Binding proteins having tethered light chains

A method of making a bispecific binding protein that binds a first antigen and a second antigen comprising an inside-out tethered light chain, a first inside-out heavy chain and a second inside-out heavy chain, comprising

• a) providing an antibody that binds the first antigen having a first light chain comprising a first light chain variable region (VL1) and a first light chain constant region (CL1), and a first heavy chain comprising a first heavy chain variable region (VH1) and a first heavy chain constant region (CH1);
• b) providing an antibody that binds the second antigen having a second light chain comprising a second light chain variable region (VL2) and a second light chain constant region (CL2), and a second heavy chain comprising a second heavy chain variable region (VH2) and a second heavy chain constant region (VC2);
• c) providing a linker;
• d) operably linking VH1-CL1-linker-VH2-CL2 from the N-terminus to the C-terminus to generate the inside-out tethered light chain;
• e) operably linking VL1-CH1 from the N-terminus to the C-terminus to generate the first inside-out heavy chain;
• f) operably linking VL2-CH2 from the N-terminus to the C-terminus to generate the second inside-out heavy chain;
• g) expressing the inside-out tethered light chain, the first inside-out heavy chain and the second inside-out heavy chain;
• and
• h) recovering the bispecfic binding protein.