公开(公告)号：US08264695B2

公开(公告)日：2012-09-11

申请号：US13030748

申请日：2011-02-18

申请人： Ralf Arnold ,  Stefan Schulte ,  Bernd Doerband

发明人： Ralf Arnold ,  Stefan Schulte ,  Bernd Doerband

IPC分类号： G01B11/02

CPC分类号： G01B9/021 ,  G01B9/02039 ,  G01B11/2441 ,  G01M11/025 ,  G01M11/0271 ,  Y10T29/49771

摘要： A method of aligning at least two wave shaping elements, a method of measuring a deviation of an optical surface from a target shape and a measuring apparatus for interferometrically measuring a deviation of an optical surface from a target shape. The method of aligning at least two wave shaping elements, each of which wave shaping elements has a diffractive measurement structure for adapting part of a wave front of incoming light to a respective portion of the target shape, includes: providing a first one of the wave shaping elements with a diffractive alignment structure, arranging the wave shaping elements relative to each other such that each of the diffractive measurement structures is traversed by a separate subset of rays of the incoming light during operation of the measuring apparatus, and aligning the first wave shaping element and a second one of the wave shaping elements relative to each other by evaluating alignment light having consecutively interacted with the diffractive alignment structure and with the second wave shaping element.

摘要翻译： 对准至少两个波形整形元件的方法，测量光学表面与目标形状的偏差的方法和用于干涉测量光学表面与目标形状的偏差的测量装置。 对准至少两个波形整形元件的方法，其中每个波形整形元件具有衍射测量结构，用于将入射光的一部分波前适应到目标形状的相应部分，包括：提供第一波 具有衍射对准结构的成形元件，将波形整形元件相对于彼此布置，使得每个衍射测量结构在测量设备的操作期间被入射光的单独的子集子穿过，并且对准第一波形整形 元件和第二波形成形元件相对于彼此，通过评估与衍射对准结构和第二波形整形元件连续相互作用的对准光。

公开(公告)号：US07936521B2

公开(公告)日：2011-05-03

申请号：US12684600

申请日：2010-01-08

申请人： Ralf Arnold ,  Stefan Schulte ,  Bernd Doerband

发明人： Ralf Arnold ,  Stefan Schulte ,  Bernd Doerband

IPC分类号： G02B13/18

CPC分类号： G01B9/021 ,  G01B9/02039 ,  G01B11/2441 ,  G01M11/025 ,  G01M11/0271 ,  Y10T29/49771

摘要： A method of aligning at least two wave shaping elements, a method of measuring a deviation of an optical surface from a target shape and a measuring apparatus for interferometrically measuring a deviation of an optical surface from a target shape. The method of aligning at least two wave shaping elements, each of which wave shaping elements has a diffractive measurement structure for adapting part of a wave front of incoming light to a respective portion of the target shape, includes: providing a first one of the wave shaping elements with a diffractive alignment structure, arranging the wave shaping elements relative to each other such that each of the diffractive measurement structures is traversed by a separate subset of rays of the incoming light during operation of the measuring apparatus, and aligning the first wave shaping element and a second one of the wave shaping elements relative to each other by evaluating alignment light having consecutively interacted with the diffractive alignment structure and with the second wave shaping element.

摘要翻译： 对准至少两个波形整形元件的方法，测量光学表面与目标形状的偏差的方法和用于干涉测量光学表面与目标形状的偏差的测量装置。 对准至少两个波形整形元件的方法，其中每个波形整形元件具有衍射测量结构，用于将入射光的一部分波前适应到目标形状的相应部分，包括：提供第一波 具有衍射对准结构的成形元件，将波形整形元件相对于彼此布置，使得每个衍射测量结构在测量设备的操作期间被入射光的单独的子集子穿过，并且对准第一波形整形 元件和第二波形成形元件相对于彼此，通过评估与衍射对准结构和第二波形整形元件连续相互作用的对准光。

