公开(公告)号：US09181521B2

公开(公告)日：2015-11-10

申请号：US13559957

申请日：2012-07-27

申请人： Alan T. Y. Cheng ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

发明人： Alan T. Y. Cheng ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

IPC分类号： C12M1/06 ,  C12M1/00 ,  C12N1/38 ,  C12M1/08 ,  C12M1/34 ,  C12M1/36

CPC分类号： C12M27/20 ,  C12M27/02 ,  C12M27/24 ,  C12M29/06 ,  C12M41/12 ,  C12M41/26 ,  C12M41/32 ,  C12M41/48 ,  C12N1/38

摘要： A bioreactor with an upward flowing impeller system for controlling a mammalian cell culture process is provided. The disclosed system enables control of the cell culture process by controlling the level of dissolved carbon dioxide in the cell culture media and prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide via surface gas exchange with little or no damage to the mammalian cells. The use of an upward flow impeller combined with vertical baffles converts the swirling motions of the cell culture media into a largely vertical flow and promotes the removal of dissolved carbon dioxide via surface gas exchange with a sweep gas flowing over the top surface of the cell culture media within the bioreactor vessel.

摘要翻译： 提供了一种具有向上流动的叶轮系统用于控制哺乳动物细胞培养过程的生物反应器。 所公开的系统能够通过控制细胞培养基中溶解的二氧化碳的水平来控制细胞培养过程，并且通过经由表面气体交换增强汽提二氧化碳来实现渗透压浓度的增加，对哺乳动物几乎没有或没有损伤 细胞。 使用与垂直挡板结合的向上流动叶轮将细胞培养基的旋转运动转化为大体垂直的流动，并通过与流过细胞培养物顶表面的吹扫气体的表面气体交换促进去除溶解的二氧化碳 生物反应器容器内的介质。

公开(公告)号：US20130189767A1

公开(公告)日：2013-07-25

申请号：US13559957

申请日：2012-07-27

申请人： Alan T. Y. Cheng ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

发明人： Alan T. Y. Cheng ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

IPC分类号： C12M1/00

CPC分类号： C12M27/20 ,  C12M27/02 ,  C12M27/24 ,  C12M29/06 ,  C12M41/12 ,  C12M41/26 ,  C12M41/32 ,  C12M41/48 ,  C12N1/38

摘要： A bioreactor with an upward flowing impeller system for controlling a mammalian cell culture process is provided. The disclosed system enables control of the cell culture process by controlling the level of dissolved carbon dioxide in the cell culture media and prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide via surface gas exchange with little or no damage to the mammalian cells. The use of an upward flow impeller combined with vertical baffles converts the swirling motions of the cell culture media into a largely vertical flow and promotes the removal of dissolved carbon dioxide via surface gas exchange with a sweep gas flowing over the top surface of the cell culture media within the bioreactor vessel.

摘要翻译： 提供了一种具有向上流动的叶轮系统用于控制哺乳动物细胞培养过程的生物反应器。 所公开的系统能够通过控制细胞培养基中溶解的二氧化碳的水平来控制细胞培养过程，并且通过经由表面气体交换增强汽提二氧化碳来实现渗透压浓度的增加，对哺乳动物几乎没有或没有损伤 细胞。 使用与垂直挡板结合的向上流动叶轮将细胞培养基的旋转运动转化为大体垂直的流动，并通过与流过细胞培养物顶表面的吹扫气体的表面气体交换促进去除溶解的二氧化碳 生物反应器容器内的介质。

公开(公告)号：US08241904B2

公开(公告)日：2012-08-14

申请号：US12536559

申请日：2009-08-06

申请人： Alan T. Y. Cheng ,  Ying Zhou ,  Balazs Hunek ,  Amitabh Gupta ,  Nigel Grinter

发明人： Alan T. Y. Cheng ,  Ying Zhou ,  Balazs Hunek ,  Amitabh Gupta ,  Nigel Grinter

IPC分类号： C12N5/02

CPC分类号： C12N1/38 ,  C12M27/02 ,  C12M29/22

摘要： A system and method for controlling a mammalian cell culture process are provided. Such control of the cell culture process involves control of the level of dissolved carbon dioxide in the cell culture media and the resulting ability to prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide with little or no damage to the mammalian cells. The disclosed methods and systems of dissolved carbon dioxide stripping include enhanced surface gas exchange mechanisms within the bioreactor vessel through the use of an upward flow impeller combined with vertical baffles to convert swirling motions of the liquid into a largely vertical flow.

