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1.再颁专利公开(公告)号：USRE41328E1
公开(公告)日：2010-05-11
申请号：US12199215
申请日：2008-08-27
申请人： Ramnath Sasisekharan , Charles L. Cooney , Robert S. Langer , Daniel L. Lohse , Robert J. Linhardt
发明人： Ramnath Sasisekharan , Charles L. Cooney , Robert S. Langer , Daniel L. Lohse , Robert J. Linhardt
CPC分类号： C12N9/88 , Y10S435/822 , Y10S435/85
摘要： A purified heparinase I, II and III free of lyase activity and each having a molecular weight of 42,800 84,100, 70,800, respectively, are produced by culturing Flavobacterium heparinum. The kinetic properties of the heparinases have been determined as well as the conditions to optimize their activity and stability.
摘要翻译： 不含裂解酶活性的纯化肝素酶I，II和III分别通过培养肝炎黄杆菌而产生，分子量分别为42,400,84,100,70,800。 已经确定了肝素酶的动力学性质以及优化其活性和稳定性的条件。
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2.再颁专利Purification, composition and specificity of Heparinase I, II, and III from Flavobacterium heparinum 有权来自肝炎黄杆菌的肝素酶I，II和III的纯化，组成和特异性公开(公告)号：USRE41461E1
公开(公告)日：2010-07-27
申请号：US12199157
申请日：2008-08-27
申请人： Daniel L. Lohse , Robert J. Linhardt , Ramnath Sasisekharan , Charles L. Cooney , Robert S. Langer
发明人： Daniel L. Lohse , Robert J. Linhardt , Ramnath Sasisekharan , Charles L. Cooney , Robert S. Langer
CPC分类号： C12N9/88 , Y10S435/822 , Y10S435/85
摘要： A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Mono-clonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.
摘要翻译： 本文公开了将来自肝素肝素的所有三种肝素裂解酶同时纯化到表观均一性的单一可再现方案。 已经确定了肝素裂解酶的动力学性质以及优化其活性和稳定性的条件。 还描述了对三种肝素酶的单克隆抗体，并且其可用于肝素酶的检测，分离和表征。
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3.发明授权
公开(公告)号：US5569600A
公开(公告)日：1996-10-29
申请号：US378789
申请日：1995-01-26
申请人： Ramnath Sasisekharan , Daniel L. Lohse , Charles L. Cooney , Robert J. Linhardt , Robert S. Langer
发明人： Ramnath Sasisekharan , Daniel L. Lohse , Charles L. Cooney , Robert J. Linhardt , Robert S. Langer
IPC分类号： G01N33/573 , C07K16/40 , C12N9/88 , C12P19/26 , C12P21/08 , C12R1/20 , C12R1/91 , C12N9/00 , C12N1/20 , C12N9/52
CPC分类号： C12N9/88 , Y10S435/822 , Y10S435/85
摘要： A single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity is disclosed herein. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. Monoclonal antibodies to the three heparinases are also described and are useful for detection, isolation and characterization of the heparinases.
摘要翻译： 本文公开了将来自肝素肝素的所有三种肝素裂解酶同时纯化到表观均一性的单一可再现方案。 已经确定了肝素裂解酶的动力学性质以及优化其活性和稳定性的条件。 还描述了三种肝素酶的单克隆抗体，并且其可用于肝素酶的检测，分离和表征。
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4.发明授权
公开(公告)号：US5389539A
公开(公告)日：1995-02-14
申请号：US983367
申请日：1992-11-30
申请人： Ramnath Sasisekharan , Daniel L. Lohse , Charles L. Cooney , Robert J. Linhardt , Robert S. Langer
发明人： Ramnath Sasisekharan , Daniel L. Lohse , Charles L. Cooney , Robert J. Linhardt , Robert S. Langer
IPC分类号： G01N33/573 , C07K16/40 , C12N9/88 , C12P19/26 , C12P21/08 , C12R1/20 , C12R1/91 , C12N9/00 , C12N1/20 , C12N9/52
CPC分类号： C12N9/88 , Y10S435/822 , Y10S435/85
摘要： A purified heparinase I, II and III free of lyase activity and each having a molecular weight of 42,800 84,100, 70,800, respectively, are produced by culturing Flavobacterium heparinum. The kinetic properties of the heparinases have been determined as well as the conditions to optimize their activity and stability.
摘要翻译： 不含裂解酶活性的纯化的肝素酶I，II和III分别通过培养肝素肝素而产生，分子量分别为42,600 84,100,70,800。 已经确定了肝素酶的动力学性质以及优化其活性和稳定性的条件。
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公开(公告)号：US5567417A
公开(公告)日：1996-10-22
申请号：US431476
申请日：1995-05-01
申请人： Ramnath Sasisekharan , Marsha A. Moses , Matthew A. Nugent , Charles L. Cooney , Robert S. Langer
发明人： Ramnath Sasisekharan , Marsha A. Moses , Matthew A. Nugent , Charles L. Cooney , Robert S. Langer
IPC分类号： A61K47/30 , A61K35/74 , A61K38/00 , A61K38/46 , A61P9/00 , A61P17/00 , A61P27/02 , A61P35/00 , C12N9/88 , A61K38/51
摘要： Pharmaceutical compositions for delivering an effective dose to a desired site of a heparinase. These compositions are based on the discovery that heparinase alone can inhibit angiogenesis. The effective dosage is dependent not only on the heparinase, but also on the method and means of delivery, which can be localized or systemic. For example, in some applications, as in the treatment of psoriasis or diabetic retinopathy, the inhibitor is delivered in a topical ophthalmic carrier. In other applications, as in the treatment of solid tumors, the inhibitor is delivered by means of a biodegradable, polymeric implant.
