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1. 发明授权

US5620688A Methods of inhibiting the activation of Factor XIII 失效
标题翻译：抑制因子XIII激活的方法
公开(公告)号：US5620688A
公开(公告)日：1997-04-15
申请号：US117052
申请日：1994-05-04
申请人： Guy L. Reed , Gary R. Matsueda , Edgar Haber
发明人： Guy L. Reed , Gary R. Matsueda , Edgar Haber
IPC分类号： A61K38/55 , A61K38/00 , A61K39/00 , A61P7/02 , C07K7/06 , C07K14/745 , C07K14/755 , C07K16/00 , C07K16/40 , C12N9/10 , A61K39/395 , A61K38/48 , A61K38/49
CPC分类号： C12N9/1044 , C07K16/40 , A61K38/00 , A61K39/00
摘要： Compositions and methods for inhibiting the activation and/or active state of a precursor protein are provided. Compositions provided can bind to a cleavage site of a precursor protein. Also provided are compounds useful for generating inhibitor compositions. Application of the invention to the treatment of myocardial infarction and other thrombotic conditions is specifically provided. Further provided are antibodies specific for active Factor XIII.
摘要翻译： PCT No.PCT / US92 / 01926 Sec。 371日期：1994年5月4日 102（e）日期1994年5月4日PCT 1991年3月11日PCT公布。公开号WO92 / 15609 日期1992年9月17日提供了抑制前体蛋白质的活化和/或活性状态的组成和方法。提供的组合物可以结合前体蛋白的切割位点。还提供了可用于产生抑制剂组合物的化合物。具体提供本发明应用于治疗心肌梗死和其它血栓形成状况。还提供了对活性因子XIII特异的抗体。

2. 发明授权

US06280730B1 Antibodies that bind to &agr;2-antiplasmin crosslinked to fibrin which do not inhibit plasma &agr;2-antiplasmin 失效
标题翻译：结合到不抑制血浆α2-抗血纤维蛋白的纤维蛋白交联的α2-抗纤溶酶的抗体
公开(公告)号：US06280730B1
公开(公告)日：2001-08-28
申请号：US08977680
申请日：1997-11-24
申请人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
发明人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
IPC分类号： A61K39395
CPC分类号： C07K16/40 , A61K38/49 , A61K39/395 , A61K45/06 , A61K2039/505 , C07K16/38 , Y10S435/975 , A61K2300/00 , A61K38/16
摘要： The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to &agr;2-antiplasmin crosslinked to fibrin (&agr;2AP-FX) which does not inhibit plasma &agr;2-antiplasmin (&agr;2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward &agr;2-antiplasmin crosslinked to fibrin which does not inhibit plasma &agr;2AP together with a thrombolytic agent.
摘要翻译：本发明涉及一种治疗患者心肌梗塞和血块的方法，更具体地涉及一种增强凝块溶解的治疗方法，包括向患者施用针对不与纤维蛋白交联的α2-抗血纤维蛋白（α2AP-FX）的抗体抑制血浆α2-抗纤溶酶（alpha2AP）。本发明还涉及用于增强凝块裂解的治疗方法，其包括给予针对不与血栓溶解剂一起抑制血浆α2AP的纤维蛋白交联的α2-抗血栓素的抗体。

