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National Institutes of Health, Public Health Service, DHHS.
The invention listed below is owned by an agency of the U.S. Government and is 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.
Licensing information and a copy of the U.S. patent application referenced below may be obtained by contacting J.R. Dixon, Ph.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804 (telephone 301/496-7056 ext 206; fax 301/402-0220; E-Mail: jd212g@NIH.GOV). A signed Confidential Disclosure Agreement is required to receive a copy of any patent application.End Preamble Start Supplemental Information
Invention Title: “Compositions and Methods for Specifically Targeting Tumors”
Inventors: Drs. Waldemar Debinski (EM) and Raj K. Puri (U.S.F.D.A.).
USPA SN: 08/706,207 [=DHHS Ref. No. E-042-00/0]—Filed with the U.S.P.T.O. on August 30, 1996.
In a chimeric molecule, two or more molecules that exist separately in their native state are joined together to form Start Printed Page 3467a single entity (i.e., molecule) having the desired functionality of all of its constituent molecules. Frequently, one of the constituent molecules of a chimeric molecule is a “targeting molecule”. The targeting molecule is a molecule such as a ligand or an antibody that specifically binds to its corresponding target, for example a receptor on a cell surface. Thus, for example, where the targeting molecule is an antibody, the chimeric molecule will specifically bind (target) cells and tissues bearing the epitope to which the antibody is directed.
Another constituent of the chimeric molecule may be an “effector molecule”. The effector molecule refers to a molecule that is to be specifically transported to the target to which the chimeric molecule is specifically directed. The effector molecule typically has a characteristic activity that is desired to be delivered to the target cell. Effector molecules include cytotoxins, labels, radionuclides, other ligands, drugs, prodrugs, liposome, etc. In particular, where the effector component is a cytotoxin, the chimeric molecule may act as a potent cell-killing agent specifically targeting the cytotoxin to cells bearing a particular target molecule. For example, chimeric fusion protein which include interleukin-4 (“IL-4”) or transforming growth factor (RGFα”) fused to Pseudomonas exotoxin (“PE”) or interleukin-2 (“IL-2”) fused to Diphtheria toxin (“DT”) have been shown to specifically target and kill cancer cells.
Generally, it is desirable to increase specificity and affinity and decrease cross-reactivity of chimeric cytotoxins with targets to be spared in order to increase their efficacy. To the extent a chimeric modecule preferentially selects and binds to its target (e.g., a tumor cell) and not to a non-target (e.g., a healthy cell), side effects of the chimeric molecule will be minimized. Unfortunately, many targets to which chimeric cytotoxins have been directed (e.g., the IL-2 receptor), while showing elevated expression on tumor cells, are also expressed to some extent, and often at significant levels, on healthy cells. Thus, chimeric cytotoxins directed to these targets frequently show adverse side-effects as they bind non-target (e.g., healthy) cells that also express the targeted receptor.
The technology disclosed in the 08/706,207 patent application is directed to a method and compositions to deliver an effector molecule to tumor cell. Specifically the technology relates to a chimeric molecule that specifically binds to IL-13 receptors which when combined with a blocker reagent (e.g., interleukin-4, an interleukin-4 antagonist, an interleukin-4 receptor binding antibody etc.) specifically delivers receptor directed cytotoxins to tumors over expressing IL-13 receptors without causing undesired cytotoxicity to normal cells. This is because a variety of human cancer cells including brain tumors, kidney tumors, and AIDS-associated Kaposi's tumors etc. over express private IL-13 receptors and normal cells express low levels of shared IL-13 receptors with IL-4 receptors. IL-13 cytotoxin remains very cytotoxic to cancel cells in the presence of IL-4 receptor blocker agents while cytotoxicity and undesired side effects of cytotoxin administration are prevented in normal cells. This approach provides unique specificity of delivering IL-13 receptor directed cytotoxic agents to cancer cells.
The above mentioned Invention is available for licensing.Start Signature
Dated: January 12, 2000.
Jack Spiegel, Ph.D.,
Director, Division of Technology Development & Transfer, Office of Technology Transfer.
[FR Doc. 00-1424 Filed 1-20-00; 8:45 am]
BILLING CODE 4140-01-M