公开(公告)号：US20120015438A1

公开(公告)日：2012-01-19

申请号：US12381938

申请日：2009-03-18

申请人： Bernhard M. Schilling ,  Linda Matlock ,  Stephen G. Zegarelli ,  William V. Burnett ,  Christoph E. Joosten ,  Jonathan D. Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

发明人： Bernhard M. Schilling ,  Linda Matlock ,  Stephen G. Zegarelli ,  William V. Burnett ,  Christoph E. Joosten ,  Jonathan D. Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

IPC分类号： C12N5/10

CPC分类号： C12P21/005 ,  C07K14/70521 ,  C12N5/0018 ,  C12N2500/34 ,  C12N2500/74 ,  C12N2501/33 ,  C12N2501/90 ,  C12N2501/905 ,  C12N2501/91 ,  C12N2510/02

摘要： The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, preferably, but not limited to, fed-batch cell cultures. In one aspect, the methods comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. Throughout their duration, the culturing processes of the invention involving two or more downward shifts in temperature sustain a high viability of the cultured cells, and can yield an increased end titer of protein product, and a high quality of protein product, as determined, e.g., by sialic acid content of the produced protein. In another aspect, the methods comprise the delayed addition of polyanionic compound during the culturing period. The delayed addition of polyanionic compound sustains a high viability of the cultured cells, and can extend the growth phase, delay the onset of the death phase, and arrest the death phase.

摘要翻译： 本发明描述了通过动物细胞或哺乳动物细胞培养物生产蛋白质，特别是糖蛋白的方法和方法，优选但不限于补料分批细胞培养物。 在一个方面，所述方法包括在培养期间进行的至少两个温度漂移，其中在培养期结束时温度比初始细胞培养时温度更低。 在整个持续时间内，涉及两个或更多个温度向下移位的本发明的培养方法维持培养细胞的高活力，并且可以产生蛋白质产物的最终滴定度和蛋白质产物的高质量，如所确定的，例如 ，通过产生蛋白质的唾液酸含量。 另一方面，所述方法包括在培养期间延迟加入聚阴离子化合物。 聚阴离子化合物的延迟添加维持培养细胞的高活力，并且可以延长生长期，延缓死亡阶段的发作并停止死亡期。

公开(公告)号：US07541164B2

公开(公告)日：2009-06-02

申请号：US10742564

申请日：2003-12-18

申请人： Bernhard M. Schilling ,  Linda Matlock ,  Stephen G. Zegarelli ,  William V. Burnett ,  Christoph E. Joosten ,  Jonathan D. Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

发明人： Bernhard M. Schilling ,  Linda Matlock ,  Stephen G. Zegarelli ,  William V. Burnett ,  Christoph E. Joosten ,  Jonathan D. Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

IPC分类号： C12N5/06 ,  A61K39/395 ,  A61K38/00

CPC分类号： C12P21/005 ,  C07K14/70521 ,  C12N5/0018 ,  C12N2500/34 ,  C12N2500/74 ,  C12N2501/33 ,  C12N2501/90 ,  C12N2501/905 ,  C12N2501/91 ,  C12N2510/02

摘要： The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, preferably, but not limited to, fed-batch cell cultures. In one aspect, the methods comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. Throughout their duration, the culturing processes of the invention involving two or more downward shifts in temperature sustain a high viability of the cultured cells, and can yield an increased end titer of protein product, and a high quality of protein product, as determined, e.g., by sialic acid content of the produced protein. In another aspect, the methods comprise the delayed addition of polyanionic compound during the culturing period. The delayed addition of polyanionic compound sustains a high viability of the cultured cells, and can extend the growth phase, delay the onset of the death phase, and arrest the death phase.

