04-7697. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

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

Reduction of HIV-1 Replication by a Mutant Apolipoprotein B mRNA Editing Enzyme-Catalytic Polypeptide-like 3G (APOBEC3G)

Vinay K. Pathak et al. (NCI).

U.S. Provisional Application filed 11 Feb 2004 (DHHS Reference No. E-073-2004/0-US-01).

Licensing Contact: Michael Ambrose; 301/594-6565; [e-mail].

The invention describes a single amino acid substitution at D128K renders the human apolipoprotein B mRNA-editing enzyme-catalytic-like 3G (APOBEC3G) (CEM15) capable of inhibiting HIV-1 replication in the presence of HIV viral infectivity factor (Vif). HIV-1 and other retroviruses occasionally undergo hypermutation, characterized by high rate of G-to-A substitution. Studies have shown that human APOBEC3G is packaged into the retrovirus and deaminates deoxycytidine to deoxyuridine in newly synthesized viral minus-strand DNA, thereby inducing G-to-A hypermutation and viral inactivation. This innate mechanism of resistance to retroviral infection is counteracted by the HIV-1 Vif, which protects the virus by preventing the incorporation of APOBEC3G into virions by rapidly inducing it ubiquitination a proteosomal degradation. The inventors substituted several amino acids in human APOBEC3G with equivalent residues in simian APOBEC3G, which are resistant to HIV-1 VIF and determined the effects of the mutations on HIV-1 replication in the presence and absence of Vif. The Vif-resistant mutant could interact with HIV-1, but unlike the wild type of APOBEC3G, its intracellular steady-state levels were not reduced in the presence of HIV-1 Vif.

This technology provides a potential breakthrough for the treatment of HIV through gene therapy. By introducing the mutant version of APOBEC3G into hematopoietic stem cells and transfusing into HIV/AIDS patients, a level of resistance can be acquired. Further, using this mutation in a more classical vaccine approach to gene therapy is also envisioned.

Mucus Shaving Apparatus for Endotracheal Tubes

Lorenzo Berra, Theodor Kolobow (NHLBI).

DHHS Reference No. E-061-2004/0-US-01 filed 05 Feb 2004.

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

DHHS seeks parties interested in manufacturing and commercializing an endotracheal tube cleaning apparatus for insertion into the inside of the endotracheal tube of a patient to shave away mucus deposits. This cleaning apparatus comprises a flexible central tube with an inflatable balloon at its distal end. Affixed to the inflatable balloon are one or more shaving rings, each having a squared leading edge to shave away mucus accumulations implicated in bacterial accumulation. In operation, the un-inflated cleaning apparatus is inserted into the endotracheal tube until its distal end is properly aligned with the distal end of the endotracheal tube. After proper alignment, the balloon is inflated by a suitable inflation device (e.g., a syringe) until the balloon's shaving rings are pressed against the inside surface of the endotracheal tube. The cleaning apparatus is then pulled out of the endotracheal tube and in the process the balloon's shaving rings shave off the mucus deposits from the inside of the endotracheal tube.

Two papers have been submitted for presentations at the forthcoming American Thoracic Society meeting in Orlando, Florida, May 21-26, 2004. The abstract numbers and titles are (1) Abstract 3655, “A Novel System for the Complete Removal of all Mucus fro the Endotracheal Tubes: The Mucus Shaver”, and (2) Abstract 3793, “A Novel System to Maintain Endotracheal Tube free from Secretions and Biofilm”, which describes laboratory studies of its usage. The abstracts are available upon request.

Thermolabile Hydroxyl Protecting Groups and Methods of Use

Serge L. Beaucage, Marcin K. Chmielewski (FDA).

U.S. Provisional Application No. 60/469,312 filed 09 May 2003 (DHHS Reference No. E-154-2003/0-US-01).

Licensing Contact: Marlene Astor; 301/435-4426; [e-mail].

