公开(公告)号：US06684124B2

公开(公告)日：2004-01-27

申请号：US10134106

申请日：2002-04-29

申请人： Thorsten Schedel ,  Karl Schumacher ,  Thomas Fischer ,  Heiko Hommen ,  Ralf Otto ,  Sebastian Schmidt

发明人： Thorsten Schedel ,  Karl Schumacher ,  Thomas Fischer ,  Heiko Hommen ,  Ralf Otto ,  Sebastian Schmidt

IPC分类号： G06F1900

CPC分类号： G03F7/70525 ,  G03F7/70625 ,  G03F7/70633 ,  H01L22/20

摘要： While a first leading semiconductor wafer (11) already processed in a process appliance (1) and belonging to a batch is being measured in a microscope measuring instrument (2) in relation to values for the structure parameters 30, a second or further semiconductor wafer (12) belonging to the batch is processed in the process appliance (1). An event signal (100) reports, for example, an inspection carried out successfully of the first wafer, so that the following wafers (12) no longer need to be inspected. Using the measured results, the process parameters (31) of the process appliance (1) are automatically readjusted. Events such as maintenance work or parameter drifts in trend maps etc. are detected in control units (8 or 9) and, via the output of an event signal (102), for example in an event database (40), lead to the event-based selection of structure parameters (30′) to be measured and/or to the initiation of a leading wafer (11). Limiting-value violations (21) of at least one process parameter (31), detected by a control unit (8), are responded to by a warning signal (101) and likewise fed into the event database (40).

摘要翻译： 虽然已经在处理器具（1）中处理并属于批次的第一个领先的半导体晶片（11）在显微镜测量仪器（2）中相对于结构参数30的值被测量，第二或另外的半导体晶片 （12）在处理器具（1）中进行处理。 事件信号（100）报告例如第一晶片成功执行的检查，使得不再需要检查以下晶片（12）。 使用测量结果，自动重新调整过程设备（1）的过程参数（31）。 在控制单元（8或9）中检测诸如维护工作或趋势图中参数漂移的事件，并且例如在事件数据库（40）中，通过事件信号（102）的输出导致事件 对待测量的结构参数（30'）和/或引导晶片（11）的启动进行选择。 由控制单元（8）检测到的至少一个处理参数（31）的限制值违反（21）由警告信号（101）响应，并且同样馈送到事件数据库（40）中。

公开(公告)号：US06979522B2

公开(公告)日：2005-12-27

申请号：US10635583

申请日：2003-08-06

申请人： Heiko Hommen ,  Ralf Otto ,  Thorsten Schedel ,  Sebastian Schmidt ,  Thomas Fischer

发明人： Heiko Hommen ,  Ralf Otto ,  Thorsten Schedel ,  Sebastian Schmidt ,  Thomas Fischer

IPC分类号： G03F7/20 ,  G03F9/00 ,  H01L21/027 ,  G03C5/00

CPC分类号： G03F7/70633 ,  G03F9/7046

摘要： A batch of semiconductor wafers are exposed after an alignment in a wafer stepper or scanner and each of their alignment parameters are determined. Using, e.g., a linear formula with tool specific coefficients, the overlay accuracy can be calculated from these alignment parameters in advance with a high degree of accuracy as if a measurement with an overlay inspection tool had been performed. The exposure tool-offset can be adjusted on a wafer-to-wafer basis to correct for the derived overlay inaccuracy. Moreover, the alignment parameters for a specific wafer can be used to change the tool-offset for the same wafer prior to exposure. The required inspection tool capacity is advantageously reduced, the wafer rework decreases, and time is saved to perform the exposure step.

摘要翻译： 一批半导体晶片在晶片步进器或扫描仪中对齐后进行曝光，并确定其每个对准参数。 使用例如具有刀具特定系数的线性公式，可以以高精确度的方式从这些对准参数中预先计算覆盖精度，如同已经执行了覆盖检查工具的测量一样。 可以在晶圆到晶圆的基础上调整曝光工具偏移量，以校正衍生的叠加误差。 此外，特定晶片的对准参数可用于在曝光之前改变相同晶片的刀具偏移。 所需的检查工具容量有利地减少，晶片返工减少，并节省时间以执行曝光步骤。

公开(公告)号：US07833787B2

公开(公告)日：2010-11-16

申请号：US10922577

申请日：2004-08-19

申请人： Ralf Otto ,  Barbara Enenkel ,  Juergen Fieder ,  Thomas Krieg

发明人： Ralf Otto ,  Barbara Enenkel ,  Juergen Fieder ,  Thomas Krieg

IPC分类号： C12N5/07 ,  C12N5/10 ,  C12N5/00 ,  C12N5/02

CPC分类号： C12N5/0694 ,  C12N2500/90 ,  C12N2502/00 ,  C12N2502/30 ,  C12N2510/02

摘要： A new method for selecting clones and recloning mammalian cells which are of importance for the production of biopharmaceuticals, preferably hamster or mouse myeloma cells, with a high degree of automation and throughput. The invention relates to methods of depositing and replicating single cell clones of the cells in question. The invention also relates to methods of preparing proteins using cells which have been obtained and replicated by single cell deposition as well as compositions which allow the replication of single cells.