摘要翻译： 本发明描述了通过动物细胞或哺乳动物细胞培养物生产蛋白质，特别是糖蛋白的方法和方法，优选但不限于补料分批细胞培养物。 在一个方面，所述方法包括在培养期间进行的至少两个温度漂移，其中在培养期结束时温度比初始细胞培养时的温度更低。 在整个持续时间内，涉及两个或更多个温度向下移位的本发明的培养方法维持培养细胞的高活力，并且可以产生蛋白质产物的最终滴定度和蛋白质产物的高质量，如所确定的，例如 ，通过产生蛋白质的唾液酸含量。 另一方面，所述方法包括在培养期间延迟加入聚阴离子化合物。 聚阴离子化合物的延迟添加维持培养细胞的高活力，并且可以延长生长期，延缓死亡阶段的发作并停止死亡期。

公开(公告)号：US07332303B2

公开(公告)日：2008-02-19

申请号：US10740645

申请日：2003-12-18

申请人： Bernhard M. Schilling ,  Scott Gangloff ,  Dharti Kothari ,  Kirk Leister ,  Linda Matlock ,  Stephen G. Zegarelli ,  Christoph E. Joosten ,  Jonathan D. Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

发明人： Bernhard M. Schilling ,  Scott Gangloff ,  Dharti Kothari ,  Kirk Leister ,  Linda Matlock ,  Stephen G. Zegarelli ,  Christoph E. Joosten ,  Jonathan D. Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

IPC分类号： C12N15/09 ,  C12N15/06 ,  C12N15/56 ,  A61K38/00

CPC分类号： C07K14/70521 ,  C12N2500/34 ,  C12P21/005

摘要： The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, illustratively, but not limited to, fed-batch cell cultures. The methods comprise feeding the cells with D-galactose, preferably with feed medium containing D-galactose, preferably daily, to sustain a sialylation effective level of D-galactose in the culture for its duration, thus increasing sialylation of the produced proteins. The methods can also comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. The cell culture processes of the invention involving two or more temperature shifts sustain a high cell viability, and can allow for an extended protein production phase. The methods can also comprise the delayed addition of polyanionic compound at a time after innoculation. Supplementation of the cultures with D-galactose, preferably in a feed medium, to sustain galactose at sialylation effective levels in the cultures until the end of a culture run reverses a decline in sialylation that accompanies culture scale up, and is advantageous for large scale culturing processes.

摘要翻译： 本发明描述了通过动物细胞或哺乳动物细胞培养生产蛋白质，特别是糖蛋白的方法和方法，例如但不限于补料分批细胞培养物。 所述方法包括用D-半乳糖喂养细胞，优选用含有D-半乳糖的饲料培养基，优选每天喂养，以维持培养基中唾液酸化有效水平的D-半乳糖的持续时间，从而增加产生的蛋白质的唾液酸化。 所述方法还可以包括在培养期间进行的至少两个温度漂移，其中在培养期结束时温度比初始细胞培养时温度更低。 涉及两个或多个温度变化的本发明的细胞培养方法维持高的细胞活力，并且可以允许延长的蛋白质生产阶段。 所述方法还可以包括在接种后延迟加入聚阴离子化合物。 用D-半乳糖，优选在饲料培养基中补充培养物，以维持培养物中唾液酸化有效水平的半乳糖，直至培养结束时反转伴随培养物扩大的唾液酸化的下降，并且有利于大规模培养 过程。

公开(公告)号：US20050084933A1

公开(公告)日：2005-04-21

申请号：US10740645

申请日：2003-12-18

申请人： Bernhard Schilling ,  Scott Gangloff ,  Dharti Kothari ,  Kirk Leister ,  Linda Matlock ,  Stephen Zegarelli ,  Christoph Joosten ,  Jonathan Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

发明人： Bernhard Schilling ,  Scott Gangloff ,  Dharti Kothari ,  Kirk Leister ,  Linda Matlock ,  Stephen Zegarelli ,  Christoph Joosten ,  Jonathan Basch ,  Sivakesava Sakhamuri ,  Steven S. Lee

IPC分类号： C07K14/705 ,  C12P21/00 ,  C12P21/02 ,  C12N5/06

CPC分类号： C07K14/70521 ,  C12N2500/34 ,  C12P21/005

摘要： The present invention describes methods and processes for the production of proteins, particularly glycoproteins, by animal cell or mammalian cell culture, illustratively, but not limited to, fed-batch cell cultures. The methods comprise feeding the cells with D-galactose, preferably with feed medium containing D-galactose, preferably daily, to sustain a sialylation effective level of D-galactose in the culture for its duration, thus increasing sialylation of the produced proteins. The methods can also comprise at least two temperature shifts performed during the culturing period, in which the temperature is lower at the end of the culturing period than at the time of initial cell culture. The cell culture processes of the invention involving two or more temperature shifts sustain a high cell viability, and can allow for an extended protein production phase. The methods can also comprise the delayed addition of polyanionic compound at a time after innoculation. Supplementation of the cultures with D-galactose, preferably in a feed medium, to sustain galactose at sialylation effective levels in the cultures until the end of a culture run reverses a decline in sialylation that accompanies culture scale up, and is advantageous for large scale culturing processes.

