主权项 |
1. A bi-specific monovalent diabody, wherein said bi-specific monovalent diabody is capable of specific binding to an epitope of gpA33 and to an epitope of CD3, wherein the bi-specific monovalent diabody comprises a first polypeptide chain and a second polypeptide chain, wherein said first and second polypeptide chains are covalently bonded to one another, and wherein:
A. the first polypeptide chain comprises, in the N-terminal to C-terminal direction:
i. a Domain 1, comprising a sub-Domain (1A), which comprises a VL Domain of a monoclonal antibody capable of binding to CD3 (VLCD3) (SEQ ID NO:5); and a sub-Domain (1B), which comprises a VH Domain of a monoclonal antibody capable of binding to gpA33 (VHgpA33) (SEQ ID NO:27); wherein said sub-Domains (1A) and (1B) are separated from one another by a peptide linker (SEQ ID NO:1);ii. a Domain 2, wherein said Domain 2 is a K-coil Domain (SEQ ID NO:4) or an E-coil Domain (SEQ ID NO:3), wherein said Domain 2 is separated from said Domain 1 by a peptide linker (SEQ ID NO:2); B. the second polypeptide chain comprises, in the N-terminal to C-terminal direction:
i. a Domain 1, comprising a sub-Domain (1A), which comprises a VL Domain of a monoclonal antibody capable of binding to gpA33 (VLgpA33) (SEQ ID NO:26) and a sub-Domain (1B), which comprises a VH Domain of a monoclonal antibody capable of binding to CD3 (VHCD3) (SEQ ID NO:25), wherein said sub-Domains (1A) and (1B) are separated from one another by a peptide linker (SEQ ID NO:1);ii. a Domain 2, wherein said Domain 2 is an E-coil Domain (SEQ ID NO:3) or a K-coil Domain (SEQ ID NO:4), wherein said Domain 2 is separated from said Domain 1 by a peptide linker (SEQ ID NO:2); and wherein said Domain 2 of said first polypeptide chain and said Domain 2 of said second polypeptide chain are not both E-coil Domains or both K-coil Domains; and wherein: (a) said VL Domain of said first polypeptide chain and said VH Domain of said second polypeptide chain form an Antigen Binding Domain capable of specific binding to an epitope of CD3; and (b) said VH Domain of said first polypeptide chain and said VL Domain of said second polypeptide chain form an Antigen Binding Domain capable of specific binding to an epitope of gpA33. |