公开(公告)号：WO2010048184A2

公开(公告)日：2010-04-29

申请号：PCT/US2009061327

申请日：2009-10-20

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  NEKTAR THERAPEUTICS ,  VARADI KATALIN ,  SCHRENK GERALD ,  ROTTENSTEINER HANSPETER ,  TURECEK PETER ,  WEBER ALFRED ,  ANDERLE HEINZ ,  CULBERTSON SEAN M ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  ZHANG PING ,  BOSSARD MARY J

Inventor： VARADI KATALIN ,  SCHRENK GERALD ,  ROTTENSTEINER HANSPETER ,  TURECEK PETER ,  WEBER ALFRED ,  ANDERLE HEINZ ,  CULBERTSON SEAN M ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  ZHANG PING ,  BOSSARD MARY J

IPC: G01N33/542 ,  G01N33/58 ,  G01N33/68 ,  G01N33/86

CPC classification number: G01N33/68 ,  G01N33/542 ,  G01N33/582 ,  G01N33/86 ,  G01N2333/76

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2005095638A2

公开(公告)日：2005-10-13

申请号：PCT/EP2005003328

申请日：2005-03-30

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  VARADI KATALIN ,  TURECEK PETER ,  KEIL BRIGITTE ,  PEYRER-HEIMSTAETT SYLVIA ,  SCHWARZ HANS-PETER

Inventor： VARADI KATALIN ,  TURECEK PETER ,  KEIL BRIGITTE ,  PEYRER-HEIMSTAETT SYLVIA ,  SCHWARZ HANS-PETER

IPC: C12Q1/56 ,  G01N33/86

CPC classification number: A61K31/66 ,  C12Q1/56 ,  G01N33/86 ,  G01N2333/745

Abstract: The invention provides a kit for measuring the thrombin generation in a sample of a patient's blood or plasma, or in a sample of clotting factors. The kit contains lyophilized tissue factor/phospholipid-complex and a lyophilized mixture containing a thrombin-substrate and CaCl2. The invention also provides processes for preparing the reagents for the kit. The kit can be used in a method for measuring the thrombin generation in a sample, wherein it is possible to detect changes in thrombin generation kinetics, for example after administration of inhibitor bypassing agents to a patient who has developed inhibitors to an exogenous clotting factor such as Factor VIII.

Abstract translation: 本发明提供了一种用于测量患者血液或血浆样品或凝血因子样品中的凝血酶产生的试剂盒。 该试剂盒含有冻干组织因子/磷脂复合物和含有凝血酶底物和CaCl 2的冻干混合物。 本发明还提供了用于制备试剂盒的试剂的方法。 该试剂盒可以用于测量样品中凝血酶产生的方法，其中可以检测凝血酶产生动力学的变化，例如在将抑制剂旁路剂施用于已经开发出外源凝血因子的抑制剂的患者之后 作为因子VIII。

公开(公告)号：WO2010065742A1

公开(公告)日：2010-06-10

申请号：PCT/US2009/066588

申请日：2009-12-03

Applicant: BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE S.A. ,  VARADI, Katalin ,  ROTTENSTEINER, Hanspeter ,  TURECEK, Peter ,  SCHWARZ, Hans-Peter ,  SCHREINER, Jutta

Inventor： VARADI, Katalin ,  ROTTENSTEINER, Hanspeter ,  TURECEK, Peter ,  SCHWARZ, Hans-Peter ,  SCHREINER, Jutta

IPC: C12Q1/37

CPC classification number: G01N33/86 ,  C12Q1/37 ,  C12Q1/56 ,  G01N33/573 ,  G01N2333/755 ,  G01N2333/96486 ,  G01N2800/224 ,  G01N2800/52

Abstract: [00135] 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 ADAMTS1 3 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.

Abstract translation: 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ADAMTS1 3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。

公开(公告)号：WO2010048184A3

公开(公告)日：2010-04-29

申请号：PCT/US2009/061327

申请日：2009-10-20

Applicant: BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE S.A. ,  NEKTAR THERAPEUTICS ,  VARADI, Katalin ,  SCHRENK, Gerald ,  ROTTENSTEINER, Hanspeter ,  TURECEK, Peter ,  WEBER, Alfred ,  ANDERLE, Heinz ,  CULBERTSON, Sean, M. ,  FANG, Zhihao ,  ZAPPE, Harold ,  ZHANG, Ping ,  BOSSARD, Mary, J.

