Multivalent single chain antibodies

Claim 1

A DNA sequence which codes for a multivalent single chain antibody, the multivalent single chain antibody comprising two or more single chain antibodies and at least one first peptide linker, each single chain antibody having affinity for TAG-72, each single chain antibody being covalently linked by at least one of said first peptide linkers to at least one other single chain antibody and each single chain antibody comprising: (a) a first polypeptide comprising a light chain variable domain encoded by a base sequence whose expression product is substantially homologous to that having the amino acid sequence (SEQ ID NO: 2) of ______________________________________ AspIleValMetSerGlnSerProSerSerLeuPro ValSerValGlyGluLysValThrLeuSerCysLys SerSerGlnSerLeuLeuTyrSerGlyAsnGlnLys AsnTyrLeuAlaTrpTyrGlnGlnLysProGlyGln SerProLysLeuLeuIleTyrTrpAlaSerAlaArg GluSerGlyValProAspArgPheThrGlySerGly SerGlyThrAspPheThrLeuSerIleSerSerVal LysThrGluAspLeuAlaValTyrTyrCysGlnGln TyrTyrSerTyrProLeuThrPheGlyAlaGlyThr LysLeuValLeuLys ______________________________________ and whose expression product retains the characteristic of functional binding to TAG-72; (b) a second polypeptide comprising a heavy chain variable domain encoded by a base sequence whose expression product is substantially homologous to that having the amino acid sequence (SEQ ID NO: 4) of ______________________________________ GluValGlnLeuGlnGlnSerAspAlaGluLeuVal LysProGlyAlaSerValLysIleSerCysLysAla SerGlyTyrThrPheThrAspHisAlaIleHisTrp ValLysGlnAsnProGluGlnGlyLeuGluTrpIle GlyTyrPheSerProGlyAsnAspAspPheLysTyr AsnGluArgPheLysGlyLysAlaThrLeuThrAla AspLysSerSerSerThrAlaTyrValGlnLeuAsn SerLeuThrSerGluAspSerAlaValTyrPheCys ThrArgSerLeuAsnMetAlaTyrTrpGlyGlnGly ThrSerValThrValSerSer ______________________________________ and whose expression product retains the characteristic of functional binding to TAG-72; and (c) a second peptide linker linking the first and second polypeptides into a functional binding moiety; wherein said first peptide linker comprises a 15-25 amino acid segment of the amino acid sequence (SEQ ID NO: 5), Leu-Ser-Ala-Asp-Asp-Ala-Lys-Lys-Asp-Ala-Ala-Lys-Lys-Asp-Asp-Ala-Lys-Lys-Asp-Asp-Ala-Lys-Lys-Asp-Leu, and said multivalent single chain antibody has an affinity of at least 60% of that of a native anti-TAG-72 antibody, as measured by a competitive binding assay.