公开(公告)号：US5232847A

公开(公告)日：1993-08-03

申请号：US613908

申请日：1990-12-11

Applicant: Richard M. Edwards ,  Keith Dawson ,  Anthony Fallon ,  Stewart Craig

Inventor： Richard M. Edwards ,  Keith Dawson ,  Anthony Fallon ,  Stewart Craig

IPC: C12N15/09 ,  A61K38/00 ,  A61K38/46 ,  A61P7/02 ,  C07H21/04 ,  C12N20060101 ,  C12N1/00 ,  C12N5/10 ,  C12N9/00 ,  C12N9/64 ,  C12N9/72 ,  C12N15/58 ,  C22B4/02 ,  C22B4/06 ,  C22C1/02

CPC classification number: C12N9/6459 ,  C12Y304/21069 ,  A61K38/00

Abstract: Tissue plasminogen activator (t-PA) analogues have at least one substitution in the growth factor (GF) domain that at least partially reduces hepatic receptor binding without substantially jeopardising physico-chemical stability in blood or fibrinolytic activity. This results in a longer plasma half life. Substitutions in the beta-sheet encompassing residues 63-72, especially at Leu 66 and/or Tyr 67 and/or Phe 68, are particularly preferred.