Immuno-conjugates and methods for producing them

An isolated protein comprising an immunoglobulin heavy chain variable region (VH) and an immunoglobulin variable region (VL), wherein at least one of the variable regions comprises:

• (i) at least two cysteine residues substituted at positions exposed to solvent within a framework region (FR) 2, wherein:
• the at least two cysteine residues consist of 2, 4, or 6 cysteine residues, and wherein:
• if the at least two cysteine residues in the FR2, are not conjugated to a compound then an intra-framework region disulphide bond is capable of forming between the at least two cysteine residues in the FR2;
• or
• (ii) at least two cysteine residues substituted at positions exposed to solvent within a framework region (FR) 3, wherein the at least two cysteine residues consist of 2, 4, or 6 cysteine residues, and wherein if the at least two cysteine residues in the FR3 are not conjugated to a compound then an intra-framework region disulphide bond is capable of forming between the at least two cysteine residues in FR3.