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1.发明授权Methods of measuring ADAMTS13-mediated in vivo cleavage of von Willebrand factor and uses thereof 有权测量von Willebrand因子的ADAMTS13介导的体内裂解的方法及其用途公开(公告)号：US08415114B2
公开(公告)日：2013-04-09
申请号：US12630509
申请日：2009-12-03
申请人： Katalin Varadi , Hanspeter Rottensteiner , Peter Turecek , Hans-Peter Schwarz , Jutta Schreiner
发明人： Katalin Varadi , Hanspeter Rottensteiner , Peter Turecek , Hans-Peter Schwarz , Jutta Schreiner
IPC分类号： C12Q1/56
CPC分类号： G01N33/86 , C12Q1/37 , C12Q1/56 , G01N33/573 , G01N2333/755 , G01N2333/96486 , G01N2800/224 , G01N2800/52
摘要： The invention generally relates to methods of measuring cleaved von Willebrand factor (VWF) fragments. More specifically, the invention relates to methods of measuring the ability of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) to cleave VWF in vivo. The invention also relates to methods of using various animal models which demonstrate ADAMTS13 activity similar to that of a human. The invention further relates to methods of measuring the cleavage products of rVWF in mammals, particularly in humans and in human plasma.
摘要翻译： 本发明一般涉及测量切割的血管性血友病因子（VWF）片段的方法。 更具体地，本发明涉及测量具有血小板反应蛋白1型基序，成员13（ADAMTS13）在体内切割VWF的解联蛋白和金属蛋白酶的能力的方法。 本发明还涉及使用表现出与人相似的ADAMTS13活性的各种动物模型的方法。 本发明还涉及测量哺乳动物，特别是人和人血浆中rVWF的切割产物的方法。
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2.发明申请METHODS OF MEASURING ADAMTS13-MEDIATED IN VIVO CLEAVAGE OF VON WILLEBRAND FACTOR AND USES THEREOF 有权方法测量ADAMTS13-介导VIV WILLEBRAND因子的血液透析及其用途公开(公告)号：US20100143957A1
公开(公告)日：2010-06-10
申请号：US12630509
申请日：2009-12-03
申请人： Katalin Varadi , Hanspeter Rottensteiner , Peter Turecek , Hans-Peter Schwarz , Jutta Schreiner
发明人： Katalin Varadi , Hanspeter Rottensteiner , Peter Turecek , Hans-Peter Schwarz , Jutta Schreiner
IPC分类号： C12Q1/34
CPC分类号： G01N33/86 , C12Q1/37 , C12Q1/56 , G01N33/573 , G01N2333/755 , G01N2333/96486 , G01N2800/224 , G01N2800/52
摘要： The invention generally relates to methods of measuring cleaved von Willebrand factor (VWF) fragments. More specifically, the invention relates to methods of measuring the ability of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) to cleave VWF in vivo. The invention also relates to methods of using various animal models which demonstrate ADAMTS13 activity similar to that of a human. The invention further relates to methods of measuring the cleavage products of rVWF in mammals, particularly in humans and in human plasma.
摘要翻译： 本发明一般涉及测量切割的血管性血友病因子（VWF）片段的方法。 更具体地，本发明涉及测量具有血小板反应蛋白1型基序，成员13（ADAMTS13）在体内切割VWF的解联蛋白和金属蛋白酶的能力的方法。 本发明还涉及使用表现出与人相似的ADAMTS13活性的各种动物模型的方法。 本发明还涉及测量哺乳动物，特别是人和人血浆中rVWF的切割产物的方法。
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3.发明授权Methods for determining active ingredients in pro-drug PEG protein conjugates with releasable PEG reagents (in vitro de-pegylation) 有权使用可释放的PEG试剂（体外去PEG化）测定前药PEG蛋白缀合物中活性成分的方法公开(公告)号：US09274122B2
公开(公告)日：2016-03-01
申请号：US12582497
申请日：2009-10-20
申请人： Katalin Varadi , Gerald Schrenk , Hanspeter Rottensteiner , Peter Turecek , Alfred Weber , Heinz Anderle , Sean M. Culbertson , Zhihao Fang , Harold Zappe , Ping Zhang , Mary J. Bossard
发明人： Katalin Varadi , Gerald Schrenk , Hanspeter Rottensteiner , Peter Turecek , Alfred Weber , Heinz Anderle , Sean M. Culbertson , Zhihao Fang , Harold Zappe , Ping Zhang , Mary J. Bossard
CPC分类号： G01N33/68 , G01N33/542 , G01N33/582 , G01N33/86 , G01N2333/76
摘要： The invention relates to the development of in vitro assay systems that force the release of a water-soluble polymer, such as polyethylene glycol (PEG) and polysialic acid (PSA), from proteins modified with a reversibly-linked water-soluble polymer. The invention includes methods for analyzing the release of the water-soluble polymer and measuring regained protein activity. The invention further includes methods appropriate for the quality control of proteins modified with releasable water-soluble polymers, including polymers like PEG and PSA.
