00-1931. Government-Owned Inventions; Availability for Licensing

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 Elaine Gese at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; Telephone: [phone] ext. 282; Fax: [phone]; E-mail: [e-mail]. A signed Confidential Disclosure Agreement is required to receive a copy of any patent application.

Variants of Humanized Anti-Carcinoma Monoclonal Antibody CC49

Syed V. Kashmiri (NCI), Eduardo A. Padlan (NIDDK), Jeffrey Schlom (NCI)

U.S. Provisional Patent Applications 60/106,534 filed 31 Oct 1998 and 60/106,757 filed 02 Nov 1998

The invention embodied in these two patent applications describes the humanization of a murine anti-carcinoma antibody which has been shown to react with Tumor Associated Glycoprotein 72 (TAG-72), an antigen which is expressed on human breast, colorectal, and other carcinomas. The humanization process, which renders the antibody minimally immunogenic to humans, has been accomplished by a method different from the current procedure for the humanization of a rodent antibody which is based on grafting all the Complementarity Determining Residues (CDRs) of a rodent antibody onto a human antibody framework. This new humanization protocol involves identifying the Specificity Determining Residues (SDRs), the amino acid residues in the hypervariable regions of an antibody that are most critical for antigen binding activity. The CDRs, which are found not to contain SDRs and hence are dispensable for antigen binding activity, are not grafted onto the human antibody frameworks. Rather, only the SDRs of the essential CDRs are transferred to the human antibody molecule. The resulting molecule is believed to elicit an immune response in humans which is significantly less than that elicited through administration of other humanized antibodies.

Embodied in the current invention are methods of identifying the SDRs, and of rendering any antibody minimally immunogenic in humans by transferring the SDRs of the antibody to a human antibody framework. The resulting humanized antibodies, including CDR variants therof (including a CH2 deleted version), are also embodied in the invention, as are methods of using the antibodies for therapeutic and diagnostic purposes.

Dated: January 20, 2000.

Jack Spiegel,

Director, Division of Technology Development and Transfer, Office of Technology Transfer.