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公开(公告)号：US08450275B2
公开(公告)日：2013-05-28
申请号：US13026070
申请日：2011-02-11
申请人： Michael Dockal , Rudolf Hartmann , Markus Fries , Friedrich Scheiflinger , Hartmut Ehrlich , Ulrich Reineke , Frank Osterkamp , Thomas Polakowski
发明人： Michael Dockal , Rudolf Hartmann , Markus Fries , Friedrich Scheiflinger , Hartmut Ehrlich , Ulrich Reineke , Frank Osterkamp , Thomas Polakowski
IPC分类号： A61K38/57
CPC分类号： A61K38/10 , A61K38/00 , A61K2121/00 , C07K1/14 , C07K7/08 , C07K14/00 , C07K14/8114 , G01N33/68 , G01N2333/745 , G01N2333/8114 , G01N2333/96444 , G01N2333/96447 , G01N2500/02 , G01N2500/04 , G01N2500/20 , G06F19/16 , G06F19/18
摘要： The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.
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公开(公告)号：US20080214461A1
公开(公告)日：2008-09-04
申请号：US12022059
申请日：2008-01-29
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors. Therefore these FIX mutants are alternatives as bypassing agents for treatment of FVIII inhibitor patients.
摘要翻译： 本发明涉及具有因子VIII（FVIII）独立因子X（FX）活化电位的重组凝血因子IX（rFIX）突变体。 在HEK 293细胞中克隆并表达具有FIX和FIX野生型功能活性重要的氨基酸突变组合的五个全长FIX蛋白。 通过在FVIII消除的血浆以及FVIII抑制的患者血浆中的活化部分凝血活酶时间（aPTT）测定来测试蛋白质。 在FVIII消耗的血浆中，FIX突变体的功能活性被计算为增加的FVIII当量活性。 突变蛋白具有增加的FVIII当量活性。 在FVIII抑制的患者血浆中，计算FEIBA等效活性以分析FVIII独立的FX激活电位。 蛋白质也增加了FEIBA等效活性。 此外，预活化的FIX蛋白在含有FVIII抑制剂的FIX耗尽血浆中具有增加的活性。 因此，这些FIX突变体是用于治疗FVIII抑制剂患者的旁路药物的替代物。
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3.发明授权公开(公告)号：US08022187B2
公开(公告)日：2011-09-20
申请号：US12022059
申请日：2008-01-29
IPC分类号： A61K35/14 , A61K38/36 , C07K14/745
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors. Therefore these FIX mutants are alternatives as bypassing agents for treatment of FVIII inhibitor patients.
摘要翻译： 本发明涉及具有因子VIII（FVIII）独立因子X（FX）活化电位的重组凝血因子IX（rFIX）突变体。 在HEK 293细胞中克隆并表达具有FIX和FIX野生型功能活性重要的氨基酸突变组合的五个全长FIX蛋白。 通过在FVIII消除的血浆以及FVIII抑制的患者血浆中的活化部分凝血活酶时间（aPTT）测定来测试蛋白质。 在FVIII消耗的血浆中，FIX突变体的功能活性被计算为增加的FVIII当量活性。 突变蛋白具有增加的FVIII当量活性。 在FVIII抑制的患者血浆中，计算FEIBA等效活性以分析FVIII独立的FX激活电位。 蛋白质也增加了FEIBA等效活性。 此外，预活化的FIX蛋白在含有FVIII抑制剂的FIX耗尽血浆中具有增加的活性。 因此，这些FIX突变体是用于治疗FVIII抑制剂患者的旁路药物的替代物。
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公开(公告)号：US20080214462A1
公开(公告)日：2008-09-04
申请号：US12022071
申请日：2008-01-29
CPC分类号： C12N9/644 , C12Y304/21022
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having improved FIX clotting activity. Three full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assays in FIX-depleted plasma. Two mutant proteins had increased specific FIX activity. Furthermore, a pre-activated FIX protein had an increased activity in FIX-depleted plasma. Therefore these FIX mutants can be used for the treatment of FIX associated bleeding disorders.
摘要翻译： 本发明涉及具有改善的FIX凝血活性的重组凝血因子IX（rFIX）突变体。 在HEK 293细胞中克隆并表达具有FIX和FIX野生型功能活性重要的氨基酸突变组合的三个全长FIX蛋白。 通过在FIX消耗的血浆中的活化部分凝血活酶时间（aPTT）测定来测试蛋白质。 两种突变蛋白具有增加的特异性FIX活性。 此外，预活化的FIX蛋白在FIX耗尽的血浆中具有增加的活性。 因此，这些FIX突变体可用于治疗FIX相关出血性疾病。
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公开(公告)号：US08513386B2
公开(公告)日：2013-08-20
申请号：US13096894
申请日：2011-04-28
IPC分类号： A61K35/14 , A61K38/36 , C07K14/745
CPC分类号： C12N9/644 , A61K38/00 , C12Y304/21022
摘要： The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors. Therefore these FIX mutants are alternatives as bypassing agents for treatment of FVIII inhibitor patients.