Synthetic oligonucleotides can be used in a wide variety of settings, which include gene therapy treatments, diagnostic and DNA sequencing microarray technology, and basic research. The NIH announces an improvement in oligonucleotide syntheses for potential application on glass microarrays. This improvement entails the incorporation of thermolytic hydroxyl protecting groups derived from 2-aminopyridine and its analogues into nucleosides and their phosphoramidite derivatives. This novel class of 2-pyridyl-substituted hydroxyl protecting groups can be efficiently cleaved under mild thermolytic conditions without the use of harsh chemicals such as strong acids or bases. As an example, this technology uses thermal cleavage (brief heat treatment at temperatures up to 90°) of terminal 5'-hydroxyl protecting groups on a growing oligonucleotide chain without inducing the formation of reactive radicals, which is in contrast to the currently used photochemical deprotection methods. In addition, the mild neutral conditions employed in the thermolytic approach, will help prevent glass surfaces from being harmed by the harsh reagents that are still being used in conventional solid phase oligonucleotide synthesis. The thermal cleavage method also permits accurate monitoring of coupling efficiency after each chain elongation step by the use of fluorescent thermolytic groups for hydroxyl protection of nucleoside phosphoramidite monomers. Thus, these thermolabile groups could be useful in manufacturing synthetic oligonucleotides on solid supports or in solution. Also, thermolabile groups may be used to protect/deprotect drug functional groups under conditions that will not affect other protecting groups on the molecule.

Long Term Retrievable Venous Filter

Ziv Neeman and Bradford Wood (NIHCC).

U.S. Provisional Application No. 60/543,766 (DHHS Reference No. E-061-2003/0-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Available for licensing and commercialization is a novel long-term or biodegradable retrievable vena cava (IVC) filter that can be retrieved indefinitely regardless of the time it was placed, or alternatively dissolves without being removed, leaving no clinically relevant traces of its presence. IVC Filters are underutilized due to the complications associated with chronic indwelling, and long term consequences of IVC filters (like chronic venous insufficiency and venous stasis) has an uncertain, but high incidence. IVC filters would be more widely used for short term prophylaxis against one of the most underdiagnosed and deadly hospital acquired diseases, namely pulmonary embolism. Patients with burns, trauma, or undergoing orthopedic procedures like hip replacement are at high risk for venous clots, that could then migrate to the lung, which can be lethal. This design leaves in only several small mm long struts that are coated with drugs that prevent early clot formation on the struts and legs of the filter. The device includes struts that, upon removal of the filter, separate from the filter legs mechanical or electrical means and are left behind permanently embedded within the venous wall. Other designs include filters made from biodegradable polymers that dissolve over time without requiring removal. This biodegradable filter may suit patients with temporary needs for protection (patients with prolonged immobility, hip replacement, trauma, intensive care patients).

Triplex Hairpin Ribozyme

Joseph A. DiPaolo (NCI), Luis Alvarez-Salas (EM).

U.S. Provisional Application No. 60/500,000 filed 23 Sep 2002 (DHHS Reference No. E-326-2002/0-US-01); PCT Application No. PCT/US03/29893 filed 23 Sep 2003 (DHHS Reference No. E-326-2002/0-PCT-02).

Licensing Contact: Michael Ambrose; 301/594-6565; [e-mail].

Much work has focused on understanding and utilizing nucleic acids as biological catalysts. Indeed, progress has been made in determining the mechanism, kinetics and conformational requirements in harnessing these potential biological catalysts. This technology has value in its potential for gene therapy applications such as gene silencing.

The technology described is a recombinant plasmid or expression vector in which a DNA-encoded trans-acting hairpin ribozyme of interest is ligated to DNA-encoded cis-acting hairpin ribozyme. In this configuration, the cis-acting ribozyme serves to cleave the 5” and 3” ends of the trans-acting ribozyme of interest. The trans-acting ribozymes can be replaced with any user-defined sequence such as antisense RNA or RNAs of viruses. This unit provides several trans-acting hairpin ribozymes that are trimmed at the ends are further generated. Thus several independent ribozymes can be produced from a single transcribed RNA.

Dated: March 30, 2004.

Steven M. Ferguson,

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