| 主权项 |
1. A method for generating a DVD-Ig binding protein capable of binding two antigens comprising the steps of
a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding TNF-α; b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding human IL-17; c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein
VD1 is a first heavy chain variable domain obtained from the first parent antibody or antigen binding portion thereof;VD2 is a second heavy chain variable domain obtained from the second parent antibody or antigen binding portion thereof;C is a heavy chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 is an Fc region; andn is 0 or 1; and d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein
VD1 is a first light chain variable domain obtained from the first parent antibody or antigen binding portion thereof;VD2 is a second light chain variable domain obtained from the second parent antibody or antigen binding thereof;C is a light chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 does not comprise an Fc region; andn is 0 or 1; and e) expressing the first, second, third and fourth polypeptide chains; such that a DVD-Ig binding protein capable of binding TNF-α and human IL-17 is generated, wherein the binding protein is capable of binding TNF-α and human IL-17; wherein, in the first and third polypeptide chains, the VD1 and VD2 heavy chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 565, 670, 720, 740, 845, and 875; and wherein in the second and fourth polypeptide chains, the VD1 or VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 570, 675, 725, 745, 850, and 880. |
