS Reference No. E-202-00/1, filed Feb 15, 2001 

*Licensing Contact:*                    Dale Berkley; 301/496-7735 ext. 270; e-mail: berkleyd@od.nih.gov

The invention is a method for modeling a carotid or renal artery to measure stenosis from 3D angiographic data that may otherwise exhibit limited image resolution and contrast. The method reconstructs vessel surfaces from 3D angiographic data using a deformable model that employs a tubular coordinate system. Vertex merging is incorporated into the coordinate system to maintain even vertex spacing and to avoid problems of self-intersection of the surface. This method produces reconstructed surfaces that have a realistic smooth appearance and accurately represent vessel shape. The method allows for an objective evaluation of vessel shape and may improve the precision of shape measurements from 3D angiography. 

## User Friendly Integrated Database for the Management of Animal Study Proposals 

Antonia F. Calzone (NIAAA), Etienne Lamoreaux (NIAAA), Karen Montijo (NIDDK) 

DHHS Reference No. E-215-00/0 

*Licensing Contact:*                    Dale Berkley; 301/496-7735 ext. 223; e-mail: berkleyd@od.nih.gov

                    The invention is a set of templates written in FileMaker-ProTM                     script that provides a convenient integrated database management system for tracking the care and disposition of laboratory animals. This software is a multifunction program that meets the needs of facility veterinarians, animal facility managers, and animal care personnel with respect to in-house records keeping and federal reporting requirements. The invention builds on the framework of the FileMaker ProTM                     software, and results in a database system that stores information pertinent to all current Animal Study Proposals (ASPs). This design permits users to access the data from a networked centralized Windows NT based server using either a Macintosh or IBM compatible workstation. The invention comprises features that facilitate the day-to-day management of the animal facility as well as powerful information storage capabilities.                 

## Identification of New Malaria Parasite Erythrocyte Binding Protein (BAEBL) that Binds to Human Red Cells 

Ghislaine D. Mayer, Louis H. Miller (NIAID) 

DHHS Reference No. E-328-00/0, filed Apr 03, 2001 

*Licensing Contact:*                    Carol Salata; 301/496-7735 ext. 232; e-mail: salatac@od.nih.gov

Malaria is endemic in many parts of the world, particularly in tropical regions such as Asia, Central America and South America. Recent estimates of the number of cases of malaria worldwide are between five hundred million and one billion. There are approximately two to three hundred million new cases of malaria each year and malaria causes a minimum of one million deaths each year. This invention relates to the identification and characterization of the binding specificity of BAEBL, a novel Plasmodium falciparum erythrocyte binding ligand that interacts with human erythrocytes in a sialic acid dependent manner. This novel Plasmodium falciparum erythrocyte binding ligand is unique and quite distinct from previously described Plasmodium falciparum erythrocyte binding proteins EBA-175. BAEBL may be used as a malaria vaccine to block human red cell recognition and invasion. 

## Attenuated Host-Range Restricted Dengue Viruses Derived by Site-Directed Mutagenesis of the Conserved 3'-Stem and Loop Structure in Genomic RNA for Use as Vaccines 

Lingling Zeng, Lewis Markoff (CBER/FDA) 

DHHS Reference No. E-067-98/2, filed Mar 02, 2001 

*Licensing Contact:*                    Carol Salata; 301/496-7735 ext. 232; e-mail: salatac@od.nih.gov

Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. The present invention is directed toward vector stage replication-defective flaviviruses that are replication-defective in mosquito vectors that transmit them to humans. The replication-defective flaviviruses of the present invention demonstrate a limited ability to replicate in the vector organisms that transmit flaviviruses from one host to another. More specifically, the present invention is directed toward the construction and propagation of flaviviruses that possess 3'-noncoding regions altered in such a way as to prevent or severely limit viral reproduction in a vector organism. Not only is the dengue 1 mutant replication defective in mosquitoes, but it is also attenuated and immunogenic in monkeys. Moreover, it protects against challenge, thus it has strong potential as a dengue vaccine. 

