Patent ID: 7122636

Claim:
A conjugate consisting essentially of an antibody fragment covalently modified by one or two nonproteinaceous polymer molecules at a free sulfhydryl group of a cysteine residue within the hinge region of the antibody fragment, wherein a disulfide bridge within the hinge region is avoided by substituting another amino acid for the corresponding cysteine residue within the hinge region in the opposite chain of said antibody fragment, and wherein (a) the apparent molecular weight of the conjugate, as determined by size exclusion chromatography, is at least about 500 kD, (b) the average actual molecular weight of each nonproteinaceous polymer molecule is at least 20 kD, (c) the conjugate has an apparent size that is at least about 8-fold greater than the apparent size of the parental antibody fragment, and (d) the conjugate binds the same antigen as the parental molecule that is not covalently modified by one or two nonproteinaceous polymer molecules.