[Federal Register Volume 65, Number 14 (Friday, January 21, 2000)]
[Notices]
[Pages 3466-3467]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-1424]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Invention; Availability for Licensing: 
``Compositions and Methods for Specifically Targeting Tumors--Using a 
Blocker Reagent''

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: 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.

ADDRESSES: 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: 
<a href="/cdn-cgi/l/email-protection#6d07095f5c5f0a2d232425432a223b"><span class="__cf_email__" data-cfemail="b1dbd5838083d6f1fff8f99ff6fee7">[email protected]</span></a>). A signed Confidential Disclosure Agreement is required 
to receive a copy of any patent application.

SUPPLEMENTARY 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.

Abstract

    In a chimeric molecule, two or more molecules that exist separately 
in their native state are joined together to form

[[Page 3467]]

a 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 (RGF<greek-a>'') 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.

Technology

    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.

    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


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