Macrogenics, Inc.

Jonathan C Li

Leslie Sydnor Johnson

Paul A Moore

Kalpana Shah

Ezio Bonvini

Francine Zhifen Chen

The present invention relates to Tri-Specific Binding Molecules, which are multi-chain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Tri-Specific Binding Molecule is preferably characterized in possessing binding domains that permit it to immunospecifically bind to: (1) an epitope of a first Cancer Antigen, (2) an epitope of a second Cancer Antigen, and (3) an epitope of a molecule that is expressed on the surface of an immune system effector cell, and are thus capable of localizing an immune system effector cell to a cell that expresses a Cancer Antigen, so as to thereby facilitate the killing of such cancer cell.

Tri-specific binding molecules that specifically bind to multiple cancer antigens

The present invention is directed to bi-specific monovalent diabodies that comprise two polypeptide chains and which possess at least one binding site specific for an epitope of CD3 and one binding site specific for an epitope of gpA33 (i.e., a 'gpA33&#xd7;CD3 bi-specific monovalent diabody'). The present invention also is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain ('bi-specific monovalent Fc diabodies') and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of gpA33 and one binding site specific for an epitope of CD3 (i.e., a &#x201c;gpA33&#xd7;CD3 bi-specific monovalent Fc diabody&#x201d;). The bi-specific monovalent diabodies and bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to gpA33 and CD3. The invention is directed to pharmaceutical compositions that contain such bi-specific monovalent diabodies or such bi-specific monovalent Fc diabodies. The invention is additionally directed to methods for the use of such diabodies in the treatment of cancer and other diseases and conditions.

Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof

Multi-chain polypeptide-containing tri-specific binding molecules that specifically bind to multiple cancer antigens

The present invention is directed to multivalent DR5-Binding Molecules that comprise Binding Domain(s) of anti-DR5 antibodies, and particularly Binding Domain(s) of anti-human DR5 antibodies. The DR5-Binding Molecules of the present invention include bivalent and tetravalent molecules having two, three or four DR5-Binding Domains each capable of binding human DR5. In particular, the present invention is directed to multivalent DR5-Binding Molecules that comprise diabodies, and more particularly, diabodies that comprise a covalently bonded complex of two or more polypeptide chains. The invention particularly pertains to such multivalent DR5-Binding Molecules that comprise of the anti-DR5 antibodies DR5 mAb 1 and/or DR5 mAb 2, and/or humanized and chimeric versions of such antibodies.

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Rockville, MD, United States of America

Jonathan C Li