Seagen Inc.
CYSTEINE MUTATED ANTIBODIES FOR CONJUGATION

Abstract:

The invention provides modified heavy chain constant regions including a cysteine at position 295 by EU numbering and optionally at position 239 by EU numbering. These cysteine residues provide sites for conjugation to a drug or label. When both cysteines are present in a normal heterodimeric antibody format, there are four such sites per molecule of antibody allowing a stoichiometry of one molecule of antibody to four of drug or label. Selection of the cysteine at position 295 with or without cysteine at position 239 is advantageous over cysteines at many other positions due to ease of expression, stability and cytotoxicity.