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1. 发明授权

US5571708A Thrombin-activatable plasminogen activator 失效
标题翻译：凝血酶激活性纤溶酶原激活物
公开(公告)号：US5571708A
公开(公告)日：1996-11-05
申请号：US49195
申请日：1993-04-19
申请人： Wen-Pin Yang , Gary R. Matsueda , Shyh-Yu Shaw
发明人： Wen-Pin Yang , Gary R. Matsueda , Shyh-Yu Shaw
IPC分类号： A61K38/00 , C07K16/18 , C12N9/72 , C12P21/08 , A61K38/48 , C07H19/00 , C07K16/00
CPC分类号： C12N9/6462 , C07K16/18 , C12Y304/21073 , A61K38/00 , C07K2319/00
摘要： A new chimeric plasminogen activator with high fibrin affinity was designed to bind to a fibrin clot and initiate clot destruction in the presence of thrombin, but not plasmin. The chimeric molecule has an antibody variable region having a fibrin-specific antigen binding site and a single chain urokinase region having a thrombin activation site but not a plasmin activation site. The preferred embodiment, 59D8-ScuPA-T, has an N-terminal fragment of an anti-fibrin antibody (59DB) and a C-terminal thrombin-activatable low molecular weight single-chain urokinase plasminogen activator (scuPA-T). The scuPA-T portion was obtained by deletion of two amino acids (Phe157 and Lys 158) that make up the plasmin activation site from low molecular weight single chain urokinase-type plasminogen activator (scuPA).
摘要翻译：设计具有高纤维蛋白亲和力的新的嵌合纤溶酶原激活物结合纤维蛋白凝块，并在凝血酶存在下引发凝块破坏，而不是纤溶酶。嵌合分子具有具有纤维蛋白特异性抗原结合位点的抗体可变区和具有凝血酶活化位点而不是纤溶酶活化位点的单链尿激酶区。优选的实施方案59D8-ScuPA-T具有抗纤维蛋白抗体（59DB）和C末端凝血酶激活的低分子量单链尿激酶纤溶酶原激活物（scuPA-T）的N-末端片段。通过从低分子量单链尿激酶型纤溶酶原激活物（scuPA）中缺失构成纤溶酶活化位点的两个氨基酸（Phe157和Lys158）获得scuPA-T部分。

2. 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。

3. 发明授权

US5116613A Antibody-thrombolytic agent product and method of use 失效
标题翻译：抗体溶血栓剂产品及使用方法
公开(公告)号：US5116613A
公开(公告)日：1992-05-26
申请号：US689851
申请日：1985-01-08
申请人： Edgar Haber , Gary R. Matsueda
发明人： Edgar Haber , Gary R. Matsueda
IPC分类号： A61K47/48
CPC分类号： A61K47/4843
摘要： A thrombolytic product comprising a fibrin-specific antibody substantially devoid of fibrinogen cross-reactivity coupled to a thrombolytic agent.
摘要翻译：一种血栓溶解产物，其包含与血栓溶解剂偶联的基本上不含纤维蛋白原交叉反应性的纤维蛋白特异性抗体。

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

US4927916A Method of producing fibrin-specific monoclonal antibodies lacking fibrinogen-cross-reactivity using fibrin-specific peptides 失效
标题翻译：使用纤维蛋白特异性肽制备缺乏纤维蛋白原交叉反应的纤维蛋白特异性单克隆抗体的方法
公开(公告)号：US4927916A
公开(公告)日：1990-05-22
申请号：US824228
申请日：1986-01-30
申请人： Gary R. Matsueda , Edgar Haber , Kwan Hui
发明人： Gary R. Matsueda , Edgar Haber , Kwan Hui
IPC分类号： A61K51/10 , C07K14/745 , C07K16/18
CPC分类号： A61K51/1018 , A61K51/1093 , C07K14/745 , C07K16/18 , A61K2123/00 , Y10S530/806 , Y10S530/807 , Y10S530/808 , Y10S530/809 , Y10S530/812
摘要： Peptides comprising fibrin-specific epitopic sequences are used to prepare hybridoma cell lines producing antifibrin-specific monoclonal antibodies substantially devoid of fibrinogen-cross-reactivity obtained by somatic cell fusion. The antibodies are useful for the in vivo and in vitro detection of thrombi and fibrin deposits.
摘要翻译：包含纤维蛋白特异性表位序列的肽用于制备产生基本上没有通过体细胞融合获得的纤维蛋白原交叉反应的抗纤维蛋白特异性单克隆抗体的杂交瘤细胞系。抗体可用于体内和体外检测血栓和纤维蛋白沉积物。