摘要翻译： 用于将有效剂量递送至肝素酶的所需位点的药物组合物。 这些组合物基于单独的肝素酶可以抑制血管发生的发现。 有效剂量不仅取决于肝素酶，而且还取决于递送的方法和手段，其可以是局部的或全身性的。 例如，在一些应用中，如在牛皮癣或糖尿病性视网膜病变的治疗中，抑制剂在局部眼科载体中递送。 在其他应用中，如在实体瘤的治疗中，抑制剂通过可生物降解的聚合物植入物递送。
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公开(公告)号：US5714376A
公开(公告)日：1998-02-03
申请号：US783706
申请日：1991-10-23
申请人： Ramnath Sasisekharan , Kelley Moremen , Charles L. Cooney , Joseph J. Zimmermann , Robert S. Langer
发明人： Ramnath Sasisekharan , Kelley Moremen , Charles L. Cooney , Joseph J. Zimmermann , Robert S. Langer
CPC分类号： C12N9/88
摘要： The cloning of the heparinase gene from Flavobacterium Heparinum using the polymerase chain reaction is described. The Open Reading Frame (ORF) corresponded to 1152 base pairs encoding a precursor protein of MW 43,800 daltons. The amino acid sequence reveals a 20-residue leader peptide. The gene was expressed in two expression systems in E. coli.
摘要翻译： 描述了使用聚合酶链反应从肝炎杆菌中克隆肝素酶基因。 开放阅读框（ORF）对应于编码MW 43,800道尔顿的前体蛋白质的1152个碱基对。 氨基酸序列显示20个残基的前导肽。 该基因在大肠杆菌中的两个表达系统中表达。
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公开(公告)号：US4396762A
公开(公告)日：1983-08-02
申请号：US295914
申请日：1981-08-24
CPC分类号： A61K31/715 , C08B37/0078 , Y10S435/85
摘要： There is disclosed a heparin product obtained by degradation of heparin with heparinase from Flavobacterium heparinum (ATCC 13125) or mutants thereof having activity to reduce the coagulation activity of factor X while not effecting the coagulation activity of thrombin.
摘要翻译： 公开了通过肝素从肝素黄素（ATCC13125）或其突变体用肝素酶降解获得的肝素产物，其具有降低因子X的凝血活性而不影响凝血酶凝血活性的活性。
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公开(公告)号：US5830726A
公开(公告)日：1998-11-03
申请号：US445342
申请日：1995-05-19
申请人： Ramnath Sasisekharan , Kelley Moremen , Charles I. Cooney , Joseph J. Zimmermann , Robert S. Langer
发明人： Ramnath Sasisekharan , Kelley Moremen , Charles I. Cooney , Joseph J. Zimmermann , Robert S. Langer
CPC分类号： C12N9/88
摘要： The cloning of the heparinase gene from Flavobacterium Heparinum using the polymerase chain reaction is described. The Open Reading Frame (ORF) corresponded to 1152 base pairs encoding a precursor protein of MW 43,800 daltons. The amino acid sequence reveals a 20-residue leader peptide. The gene was expressed in two expression systems in E. coli.
摘要翻译： 描述了使用聚合酶链反应从肝炎杆菌中克隆肝素酶基因。 开放阅读框（ORF）对应于编码MW 43,800道尔顿的前体蛋白的1152个碱基对。 氨基酸序列显示20个残基的前导肽。 该基因在大肠杆菌中的两个表达系统中表达。
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公开(公告)号：US4906474A
公开(公告)日：1990-03-06
申请号：US613001
申请日：1984-05-21
申请人： Robert S. Langer , Howard Rosen , Robert J. Linhardt , Kam Leong
发明人： Robert S. Langer , Howard Rosen , Robert J. Linhardt , Kam Leong
摘要： A composition of matter suitable for implantation in the body to effect zero order drug release comprising a drug and a polymer of the formula: ##STR1## wherein R and R' can be the same or different and are hydrophobic organic linkages and n and m are integers of 1 or greater.
摘要翻译： 适于植入体内以实现零级药物释放的物质组合物，其包含药物和下式的聚合物：其中R和R'可以相同或不同，并且是疏水性有机键，并且n和m是 1或更大的整数。
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公开(公告)号：US4373023A
公开(公告)日：1983-02-08
申请号：US196720
申请日：1980-10-14
申请人： Robert S. Langer , Robert Linhardt , Charles L. Cooney , Parrish M. Galliher , Margaret M. Flanagan , Michael D. Klein
发明人： Robert S. Langer , Robert Linhardt , Charles L. Cooney , Parrish M. Galliher , Margaret M. Flanagan , Michael D. Klein
CPC分类号： A61M1/3675 , A61K33/00 , A61K35/14 , C12N11/02
摘要： Blood containing heparin and treated extracorporeally is contacted with immobilized heparinase prior to being reintroduced into the patient.
摘要翻译： 血液含有肝素并经体外治疗与被固定的肝素酶接触，然后再次引入患者。
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