| 主权项 |
1. An in vitro method for generating a heterodimeric antibody, said method comprising the following steps:
a) providing a first chimeric, humanized, or human homodimeric antibody comprising an Fc region, said Fc region comprising the CH3 region of SEQ ID NO: 1, but with an amino acid substitution at a position selected from the group consisting of: 366, 368, 370, 399, 405, 407, and 409 (numbering according to the EU Index); b) providing a second chimeric, humanized, or human homodimeric antibody comprising an Fc region, said Fc region comprising the CH3 region of SEQ ID NO: 1, but with an amino acid substitution at a position selected from the group consisting of: 366, 368, 370, 399, 405, 407, and 409 (numbering according to the EU Index), wherein the sequences of said first and second antibody CH3 regions are different, c) incubating said first antibody together with said second antibody under reducing conditions sufficient to allow the cysteines in the hinge region to undergo disulfide-bond isomerization, wherein the heterodimeric interaction between said first and second antibodies in the resulting heterodimeric antibody is such that no Fab-arm exchange occurs at 0.5 mM GSH after 24 hours at 37° C., and d) obtaining said heterodimeric antibody. |