摘要翻译： 本发明描述了通过动物细胞或哺乳动物细胞培养物生产蛋白质，特别是糖蛋白的方法和方法，例如但不限于补料分批细胞培养物。 所述方法包括用D-半乳糖喂养细胞，优选用含有D-半乳糖的饲料培养基，优选每天喂养，以维持培养基中唾液酸化有效水平的D-半乳糖的持续时间，从而增加产生的蛋白质的唾液酸化。 所述方法还可以包括在培养期间进行的至少两个温度漂移，其中在培养期结束时温度比初始细胞培养时温度更低。 涉及两个或多个温度变化的本发明的细胞培养方法维持高的细胞活力，并且可以允许延长的蛋白质生产阶段。 所述方法还可以包括在接种后延迟加入聚阴离子化合物。 用D-半乳糖，优选在饲料培养基中补充培养物，以维持培养物中唾液酸化有效水平的半乳糖，直至培养结束时反转伴随培养物扩大的唾液酸化的下降，并且有利于大规模培养 过程。

公开(公告)号：US06943413B2

公开(公告)日：2005-09-13

申请号：US10428592

申请日：2003-05-01

申请人： Steven S. Lee

发明人： Steven S. Lee

IPC分类号： H01L21/8249 ,  H01L29/76

CPC分类号： H01L21/8249

摘要： The invention concerns a BI-CMOS process, in which Field-Effect Transistors (FETs) and Bipolar Junction Transistors (BJTs) are manufactured on a common substrate. In several processing steps, FET structures are formed simultaneously with BJT structures. For example, in one step, polysilicon gate electrodes for the FETs and polysilicon emitters for the BJTs are formed simultaneously. In another aspect of the invention, a polysilicon layer is used to reduce channeling which would otherwise occur during an implant step.

摘要翻译： 本发明涉及一种BI-CMOS工艺，其中在公共衬底上制造场效应晶体管（FET）和双极结晶体管（BJT）。 在几个处理步骤中，与BJT结构同时形成FET结构。 例如，在一个步骤中，同时形成用于BJT的用于FET的多晶硅栅电极和多晶硅发射极。 在本发明的另一方面，多晶硅层用于减少否则在植入步骤期间会发生的沟道化。

公开(公告)号：US5904535A

公开(公告)日：1999-05-18

申请号：US748969

申请日：1996-11-13

申请人： Steven S. Lee

发明人： Steven S. Lee

IPC分类号： H01L21/8249 ,  H01L21/84 ,  H01L27/12 ,  H01L21/331

CPC分类号： H01L21/84 ,  H01L21/8249 ,  H01L27/1203

摘要： A process for fabricating a bipolar transistor on a silicon-on-insulator substrate which includes etching a bipolar transistor area into the substrate, wherein the bipolar transistor area has substantially vertical sidewalls and a bottom, and forming a buried collector in bottom of the bipolar transistor area. Polysilicon sidewalls are formed adjacent to the vertical sidewalls in the bipolar transistor area, wherein the polysilicon sidewalls are connected to the buried collector. The polysilicon sidewalls are oxidized to form a layer of oxidized polysilicon. Oxide sidewalls are formed on the oxidized polysilicon sidewalls, and epitaxial silicon is formed to fill the bipolar transistor area. A base and an emitter are formed for the bipolar transistor, within the epitaxial barrier.

摘要翻译： 一种用于在绝缘体上硅衬底上制造双极晶体管的工艺，其包括将双极晶体管区域蚀刻到衬底中，其中双极晶体管区域具有基本垂直的侧壁和底部，并且在双极晶体管的底部形成掩埋集电极 区。 多晶硅侧壁形成在双极晶体管区域中与垂直侧壁相邻，其中多晶硅侧壁连接到埋地集电器。 多晶硅侧壁被氧化以形成氧化多晶硅层。 在氧化的多晶硅侧壁上形成氧化物侧壁，并且形成外延硅以填充双极晶体管区域。 在外延阻挡层内为双极晶体管形成基极和发射极。