公开(公告)号：US07274467B2

公开(公告)日：2007-09-25

申请号：US11027989

申请日：2005-01-04

申请人： Bernd Doerband ,  Stefan Schulte

发明人： Bernd Doerband ,  Stefan Schulte

IPC分类号： G01B11/02

CPC分类号： G03F7/706 ,  G01B9/02005 ,  G01B9/02038 ,  G01B9/02057 ,  G01B11/2441 ,  G01B2290/35 ,  G01M11/005 ,  G01M11/025 ,  G01M11/0271 ,  G03F1/26 ,  G03F1/84

摘要： A phase shifting interferometric method and apparatus comprises generating at least four different phase shifts and recording interferograms corresponding to the different phase settings and recording interferograms corresponding to the different phase settings. In the analysis of the recorded interferograms the generated phase shifts between the at least four different phase settings are determined from the measurement, i.e. from the recorded interferograms. A model simulating the interferogram intensities may be used for determining the phase shifts. The phase shifts are free adaptable parameters of the model.

摘要翻译： 相移干涉测量方法和装置包括产生至少四个不同的相移和记录对应于不同相位设置的干涉图并记录对应于不同相位设置的干涉图。 在记录的干涉图的分析中，从测量确定至少四个不同相位设置之间的所产生的相移，即从所记录的干涉图中确定。 可以使用模拟干涉图强度的模型来确定相移。 相移是模型的自由适应参数。

公开(公告)号：US20060146342A1

公开(公告)日：2006-07-06

申请号：US11027989

申请日：2005-01-04

申请人： Bernd Doerband ,  Stefan Schulte

发明人： Bernd Doerband ,  Stefan Schulte

IPC分类号： G01B11/02

CPC分类号： G03F7/706 ,  G01B9/02005 ,  G01B9/02038 ,  G01B9/02057 ,  G01B11/2441 ,  G01B2290/35 ,  G01M11/005 ,  G01M11/025 ,  G01M11/0271 ,  G03F1/26 ,  G03F1/84

摘要： A phase shifting interferometric method and apparatus comprises generating at least four different phase shifts and recording interferograms corresponding to the different phase settings and recording interferograms corresponding to the different phase settings. In the analysis of the recorded interferograms the generated phase shifts between the at least four different phase settings are determined from the measurement, i.e. from the recorded interferograms. A model simulating the interferogram intensities may be used for determining the phase shifts. The phase shifts are free adaptable parameters of the model.

摘要翻译： 相移干涉测量方法和装置包括产生至少四个不同的相移和记录对应于不同相位设置的干涉图并记录对应于不同相位设置的干涉图。 在记录的干涉图的分析中，从测量确定至少四个不同相位设置之间的所产生的相移，即从所记录的干涉图中确定。 可以使用模拟干涉图强度的模型来确定相移。 相移是模型的自由适应参数。

公开(公告)号：US20100120664A1

公开(公告)日：2010-05-13

申请号：US12520840

申请日：2007-12-21

申请人： Stefan Schulte ,  Thomas Weimer ,  Hubert Metzner

发明人： Stefan Schulte ,  Thomas Weimer ,  Hubert Metzner

IPC分类号： A61K38/16 ,  C07K14/745 ,  C07K14/755 ,  C07H21/00 ,  C12N15/74 ,  C12N5/10 ,  C12P21/00 ,  A61P7/04

CPC分类号： C07K14/755 ,  C07K14/745 ,  C07K14/765 ,  C07K16/18 ,  C07K2319/31

摘要： The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such nucleic acid sequences.

摘要翻译： 本发明涉及编码改性凝血因子，优选凝血因子VIII及其衍生物的核酸序列; 含有该核酸序列的重组表达载体; 用这些重组表达载体转化的宿主细胞; 和由所述核酸序列编码的重组多肽和衍生物，其中与未修饰的野生型蛋白相比，所述重组多肽和衍生物具有生物学活性和延长的体内半衰期。 本发明还涉及导致体外稳定性改善的相应序列。 本发明还涉及制备这些重组蛋白及其衍生物的方法。 本发明还涉及用于人基因治疗的转移载体，其包含这样的核酸序列。

公开(公告)号：US07550567B2

公开(公告)日：2009-06-23

申请号：US11062432

申请日：2005-02-23

申请人： Hubert Metzner ,  Uwe Liebing ,  Annette Feussner ,  Joerg Lemmer ,  Stefan Schulte ,  Volker Gawantka

