Dual variable region antibody-like binding proteins having cross-over binding region orientation

摘要

The invention provides antibody-like binding proteins comprising four polypeptide chains that form four antigen binding sites, wherein each pair of polypeptides forming an antibody-like binding protein possesses dual variable domains having a cross-over orientation. The invention also provides methods for making such antigen-like binding proteins.

主权项

1. 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 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; VH1 is a first immunoglobulin heavy chain variable domain; VH2 is a second immunoglobulin heavy chain variable domain; CL is an immunoglobulin light chain constant domain; CH1 is the immunoglobulin CH1 heavy chain constant domain; Fc is the immunoglobulin hinge region and CH2, CH3 immunoglobulin heavy chain constant domains; and L1, L2, L3, and L4 are amino acid linkers;wherein L2 and L4 are both at least one amino acid in length, and
(a) the length of L2 is at least twice the length of L4; or (b) the length of L4 is at least twice the length of L2;and wherein the polypeptides of formula I and the polypeptides of formula II form a cross-over light chain-heavy chain pair.