公开(公告)号：US10155802B2

公开(公告)日：2018-12-18

申请号：US14112565

申请日：2012-04-13

申请人： Feng Ni ,  Ping Xu ,  Sazzard Hossain ,  Dmitri Tolkatchev ,  Kenji Tonan

发明人： Feng Ni ,  Ping Xu ,  Sazzard Hossain ,  Dmitri Tolkatchev ,  Kenji Tonan

IPC分类号： C07K14/745 ,  C07K14/81 ,  C12N9/74 ,  C07K5/107 ,  C07K16/36 ,  A61K38/00

摘要： A locally-activatable bivalent thrombin binding agent is provided having two thrombin binding moieties for non-overlapping sites on a surface of thrombin linked together by a linker. The linker is a polypeptide having 5 to 30 amino acid residues existing in a folded state under an environmental condition where the binding agent is inactive. The linker changes conformation from the folded state to an unfolded state in response to a change in bulk temperature and/or to the presence of hyper-mobile water thereby activating the binding agent. Such locally-activatable thrombin binding agents can be administered systemically while only targeting specific sites of coagulation or inflammation since the thrombin binding agent will only activate at the site where the existence of atherosclerotic plaques has changed the local bulk temperature and/or created hyper-mobile water sufficiently to unfold the linker and activate the binding agent. Such binding agents are useful as site-specific anti-coagulant, anti-thrombotic and/or antiinflammatory agents.

公开(公告)号：US20140113854A1

公开(公告)日：2014-04-24

申请号：US14112565

申请日：2012-04-13

申请人： Feng Ni ,  Ping Xu ,  Sazzard Hossain ,  Dmitri Tolkatchev ,  Kenji Tonan

发明人： Feng Ni ,  Ping Xu ,  Sazzard Hossain ,  Dmitri Tolkatchev ,  Kenji Tonan

IPC分类号： C07K14/745

CPC分类号： C07K14/745 ,  A61K38/00 ,  C07K5/1016 ,  C07K14/811 ,  C07K16/36 ,  C07K2319/00 ,  C07K2319/70 ,  C12N9/6429 ,  C12Y304/21005

摘要： A locally-activatable bivalent thrombin binding agent is provided having two thrombin binding moieties for non-overlapping sites on a surface of thrombin linked together by a linker. The linker is a polypeptide having 5 to 30 amino acid residues existing in a folded state under an environmental condition where the binding agent is inactive. The linker changes conformation from the folded state to an unfolded state in response to a change in bulk temperature and/or to the presence of hyper-mobile water thereby activating the binding agent. Such locally-activatable thrombin binding agents can be administered systemically while only targeting specific sites of coagulation or inflammation since the thrombin binding agent will only activate at the site where the existence of atherosclerotic plaques has changed the local bulk temperature and/or created hyper-mobile water sufficiently to unfold the linker and activate the binding agent. Such binding agents are useful as site-specific anti-coagulant, anti-thrombotic and/or antiinflammatory agents.

摘要翻译： 提供了局部可活化的二价凝血酶结合剂，其具有两个凝血酶结合部分，用于通过连接体连接在一起的凝血酶表面上的非重叠位点。 接头是在粘合剂无活性的环境条件下以折叠状态存在的具有5-30个氨基酸残基的多肽。 连接器响应于体温的变化和/或超移动水的存在而将构象从折叠状态改变到展开状态，从而激活粘合剂。 这种局部可活化的凝血酶结合剂可以全身给药，同时只靶向凝固或炎症的特定部位，因为凝血酶结合剂将仅在动脉粥样硬化斑块的存在已经改变局部体温和/或产生的超移动 水足以展开接头并活化粘合剂。 这种结合剂可用作位点特异性抗凝血剂，抗血栓形成和/或抗炎剂。