2011-13521. Government-Owned Inventions; Availability for Licensing

AGENCY:

Public Health Service, National Institutes of Health, 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.

Thrombolytic Temperature-Sensitive Liposomes

Description of Technology: The subject technology discloses a novel method for inducing targeted thrombolysis in blood vessels. In this technology, a thrombolytic agent is encapsulated within temperature-sensitive liposomes. This composition is administered into the patient's blood circulation. Certain clots and vulnerable atherosclerotic processes elicit an endogenous heat that facilitates local thrombolytic drug release. The thermosensitive liposome can also be exogenously heated to at least its phase transition temperature to induce the release the thrombolytic agent from the liposome at the thrombus for targeted thrombolysis. The temperature for activated release can be varied, depending on the specific composition of the liposome.

Applications: Thrombolysis of blood clots formed in blood vessels, primarily in thromboemblic diseases such as myocardial infarction and stroke, venous thromboemblic diseases such as deep vein thrombosis (DVT), and pulmonary embolism (PE).

Advantages:

• Due to the protection of the thrombolytic agent within the liposome structure until the time that release is induced, this technology provides for better stability and longer half-life of the agent.

—Enhanced efficacy compared to the currently used thrombolytic treatments.

—Decreased side effects compared to the currently used thrombolytic treatments.

—Potentially decreased immunogenicity.

• Lower treatment dose may be required compared to current methods using free thrombolytic agent.

—Increases safety profile and reduces the risk of dose-related intracranial hemorrhage in treated patients.

Development Status: Proof of principle has been demonstrated in vitro.

Inventors: Bradford Wood, Matt Dreher, et al. (NIHCC).

Patent Status: U.S. Provisional Application No. 61/473,665 filed 08 Apr 2011 (HHS Reference No. E-090-2011/0-US-01).

Relevant Publications:

1. Collen D. Staphylokinase: A potent, uniquely fibrin-selective thrombolytic agent. Nat Med. 1998 Mar;4(3):279-284. [PMID: 9500599]

2. Elbayoumi TA, Torchilin VP. Liposomes for targeted delivery of antithrombotic drugs. Expert Opin Drug Deliv. 2008 Nov;5(11):1185-1198. [PMID: 18976130]

3. Heeremans JL, Prevost R, Bekkers ME, et al. Thrombolytic treatment with tissue-type plasminogen activator (t-PA) containing liposomes in rabbits: A comparison with free t-PA. Thromb Haemost. 1995;73(3):488-494. [PMID: 7667833]

4. Tiukinhoy-Laing SD, Huang S, Klegerman M, Holland CK, McPherson DD. Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes. Thromb Res. 2007;119(6):777-784. [PMID: 16887172]

5. Needham D, Dewhirst MW. The development and testing of a new temperature sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev. 2001 Dec 31;53(3):285-305. [PMID: 11744173]

6. Frenkel V, Oberoi J, Stone MJ, et al. Pulsed-high intensity focused ultrasound enhances thrombolysis in an in vitro model. Radiology 2006 Apr;239(1);86-93. [PMID: 16493016]

Licensing Status: Available for licensing.

Licensing Contacts:

• Uri Reichman, PhD, MBA; 301-435-4616; [e-mail].
• Michael Shmilovich, Esq.; 301-435-5019; [e-mail].

Collaborative Research Opportunity: The NIH Clinical Center, Interventional Radiology Section & Center for Interventional Oncology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this novel approach to thrombolysis. Please contact Ken Rose, PhD at 301-435-3132 or [e-mail] for more information.

Methods and Devices for Transcatheter Cerclage Annuloplasty

Description of Technology: The invention relates to techniques and devices for cardiovascular valve repair, particularly annuloplasty techniques and devices in which tensioning elements are positioned to treat regurgitation of the mitral valve or tricuspid valve. More specifically, the technology pertains to a new device for myocardial septal traversal (“cerclage reentry”) that also serves to capture (ensnare) and externalize the traversing guidewire. The focus of the invention is to avoid a phenomenon in cardiac surgery known as “trabecular entrapment.” The device features an expandable and collapsible mesh deployed in the right ventricle to simplify capture of a reentering guidewire during transcatheter cerclage annuloplasty. The wire mesh exerts pressure against trabecular-papillary elements of the tricuspid valve to displace them against the right ventricular septal wall. By abutting the right ventricular reentry site of the cercalge guidewire, trabecular entrapment is avoided. The device comprises a shaft having a distal loop which provides a target in the interventrical myocardial septum through which a catheter-delivered tensioning system is guided. The loop ensnares the catheter-delivered tensioning system as it reenters the right ventricle or right atrium. The expandable and collapsible mesh is disposed within the right ventricle such that the catheter-delivered tensioning system is directed from the ventricular septum into the right ventricular cavity through only a suitable opening in the mesh and such that the catheter delivered tensioning system is captured or ensnared within the mesh opening.

Applications: Cardiovascular valve repair surgeries.

Features and Advantages:

• The device avoids trabecular entrapment of the cerclage guidewire during septal-perforator-to-right-ventricular myocardial guidewire traversal
• The device allows ensnarement of reentering guidewire.
• The device provides an X-ray target for guidewire reentry from the septal perforator veins.
• Collapsible transcatheter device that can be introduced from a cephalad (typically transjugular or transaxillary) or caudad (typically transfemoral) approach.
• The device is intended to allow straightforward removal from the same vascular sheath as the cerclage retrograde traversal guidewire, to allow both free ends of the guidewire to be externalized through the same sheath.

Development Status:

• Practical usefulness of the technology has been demonstrated.
• Preclinical testing of extant prototype is planned.
• Clinical development is planned.

Inventors: Robert J. Lederman and Ozgur Kocaturk (NHLBI).

Relevant Publication: Kim JH, et al. Mitral cerelage annuloplasty, a novel transcatheter treatment for secondary mitral valve regurgitation: initial results in swine. J Am Coll Cardiol. 2009 Aug 11;54(7):638-651. [PMID: 19660696].

Patent Status: U.S. Provisional Application No. 61/383,061 filed 15 Sep 2010 (HHS Reference No. E-108-2010/0-US-01).

Licensing Status: Available for licensing.

Licensing Contacts:

• Uri Reichman, PhD, MBA; 301-435-4616; [e-mail].
• Michael Shmilovich, Esq.; 301-435-5019; [e-mail].

Collaborative Research Opportunity: The National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Peg Koelble at [e-mail] for more information.

Dated: May 25, 2011

Richard U. Rodriguez,

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