摘要翻译： 本发明涉及具有因子VIII（FVIII）独立因子X（FX）活化电位的重组凝血因子IX（rFIX）突变体。 在HEK 293细胞中克隆并表达具有FIX和FIX野生型功能活性重要的氨基酸突变组合的五个全长FIX蛋白。 通过在FVIII消除的血浆以及FVIII抑制的患者血浆中的活化部分凝血活酶时间（aPTT）测定来测试蛋白质。 在FVIII消耗的血浆中，FIX突变体的功能活性被计算为增加的FVIII当量活性。 突变蛋白具有增加的FVIII当量活性。 在FVIII抑制的患者血浆中，计算FEIBA等效活性以分析FVIII独立的FX激活电位。 蛋白质也增加了FEIBA等效活性。 此外，预活化的FIX蛋白在含有FVIII抑制剂的FIX耗尽血浆中具有增加的活性。 因此，这些FIX突变体是用于治疗FVIII抑制剂患者的旁路药物的替代物。
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公开(公告)号：US20070205348A1
公开(公告)日：2007-09-06
申请号：US11526606
申请日：2006-09-26
申请人： Hans-Michael Schmitt , Juergen Bach , Thomas Polzer , Dirk Erdloff , Rudolf Hartmann , Jochen Gans , Andrejus Afanasjevas
发明人： Hans-Michael Schmitt , Juergen Bach , Thomas Polzer , Dirk Erdloff , Rudolf Hartmann , Jochen Gans , Andrejus Afanasjevas
IPC分类号： A47B97/00
CPC分类号： B60S1/0822 , B60S1/0881
摘要： A retaining frame for a support element of a sensor in a motor vehicle is disclosed. The retaining frame has a flat underside that can be adhered to a window of a motor vehicle, and having an opening with at least one contact surface for the support element in which opening the support element can be positioned flat on the window and against the contact surface, and has a spring element by which a force can be applied to the support element.
摘要翻译： 公开了一种用于机动车辆中的传感器的支撑元件的保持框架。 保持框架具有平坦的下侧，其可以粘附到机动车辆的窗口，并且具有用于支撑元件的具有至少一个接触表面的开口，在该开口中支撑元件可以平坦地定位在窗口上并且抵靠接触 并且具有弹簧元件，通过该弹簧元件可以将力施加到支撑元件。
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公开(公告)号：US5020783A
公开(公告)日：1991-06-04
申请号：US459696
申请日：1990-01-26
申请人： Bernd Schroder , Rudolf Hartmann , Helmut Thate
发明人： Bernd Schroder , Rudolf Hartmann , Helmut Thate
IPC分类号： B62D55/108 , F16F1/14 , F16F1/366
CPC分类号： F16F1/14 , B62D55/108 , F16F1/366 , B60G2200/132 , B60G2202/134 , B60G2204/122 , B60G2206/42 , B60G2206/427 , B60G2206/7101 , B60G2206/8103 , B60G2206/82013
摘要： A torsional spring to be secured non-rotating to mutually rotating components at each end. At least two thin-walled piping sections are positioned loosely coaxial and secured together non-rotating at one end, accordingly functioning as a series of resilient sections. There are means of securing them non-rotating to the mutually rotating components at the other end. The spring especially constitutes a torsion bar for a connecting rod that pivots in a bearing mounted stationary in a vehicle and positions either a running wheel or a caterpillar cogwheel at the end remote from the bearing. The piping sections are integrated into each other such that one merges directly into the other at the end where they are secured together non-rotating in a turnback that represents a transition point. The piping sections are preferably made of fiber-reinforced plastic and may have several layers.
