E6-22187. Prospective Grant of Exclusive License: Convection Enhanced Delivery and Tracking of Gadolinium Conjugated Therapeutic Agents to the Central Nervous System

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR 404.7(a)(1)(i), that the National Institutes of Health (NIH), Department of Health and Human Services, is contemplating the grant of an exclusive worldwide license to practice the invention embodied in: HHS. Ref. No. E-202-2002 “Method for Convection Enhanced Delivery of Therapeutic Agents,” Provisional Patent Application, 60/413,673; International Patent Application PCT/US03/30155, U.S. Patent Application Serial No. 10/528,310; European Patent Application Serial No. 03756863.1; Australian Patent Application No. 2003299140; Canadian Patent Application No. 2,499,573; and HHS Ref. No. E-206-2000/0 and /1 “Method for Increasing the Distribution of Therapeutic Agents;” and “Method for Increasing the Distribution of Nucleic Acids;” Provisional Patent Application 60/250,286; Provisional Patent Application No. 60/286,308; U.S. Patent Application No. 09/999,203; U.S. Patent Application No. 10/132,681; and Canadian Patent Application No. 2327208, to Medtronic Neurological, a Division of the Medtronic Corporation, having its headquarters in Minneapolis, Minnesota. The United States of America is the assignee of the patent rights of the above invention. The contemplated exclusive license may be granted in a field of use limited to the development and sales of a clinical grade surrogate tracer for tracking the distribution of convection enhanced delivered central nervous system therapeutics, excluding lipid based systems.

DATES:

Only written comments and/or applications for a license received by the NIH Office of Technology Transfer on or before February 26, 2007 will be considered.

ADDRESSES:

Requests for a copy of the patent application, inquiries, comments and other materials relating to the contemplated license should be directed to: Michael A. Shmilovich, Esq., Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804; Telephone: [phone]; Facsimile: [phone]; E-mail: [e-mail]. A signed confidentiality nondisclosure agreement will be required to receive copies of the patent applications.

SUPPLEMENTARY INFORMATION:

The patent applications intended for licensure disclose and/or cover the following:

E-202-2002 “Method for Convection Enhanced Delivery of Therapeutic Agents”

The invention is a method for monitoring the spatial distribution of therapeutic substances by MRI or CT that have been administered to tissue using convection enhanced delivery, a technique that is the subject of NIH-owned U.S. Patent No. 5,720,720. In one embodiment, the tracer is a molecule, detectable by MRI or CT, which functions as a surrogate for the motion of the therapeutic agent through the solid tissue. In other particular embodiments, the tracer is the therapeutic agent conjugated to an imaging moiety. The method of this invention uses non-toxic macromolecular MRI contrast agents comprised of chelated Gd(III). In particular, the surrogate tracer used in this invention is a serum albumin conjugated with either a gadolinium chelate of 2-(p-isothiocyanotobenzyl)-6-methyldiethylenetriamine pentaacetic acid or with iopanoic acid. These macromolecular imaging agents have clearance properties that mimic the pharmacokinetic properties of co-administrated drugs, so as to be useful in quantifying the range and dosage level of therapeutic drugs using MR imaging.

E-206-2000 “Method for increasing the distribution of therapeutic agents;” “Method for increasing the distribution of nucleic acids”

The invention pertains to the reliance of therapies on the local parenchymal delivery of macromolecules or nucleic acids for success. However, the volume of distribution of many of these potential therapeutic agents is restricted by their interactions with the extracellular matrix and cellular receptors. Heparin-sulfate proteoglycans are cell surface components which bind to an array of molecules such as growth factors, cytokines and chemokines and viruses such as cytomegalovirus, herpes simplex virus and HIV. The invention provides a method of dramatically increasing the volume of distribution and effectiveness of certain therapeutic agents after local delivery by the use of facilitating agents as described in Neuroreport. 2001 Jul 3;12(9):1961-4 entitled “Convection enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain” and in Exp Neurol. 2001 Mar;168(1):155-61 entitled “Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin.” These methods are especially useful when used in conjunction with technology described and claimed in the convection enhanced delivery technology claimed in U.S. Patent 5,720,720.

The prospective exclusive license will be royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR 404.7. The prospective exclusive license may be granted unless, within sixty (60) days from the date of this published notice, NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR 404.7.

Properly filed competing applications for a license filed in response to this notice will be treated as objections to the contemplated license. Comments and objections submitted in response to this notice will not be made available for public inspection, and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552.

Dated: December 20, 2006.

Steven M. Ferguson

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