公开(公告)号：US5759542A

公开(公告)日：1998-06-02

申请号：US286748

申请日：1994-08-05

申请人： Victor Gurewich

发明人： Victor Gurewich

IPC分类号： A61K38/00 ,  C07K14/49 ,  C07K14/655 ,  C07K14/815 ,  C12N9/72 ,  A61K38/49

CPC分类号： C12N9/6462 ,  C07K14/49 ,  C07K14/655 ,  C07K14/815 ,  C12Y304/21073 ,  A61K38/00 ,  C07K2319/00

摘要： A fusion drug including an isolated portion of the A-chain of a urokinase-type plasminogen activator linked to a drug, wherein the A-chain portion binds stably to an outer membrane of a platelet. The T.sub.1/2 of the fusion drug in plasma is thereby increased to about 4 to 5 days, and the fusion drug is automatically targeted to forming thrombi and sites of vascular injury. The fusion drug can thus be used to treat cardiovascular diseases, e.g., as adjunctive therapy to inhibit reocclusions in a patient after thrombolytic therapy or angioplasty.

摘要翻译： 一种融合药物，其包括与药物连接的尿激酶型纤溶酶原激活物的A链的分离部分，其中所述A链部分稳定地结合于血小板的外膜。 血浆中融合药物的T + E，fra 1/2 + EE由此增加至约4至5天，并且融合药物被自动靶向以形成血栓和血管损伤部位。 因此，融合药物可用于治疗心血管疾病，例如作为在溶栓治疗或血管成形术之后抑制患者的再粘连的辅助治疗。

公开(公告)号：US20110081334A1

公开(公告)日：2011-04-07

申请号：US12947573

申请日：2010-11-16

申请人： Victor Gurewich ,  Ralph Pannell

发明人： Victor Gurewich ,  Ralph Pannell

IPC分类号： A61K38/48 ,  A61P7/02

CPC分类号： A61K38/57 ,  A61K38/49 ,  C12Y304/21073 ,  A61K2300/00

摘要： A mutant prourokinase plasminogen activator (M5) was developed to make prouPA less subject to spontaneous activation during fibrinolysis. C1-inhibitor complexes with tcM5. The effect of C1-inhibitor on fibrinolysis and fibrinogenolysis by M5 was determined. Supplemental C1-inhibitor restores the stability of M5 but not that of prouPA. Clot lysis by M5 with supplemental C1-inhibitor showed no attenuation of the rate of fibrinolysis, whereas fibrinogenolysis was prevented by C1-inhibitor. Due to higher dose tolerance of M5 with C1-inhibitor, the rate of fibrin-specific lysis reached that achievable by nonspecific fibrinolysis without inhibitor. Plasma C1-inhibitor stabilized M5 in plasma by inhibiting tcM5 and thereby non-specific plasminogen activation. At the same time, fibrin-specific plasminogen activation remained unimpaired. This unusual dissociation of effects has significant implications for improving the safety and efficacy of fibrinolysis. Methods of reducing bleeding and non-specific plasminogen activation during fibrinolysis by administering M5 along with exogenous C1-inhibitor are disclosed.

摘要翻译： 开发了突变型prourokinase纤溶酶原激活物（M5），使prouPA在纤维蛋白溶解过程中较少受到自发激活。 C1抑制剂与tcM5复合物。 测定了C1抑制剂对M5纤维蛋白溶解和纤维蛋白原分解的影响。 补充的C1抑制剂恢复M5的稳定性，而不是prouPA的稳定性。 M5与补体C1抑制剂的凝血酶裂解显示纤维蛋白溶解速率没有减弱，而C1抑制剂阻止了纤维蛋白原分解。 由于M5与C1抑制剂的较高剂量耐受性，纤维蛋白特异性裂解的速率达到通过非特异性纤维蛋白溶解而无抑制剂可达到的速率。 血浆C1抑制剂通过抑制tcM5稳定M5，从而抑制非特异性纤溶酶原激活。 同时，纤维蛋白特异性纤溶酶原激活仍然没有受到损害。 这种不寻常的效应解离对于提高纤维蛋白溶解的安全性和有效性具有重要意义。 公开了通过与外源性C1抑制剂一起施用M5来减少纤维蛋白溶解期间出血和非特异性纤溶酶原激活的方法。

公开(公告)号：US5626841A

公开(公告)日：1997-05-06

申请号：US254922

申请日：1994-06-07

申请人： Victor Gurewich

发明人： Victor Gurewich

IPC分类号： A61K38/49 ,  C12N15/57 ,  C12N9/64 ,  C12N9/72

CPC分类号： A61K38/49

摘要： A method of adjunctive therapy to inhibit reocclusions in a patient, e.g., after thrombolytic therapy or angioplasty, by administering to the patient a bolus of an amount of purified pro-urokinase ("pro-UK") that inhibits the formation of occlusive thrombi without inducing a systemic effect in the patient, the pro-UK is administered after the completion of the thrombolytic treatment and periodically thereafter for the duration of therapy, and becomes incorporated into the outer membrane of the platelets of the patient, thereby increasing the T.sub. 1/2 of the pro-UK in plasma, which is about 7 to 8 minutes, to about 4 to 5 days, and inhibiting reocclusion without inducing a systemic effect.