3. 发明授权

US5582862A Antibodies that bind to .alpha.2-antiplasmin crosslinked to fibrin which do not inhibit plasma .alpha.2-antiplasmin 失效
标题翻译：结合到不抑制血浆α2-抗血纤维蛋白的纤维蛋白交联的α2-抗血纤维蛋白的抗体
公开(公告)号：US5582862A
公开(公告)日：1996-12-10
申请号：US980520
申请日：1992-12-01
申请人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
发明人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
IPC分类号： A61K38/00 , A61K38/49 , A61K39/395 , A61K45/06 , C07K16/38 , C07K16/40 , C12P21/08 , A61K38/48
CPC分类号： C07K16/40 , A61K38/49 , A61K39/395 , A61K45/06 , C07K16/38 , A61K2039/505 , Y10S435/975
摘要： The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to .alpha.2-antiplasmin crosslinked to fibrin (.alpha.2AP-Fx) which does not inhibit plasma .alpha.2-antiplasmin (.alpha.2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward .alpha.2-antiplasmin crosslinked to fibrin which does not inhibit plasma .alpha.2AP together with a thrombolytic agent.
摘要翻译：本发明涉及治疗患者内的心肌梗塞和血块，更具体地涉及增强凝块裂解的治疗方法，其包括向患者施用针对与纤维蛋白交联的α2-抗血纤维蛋白（α2AP-Fx）的抗体，其中不抑制血浆α2 - 抗血纤蛋白（alpha 2AP）。本发明还涉及一种用于增强凝块溶解的治疗方法，其包括给予针对不依赖于血栓溶解剂抑制血浆α2AP的纤维蛋白交联的α2-抗血浆素的抗体。

4. 发明授权

US06576431B2 Antibodies that bind to &agr;2-antiplasmin crosslinked to fibrin which do not inhibit plasma &agr;2-antiplasmin 失效
公开(公告)号：US06576431B2
公开(公告)日：2003-06-10
申请号：US09930307
申请日：2001-08-16
申请人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
发明人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
IPC分类号： G01N3353
CPC分类号： C07K16/40 , A61K38/49 , A61K39/395 , A61K45/06 , A61K2039/505 , C07K16/38 , Y10S435/975 , A61K2300/00 , A61K38/16
摘要： The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to &agr;2-antiplasmin crosslinked to fibrin (&agr;2AP-FX) which does not inhibit plasma &agr;2-antiplasmin (&agr;2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward &agr;2-antiplasmin crosslinked to fibrin which does not inhibit plasma &agr;2AP together with a thrombolytic agent.

5. 发明授权

US5372812A Composition and method for acceleration of clot lysis 失效
标题翻译：用于加速凝块裂解的组合物和方法
公开(公告)号：US5372812A
公开(公告)日：1994-12-13
申请号：US943372
申请日：1992-09-10
申请人： Guy L. Reed , Gary R. Matsueda , Edgar Haber
发明人： Guy L. Reed , Gary R. Matsueda , Edgar Haber
IPC分类号： A61K38/00 , A61K38/49 , A61K39/395 , A61K45/06 , C07K16/38 , C07K16/40 , A61K37/54 , A61K37/547 , A61K39/00 , C07K15/28
CPC分类号： C07K16/40 , A61K38/49 , A61K39/395 , A61K45/06 , C07K16/38 , A61K2039/505
摘要： The present invention relates to a novel treatment for blood clots within a patient or myocardial infarction which comprises administering a hapten-binding molecule capable of preventing inhibition of plasmin by endogenous alpha-2-antiplasmin. The invention also relates to a treatment for blood clots within a patient or myocardial infarction comprising coadministrating the hapten-binding molecule of the invention together with a thrombolytic agent capable of either dissolving fibrin-platelet clots or inhibiting their formation. The therapy of the invention is capable of increasing clot lysis while minimizing fibrinogen breakdown and preventing the reocclusion of the affected coronary artery. The therapy of the present invention is capable of achieving this goal even in the absence of heparin and when the concentration of thrombolytic agent is lower than that required by other potential therapies.
摘要翻译：本发明涉及一种患者或心肌梗塞内血凝块的新型治疗方法，其包括施用能够通过内源性α-2-抗血纤维蛋白抑制纤溶酶的半抗原结合分子。本发明还涉及治疗患者或心肌梗塞内的血凝块，其包括将本发明的半抗原结合分子与能够溶解血纤维蛋白血小板凝块或抑制其形成的溶栓剂共同给药。本发明的治疗能够增加凝块溶解，同时使纤维蛋白原分解最小化并防止受影响的冠状动脉的再闭塞。本发明的治疗即使在不存在肝素的情况下也能够实现该目的，并且当溶血栓剂的浓度低于其它潜在疗法所需的浓度时。