摘要翻译： 提供了一种用于控制哺乳动物细胞培养方法的系统和方法。 细胞培养过程的这种控制涉及控制细胞培养基中溶解的二氧化碳的水平，并且通过增强对二氧化碳的去除而对哺乳动物细胞几乎没有或没有损伤来实现所产生的渗透压浓度增加的能力。 所公开的溶解二氧化碳汽提方法和系统包括通过使用与垂直挡板结合的向上流动叶轮将生物反应器容器内的表面气体交换机制改进为将液体的旋转运动转化成大体垂直的流动。

公开(公告)号：US08178318B2

公开(公告)日：2012-05-15

申请号：US12702428

申请日：2010-02-09

申请人： Alan T. Y. Cheng ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

发明人： Alan T. Y. Cheng ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

IPC分类号： C12P21/02

CPC分类号： C12N5/0018 ,  C12N1/38 ,  C12N2500/02 ,  C12N2500/60

摘要： Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.

摘要翻译： 提供了用于在哺乳动物细胞培养过程中控制溶解二氧化碳水平和限制重量克分子渗透浓度以增强细胞生长，活力和密度以及提高生物产物浓度和产量的方法。 通过在哺乳动物细胞培养过程中采用替代的pH控制策略和CO 2汽提技术来实现对哺乳动物细胞培养过程中溶解的二氧化碳和pH的水平的控制以及所产生的限制重量克分子渗透浓度的能力。 这种pH控制技术和二氧化碳汽提不发生泡沫，对哺乳动物细胞几乎没有或没有损害。

公开(公告)号：US20100035343A1

公开(公告)日：2010-02-11

申请号：US12536559

申请日：2009-08-06

申请人： Alan T.Y. Cheng ,  Ying Zhou ,  Balazs Hunek ,  Amitabh Gupta ,  Nigel Grinter

发明人： Alan T.Y. Cheng ,  Ying Zhou ,  Balazs Hunek ,  Amitabh Gupta ,  Nigel Grinter

IPC分类号： C12N5/02 ,  C12M1/02 ,  C12M1/34 ,  C12M1/36 ,  C12M1/00

CPC分类号： C12N1/38 ,  C12M27/02 ,  C12M29/22

摘要： A system and method for controlling a mammalian cell culture process are provided. Such control of the cell culture process involves control of the level of dissolved carbon dioxide in the cell culture media and the resulting ability to prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide with little or no damage to the mammalian cells. The disclosed methods and systems of dissolved carbon dioxide stripping include enhanced surface gas exchange mechanisms within the bioreactor vessel through the use of an upward flow impeller combined with vertical baffles to convert swirling motions of the liquid into a largely vertical flow.

摘要翻译： 提供了一种用于控制哺乳动物细胞培养方法的系统和方法。 细胞培养过程的这种控制涉及控制细胞培养基中溶解的二氧化碳的水平，并且通过增强对二氧化碳的去除而对哺乳动物细胞几乎没有或没有损伤来实现所产生的渗透压浓度增加的能力。 所公开的溶解二氧化碳汽提方法和系统包括通过使用与垂直挡板结合的向上流动叶轮将生物反应器容器内的表面气体交换机制改进为将液体的旋转运动转化成大体垂直的流动。

公开(公告)号：US20100184147A1

公开(公告)日：2010-07-22

申请号：US12702428

申请日：2010-02-09

申请人： ALAN T.Y. CHENG ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

发明人： ALAN T.Y. CHENG ,  Ying Zhou ,  Amitabh Gupta ,  Balazs Hunek ,  Nigel Grinter

IPC分类号： C12P21/06 ,  C12N5/02

CPC分类号： C12N5/0018 ,  C12N1/38 ,  C12N2500/02 ,  C12N2500/60

摘要： Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.

摘要翻译： 提供了用于在哺乳动物细胞培养过程中控制溶解二氧化碳水平和限制重量克分子渗透浓度以增强细胞生长，活力和密度以及提高生物产物浓度和产量的方法。 通过在哺乳动物细胞培养过程中采用替代的pH控制策略和CO 2汽提技术来实现对哺乳动物细胞培养过程中溶解的二氧化碳和pH的水平的控制以及所产生的限制重量克分子渗透浓度的能力。 这种pH控制技术和二氧化碳汽提不发生泡沫，对哺乳动物细胞几乎没有或没有损害。

公开(公告)号：US20140325868A1

公开(公告)日：2014-11-06

申请号：US14334722

申请日：2014-07-18

申请人： Theodore Hall Gasteyer, III ,  Robert Rex Sever ,  Balazs Hunek ,  Nigel Grinter ,  Melinda Lee Verdone

发明人： Theodore Hall Gasteyer, III ,  Robert Rex Sever ,  Balazs Hunek ,  Nigel Grinter ,  Melinda Lee Verdone

IPC分类号： F26B5/06

CPC分类号： F26B5/06

摘要： System and method for lyophilization or freeze-drying is provided. During the freezing step, the material or solution to be frozen is initially brought to a temperature near or below its freezing temperature after which the pressure in the freeze-dryer chamber is reduced to induce nucleation of the material.