摘要翻译： 一种辅助治疗方法，例如在溶栓治疗或血管成形术之后，通过对患者施用一定量的纯化的尿激酶（“pro-UK”），其抑制闭塞血栓的形成而不在 在患者中引起全身效应，在溶栓治疗完成后施用pro-UK，并在治疗期间定期施用，并且将其并入患者血小板的外膜中，从而增加T + E ，英制血浆中的1/2 + EE，其为约7至8分钟至约4至5天，并且抑制再闭合而不引起全身作用。

公开(公告)号：USRE32271E

公开(公告)日：1986-10-28

申请号：US727807

申请日：1985-04-26

申请人： Syed S. Husain ,  Boguslaw Lipinski ,  Victor Gurewich

发明人： Syed S. Husain ,  Boguslaw Lipinski ,  Victor Gurewich

IPC分类号： A61K38/00 ,  C12N9/72

CPC分类号： C12N9/6456 ,  A61K38/00

摘要： The existence of high fibrin-affinity urokinase is discovered by an isolation procedure using fibrin precipitated on an adsorptive-solid matrix. By the method described, the high affinity form of plasminogen activator can be isolated directly from urine or from kidney tissue culture medium. The method is economical and provides a relatively high yield of the activator. The high affinity that this plasminogen activator has for fibrin is a property that makes it an improved thrombolytic agent and when radiolabelled provides a new diagnostic agent for the specific detection of fibrin thrombi through nuclear scanning. The newly-isolated plasminogen activator has the following characteristics: a molecular weight of about 56,000 Daltons, a specific activity of about 40,000-50,000 CTA units/mg, the appearance of a single chain structure and a high affinity for fibrin.

公开(公告)号：US20130085111A1

公开(公告)日：2013-04-04

申请号：US13634776

申请日：2011-03-18

申请人： Victor Gurewich ,  Alexis Wallace

发明人： Victor Gurewich ,  Alexis Wallace

IPC分类号： C12P21/00

CPC分类号： C12P21/005 ,  A61K38/005 ,  C07K14/8121 ,  C07K2319/21

摘要： Vector constructs comprising the coding sequence for human C1 inhibitor are described. Expression of glycosylated recombinant human C1 inhibitor is achieved human cells in high yields.

摘要翻译： 描述了包含人C1抑制剂编码序列的载体构建体。 糖基化重组人C1抑制剂的表达以高产率获得人类细胞。

公开(公告)号：US07837992B2

公开(公告)日：2010-11-23

申请号：US11732620

申请日：2007-04-04

申请人： Victor Gurewich ,  Ralph Pannell

发明人： Victor Gurewich ,  Ralph Pannell

IPC分类号： A61K38/48 ,  C12N9/72 ,  C12N9/68

CPC分类号： A61K38/57 ,  A61K38/49 ,  C12Y304/21073 ,  A61K2300/00

摘要： A mutant prourokinase plasminogen activator (M5) was developed to make prouPA less subject to spontaneous activation during fibrinolysis. C1-inhibitor complexes with tcM5. The effect of C1-inhibitor on fibrinolysis and fibrinogenolysis by M5 was determined. Supplemental C1-inhibitor restores the stability of M5 but not that of prouPA. Clot lysis by M5 with supplemental C1-inhibitor showed no attenuation of the rate of fibrinolysis, whereas fibrinogenolysis was prevented by C1-inhibitor. Due to higher dose tolerance of M5 with C1-inhibitor, the rate of fibrin-specific lysis reached that achievable by nonspecific fibrinolysis without inhibitor. Plasma C1-inhibitor stabilized M5 in plasma by inhibiting tcM5 and thereby non-specific plasminogen activation. At the same time, fibrin-specific plasminogen activation remained unimpaired. This unusual dissociation of effects has significant implications for improving the safety and efficacy of fibrinolysis. Methods of reducing bleeding and non-specific plasminogen activation during fibrinolysis by administering M5 along with exogenous C1-inhibitor are disclosed.

摘要翻译： 开发了突变型prourokinase纤溶酶原激活物（M5），使prouPA在纤维蛋白溶解过程中较少受到自发激活。 C1抑制剂与tcM5复合物。 测定了C1抑制剂对M5纤维蛋白溶解和纤维蛋白原分解的影响。 补充的C1抑制剂恢复M5的稳定性，而不是prouPA的稳定性。 M5与补体C1抑制剂的凝血酶裂解显示纤维蛋白溶解速率没有减弱，而C1抑制剂阻止了纤维蛋白原分解。 由于M5与C1抑制剂的较高剂量耐受性，纤维蛋白特异性裂解的速率达到通过非特异性纤维蛋白溶解而无抑制剂可达到的速率。 血浆C1抑制剂通过抑制tcM5稳定M5，从而抑制非特异性纤溶酶原激活。 同时，纤维蛋白特异性纤溶酶原激活仍然没有受到损害。 这种不寻常的效应解离对于提高纤维蛋白溶解的安全性和有效性具有重要意义。 公开了通过与外源性C1抑制剂一起施用M5来减少纤维蛋白溶解期间出血和非特异性纤溶酶原激活的方法。

公开(公告)号：US20100143325A1

公开(公告)日：2010-06-10

申请号：US12330557

申请日：2008-12-09

申请人： Victor Gurewich

发明人： Victor Gurewich

IPC分类号： A61K38/48 ,  A61P9/00

CPC分类号： A61K38/49 ,  A61K38/57 ,  A61K2300/00

摘要： Treatment or prevention methods are described wherein t-PA and C1-inhibtor are used together in order to minimize the hemorrhagic complications of tPA Preferably, C1-inhibitor is infused prior to treatment with t-PA, thereby allowing for a safer thrombolysis without the excessive and dangerous bleeding associated with the use of t-PA alone particularly in the treatment of ischemic stroke.

摘要翻译： 描述了治疗或预防方法，其中t-PA和C1-抑制剂一起使用以使tPA的出血并发症最小化。优选地，在用t-PA治疗之前输注C1抑制剂，从而允许更安全的溶栓而不过量 和与单独使用t-PA有关的危险性出血，特别是在治疗缺血性卒中。