6. 发明授权

US5831031A Antibodies that bind to .alpha.2-antiplasmin crosslinked to fibrin which do not inhibit plasma .alpha.2-antiplasmin 失效
标题翻译：结合到不抑制血浆α2-抗血纤维蛋白的纤维蛋白交联的α2-抗血纤维蛋白的抗体
公开(公告)号：US5831031A
公开(公告)日：1998-11-03
申请号：US680634
申请日：1996-07-16
申请人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
发明人： Guy L. Reed , Edgar Haber , Gary R. Matsueda
IPC分类号： A61K38/00 , A61K38/49 , A61K39/395 , A61K45/06 , C07K16/38 , C07K16/40 , C12P21/08 , C07K16/00
CPC分类号： C07K16/40 , A61K38/49 , A61K39/395 , A61K45/06 , C07K16/38 , A61K2039/505 , Y10S435/975
摘要： The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to .alpha.2-antiplasmin crosslinked to fibrin (.alpha.2AP-FX) which does not inhibit plasma .alpha.2-antiplasmin (.alpha.2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward .alpha.2-antiplasmin crosslinked to fibrin which does not inhibit plasma .alpha.2AP together with a thrombolytic agent.
摘要翻译：本发明涉及治疗患者内的心肌梗塞和血块，更具体地涉及增强凝块裂解的治疗方法，其包括向患者施用针对与纤维蛋白交联的α2-抗血栓素（α2AP-FX）的抗体，其中不抑制血浆α2 - 抗血纤蛋白（alpha 2AP）。本发明还涉及一种用于增强凝块溶解的治疗方法，其包括给予针对不依赖于血栓溶解剂抑制血浆α2AP的纤维蛋白交联的α2-抗血浆素的抗体。

7. 发明授权

US5773228A Activation-dependent protein expressed on the surface of activated platelets and antibodies thereto 失效
标题翻译：在活化的血小板表面上表达的活化依赖性蛋白及其抗体
公开(公告)号：US5773228A
公开(公告)日：1998-06-30
申请号：US460808
申请日：1995-06-02
申请人： Guy L. Reed , Gary R. Matsueda
发明人： Guy L. Reed , Gary R. Matsueda
IPC分类号： A61K39/395 , C07K14/705 , C07K14/745 , C07K16/00 , C07K16/28 , C07K16/30 , C07K19/00 , G01N33/53 , A61K51/00 , G01N33/50
CPC分类号： C07K14/705 , C07K16/28 , C07K16/3061
摘要： The present invention provides a thrombin-activated platelet protein (TAPP). The protein is selectively expressed on the surface of thrombin-activated platelets. Antibodies which selectively bind to the thrombin-activated platelet protein are also provided. These compositions find use in the detection and treatment of blood clots.
摘要翻译：本发明提供凝血酶活化的血小板蛋白（TAPP）。蛋白质在凝血酶活化血小板的表面上选择性表达。还提供选择性结合凝血酶活化的血小板蛋白的抗体。这些组合物可用于检测和治疗血块。

8. 发明授权

US5446132A Thrombin-activated platelet protein-2 (TAPP-2) 失效
标题翻译：凝血酶激活的血小板蛋白-2（TAPP-2）
公开(公告)号：US5446132A
公开(公告)日：1995-08-29
申请号：US86472
申请日：1992-10-01
申请人： Guy L. Reed , Gary R. Matsueda
发明人： Guy L. Reed , Gary R. Matsueda
IPC分类号： A61K38/00 , C07K14/47 , C07K14/705 , C07K16/28 , C07K14/435 , C07K14/46 , C07K14/52
CPC分类号： C07K14/705 , C07K14/47 , C07K16/28 , A61K38/00
摘要： The present invention provides a thrombin-activated platelet protein (TAPP). The protein is selectively expressed on the surface of thrombin-activated platelets. Antibodies which selectively bind to the thrombin-activated platelet protein are also provided. These compositions find use in the detection and treatment of blood clots.
摘要翻译：本发明提供凝血酶活化的血小板蛋白（TAPP）。蛋白质在凝血酶活化血小板的表面上选择性表达。还提供选择性结合凝血酶活化的血小板蛋白的抗体。这些组合物可用于检测和治疗血块。