摘要翻译： 本发明涉及从用可逆连接的水溶性聚合物改性的蛋白质强制释放水溶性聚合物如聚乙二醇（PEG）和聚唾液酸（PSA）的体外测定系统的开发。 本发明包括用于分析水溶性聚合物的释放并测量重新获得的蛋白质活性的方法。 本发明还包括适用于用可释放水溶性聚合物（包括聚合物如PEG和PSA）改性的蛋白质的质量控制的方法。
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4.发明申请METHODS FOR DETERMINING ACTIVE INGREDIENTS IN PRO-DRUG PEG PROTEIN CONJUGATES WITH RELEASABLE PEG REAGENTS (IN VITRO DE-PEGYLATION) 有权使用可释放的PEG试剂（在体外去PEG化）中测定丙型肝素PEG蛋白质结合物中活性成分的方法公开(公告)号：US20100112607A1
公开(公告)日：2010-05-06
申请号：US12582497
申请日：2009-10-20
申请人： Katalin Varadi , Gerald Schrenk , Hanspeter Rottensteiner , Peter Turecek , Alfred Weber , Heinz Anderle , Sean M. Culbertson , Zhihao Fang , Harold Zappe , Ping Zhang , Mary J. Bossard
发明人： Katalin Varadi , Gerald Schrenk , Hanspeter Rottensteiner , Peter Turecek , Alfred Weber , Heinz Anderle , Sean M. Culbertson , Zhihao Fang , Harold Zappe , Ping Zhang , Mary J. Bossard
CPC分类号： G01N33/68 , G01N33/542 , G01N33/582 , G01N33/86 , G01N2333/76
摘要： The invention relates to the development of in vitro assay systems that force the release of a water-soluble polymer, such as polyethylene glycol (PEG) and polysialic acid (PSA), from proteins modified with a reversibly-linked water-soluble polymer. The invention includes methods for analyzing the release of the water-soluble polymer and measuring regained protein activity. The invention further includes methods appropriate for the quality control of proteins modified with releasable water-soluble polymers, including polymers like PEG and PSA.
摘要翻译： 本发明涉及从用可逆连接的水溶性聚合物改性的蛋白质强制释放水溶性聚合物如聚乙二醇（PEG）和聚唾液酸（PSA）的体外测定系统的开发。 本发明包括用于分析水溶性聚合物的释放并测量重新获得的蛋白质活性的方法。 本发明还包括适用于用可释放水溶性聚合物（包括聚合物如PEG和PSA）改性的蛋白质的质量控制的方法。
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公开(公告)号：US08642737B2
公开(公告)日：2014-02-04
申请号：US13194038
申请日：2011-07-29
申请人： Juergen Siekmann , Stefan Haider , Hanspeter Rottensteiner , Andreas Ivens , Peter Turecek , Oliver Zoechling
发明人： Juergen Siekmann , Stefan Haider , Hanspeter Rottensteiner , Andreas Ivens , Peter Turecek , Oliver Zoechling
IPC分类号： C07K14/62 , C07K14/48 , C07K14/475 , C07K16/00
CPC分类号： C07K1/1077 , A61K47/60 , A61K47/61 , C07K1/20 , C07K1/34 , C07K14/755
摘要： The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.
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公开(公告)号：US09795683B2
公开(公告)日：2017-10-24
申请号：US12843284
申请日：2010-07-26
申请人： Sanjay Jain , Gregory Gregoriadis , Archana Dwivedi , Srijit Nath , Juergen Siekmann , Stefan Haider , Hanspeter Rottensteiner , Peter Turecek
发明人： Sanjay Jain , Gregory Gregoriadis , Archana Dwivedi , Srijit Nath , Juergen Siekmann , Stefan Haider , Hanspeter Rottensteiner , Peter Turecek
CPC分类号： A61K47/6455 , A61K47/60 , A61K47/61 , A61K47/65
摘要： A water soluble polymer, in particular polysialic acid (PSA) or a modified PSA (mPSA), is conjugated to an oxidized carbohydrate moiety of a glycoprotein other than a blood coagulation protein or to a ganglioside or drug delivery system by contacting the oxidized carbohydrate moiety with the water soluble polymer, wherein said water soluble polymer contains an aminooxy group and an oxime linkage is formed between the oxidized carbohydrate moiety and the aminooxy group on the water soluble polymer or wherein said water soluble polymer contains a hydrazide group and a hydrazone linkage is formed between the oxidized carbohydrate moiety and the hydrazide group on the water soluble polymer. Conjugates of aminooxy- or hydrazide-water soluble polymer, such as PSA and mPSA, are thus obtained in which the PSA or mPSA is attached via a carbohydrate moiety.
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7.发明授权Materials and methods for conjugating a water soluble fatty acid derivative to a protein 有权将水溶性脂肪酸衍生物与蛋白质共轭的材料和方法公开(公告)号：US08945897B2
公开(公告)日：2015-02-03
申请号：US13329002
申请日：2011-12-16
IPC分类号： C12N9/96 , C07K14/475 , A61K47/48
CPC分类号： A61K47/48038 , A61K47/542 , A61K47/60
摘要： The invention relates to materials and methods of conjugating a water soluble fatty acid derivative to a therapeutic protein comprising contacting the therapeutic protein with an activated water soluble fatty acid derivative under conditions that allow conjugation.