Inventor： VARADI, Katalin ,  SCHRENK, Gerald ,  ROTTENSTEINER, Hanspeter ,  TURECEK, Peter ,  WEBER, Alfred ,  ANDERLE, Heinz ,  CULBERTSON, Sean, M. ,  FANG, Zhihao ,  ZAPPE, Harold ,  ZHANG, Ping ,  BOSSARD, Mary, J.

IPC: G01N33/542 ,  G01N33/58 ,  G01N33/68 ,  G01N33/86

Abstract: 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.

公开(公告)号：WO2009086356A2

公开(公告)日：2009-07-09

申请号：PCT/US2008088131

申请日：2008-12-23

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  TURECEK PETER ,  SIEKMANN JUERGEN ,  WEBER ALFRED ,  GRITSCH HERBERT ,  VARADI KATALIN ,  VEJDA SUSANNE

Inventor： TURECEK PETER ,  SIEKMANN JUERGEN ,  WEBER ALFRED ,  GRITSCH HERBERT ,  VARADI KATALIN ,  VEJDA SUSANNE

IPC: G01N33/53

CPC classification number: G01N33/86 ,  G01N33/5308 ,  G01N2430/60

Abstract: The present invention relates to a method for determining the amount of a physiologically acceptable polymer molecule bound to a protein, an antibody or other composition being capable of specifically binding to a physiologically acceptable polymer molecule, and a kit containing said antibody or composition.

Abstract translation: 本发明涉及测定与蛋白质结合的生理上可接受的聚合物分子的量，能够特异性结合生理上可接受的聚合物分子的抗体或其它组合物的方法，以及含有所述抗体或组合物的试剂盒。

公开(公告)号：WO2008082669A3

公开(公告)日：2009-04-09

申请号：PCT/US2007026522

申请日：2007-12-27

Applicant: NEKTAR THERAPEUTICS AL CORP ,  BAXTER INT ,  BAXTER HEALTHCARE SA ,  BOSSARD MARY J ,  STEPHENSON GAYLE ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  MITCHELL STACY ,  ZHANG PING ,  SCHEIFLINGER FRITZ ,  TURECEK PETER ,  SIEKMANN JUERGEN ,  VARADI KATALIN ,  GRITSCH HERBERT

Inventor： BOSSARD MARY J ,  STEPHENSON GAYLE ,  FANG ZHIHAO ,  ZAPPE HAROLD ,  MITCHELL STACY ,  ZHANG PING ,  SCHEIFLINGER FRITZ ,  TURECEK PETER ,  SIEKMANN JUERGEN ,  VARADI KATALIN ,  GRITSCH HERBERT

IPC: A61K47/48 ,  A61P7/00

CPC classification number: C07K14/755 ,  A61K47/60

Abstract: The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.

Abstract translation: 本发明提供了von Willebrand因子 - 聚合物共轭物和因子VIII-聚合物缀合物，其各自具有可释放的连接。 还提供了制备缀合物的方法，用于施用缀合物的方法。

公开(公告)号：WO2005095638B1

公开(公告)日：2006-11-02

申请号：PCT/EP2005003328

申请日：2005-03-30

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  VARADI KATALIN ,  TURECEK PETER ,  KEIL BRIGITTE ,  PEYRER-HEIMSTAETT SYLVIA ,  SCHWARZ HANS-PETER

Inventor： VARADI KATALIN ,  TURECEK PETER ,  KEIL BRIGITTE ,  PEYRER-HEIMSTAETT SYLVIA ,  SCHWARZ HANS-PETER

IPC: C12Q1/56 ,  G01N33/86

CPC classification number: A61K31/66 ,  C12Q1/56 ,  G01N33/86 ,  G01N2333/745

Abstract: The invention provides a kit for measuring the thrombin generation in a sample of a patient's blood or plasma, or in a sample of clotting factors. The kit contains lyophilized tissue factor/phospholipid-complex and a lyophilized mixture containing a thrombin-substrate and CaCl 2 . The invention also provides processes for preparing the reagents for the kit. The kit can be used in a method for measuring the thrombin generation in a sample, wherein it is possible to detect changes in thrombin generation kinetics, for example after administration of inhibitor bypassing agents to a patient who has developed inhibitors to an exogenous clotting factor such as Factor VIII.

