Government-Owned Invention Availability for Licensing: “Therapeutic and Diagnostic Antibodies and Immunotoxins to a Mutant Form of Epidermal Growth Factor Receptor, Designated “EGFRVIII”, Which is Highly Expressed in Glioblastomas, Carcinomas of the Breast and Ovary, and Non-Small Cell Lung Carcinomas”

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

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: jd212g@NIH.GOV). A signed Confidential Disclosure Agreement is required to receive a copy of any patent application.

SUPPLEMENTARY INFORMATION:

Invention Title: “Anti-EGFRvIII ScFvs with Improved Cytotoxicity and Yield, Immunotoxins Based Thereon, and Methods of Use Thereof”.

Inventors: Drs. Ira H. Pastan (NCI), Richard Beers (NCI), Partha S. Chowdury (NCI) and Darell Bigner (EM).

USPA SN: [= DHHS Ref. No. E-009-00/0]—Filed with the U.S.P.T.O. on January 25, 2000.

Abstract

A mutant form of the epidermal growth factor receptor, designated “EGFRvIII,” is highly expressed in some 50-60% of glioblastomas and has also been shown to be present in some 70-80% of carcinomas of the breast and ovary, and about 16% of non-small cell lung carcinomas. The mutation consists of an in-frame deletion of exons 2-7 near the amino-terminus of the extracellular domain which results in the expression of an EGFR mRNA with an 801 base deletion. The mutant protein contains a new glycine codon at the splice junction. The receptor has constitutive tyrosine activity that enhances the tumorigenicity of glioblastomas in vivo. Because of the tumor-specific extracellular sequence, the mutant receptor is an attractive potential target for cancer therapy, particular via the use of immunotoxins (e.g., MR1(Fv)-PE38).

Technology

The technology claimed in the patent application is directed to antibodies to an epidermal growth factor receptor known as EGFRvIII. In particular, the invention provides an antibody, designated MR1-1, which mutates MR1 in the CDR3 of the (V_H) and (V_L) chains to provide an antibody with especially good cytotoxicity. The described polypeptides can be coupled, attached or otherwise linked to an effector molecule, therapeutic moiety, or detectable label. The patent application provides nucleic acid molecules encoding the polypeptides with a mutated antibody variable heavy (V_H) chain regions or a mutated light chain (V_L) region, or both. The invention also provides methods of killing a cell bearing an antigen comprising contacting the cell with an immunotoxin comprising a toxic moiety and a targeting moiety. The Antibodies and Immunotoxins of claimed in this patent application could be used to develop cancer therapeutics and diagnostics.

The above mentioned Invention is available, including any available foreign intellectual property rights, for licensing.