The present invention provides a bi-functional fusion protein, (AT)a-Fc-(VT)b, simultaneously targeting vascular endothelial growth factor (VEGF) and angiopoietins (ANGs), wherein AT is an ANG binding motif; and VT is a VEGF binding motif, Fc is an N-terminal of IgG; each of a and b is an integer from 1 to 10. The bi-functional fusion proteins contain two or more domains of human proteins and are of all human sequences, and thus are expected to be non-immunogenic, and potentially can be used therapeutically in human targeting angiogenesis-associated diseases.本發明提供一種雙功能融合蛋白,其為同時靶向血管內皮生長因子(VEGF)及血管生成素(ANG)的(AT)a-Fc-(VT)b,其中AT是ANG結合模體;VT是VEGF結合模體;Fc是IgG的N端;a及b的每一者是1至10的整數。該雙功能融合蛋白含有兩種或多種人類蛋白且全部為人類序列的結構域,因此預期其為非免疫原性的,並且可能用於治療人類靶向血管新生相關疾病。