Antibody-like binding proteins with dual variable regions with a cross-linking orientation of the binding region

摘要

An antibody-like binding protein comprising four polypeptide chains that form four antigen binding sites, wherein two polypeptide chains have a structure represented by the formula: VL1-L1-VL2-L2-CL [I] and two polypeptide chains they have a structure represented by the formula: VH2-L3-VH1-L4-CH1-Fc [II] wherein: VL1 is a first immunoglobulin light chain variable domain; VL2 is a second immunoglobulin light chain variable domain; 10 VH1 is a first immunoglobulin heavy chain variable domain; VH2 is a second immunoglobulin heavy chain variable domain; CL is a constant domain of the immunoglobulin light chain; CH1 is the constant domain of the immunoglobulin CH1 heavy chain; Fc is the immunoglobulin hinge region and CH2, CH3 are the constant domains of the immunoglobulin heavy chain; L1, L2, L3 and L4 are amino acid linkers; wherein: L1 is 3 to 12 amino acid residues in length; L2 is 3 to 14 amino acid residues in length; L3 is 1 to 8 amino acid residues in length; L4 is 1 to 3 amino acid residues in length; and wherein the polypeptides of formula I and polypeptides of formula II form a light chain-heavy chain cross-linking pair.