摘要翻译： 本发明涉及将水溶性脂肪酸衍生物与治疗性蛋白质缀合的材料和方法，包括在允许缀合的条件下使治疗性蛋白质与活化的水溶性脂肪酸衍生物接触。
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8.发明申请MATERIALS AND METHODS FOR CONJUGATING A WATER SOLUBLE FATTY ACID DERIVATIVE TO A PROTEIN 有权将水溶性脂肪酸引入蛋白质的材料和方法公开(公告)号：US20120190096A1
公开(公告)日：2012-07-26
申请号：US13329002
申请日：2011-12-16
IPC分类号： C12N9/96 , C07K14/54 , C07K14/50 , C07K14/485 , C07K14/545 , C07K14/525 , C07K14/56 , C07K14/565 , C07K14/57 , C07K14/475 , C07K14/51 , C07K14/555 , C07K14/55
CPC分类号： A61K47/48038 , A61K47/542 , A61K47/60
摘要： The invention relates to materials and methods of conjugating a water soluble fatty acid derivative to a therapeutic protein comprising contacting the therapeutic protein with an activated water soluble fatty acid derivative under conditions that allow conjugation.
摘要翻译： 本发明涉及将水溶性脂肪酸衍生物与治疗性蛋白质缀合的材料和方法，包括在允许缀合的条件下使治疗性蛋白质与活化的水溶性脂肪酸衍生物接触。
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公开(公告)号：US20110027350A1
公开(公告)日：2011-02-03
申请号：US12843284
申请日：2010-07-26
申请人： Sanjay Jain , Gregory Gregoriadis , Archana Dwivedi , Srijit Nath , Juergen Siekmann , Stefan Haider , Hanspeter Rottensteiner , Peter Turecek
发明人： Sanjay Jain , Gregory Gregoriadis , Archana Dwivedi , Srijit Nath , Juergen Siekmann , Stefan Haider , Hanspeter Rottensteiner , Peter Turecek
IPC分类号： A61K9/127 , C08L101/00 , C08L89/00 , A61K47/48 , A61P7/00
CPC分类号： A61K47/6455 , A61K47/60 , A61K47/61 , A61K47/65
摘要： A water soluble polymer, in particular polysialic acid (PSA) or a modified PSA (mPSA), is conjugated to an oxidized carbohydrate moiety of a glycoprotein other than a blood coagulation protein or to a ganglioside or drug delivery system by contacting the oxidized carbohydrate moiety with the water soluble polymer, wherein said water soluble polymer contains an aminooxy group and an oxime linkage is formed between the oxidized carbohydrate moiety and the aminooxy group on the water soluble polymer or wherein said water soluble polymer contains a hydrazide group and a hydrazone linkage is formed between the oxidized carbohydrate moiety and the hydrazide group on the water soluble polymer. Conjugates of aminooxy- or hydrazide-water soluble polymer, such as PSA and mPSA, are thus obtained in which the PSA or mPSA is attached via a carbohydrate moiety.
摘要翻译： 将水溶性聚合物，特别是聚唾液酸（PSA）或修饰的PSA（mPSA）与不同于凝血蛋白的糖蛋白的氧化碳水化合物部分或通过使氧化的碳水化合物部分接触而与神经节苷脂或药物递送系统结合 其中所述水溶性聚合物含有氨基氧基，并且在水溶性聚合物上的氧化碳水化合物部分和氨基氧基之间形成肟键，或者其中所述水溶性聚合物含有酰肼基团，腙键是 形成在水溶性聚合物上的氧化碳水化合物部分和酰肼基团之间。 因此得到氨基氧基或酰肼 - 水溶性聚合物如PSA和mPSA的结合物，其中PSA或mPSA通过碳水化合物部分连接。
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公开(公告)号：US08637640B2
公开(公告)日：2014-01-28
申请号：US12843542
申请日：2010-07-26
IPC分类号： C07K14/755 , C07K14/745 , C07K1/107
CPC分类号： A61K47/4823 , A61K38/37 , A61K38/4846 , A61K47/60 , A61K47/61 , C08B37/0006 , C12N9/6437 , C12N9/644 , C12N9/96 , C12Y304/21021 , C12Y304/21022
摘要： The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBH3 to form an alkoxyamine linkage.
摘要翻译： 本发明涉及将水溶性聚合物与血液凝固蛋白的氧化碳水化合物部分缀合的材料和方法，包括在允许缀合的条件下使氧化的碳水化合物部分与活化的水溶性聚合物接触。 更具体地说，本发明涉及上述材料和方法，其中水溶性聚合物含有活性氨氧基并且其中在水溶性聚合物上的氧化碳水化合物部分和活性氨基氧基之间形成肟键。 在本发明的一个实施方案中，缀合在亲核催化剂苯胺的存在下进行。 此外，通过用NaCNBH 3还原形成烷氧基胺键可以稳定生成的肟键。
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