公开(公告)号：EP0473689A1

公开(公告)日：1992-03-11

申请号：EP90908772.0

申请日：1990-05-21

申请人： Temple University of the Commonwealth System of Higher Education

发明人： BUDZYNSKI, Andrei, Z. ,  KNIGHT, Linda, C. ,  HASAN, Ahmed, Ak.

IPC分类号： A61K38 ,  C07K1 ,  C07K14 ,  C07K19 ,  C12N9

CPC分类号： C12N9/6456 ,  A61K38/49 ,  C07K14/75

摘要： Des agents hybrides thrombolytiques sont obtenus sous la forme de complexes covalents ou non covalents de fragments de fibrine et de molécules d'un activateur de plasminogène. Des fragments de dégradation de plasmine naturelle de fibrine ou des fragments de fibrine non naturels sont liés de manière covalente ou non covalente à des activateurs de plasminogène tels que tPA, scu-A, urokinase, streptokinase, et autres. Des fragments de fibrine naturels utiles pouvant être utilisés pour former des complexes avec des activateurs de plasminogène comprennent les fragments E1, E2, E3, D et DD, et le complexe (DD)E. Le composant de fragment de fibrine cible l'agent hybride sur les thrombus vasculaires immobilisant la molécule de plasminogène sur la surface de la fibrine du thrombus. Une fois localisé sur la surface d'un thrombus, le composant de l'activateur de plasminogène de l'agent hybride active uniquement le plasminogène lié à la surface du caillot transporté par le véhicule de fragment de fibrine, sans activation systémique significative de plasminogène.

公开(公告)号：EP0473689B1

公开(公告)日：1994-12-14

申请号：EP90908772.8

申请日：1990-05-21

申请人： Temple University of the Commonwealth System of Higher Education

发明人： BUDZYNSKI, Andrei, Z. ,  KNIGHT, Linda, C. ,  HASAN, Ahmed, Ak.

IPC分类号： A61K37/54 ,  A61K37/547 ,  A61K37/02 ,  C12N9/50 ,  C12N9/70 ,  C12N9/72 ,  C07K15/06

CPC分类号： C12N9/6456 ,  A61K38/49 ,  C07K14/75

摘要： Thrombolytic hybrids are formed as covalent or non-covalent complexes of fibrin fragments and plasminogen activator molecules. Native plasmin degradation fragments of fibrin or non-native fibrin fragments are covalently or non-covalently linked to plasminogen activators such as t-PA, scu-PA, urokinase, streptokinase, and the like. Useful native fibrin fragments which may be utilized to form complexes with plasminogen activators include fragments E1, E2, E3, D and DD, and (DD)E complex. The fibrin fragment component targets the hybrid to vascular thrombi, immobilizing the plasminogen activator molecule onto the fibrin surface of the thrombus. Once localized on a thrombus surface, the plasminogen activator component of the hybrid activates only the clot-surface bound plasminogen transported by the fibrin fragment vehicle, without significant systemic activation of plasminogen. The hybrids are strong potentiators of plasminogen activator activity, generating more plasmin from fibrin-surface bound plasminogen than the plasminogen activator molecule alone. The hybrids have a longer half-life in circulation than the corresponding unprotected plasminogen activator molecules.

公开(公告)号：EP0679162A1

公开(公告)日：1995-11-02

申请号：EP93923267.0

申请日：1993-10-05

申请人： Temple University of the Commonwealth System of Higher Education

发明人： KNIGHT, Linda, C. ,  MAURER, Alan, H.

IPC分类号： G01N33 ,  A61K51 ,  C07K14

CPC分类号： A61K51/08 ,  A61K2123/00 ,  C07K14/46

摘要： Radiolabelled polypeptides derived from the Viperidae disintegrins are provided as well as a method for the detection of venous and arterial thrombi, pulmonary emboli and tumors or abscesses that have a thrombus component. Compositions suitable for parenteral administration comprising the radiolabelled polypeptides and a pharmaceutically acceptable carrier are also provided.