公开(公告)号：EP0275606A1

公开(公告)日：1988-07-27

申请号：EP87202610.9

申请日：1987-12-22

申请人： Leuven Research & Development V.Z.W. ,  Collen, Désiré José

发明人： Collen, Désiré José ,  Holmes, William Evans ,  Nelles, Lucien Georges Raymond ,  Lijnen, Henri Roger

IPC分类号： C12N15/00 ,  C12N9/72 ,  A61K37/54

CPC分类号： C12N9/6456 ,  C07K14/53 ,  C07K2319/00 ,  C12N9/64

摘要： The invention relates to plasminogen activators obtained by expression of fused cDNA encoding fragments of human tissue-type plasminogen activator (t-PA) and of human urokinase-type plasminogen activator (u-PA), by combining the fibrin-affinity of t-PA with the fibrin-specificity of u-PA in the single chain form (scu-PA) and,or with the enzymatic activity of u-PA having the two-chain form (tcu-PA). It is preferably a hybrid molecule obtained by fusion of at least a region part of the NHz-terminal region of t-PA to at least a part region of the COOH-terminal region of scu-PA, most preferably the NH 2 -terminal amino acids 1 to 263 of t-PA, fused to the COOH-terminal amino acids 144 to 411 of scu-PA.
The invention relates further to a recombinant DNA molecule which yields said hybrid plasminogen activators; the respective mammalian expression vector containing said DNA sequence; a transfected mammalian cell line which comprises said recombinant DNA molecule; and to the method for the preparation of plasminogen activators.

摘要翻译： 本发明涉及通过表达编码人组织型纤溶酶原激活物（t-PA）和人尿激酶型纤溶酶原激活物（u-PA）片段的融合cDNA获得的纤溶酶原激活物，通过结合t-PA的纤维蛋白亲和力 其中u-PA在单链形式（scu-PA）中的纤维蛋白特异性和/或具有双链形式（tcu-PA）的u-PA的酶活性。 优选通过将t-PA的NH 2末端区域的至少一部分区域与scu-PA的COOH末端区域的至少一部分区域融合而得到的杂合分子，最优选NH 2末端氨基酸 1至263的t-PA，与scu-PA的COOH末端氨基酸144至411融合。 本发明还涉及产生所述杂合纤溶酶原激活物的重组DNA分子; 含有所述DNA序列的各个哺乳动物表达载体; 包含所述重组DNA分子的转染的哺乳动物细胞系; 以及制备纤溶酶原激活物的方法。