发明人： Hubert Metzner ,  Uwe Liebing ,  Annette Feussner ,  Joerg Lemmer ,  Stefan Schulte ,  Volker Gawantka

IPC分类号： C07K14/75 ,  C07K1/16

CPC分类号： C07K14/75

摘要： The present invention relates to a process for purifying fibrinogen, which comprises one or more process steps in which one or more contaminating proteins are depleted by negative chromatography and/or negative adsorption using cation exchanger, hydrophobic gel and/or dye gel. In addition, the invention relates to the fibrinogen which is obtained by the process of the invention and which is notable for improved stability, and to the production and use of pharmaceutical preparations comprising this fibrinogen.

摘要翻译： 本发明涉及一种用于纯化纤维蛋白原的方法，其包括一个或多个工艺步骤，其中一种或多种污染蛋白质通过阴离子色谱法和/或使用阳离子交换剂，疏水性凝胶和/或染料凝胶的负吸附来消耗。 此外，本发明涉及通过本发明的方法获得并且其显着改进的稳定性的纤维蛋白原以及包含该纤维蛋白原的药物制剂的生产和使用。

公开(公告)号：US20080260755A1

公开(公告)日：2008-10-23

申请号：US12000739

申请日：2007-12-17

申请人： Hubert Metzner ,  Thomas Weimer ,  Stefan Schulte

发明人： Hubert Metzner ,  Thomas Weimer ,  Stefan Schulte

IPC分类号： A61K39/395 ,  C07K16/18 ,  C07K14/00 ,  C12N15/11 ,  A61K31/70 ,  A61P7/00 ,  A61K38/00 ,  C12N15/00 ,  C12N5/06 ,  C12P21/04

CPC分类号： C12N9/6437 ,  A61K38/00 ,  A61K48/00 ,  C07K14/745 ,  C07K14/755 ,  C07K14/76 ,  C07K14/765 ,  C07K2319/31 ,  C07K2319/50 ,  C12N9/6424 ,  C12N9/6443 ,  C12N9/6472 ,  C12Y304/21021 ,  C12Y304/21022

摘要： The invention relates to therapeutic fusion proteins in which a coagulation factor is fused to a half-life enhancing polypeptide, and in which both are connected by a linker peptide that is proteolytically cleavable. The cleavage of such linkers liberates the coagulation factor from activity-compromising steric hindrance caused by the half-life enhancing polypeptide and thereby allows the generation of fusion proteins may show relatively high molar specific activity when tested in coagulation-related assays. Furthermore, the fact that the linker is cleavable can enhance the rates of inactivation and/or elimination after proteolytic cleavage of the peptide linker compared to the rates measured for corresponding therapeutic fusion proteins linked by the non-cleavable linker having the amino acid sequence GGGGGGV.

摘要翻译： 本发明涉及治疗融合蛋白，其中凝血因子与半衰期增强多肽融合，并且其中两者通过可蛋白水解切割的接头肽连接。 这种接头的切割将凝血因子从半衰期增强多肽引起的活性损害的空间位阻释放，从而允许融合蛋白的产生在凝血相关测定中测试时可显示相对高的摩尔比活性。 此外，与通过具有氨基酸序列GGGGGGV的不可切割接头连接的相应治疗性融合蛋白测量的速率相比，接头可切割的事实可增加肽接头的蛋白水解切割后的失活和/或消除速率。

公开(公告)号：US07123365B1

公开(公告)日：2006-10-17

申请号：US10792755

申请日：2004-03-05

申请人： Stefan Schulte

发明人： Stefan Schulte

IPC分类号： G01B9/02

CPC分类号： G01M11/0271 ,  G01B9/02038 ,  G01B9/02057 ,  G01B9/02072 ,  G01M11/025

摘要： A method of processing an optical element comprises providing an interferometer optics; arranging a calibrating substrate in a beam of measuring light emitted by the interferometer optics; superimposing measuring light having traversed the first and second surfaces of the calibrating substrate with reference light, and taking a first interferometric measurement of the superimposed measuring light and reference light; arranging the aspherical surface of the optical element in the beam of measuring light emitted by the interferometer optics, while the calibrating substrate is not arranged in the beam of measuring light; superimposing measuring light having interacted with the aspherical surface and the reference light, and taking a second interferometric measurement of the superimposed measuring light and reference light; determining deviations of the aspherical surface from a target shape thereof in dependence of the first and second measurements; and machining the aspherical surface of the optical element.

