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1. 发明申请

WO2007146104A3 SUBSTRATES AND INHIBITORS OF ANTIPLASMIN CLEAVING ENZYME AND METHODS OF USE 审中-公开
标题翻译：抗菌素清除酶基质和抑制剂及其使用方法
公开(公告)号：WO2007146104A3
公开(公告)日：2008-10-16
申请号：PCT/US2007013480
申请日：2007-06-06
申请人： MCKEE PATRICK A , LEE KYUNG N , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
发明人： MCKEE PATRICK A , LEE KYUNG N , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
IPC分类号： G01N33/53
CPC分类号： G01N33/542 , A61K38/00 , A61K47/60 , C07K7/02 , C07K7/06 , C07K7/08 , C07K14/001 , C12Q1/37 , G01N33/86
摘要： The present invention is directed toward inhibitors of antiplasmin cleaving enzyme for use in various therapies related to fibrin and a 2 -antiplasmin, and to substrates of APCE, which may be used, for example, in screening methods for identifying such inhibitors. The present invention is further directed to methods of treating or inhibiting atherosclerosis and thrombus disorders by altering the rations of types of plasma a 2 -antiplasmin.
摘要翻译：本发明涉及用于与纤维蛋白和2β-对映体相关的各种疗法的抗血浆酶切割酶的抑制剂，以及APCE的底物，其可用于例如筛选方法鉴定这种抑制剂。本发明还涉及通过改变等离子体类型的比例来治疗或抑制动脉粥样硬化和血栓紊乱的方法。

2. 发明申请

WO2004072240A2 ANTIPLASMIN CLEAVING ENZYME 审中-公开
标题翻译：抗菌清洁酶
公开(公告)号：WO2004072240A2
公开(公告)日：2004-08-26
申请号：PCT/US2004003398
申请日：2004-02-07
申请人： MCKEE PATRICK A , LEE KYUNG N , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
发明人： MCKEE PATRICK A , LEE KYUNG N , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
IPC分类号： A61K38/00 , C07K14/745 , C07K14/81 , C12N9/64 , C12P21/06 , C12Q1/37 , C12N
CPC分类号： C12Q1/37 , A61K38/00 , C07K14/745 , C07K14/8121 , C12N9/6421 , C12P21/06 , G01N2500/00
摘要： Human alpha2-antiplasmin (alpha2AP) is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. Two forms of alpha2AP circulate in human plasma: a 464-residue protein, which we have termed "pro"-form, or alpha2APpro,and an N-terminally-shortened 452-residue "activated"-form, or alpha2APact. The latter becomes crosslinked to fibrin by activated factor XIII about 5-fold more rapidly than alpha2APpro and makes fibrin resistant to digestion by plasmin. A new human plasma proteinase has been identified herein that cleaves the Pro12-Asn13 bond of alpha2APpro to yield alpha2APact. This enzyme is identified herein as Antiplasmin Cleaving Enzyme (APCE). Novel inhibitors of circulating APCE can diminish alpha2AP inhibitory capacity within forming fibrin or blood clots thereby making fibrin deposits or blood clots more susceptible to removal by plasmin. Patients who are susceptible to atherosclerotic plaque formation or are susceptible to developing thrombi that compromise organ function will benefit by therapies providing such inhibitors on a long term basis.
摘要翻译：人α2-抗纤溶酶（alpha2AP）是消化纤维蛋白的蛋白水解酶纤溶酶的主要抑制剂。两种形式的α2AP在人血浆中循环：464残基蛋白，我们称之为“pro”型或α2APpro，以及N-末端缩短的452残基“活化”形式或α2APact。后者通过活化因子XIII与α2APpro快速交联至纤维蛋白，比alpha2APpro快5倍，并使纤维蛋白对纤溶酶消化具有抗性。本文已经鉴定出新的人血浆蛋白酶，其切割α2APpro的Pro12-Asn13键以产生α2APact。该酶在本文中被鉴定为抗血小板裂解酶（APCE）。循环APCE的新型抑制剂可以降低形成纤维蛋白或血凝块的α2AP抑制能力，从而使纤维蛋白沉积物或血块更容易被纤溶酶去除。易受动脉粥样硬化斑块形成或容易发生危及器官功能的血栓的患者将通过长期提供这种抑制剂的疗法而受益。

