主权项 |
1. An in vitro method for production of a heterodimeric protein comprising the following steps:
a) incubating a first homodimeric protein with a second homodimeric protein under reducing conditions sufficient to allow reduction of the inter-chain disulfide bonds in the hinge region, and
wherein said first homodimeric protein comprises an Fc region of an immunoglobulin, said Fc region comprising a first CH3 region, and said second homodimeric protein comprises an Fc region of an immunoglobulin, said Fc region comprising a second CH3 region, and wherein the sequences of said first and second CH3 regions are different and are such that the heterodimeric interaction between said first and second CH3 regions is stronger than each of the homodimeric interactions of said first and second CH3 regions, b) subjecting the composition obtained from step a) to oxidizing conditions sufficient to allow oxidation of cysteines in the heterodimeric protein to inter-chain disulfide bonds. |