摘要翻译： PCT No.PCT / DE89 / 00364 Sec。 371 1990年1月26日第 102（e）日期1990年1月26日PCT提交1989年6月2日PCT公布。 WO89 / 11993 PCT出版物 日期是1989年12月14日。一个扭转弹簧被固定在每个端部不旋转到相互旋转的部件。 至少两个薄壁管道段被松散地同轴并且固定在一端不旋转的一端，因此用作一系列的弹性部分。 在另一端有固定它们不旋转到相互旋转的部件的装置。 弹簧特别构成用于连接杆的扭杆，该连杆在固定在车辆中的轴承中枢转，并且在远离轴承的一端定位跑步轮或履带式齿轮。 管道部分彼此集成在一起，使得它们在末端被合并到另一个端部，在它们的端部处，它们被固定在一起，在转向中的转动中不旋转。 管道部分优选地由纤维增强塑料制成，并且可以具有几层。
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公开(公告)号：US4296292A
公开(公告)日：1981-10-20
申请号：US94891
申请日：1979-11-16
摘要： A variable electromechanical device, such as a rotary potentiometer, incls a housing with a sleeve having a bore through which an actuation shaft extends. The shaft is provided with an annular groove. A portion of the sleeve is displaced by stamping so that it extends into the annular groove of the shaft to prevent axial movement of the latter. A projection formed on the shaft within the annular groove cooperates with the displaced portion of the sleeve for limiting the rotation of the shaft. A lubricating and braking liquid of high viscosity is filled in the groove, and one or more passages are formed on the projection so that the liquid can pass from one side of the projection to the other side thereof when the shaft is rotated.
摘要翻译： 诸如旋转电位计的可变机电装置包括具有套筒的壳体，所述套筒具有致动轴延伸穿过的孔。 轴设有环形槽。 套筒的一部分通过冲压而移位，使其延伸到轴的环形槽中，以防止轴的轴向移动。 形成在该环内的轴上的突起与套筒的移位部分配合，以限制该轴的转动。 在该凹槽中填充有高粘度的润滑制动液，在突出部上形成有一个或多个通道，使得当轴旋转时，液体可以从突出部的一侧通过到另一侧。
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公开(公告)号：US20060115566A1
公开(公告)日：2006-06-01
申请号：US10559302
申请日：2004-05-27
IPC分类号： A21D10/00
CPC分类号： A21D10/045 , A21D2/181 , A21D2/186 , A21D6/001
摘要： Liquid dough whose Aw is less than 0.9 and which comprises 10 to 40% flour, from 20 to 30% fat, from 10 to 30% water, up to 2% salt and a mixture of at least one carbohydrate with low or zero sweetening power in a sufficient quantity to reduce the Aw of said dough to a desired value of less than 0.9. The dough substantially contains no carbohydrate having a substantially perceptible sweetening power and as a result does not have a sweet taste. This dough allows the production of savory bakery products such as fruit cakes with olives, lardoons or cheese for example. The dough can be preserved for several weeks in the refrigerated state and exists in liquid or fluid form which makes it possible to pour it directly into baking molds. Process for the manufacture of such a dough.
摘要翻译： 其Aw小于0.9的液体面团，其包含10至40％的面粉，20至30％的脂肪，10至30％的水，至多2％的盐和至少一种具有低或零甜味力的碳水化合物的混合物 以足够的量将所述面团的Aw减少到小于0.9的期望值。 面团基本上不含具有基本上可感知的甜味力的碳水化合物，结果不具有甜味。 这种面团允许生产例如含有橄榄，柠檬或奶酪的水果蛋糕的美味面包店产品。 面团可以在冷藏状态下保存数周，并以液体或流体形式存在，这样可以将其直接倒入烘烤模具中。 用于制造这种面团的方法。
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公开(公告)号：US06888465B2
公开(公告)日：2005-05-03
申请号：US10281363
申请日：2002-10-28
CPC分类号： B60H1/00785 , B60S1/0822 , B60S1/0825 , G01N27/226
摘要： The invention relates to a sensor unit for detecting the wetting of a window. Signals from the condensation sensor are used to control an air conditioning, heating, and/or ventilation unit. The signals of the rain sensor, on the contrary, are used to control a windshield wiper or washing unit for vehicles. A sensor unit, which comprises two sensors, is placed on the interior of the window. In a preferred variant, both are coupled to a common switchable evaluation unit, so that through mutual evaluation of the two sensors or their signals, both incipient condensation on the interior of a vehicle window and the wetting of the exterior, e.g., by rain, is detected. In an improvement of the invention, both sensors are integrated into a sensor module.
摘要翻译： 本发明涉及一种用于检测窗口润湿的传感器单元。 来自冷凝传感器的信号用于控制空调，加热和/或通风单元。 相反，雨水传感器的信号用于控制用于车辆的挡风玻璃刮水器或洗涤单元。 包括两个传感器的传感器单元放置在窗户的内部。 在一个优选的变型中，两者都耦合到公共可切换评估单元，使得通过两个传感器或它们的信号的相互评估，车窗内部的初始冷凝和外部的润湿（例如雨） 被检测到。 在本发明的改进中，两个传感器被集成到传感器模块中。
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