摘要翻译： 一种处理光学元件的方法包括提供干涉仪光学元件; 将校准基板布置在由所述干涉仪光学器件发射的测量光束中; 叠加用参考光穿过校准基板的第一表面和第二表面的测量光，并对叠加的测量光和参考光进行第一干涉测量; 将光学元件的非球面布置在由干涉仪光学器件发射的测量光束中，同时校准基板未布置在测量光束中; 叠加与非球面和参考光相互作用的测量光，并对叠加的测量光和参考光进行第二干涉测量; 根据第一和第二测量确定非球面与其目标形状的偏差; 并加工光学元件的非球面。

公开(公告)号：US20050197493A1

公开(公告)日：2005-09-08

申请号：US11062432

申请日：2005-02-23

申请人： Hubert Metzner ,  Uwe Liebing ,  Annette Feussner ,  Joerg Lemmer ,  Stefan Schulte ,  Volker Gawantka

发明人： Hubert Metzner ,  Uwe Liebing ,  Annette Feussner ,  Joerg Lemmer ,  Stefan Schulte ,  Volker Gawantka

IPC分类号： A61K38/00 ,  A61P7/04 ,  C07K1/16 ,  C07K1/30 ,  C07K1/34 ,  C07K14/75

CPC分类号： C07K14/75

摘要： The present invention relates to a process for purifying fibrinogen, which comprises one or more process steps in which one or more contaminating proteins are depleted by negative chromatography and/or negative adsorption using cation exchanger, hydrophobic gel and/or dye gel. In addition, the invention relates to the fibrinogen which is obtained by the process of the invention and which is notable for improved stability, and to the production and use of pharmaceutical preparations comprising this fibrinogen.

摘要翻译： 本发明涉及一种用于纯化纤维蛋白原的方法，其包括一个或多个工艺步骤，其中一种或多种污染蛋白质通过阴离子色谱法和/或使用阳离子交换剂，疏水性凝胶和/或染料凝胶的负吸附来消耗。 此外，本发明涉及通过本发明的方法获得并且其显着改进的稳定性的纤维蛋白原以及包含该纤维蛋白原的药物制剂的生产和使用。

公开(公告)号：US09290561B2

公开(公告)日：2016-03-22

申请号：US14028869

申请日：2013-09-17

申请人： Thomas Weimer ,  Stefan Schulte ,  Hubert Metzner ,  Ulrich Kronthaler ,  Holger Lind ,  Wiegand Lang

发明人： Thomas Weimer ,  Stefan Schulte ,  Hubert Metzner ,  Ulrich Kronthaler ,  Holger Lind ,  Wiegand Lang

IPC分类号： A61K38/37 ,  A61K38/36 ,  A61K38/38 ,  A61K38/16 ,  A61K35/14 ,  C07K1/00 ,  C07K14/76 ,  C07K14/755 ,  A61K38/00

CPC分类号： C07K14/76 ,  A61K38/00 ,  C07K14/755 ,  C07K2319/31

摘要： The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.

摘要翻译： 本发明涉及编码凝血因子VIII（FVIII）和von Willebrand因子（VWF）的修饰的核酸序列及其复合物及其衍生物，含有此类核酸序列的重组表达载体，用这种重组表达转化的宿主细胞 载体，重组多肽和由所述核酸序列编码的衍生物，所述重组多肽和衍生物与未修饰的野生型蛋白质相比具有生物活性以及延长的体内半衰期和/或改善的体内恢复。 本发明还涉及导致表达产量提高的相应FVIII序列。 本发明还涉及制备这些重组蛋白及其衍生物的方法。 本发明还涉及用于人基因治疗的转移载体，其包含这种修饰的核酸序列。