摘要翻译： 提供了用于冻干或冷冻干燥的系统和方法。 在冷冻步骤期间，待冷冻的材料或溶液最初达到接近或低于其冷冻温度的温度，之后冷冻干燥室中的压力降低以引起材料成核。

公开(公告)号：US09453675B2

公开(公告)日：2016-09-27

申请号：US11702472

申请日：2007-02-05

申请人： Theodore Hall Gasteyer, III ,  Robert Rex Sever ,  Balazs Hunek ,  Nigel Grinter ,  Melinda Lee Verdone

发明人： Theodore Hall Gasteyer, III ,  Robert Rex Sever ,  Balazs Hunek ,  Nigel Grinter ,  Melinda Lee Verdone

IPC分类号： F25C1/00 ,  F26B5/06

CPC分类号： F26B5/06

摘要： Methods of inducing nucleation of a material is provided. The disclosed methods comprise the steps of bringing the material to a temperature near or below a phase transition temperature and altering the pressure to induce nucleation of the material. The disclosed methods are useful in freeze-drying processes, particularly pharmaceutical freeze-drying processes.

摘要翻译： 提供了诱导材料成核的方法。 所公开的方法包括使材料达到接近或低于相变温度的温度并改变压力以诱导材料成核的步骤。 所公开的方法在冷冻干燥方法，特别是药物冷冻干燥方法中是有用的。

公开(公告)号：US09200836B2

公开(公告)日：2015-12-01

申请号：US14334722

申请日：2014-07-18

申请人： Theodore Hall Gasteyer, III ,  Robert Rex Sever ,  Balazs Hunek ,  Nigel Grinter ,  Melinda Lee Verdone

发明人： Theodore Hall Gasteyer, III ,  Robert Rex Sever ,  Balazs Hunek ,  Nigel Grinter ,  Melinda Lee Verdone

IPC分类号： F26B5/06

CPC分类号： F26B5/06

摘要： System and method for lyophilization or freeze-drying is provided. During the freezing step, the material or solution to be frozen is initially brought to a temperature near or below its freezing temperature after which the pressure in the freeze-dryer chamber is reduced to induce nucleation of the material.

摘要翻译： 提供了用于冻干或冷冻干燥的系统和方法。 在冷冻步骤期间，待冷冻的材料或溶液最初达到接近或低于其冷冻温度的温度，之后冷冻干燥室中的压力降低以引起材料成核。

公开(公告)号：US20090001042A1

公开(公告)日：2009-01-01

申请号：US12144872

申请日：2008-06-24

申请人： Robert Sever ,  Balazs Hunek ,  Nigel Grinter ,  Gurjit Baring

发明人： Robert Sever ,  Balazs Hunek ,  Nigel Grinter ,  Gurjit Baring

IPC分类号： B65D51/16 ,  B65D41/50

CPC分类号： B65D51/241 ,  A61J1/1468 ,  B65D41/28 ,  B65D51/002 ,  B65D2251/0015 ,  B65D2251/0075 ,  B65D2539/005

摘要： A container closure system for use in lyophilization processes employing depressurization to initiate nucleation is provided. The present container closure system includes a container and a closure element disposed proximate to and adapted for sealing the opening of the container. The closure element includes a first sealing surface adapted for sealably contacting an interior surface of the container and a second sealing surface adapted for sealably contacting the top surface of the container when the container closure system is in a closed position. The closure element also includes a plurality of closure legs extending from the second sealing surface that define a plurality of side vents between each of the closure legs when the container closure system is in the open position. The length, thickness, number, and shape of the legs are chosen to produce an effective total side vent area that is at least 50% of the area of the container opening. Alternatively, the length, thickness, number, and shape of the legs are chosen to produce an effective total side vent area that is greater than the cumulative surface area of the outwardly facing surface of the closure legs.

摘要翻译： 提供了一种用于使用减压引发成核的冻干方法的容器封闭系统。 本发明的容器封闭系统包括容器和靠近并适于密封容器开口的封闭元件。 闭合元件包括适于密封地接触容器的内表面的第一密封表面和适于在容器封闭系统处于关闭位置时密封地接触容器的顶表面的第二密封表面。 闭合元件还包括从第二密封表面延伸的多个封闭柱，当容器封闭系统处于打开位置时，封闭件在每个封闭支柱之间限定多个侧通风口。 选择腿的长度，厚度，数量和形状以产生至少占容器开口面积的50％的有效总侧排气面积。 或者，选择腿的长度，厚度，数量和形状以产生大于闭合腿的面向外的表面的累积表面积的有效总侧排气面积。