摘要翻译： 用于选择克隆和重新克隆哺乳动物细胞的新方法，其对于生产生物药物，优选仓鼠或小鼠骨髓瘤细胞具有重要性，具有高度的自动化和生产能力。 本发明涉及沉积和复制所述细胞的单细胞克隆的方法。 本发明还涉及使用通过单细胞沉积获得和复制的细胞以及允许单细胞复制的组合物制备蛋白质的方法。

公开(公告)号：US20090162900A1

公开(公告)日：2009-06-25

申请号：US12031865

申请日：2008-02-15

申请人： Barbara ENENKEL ,  Juergen Fieder ,  Ralf Otto ,  Stefanos Grammatikos

发明人： Barbara ENENKEL ,  Juergen Fieder ,  Ralf Otto ,  Stefanos Grammatikos

IPC分类号： C12P21/00 ,  C12N15/63 ,  C12N5/10

CPC分类号： C12N15/65 ,  C12N15/67 ,  C12N15/69 ,  C12N15/79

摘要： An expression vector for eukaryotic cells comprising a gene which codes for a protein of interest, functionally linked to a hamster-ubiquitin/S27a-promoter and a gene which codes for a fluorescent protein. Preferably the expression vector also contains an amplifiable selectable marker gene.The invention also describes host cells, preferably mammalian cells, which have been transfected with the expression vector, processes for producing heterologous gene products and a method of selecting high-producing cells.

摘要翻译： 用于真核细胞的表达载体，其包含编码与仓鼠 - 泛素/ S27a启动子功能相关的感兴趣的蛋白质的基因和编码荧光蛋白的基因。 优选地，表达载体还含有可扩增选择标记基因。 本发明还描述了已经用表达载体转染的宿主细胞，优选哺乳动物细胞，用于产生异源基因产物的方法和选择高产细胞的方法。

公开(公告)号：US20060121444A1

公开(公告)日：2006-06-08

申请号：US11270236

申请日：2005-11-09

申请人： Hitto Kaufmann ,  Juergen Fieder ,  Ralf Otto

发明人： Hitto Kaufmann ,  Juergen Fieder ,  Ralf Otto

IPC分类号： C12Q1/00 ,  C12N5/06

CPC分类号： G01N33/56966 ,  G01N2333/4718

摘要： Production of biopharmaceuticals from CHO cells requires generation of master-, working- and post-production cell banks of high quality, partly under GMP conditions. An optimal cryopreservation strategy is needed for each new production cell line, particularly with regard to the desire to establish production processes that are completely devoid of serum or even any animal components and to ensure robust thaw performance for reliable production. Here we describe a novel strategy employing flow cytometric (FC) analysis of Annexin V-stained cells for high-throughput characterization of CHO cell banks. Our data show that this method enables evaluation of a cryopreservation procedure just 6 h after thaw.

公开(公告)号：US20060057689A1

公开(公告)日：2006-03-16

申请号：US10513812

申请日：2003-04-29

申请人： Ralf Otto ,  Georg Fieg ,  Sabine Both ,  Ulrich Schoerken ,  Levent Yueksel ,  Ingomar Mrozek ,  Carolin Meyer ,  Norbert Klein ,  Albrecht Weiss

发明人： Ralf Otto ,  Georg Fieg ,  Sabine Both ,  Ulrich Schoerken ,  Levent Yueksel ,  Ingomar Mrozek ,  Carolin Meyer ,  Norbert Klein ,  Albrecht Weiss

IPC分类号： C12P7/64 ,  C12P7/40

CPC分类号： C12P7/6418 ,  C12P7/40

摘要： Processes for preparing fatty acids are described wherein a C4-C12 fatty acid methyl ester is subjected to hydrolysis in the presence of an enzyme to form an organic phase comprising a C4-C12 fatty acid and an aqueous phase comprising methanol, wherein at least a portion of the methanol is continuously removed; and the organic phase is subsequently separated from the aqueous phase, and optionally, where the organic phase further comprises an unhydrolyzed portion of the C4-C12 fatty acid methyl ester, the unhydrolyzed portion of the C4-C12 fatty acid methyl ester is separated from the C4-C12 fatty acid.