9. 发明申请

US20100086536A1 Method of Increasing Plasmin Activity through Antiplasmin Conversion 有权
标题翻译：通过抗血小板转化增加纤溶酶活性的方法
公开(公告)号：US20100086536A1
公开(公告)日：2010-04-08
申请号：US12597311
申请日：2008-04-25
申请人： Guy L. Reed
发明人： Guy L. Reed
IPC分类号： A61K38/48 , A61K38/46 , G01N33/573 , A61K31/727 , A61K31/60
CPC分类号： C07K16/38 , A61K39/3955 , A61K2039/505 , C12Q1/56 , G01N33/86
摘要： Methods for increasing plasmin activity in a patient in need thereof are provided, comprising administering to the patient a therapeutic amount of an agent which binds to α2-antiplasmin at a binding site to increase conversion of cc2-antiplasmin from an inhibitor to a plasmin substrate, thereby increasing plasmin activity in the patient. Also provided are methods for the identification of compounds or molecules that increase plasmin activity, comprising determining whether the compound or molecule binds to a binding site on α2-antiplasmin which increases the conversion of α2-antiplasmin from an inhibitor to a plasmin substrate, wherein the compound or molecule is not an antibody, thereby identifying a compound or molecule which increases plasmin activity. Further provided are pharmaceutical compositions and methods of use thereof for the treatment of myocardial infarction, thrombosis, ischemic stroke, and pulmonary embolism.
摘要翻译：提供了在有需要的患者中增加纤溶酶活性的方法，包括向患者施用治疗量的在结合部位结合α2-抗血纤蛋白的药剂，以增加从抑制剂到纤溶酶原基质的转化，从而增加患者的纤溶酶活性。还提供了用于鉴定增加纤溶酶活性的化合物或分子的方法，包括确定该化合物或分子是否结合α2-抗血纤蛋白上的结合位点，其增加α2-抗血纤维蛋白从抑制剂向纤溶酶原底物的转化，其中化合物或分子不是抗体，从而鉴定增加纤溶酶活性的化合物或分子。还提供了药物组合物及其用于治疗心肌梗塞，血栓形成，缺血性卒中和肺栓塞的方法。

10. 发明授权

US5854049A Plasmin-resistant streptokinase 失效
标题翻译：抗纤维蛋白溶酶链激酶
公开(公告)号：US5854049A
公开(公告)日：1998-12-29
申请号：US488940
申请日：1995-06-09
申请人： Guy L. Reed
发明人： Guy L. Reed
IPC分类号： A61K38/00 , C07K14/315 , C12N9/70 , C12N15/31 , C12P21/04 , A61K35/14 , C07K1/00
CPC分类号： C07K14/3153 , A61K38/00 , C07K2319/00
摘要： The invention features modified streptokinase (SK) molecules which are resistant to plasmin cleavage including a recombinant fusion protein in which the amino terminus of SK was blocked with a peptide, a recombinant fusion protein in which an amino-terminal deleted SK was blocked with a peptide, and a mutated SK in which plasmin-cleavage sites were altered to render those sites resistant to enzymatic cleavage.
摘要翻译：本发明具有对纤溶酶切割有抗性的修饰链激酶（SK）分子，包括重组融合蛋白，其中SK的氨基末端用肽封闭，其中氨基末端缺失的SK被肽封闭的重组融合蛋白和突变的SK，其中改变纤溶酶切割位点以使这些位点对酶裂解具有抗性。

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