7. 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。

8. 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。

9. 发明授权

US5357042A Synthetic peptides capable of eliciting fibrin-specific monoclonal antibodies lacking fibrinogen-cross-reactivity 失效
标题翻译：能够诱导纤维蛋白特异性单克隆抗体缺乏纤维蛋白原交叉反应性的合成肽
公开(公告)号：US5357042A
公开(公告)日：1994-10-18
申请号：US932729
申请日：1992-08-24
申请人： Gary R. Matsueda , Edgar Haber , Kwan Hui
发明人： Gary R. Matsueda , Edgar Haber , Kwan Hui
IPC分类号： A61K49/00 , A61K51/10 , C07K14/745 , C07K16/18 , A61K31/02 , C07K7/06 , C07K15/28
CPC分类号： A61K51/1018 , A61K49/00 , A61K51/1093 , C07K14/745 , C07K16/18 , A61K2123/00
摘要： Peptides comprising fibrin-specific epitopic sequences are used to prepare hybridoma cell lines producing antifibrin-specific monoclonal antibodies substantially devoid of fibrinogen-cross-reactivity obtained by somatic cell fusion. The antibodies are useful for the in vivo and in vitro detection of thrombi and fibrin deposits.
摘要翻译：包含纤维蛋白特异性表位序列的肽用于制备产生基本上没有通过体细胞融合获得的纤维蛋白原交叉反应的抗纤维蛋白特异性单克隆抗体的杂交瘤细胞系。抗体可用于体内和体外检测血栓和纤维蛋白沉积物。

10. 发明授权

US07091331B2 Nucleic acid molecules and polypeptides encoding baboon TAFI 有权
标题翻译：编码狒狒TAFI的核酸分子和多肽
公开(公告)号：US07091331B2
公开(公告)日：2006-08-15
申请号：US10379836
申请日：2003-03-04
申请人： James K. Tamura , Gary R. Matsueda , Mei-Yin Hsu , Akbar Nayeem
发明人： James K. Tamura , Gary R. Matsueda , Mei-Yin Hsu , Akbar Nayeem
IPC分类号： C07H21/01 , C07H21/04 , C07K1/14
CPC分类号： C12N9/48 , A61K38/00
摘要： The present invention relates to the isolation and identification of novel baboon nucleic acid molecules and proteins and polypeptides encoded by such nucleic acid molecules, or degenerate variants thereof, which proteins and polypeptides comprise novel baboon thrombin-activatable fibrinolysis inhibitors or “TAFI” enzyme molecules. Because the novel baboon TAFI proteins and polypeptides of the invention inhibit the breakdown of blood clots, they may be therapeutically useful for the treatment of blood disorders wherein clotting needs to be regulated or promoted, such as hemophilia or von Willebrand's disease or in other situations, such as trauma, wherein blood clotting or coagulation needs to be regulated or promoted. The sequences of the invention are also useful in screening methods for the identification of compounds that modulate the expression of the baboon TAFI nucleic acids and/or the activity of the baboon TAFI proteins and polypeptides of the invention. Such agonist or antagonist compounds may be useful in the treatment of various blood clotting disorders and conditions requiring hemostatic control such as hemophilia or various thrombotic diseases such as deep venous thrombosis, coronary artery disease, stroke associated with atrial fibrillation and recurrent thrombosis following stroke or myocardial infarction.
摘要翻译：本发明涉及分离和鉴定由这种核酸分子或其简并变体编码的新型狒狒核酸分子和蛋白质和多肽，其蛋白质和多肽包含新型狒狒凝血酶可激活的纤维蛋白溶解抑制剂或“TAFI”酶分子。因为本发明的新型狒狒TAFI蛋白质和多肽抑制血凝块的分解，所以它们可用于治疗需要调节或促进凝血的血液病症，例如血友病或血管性血友病或其他情况，例如创伤，其中需要调节或促进凝血或凝血。本发明的序列也可用于鉴定调节狒狒TAFI核酸表达的化合物和/或本发明的狒狒TAFI蛋白和多肽的活性的筛选方法。这样的激动剂或拮抗剂化合物可用于治疗各种血液凝固病症和需要止血控制的病症，例如血友病或各种血栓形成疾病如深静脉血栓形成，冠状动脉疾病，与心房颤动相关的中风和中风或心肌复发性血栓形成梗死。

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