Abstract translation: 本发明提供了一种用于测量患者血液或血浆样品或凝血因子样品中的凝血酶产生的试剂盒。 试剂盒含有冻干组织因子/磷脂复合物和含有凝血酶底物和CaCl 2 2的冻干混合物。 本发明还提供了用于制备试剂盒的试剂的方法。 该试剂盒可以用于测量样品中凝血酶产生的方法，其中可以检测凝血酶产生动力学的变化，例如在将抑制剂旁路剂施用于已经开发出外源凝血因子的抑制剂的患者之后 作为因子VIII。

公开(公告)号：WO2009086356A3

公开(公告)日：2009-07-09

申请号：PCT/US2008/088131

申请日：2008-12-23

Applicant: BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE S.A. ,  TURECEK, Peter ,  SIEKMANN, Juergen ,  WEBER, Alfred ,  GRITSCH, Herbert ,  VARADI, Katalin ,  VEJDA, Susanne

Inventor： TURECEK, Peter ,  SIEKMANN, Juergen ,  WEBER, Alfred ,  GRITSCH, Herbert ,  VARADI, Katalin ,  VEJDA, Susanne

IPC: G01N33/53

Abstract: The present invention relates to a method for determining the amount of a physiologically acceptable polymer molecule bound to a protein, an antibody or other composition being capable of specifically binding to a physiologically acceptable polymer molecule, and a kit containing said antibody or composition.

公开(公告)号：WO2008082669A2

公开(公告)日：2008-07-10

申请号：PCT/US2007/026522

申请日：2007-12-27

Applicant: NEKTAR THERAPEUTICS AL, CORPORATION ,  BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE SA ,  BOSSARD, Mary, J. ,  STEPHENSON, Gayle ,  FANG, Zhihao ,  ZAPPE, Harold ,  MITCHELL, Stacy ,  ZHANG, Ping ,  SCHEIFLINGER, Fritz ,  TURECEK, Peter ,  SIEKMANN, Juergen ,  VARADI, Katalin ,  GRITSCH, Herbert

Inventor： BOSSARD, Mary, J. ,  STEPHENSON, Gayle ,  FANG, Zhihao ,  ZAPPE, Harold ,  MITCHELL, Stacy ,  ZHANG, Ping ,  SCHEIFLINGER, Fritz ,  TURECEK, Peter ,  SIEKMANN, Juergen ,  VARADI, Katalin ,  GRITSCH, Herbert

IPC: A61K47/48 ,  A61P7/00

CPC classification number: C07K14/755 ,  A61K47/60

Abstract: The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.

Abstract translation: 本发明提供了von Willebrand因子 - 聚合物共轭物和因子VIII-聚合物缀合物，其各自具有可释放的连接。 还提供了制备缀合物的方法，用于施用缀合物的方法。

公开(公告)号：WO2007126808A1

公开(公告)日：2007-11-08

申请号：PCT/US2007/007560

申请日：2007-03-29

Applicant: BAXTER INTERNATIONAL INC ,  BAXTER HEALTHCARE S.A. ,  SIEKMANN, Juergen ,  VARADI, Katalin ,  GRITSCH, Herbert ,  TURECEK, Peter

Inventor： SIEKMANN, Juergen ,  VARADI, Katalin ,  GRITSCH, Herbert ,  TURECEK, Peter

IPC: A61K47/48 ,  C07K14/755

CPC classification number: C07K14/755 ,  A61K47/60 ,  C07K14/745

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.

Abstract translation: 本发明是包含具有至少一部分B结构域的因子VIII分子的蛋白质构建体，其与水溶性聚合物如分子量大于10,000道尔顿的聚乙二醇缀合。 该构建体具有天然因子VIII的生物活性的至少80％的生物活性，与天然因子FVIII的体内生命周期相比，构建体的体内半衰期增加至少1.5倍。