3. 发明申请

WO2004072240A8 ANTIPLASMIN CLEAVING ENZYME 审中-公开
标题翻译：抗胰蛋白酶酶解酶
公开(公告)号：WO2004072240A8
公开(公告)日：2005-11-03
申请号：PCT/US2004003398
申请日：2004-02-07
申请人： MCKEE PATRICK A , LEE KYUNG N , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
发明人： MCKEE PATRICK A , LEE KYUNG N , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
IPC分类号： A61K38/00 , C07K14/745 , C07K14/81 , C12N9/64 , C12P21/06 , C12Q1/37 , C12N9/00 , C07K1/00 , C07K16/00 , C12N9/48 , C12N9/50
CPC分类号： C12Q1/37 , A61K38/00 , C07K14/745 , C07K14/8121 , C12N9/6421 , C12P21/06 , G01N2500/00
摘要： Human alpha2-antiplasmin (alpha2AP) is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. Two forms of alpha2AP circulate in human plasma: a 464-residue protein, which we have termed "pro"-form, or alpha2APpro,and an N-terminally-shortened 452-residue "activated"-form, or alpha2APact. The latter becomes crosslinked to fibrin by activated factor XIII about 5-fold more rapidly than alpha2APpro and makes fibrin resistant to digestion by plasmin. A new human plasma proteinase has been identified herein that cleaves the Pro12-Asn13 bond of alpha2APpro to yield alpha2APact. This enzyme is identified herein as Antiplasmin Cleaving Enzyme (APCE). Novel inhibitors of circulating APCE can diminish alpha2AP inhibitory capacity within forming fibrin or blood clots thereby making fibrin deposits or blood clots more susceptible to removal by plasmin. Patients who are susceptible to atherosclerotic plaque formation or are susceptible to developing thrombi that compromise organ function will benefit by therapies providing such inhibitors on a long term basis.
摘要翻译：人类alpha2-antiplasmin（alpha2AP）是消化纤维蛋白的蛋白水解酶纤溶酶的主要抑制剂。两种形式的alpha2AP在人血浆中循环：464个残基的蛋白质，我们称之为“pro”形式，或alpha2APpro，和一个N末端缩短的452残基“激活”形式，或alpha2APact。后者通过活化因子XIII交联成纤维蛋白，比α2APpro快约5倍，并使纤维蛋白对纤溶酶的消化具有抗性。本文已经鉴定了新的人血浆蛋白酶，其裂解α2APpro的Pro12-Asn13键以产生α2APact。这种酶在本文中被确定为抗血纤维蛋白裂解酶（APCE）。新型循环APCE抑制剂可以减少形成纤维蛋白或血块内的α2AP抑制能力，从而使纤维蛋白沉积物或血块更易于被纤溶酶清除。对动脉粥样硬化斑块形成敏感或容易发生危及器官功能的血栓的患者将受益于长期提供这种抑制剂的疗法。

4. 发明申请

WO2013166438A4 SUBSTRATES AND INHIBITORS OF PROLYL OLIGOPEPTIDASE AND FIBROBLAST ACTIVATION PROTEIN AND METHODS OF USE 审中-公开
标题翻译：低聚赖氨酸和纤维蛋白激活蛋白的基质和抑制剂及其使用方法
公开(公告)号：WO2013166438A4
公开(公告)日：2014-01-09
申请号：PCT/US2013039543
申请日：2013-05-03
申请人： UNIV OKLAHOMA , MCKEE PATRICK A , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
发明人： MCKEE PATRICK A , JACKSON KENNETH W , CHRISTIANSEN VICTORIA J
IPC分类号： A61K31/401 , A61K31/185 , A61K31/19 , A61K31/198 , A61P25/28
CPC分类号： C07K5/1019 , A61K38/00 , A61K38/1825 , A61K38/1858 , A61K38/21 , A61K38/28 , A61K38/30 , C07K5/0202 , C07K5/06043 , C07K5/06069 , C07K5/06086 , C07K5/06095 , C07K5/06104 , C07K5/06113 , C07K5/06147 , C07K5/0815 , C07K5/0817 , C07K5/0819 , C07K5/0821 , C07K7/06 , A61K2300/00
摘要： Inhibitors of fibroblast activation protein alpha (FAP) and Prolyl Oligopeptidase (POP) are disclosed, along with their use in various therapies related to conditions, diseases, and disorders involving abnormal cell proliferation such as malignancies and angiogenesis, and in neural disorders such as Alzheimer's disease. Stalk portions of the inhibitor molecules, and substrates of FAP and POP, are also disclosed and may be used, for example, in screening methods for identifying such inhibitors.
摘要翻译：公开了成纤维细胞活化蛋白α（FAP）和脯氨酰寡肽酶（POP）的抑制剂，以及它们在与涉及异常细胞增殖如恶性肿瘤和血管发生的病症，疾病和病症的各种疗法中的用途，以及神经障碍如阿尔茨海默病疾病。还公开了抑制剂分子的茎部分和FAP和POP的底物，并且可以用于例如鉴定这种抑制剂的筛选方法中。

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