摘要翻译： 描述了制备脂肪酸的方法，其中在酶的存在下使C 4 -C 12脂肪酸甲酯进行水解以形成包含C 脂肪酸和包含甲醇的水相，其中至少部分甲醇被连续除去; 随后将有机相与水相分离，任选地，当有机相进一步包含C 6-14脂肪酸甲酯的未水解部分时， 将C 4 -C 12脂肪酸甲酯的未水解部分与C 4 -C 12脂肪酸甲酯分离 >脂肪酸。

公开(公告)号：US06750332B1

公开(公告)日：2004-06-15

申请号：US09856835

申请日：2002-02-26

申请人： Ralf Otto ,  Albrecht Weiss

发明人： Ralf Otto ,  Albrecht Weiss

IPC分类号： C07H1500

CPC分类号： C07H15/04 ,  A61K8/602 ,  A61Q19/00 ,  C08B37/00 ,  C12P7/62 ,  C12P19/44

摘要： Novel salicyl alcohol derivatives having valuable cosmetically and pharmaceutically useful properties, such as prostaglandin synthesis inhibition, corresponding to the formula (I): R1—OCH2—Ph—O—Z—(R2)n  (I), a method for producing the same and their utilization in cosmetics and pharmacy.

摘要翻译： 新颖的水杨醇衍生物具有有价值的美容和药学上有用的性质，如前列腺素合成抑制，对应于式（I）：其制备方法及其在化妆品和药学中的应用。

公开(公告)号：US06265225B1

公开(公告)日：2001-07-24

申请号：US09172852

申请日：1998-10-15

申请人： Ralf Otto ,  Dieter Bickoni ,  Hugo Wilmes

发明人： Ralf Otto ,  Dieter Bickoni ,  Hugo Wilmes

IPC分类号： G01N3500

CPC分类号： B01L3/50825 ,  B65D45/02 ,  G01N35/1002 ,  G01N2035/0405 ,  Y10T436/2575

摘要： A description is given of a cap for a reagent container having a sealable lid, where the lid can be pivoted laterally upward from the cap sealing position, with the container being opened, by means of an inclined bistable hinge, bears one or more catches which can come into contact with an apparatus for opening or closing the lid, and the cap has one or more centering elements by means of which the reagent-container setting position in the analyzer is fixed.

摘要翻译： 给出了具有可密封盖的试剂容器的盖子的描述，其中盖子可以通过倾斜的双稳态铰链从盖密封位置横向向上枢转，容器被打开，承载一个或多个可以 与用于打开或关闭盖的装置接触，并且盖具有一个或多个定心元件，通过该定心元件固定分析器中的试剂容器设置位置。

公开(公告)号：US08338179B2

公开(公告)日：2012-12-25

申请号：US11969644

申请日：2008-01-04

申请人： Barbara Enenkel ,  Juergen Fieder ,  Ralf Otto ,  Kerstin Sautter ,  Klaus Bergemann

发明人： Barbara Enenkel ,  Juergen Fieder ,  Ralf Otto ,  Kerstin Sautter ,  Klaus Bergemann

IPC分类号： C12N9/12 ,  C12N15/63 ,  C12N5/00 ,  C07H21/04

CPC分类号： C12N9/1205 ,  C12Y207/01095

摘要： The invention relates to modified neomycin phosphotransferase genes and their use in a selection method for high-producing recombinant cells. The invention further relates to expression vectors which contain a modified neomycin phosphotransferase gene and a gene of interest functionally linked to a heterologous promoter and a method of preparing heterologous gene products using these expression vectors.

摘要翻译： 本发明涉及修饰的新霉素磷酸转移酶基因及其在高产重组细胞筛选方法中的应用。 本发明还涉及含有修饰的新霉素磷酸转移酶基因和与异源启动子功能连接的目的基因的表达载体和使用这些表达载体制备异源基因产物的方法。

公开(公告)号：US07569339B2

公开(公告)日：2009-08-04

申请号：US11270236

申请日：2005-11-09

申请人： Hitto Kaufmann ,  Juergen Fieder ,  Ralf Otto

发明人： Hitto Kaufmann ,  Juergen Fieder ,  Ralf Otto

IPC分类号： C12Q1/00 ,  G01N33/48 ,  C12N5/02

CPC分类号： G01N33/56966 ,  G01N2333/4718

摘要： Production of biopharmaceuticals from CHO cells requires generation of master-, working- and post-production cell banks of high quality, partly under GMP conditions. An optimal cryopreservation strategy is needed for each new production cell line, particularly with regard to the desire to establish production processes that are completely devoid of serum or even any animal components and to ensure robust thaw performance for reliable production. Here we describe a novel strategy employing flow cytometric (FC) analysis of Annexin V-stained cells for high-throughput characterization of CHO cell banks. Our data show that this method enables evaluation of a cryopreservation procedure just 6 h after thaw.

摘要翻译： 从CHO细胞生产生物药物需要生产高质量的母体，工作和后期生产细胞库，部分是在GMP条件下生产。 每个新的生产细胞系都需要最佳的冷冻保存策略，特别是关于建立完全没有血清或甚至任何动物成分的生产过程的愿望，并确保可靠生产的强大的解冻性能。 在这里，我们描述了一种采用流式细胞术（FC）分析Annexin V染色细胞用于CHO细胞库的高通量表征的新策略。 我们的数据显示，这种方法能够在融化6小时后进行冷冻保存程序的评估。