公开(公告)号：US5672905A

公开(公告)日：1997-09-30

申请号：US935306

申请日：1992-08-26

申请人： Steven S. Lee ,  Gayle W. Miller

发明人： Steven S. Lee ,  Gayle W. Miller

IPC分类号： H01L21/768 ,  H01L23/525 ,  H01L29/00

CPC分类号： H01L21/76888 ,  H01L23/5256 ,  H01L2924/0002

摘要： A semiconductor fuse and method for fabricating the same An insulating layer is provided and a trench formed therein. A fusible link is then formed across the insulating layer and trench and conformal therewith. The link has a break region of minimum thickness and width at an intersection of a sidewall and bottom surface of the trench.

摘要翻译： 半导体熔丝及其制造方法设置有绝缘层，并形成有沟槽。 然后在绝缘层和沟槽之间形成可熔连接并与其保持共形。 连接件在沟槽的侧壁和底面的交点处具有最小厚度和宽度的断裂区域。

公开(公告)号：US5581861A

公开(公告)日：1996-12-10

申请号：US460485

申请日：1995-06-02

申请人： Steven S. Lee ,  Gayle W. Miller

发明人： Steven S. Lee ,  Gayle W. Miller

IPC分类号： B41J2/045 ,  B41J2/055 ,  B41J2/16 ,  H01L41/22

CPC分类号： B41J2/1629 ,  B41J2/161 ,  B41J2/1623 ,  B41J2/1631 ,  B41J2/1634 ,  B41J2/1639 ,  B41J2/1642 ,  B41J2002/14387 ,  Y10T29/42 ,  Y10T29/49401

摘要： An ink-jet print head comprises an ink drive unit formed on a first substrate and an ink reservoir unit formed on a second substrate. The ink drive unit includes a thin film piezoelectric transducer formed on one side of the substrate. The reservoir unit includes an etched cavity in the substrate for forming an ink reservoir, the cavity having an aperture in the base extending through the substrate to form an ink nozzle. The ink drive and ink reservoir units are bonded together with the piezoelectric transducer within the ink reservoir. Activating the transducer expels ink from the reservoir via the ink nozzle.

摘要翻译： 喷墨打印头包括形成在第一基板上的墨驱动单元和形成在第二基板上的墨存储单元。 墨驱动单元包括形成在基板一侧的薄膜压电换能器。 储存器单元包括用于形成油墨储存器的衬底中的蚀刻腔，该空腔在基体中具有延伸穿过衬底的孔以形成油墨喷嘴。 墨水驱动器和墨水储存器单元与墨水储存器内的压电换能器结合在一起。 激活传感器通过墨水喷嘴从储存器排出墨水。

公开(公告)号：US5332957A

公开(公告)日：1994-07-26

申请号：US937569

申请日：1992-08-31

申请人： Steven S. Lee

发明人： Steven S. Lee

IPC分类号： H02J7/00 ,  H02J1/00

CPC分类号： H02J7/0006

摘要： A battery module (200) includes a preselected one (105) of a plurality of discrete electrodes (102-105) that is either electrically uncoupled, or is coupled in a fashion that is redundant with respect to one of the other electrodes (102-104). A battery module constructed in this fashion is compatible with both a microprocessor controlled rapid charger (400) and a trickle charger (500) constructed from simple discrete circuitry.

摘要翻译： 电池模块（200）包括多个分立电极（102-105）中的预选的一个（105），所述多个分立电极（102-105）电解脱耦合，或者以相对于其它电极（102- 104）。 以这种方式构造的电池模块与由简单的离散电路构成的微处理器控制的快速充电器（400）和涓流充电器（500）兼容。

公开(公告)号：US06610822B2

公开(公告)日：2003-08-26

申请号：US09920497

申请日：2001-08-01

申请人： Martin A. Chandler ,  Kent E. Goklen ,  Steven S. Lee ,  David J. Roush

发明人： Martin A. Chandler ,  Kent E. Goklen ,  Steven S. Lee ,  David J. Roush

IPC分类号： C07K114

CPC分类号： C07K7/56

摘要： There is disclosed a process for purifying a natural product using a two-phase, multi-solvent system followed by vacuum concentration and back extraction. The method allows for the removal of impurities by controlling the polarity balance of a two-phase system by manipulating the proportions of the four solvents and subsequently the relative distribution of the product versus the impurities.