Engineered multivalent and multispecific binding proteins that bind two different (e.g., nonoverlapping) epitopes of the same receptor or two different receptors expressed on the same cell are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.本發明提供可結合相同受體之兩種不同(例如,非重疊)抗原決定基或表現在相同細胞上之兩種不同受體的經改造多價及多特異性結合蛋白,以及製備方法及在預防、診斷及/或治療疾病中之用途。