## A Chimeric Protein Comprising Non-Toxic Pseudomonas Exotoxin A and Type IV Pilin Sequences 

David FitzGerald (NCI) 

DHHS Reference No. E-283-00/0, filed Dec 21,  2000 

*Licensing Contact:*                    Carol Salata; 301/496-7735 ext. 232; e-mail: salatac@od.nih.gov

This invention provides candidate chimeric vaccines that generate antibodies which interfere with adherence of Pseudomonas aeruginosa exotoxin A to epithelial cells and neutralize the cytotoxicity of exotoxin A. This invention specifically relates to a chimeric protein wherein key sequences from a Type IV pilin protein are inserted into a non toxic version of Pseudomonas aeruginosa exotoxin A. Pilin is a protein that is present on the surface of bacteria and other microorganisms, including P. aeruginosa. The key sequences are known to interact with asialoGM1 receptors on human epithelial cells, and allow bacteria and other microorganisms to adhere to epithelial cells and colonize. The present invention may be particularly useful for cystic fibrosis patients who are prone to infections with P. aeruginosa. Also, this invention could be a broad approach to vaccines against all gram negative bacteria, not just Pseudomonas aeruginosa. Pilin epitopes of other gram negative bacteria could be inserted into the Pseudomonas aeruginosa exotoxin A and used as a vaccine against that specific bacteria. 

                    Dr. FitzGerald and his colleagues have demonstrated that the chimeric protein reacted with asialoGM1, a receptor on                           ( print page 29155)                        epithelial cells and blocked adherence of P. aeruginosa on epithelial cells. When the chimeric protein was injected into rabbits, the rabbits produced antibodies that blocked bacterial adherence and neutralized the cell killing activity of native exotoxin A.                 

## A Plasmid for Expression of a More Soluble Form of HIV Integrase Protein in E. coli 

Robert Craigie (NIDDK) 

DHHS Reference No. E-110-01/0 

*Licensing Contact:*                    Sally Hu; 301/496-7056 ext. 265; e-mail: hus@od.nih.gov

The invention describes a plasmid that provides a convenient method for producing large quantities of integrase protein. This integrase protein is more soluble because amino acid residue Phe185 is changed to Lsy. This change does not affect the in vitro activity of the protein, but the improved solubility facilitates large-scale purification and handling. Since HIV integrase is a candidate target for antiviral drugs and an assay system or a source of HIV integrase is required to identify lead compounds, this invention could be very useful for an efficient means of producing integrase protein on a large scale. The integrase protein could be used in screening for integrase inhibitors that could be developed as anti-HIV drugs. This invention is available for licensing through a Biological Materials License, as no patent application exists. 

## Benzoylalkylindolepyridinium Compounds and Pharmaceutical Compositions Comprising Such Compounds 

William G. Rice, Mingjun Huang, Robert W. Buckheit, Jr., David G, Covell, Grzegorz Czerwinski, Christopher Michejda, and Vadim Makarov (NCI) 

DHHS Reference Nos. E-278-98/0 and E-278-98/1, filed Dec 18, 2000 

*Licensing Contact:*                    Sally Hu; 301/496-7056 ext. 265; e-mail: hus@od.nih.gov

The present invention provides novel antiviral compounds active against HIV. These compounds, referred to as benzoylalkylindolepyridinium compounds (BAIPs) are effective against HIV isolates that have developed mutations rendering conventional drugs ineffective. BAIPs apparently do not require intracellular phosphorylation nor bind to the reverse transcriptase (RT) active site, which distinguishes their mechanism of action from the dideoxynucleoside (ddN) and acyclic nucleoside phosphonate (ANP) nucleoside analog drugs. ddN and ANP have proven clinically effective against limiting human immunodeficiency virus (HIV) infection, but resistance rapidly emerges due to mutations in and around the RT active site. The BAIPs also may be distinguished from non-nucleoside reverse transcriptase inhibitors (NNRTIs), in part because the BAIPs bind to a different site on the RT enzyme. The usage of NNRTIs is limited by the rapid emergence of resistant strains also. Moreover, unlike the NNRTIs, BAIPs of the present invention have been shown to be effective against HIV-1, HIV-2 and simian immunodeficiency virus (SIV) proliferation. Thus, BAIPs are broadly antiviral, non-nucleoside reverse transcriptase inhibitors (BANNRTIs). 

                    This abstract modifies an abstract for this technology published in the                     **Federal Register**                     on Tuesday, February 13, 2001 (66 FR 10027).                 

Dated: May 17, 2001. 

Jack Spiegel, 

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

[FR Doc. 01-13345 Filed 5-25-01; 8:45 am] 

BILLING CODE 4140-01-P