02-32348. 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 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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Improved Non-Viral Mammalian Expression Vector

Gary Nabel, Zhi-yong Yang (NIAID/VRC).

DHHS Reference No. E-318-2002/0 filed 24 Sep 2002.

Licensing Contact: Carol Salata; 301/435-5018; [e-mail].

This invention provides an improved expression vector that generates a higher level of protein than vectors currently in use. The expression vector is unique in that it uses a specific translational enhancer in combination with specific enhancer/promoters to yield high levels of protein expression and enhanced immunogenicity for DNA vaccines. This is particularly important because the potency of these vaccines in humans is marginal and this type of improvement can increase the effectiveness of various DNA vaccines. The expression vector cassettes can be used in other gene based vaccines as well, or for production of recombinant proteins from eukaryotic expression vectors. The invention may be useful in the production of genetic vaccines and gene therapies for a wide variety of diseases, including cancer and viral diseases such as HIV.

Contiguous Capillary Separation and Electrospray Ionization Sources and Analytical Devices

George Janini et al. (NCI)

DHHS Reference No. E-307-2002/0 filed 21 Oct 2002

Licensing Contact: Dale Berkley; 301/435-5019; [e-mail]

The invention is a device that acts as an interface between micro-scale separation instruments and electrospray ionization (ESI) mass spectrometers (MS), thus facilitating the separation and MS characterization of almost any type of analyte such as proteins, peptides, and small molecules. The device may be used as an interface between ESI-MS and any micro-scale separation technology such as capillary zone electrophoresis (CZE) capillary electrochromatography (CEC), capillary isoelectric focusing (cIEF), capillary isotachophoresis (cITF), electrokinetic chromatography (EKC), and high performance liquid chromatography (HPLC). The invention integrates a separation column, an electrical junction and a spray tip on a single piece of fused silica capillary. This invention offers advantages over existing ESI-MS interfaces, including ease of fabrication, ruggedness and a true zero dead volume junction between the separation column and the ESI tip.

Methods and Devices for Intramuscular Stimulation of Upper Airway and Swallowing Muscle Groups

Christy Ludlow et al. (NINDS)

DHHS Reference No. E-181-2002/0 filed 27 Sep 2002

Licensing Contact: Dale Berkley; 301/435-5019; [e-mail]

The invention is a method and device that induces intramuscular stimulation of the extrinsic and intrinsic laryngeal musculature to improve swallowing and voice and upper esophageal sphincter opening in humans. The device may be used to augment airway protection in persons with swallowing problems (dysphagia) who are at risk of aspiration. This invention will assist those persons who have chronic long-standing dysphagia and have not been benefited from early rehabilitative efforts, putting them at chronic risk of developing life-threatening pneumonia because of repeated aspiration. Limiting the entry of food or liquids into the lungs while swallowing, which is the objective of this invention, can prevent aspiration. Patients at risk of aspiration pneumonia currently require enteric (tube) feeding, a costly method for sustaining nutrition and one that greatly reduces quality of life. The invention comprises three unique components for preventing aspiration during swallowing for some persons now requiring enteric feeding: (1) Intramuscular implantation to produce two synergistic actions; (2) independent long term control of stimulation during swallowing by patients; and, (3) a unique system of combining indwelling intramuscular electrodes and controllers.

Assays for Assembly of Ebola Virus Pseudoparticles Relevant to Antiviral Therapy and Vaccines

Gary Nabel, Yue Huang (NIAID/VRC)

DHHS Reference No. E-090-2002/0 filed 12 Jul 2002

Licensing Contact: Carol Salata; 301/435-5018; [e-mail]

This invention relates to assays for the identification of compounds that inhibit assembly of NP, VP35, and VP24, or inhibit the glycosylation of NP, required for nucleocapsid formation for the use as anti-viral agents. The invention also relates to assays for the identification of compounds that block glycosylation of proteins having a glycosylation domain that is substantially homologous to a glycosylation domain of NP required for polymerization. The invention further relates to pseudoparticles for presentation of antigens or antigenic epitopes for immunogenic or vaccination purposes especially filovirus vaccines such as Ebola.

Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3′-UTR of Dengue Types 1, 2, 3, and 4

Stephen S. Whitehead (NIAID), Brian R. Murphy (NIAID), Lewis Markoff (FDA), Barry Falgout (FDA)

DHHS Reference No. E-089-2002/0 filed 03 May 2002

Licensing Contact: Carol Salata; 301/435-5018; [e-mail]

The invention relates to a dengue virus tetravalent vaccine containing a common 30-nucleotide deletion (Δ30) in the 3′-untranslated region (UTR) of the genome of dengue virus serotypes 1, 2, 3, and 4. The previously identified Δ30 attenuating mutation, created in dengue virus type 4 (DEN4) by the removal of 30 nucleotides from the 3′-UTR, is also capable of attenuating a wild-type strain of dengue virus type 1 (DEN1). Removal of 30 nucleotides from the DEN1 3′-UTR in a highly conserved region homologous to the DEN4 region encompassing the Δ30 mutation yielded a recombinant virus attenuated in rhesus monkeys to a level similar to recombinant virus DEN4Δ30. This established the transportability of the Δ30 mutation and its attenuation phenotype to a dengue virus type other than DEN4. The effective transferability of the Δ30 mutation establishes the usefulness of the Δ30 mutation to attenuate and improve the safety of commercializable dengue virus vaccines of any serotype.

A tetravalent dengue virus vaccine containing dengue virus types 1, 2, 3, and 4 each attenuated by the Δ30 mutation is being developed. The presence of the Δ30 attenuating mutation in each virus component precludes the reversion to a wild-type virus by intertypic recombination. In addition, because of the inherent genetic stability of deletion mutations, the Δ30 mutation represents an excellent alternative for use as a common mutation shared among each component of a tetravalent vaccine.

VAC-BAC Shuttle Vector System

Bernard Moss, Arban Domi (NIAID)

DHHS Reference No. E-355-2001/0 filed 10 Apr 2002

Licensing Contact: Carol Salata; 301/435-5018; [e-mail]

This invention relates to a VAC-BAC shuttle vector system for the creation of recombinant poxviruses from DNA cloned in a bacterial artificial chromosome. A VAC-BAC is a bacterial artificial chromosome (BAC) containing a vaccinia virus genome (VAC) that can replicate in bacteria and produce infectious virus in mammalian cells.

The following are some of the uses for a VAC-BAC:

1.VAC-BACs can be used to modify vaccinia virus DNA by deletion, insertion or point mutation or add new DNA to the VAC genome with methods developed for bacterial plasmids, rather than by recombination in mammalian cells.

2. It can be used to produce recombinant vaccinia viruses for gene expression.

3. It can be used for the production of modified vaccinia viruses that have improved safety or immunogenicity.

Advantages of the VAC-BAC shuttle system:

1. VAC-BACs are clonally purified from bacterial colonies before virus reconstitution in mammalian cells.

2. Manipulation of DNA is much simpler and faster in bacteria than in mammalian cells.

3. Modified genomes can be characterized prior to virus reconstitution.

4. Only virus with modified genomes will be produced so that virus plaque isolations are not needed.

5. Generation of a stock of virus from a VAC-BAC is accomplished within a week rather than many weeks.

6. Multiple viruses can be generated at the same time since plaque purification is unnecessary.

Dated: December 13, 2002.

Jack Spiegel,

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