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公开(公告)号：US4373023A
公开(公告)日：1983-02-08
申请号：US196720
申请日：1980-10-14
申请人： Robert S. Langer , Robert Linhardt , Charles L. Cooney , Parrish M. Galliher , Margaret M. Flanagan , Michael D. Klein
发明人： Robert S. Langer , Robert Linhardt , Charles L. Cooney , Parrish M. Galliher , Margaret M. Flanagan , Michael D. Klein
CPC分类号： A61M1/3675 , A61K33/00 , A61K35/14 , C12N11/02
摘要： Blood containing heparin and treated extracorporeally is contacted with immobilized heparinase prior to being reintroduced into the patient.
摘要翻译： 血液含有肝素并经体外治疗与被固定的肝素酶接触，然后再次引入患者。
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公开(公告)号：US4443545A
公开(公告)日：1984-04-17
申请号：US337910
申请日：1982-01-08
IPC分类号： C12N9/88
CPC分类号： C12N9/88
摘要： Heparinase is produced by growing the bacterium, Flavobacterium heparinum in an improved defined medium consisting of a carbon source, two or more amino acids and several salts in the absence of protein. The carbon source concentration is specifically kept below a certain level to promote improved heparinase production. The sulfate source concentration is also specifically kept below a certain level to promote improved heparinase synthesis. Heparinase can be produced in this medium with or without the addition of an inducer compound.
摘要翻译： 通过在不存在蛋白质的情况下，在由碳源，两种或更多种氨基酸和几种盐组成的改进的限定培养基中生长细菌，肝素黄杆菌来生产肝素酶。 碳源浓度特别保持在一定水平以促进肝素酶的产生。 硫酸根源浓度也被特异地保持在一定水平以促进改善的肝素酶合成。 肝素酶可以在该培养基中产生或不加入诱导剂化合物。
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公开(公告)号：US4341869A
公开(公告)日：1982-07-27
申请号：US180780
申请日：1980-08-25
CPC分类号： C12N9/88 , Y10S435/815 , Y10S435/85
摘要： Heparinase is produced by growing the bacteria, Flavobacterium heparinum, in a defined medium consisting of a carbon source, two or more amino acids and mineral salts in the absence of protein. Heparinase is recovered by batch chromatography of the cell extract from hydroxylapatite by elution with sodium chloride and sodium phosphate buffer washes.
摘要翻译： 肝素酶通过在不存在蛋白质的情况下在由碳源，两种或更多种氨基酸和矿物盐组成的限定培养基中生长细菌，肝素黄杆菌而产生。 通过用氯化钠和磷酸钠缓冲液洗涤洗脱，从羟基磷灰石的细胞提取物的间歇色谱法回收肝素酶。
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公开(公告)号：US09127242B2
公开(公告)日：2015-09-08
申请号：US13262155
申请日：2010-04-05
申请人： Patrick M. Guertin , Parrish M. Galliher , Michael Fisher , Joseph D. Crowell , Colin R. Tuohey , Laura A. Niklason , William E. Tente , Shannon M. Dahl , Juliana Blum , Justin Strader
发明人： Patrick M. Guertin , Parrish M. Galliher , Michael Fisher , Joseph D. Crowell , Colin R. Tuohey , Laura A. Niklason , William E. Tente , Shannon M. Dahl , Juliana Blum , Justin Strader
摘要： A single-use, single or multiple tissue, organ, and graft bioreactor and environmental control system is designed to replicate the necessary conditions for growth of tissues, organs, or grafts, while addressing problems in scaling up the tissue growth; adaptation to a single-use or disposable format; and operation as a stand-alone unit that provides full environmental control of cell culture conditions.
摘要翻译： 单次使用，单次或多次组织，器官和移植物生物反应器和环境控制系统被设计为复制组织，器官或移植物生长所必需的条件，同时解决扩大组织生长的问题; 适应一次性或一次性格式; 作为提供细胞培养条件的全面环境控制的独立单元的操作。
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公开(公告)号：US4999422A
公开(公告)日：1991-03-12
申请号：US181963
申请日：1988-04-15
申请人： Parrish M. Galliher
发明人： Parrish M. Galliher
IPC分类号： C07K1/113
CPC分类号： C07K1/1136
摘要： A process is disclosed for continuously treating a solubilized protein solution containing a protein unfolded to some degree, in a small volume continuous flow reactor, to obtain the protein in a conformation exhibiting the protein's characteristic biological activity by continuously diluting out the solubilizing agent, while continuously withdrawing the refolded protein. The continuous process may be carried out using deionized water as a diluent, rather than buffer solutions.
摘要翻译： 公开了一种在小容量连续流动反应器中连续处理含有在某种程度上未折叠的蛋白质的溶解蛋白质溶液的方法，通过连续稀释增溶剂以获得呈现出蛋白质特征性生物学活性的构象的蛋白质，同时连续地 取出重折叠的蛋白质。 连续方法可以使用去离子水作为稀释剂而不是缓冲溶液进行。
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公开(公告)号：US09969965B2
公开(公告)日：2018-05-15
申请号：US13978726
申请日：2012-01-11
申请人： Colin Tuohey , Ted Deloggio , Thomas Erdenberger , Kenneth P. Clapp , Richard Damren , Parrish M. Galliher , Patrick Guertin , Jiyoung Lee , Michael Fisher
发明人： Colin Tuohey , Ted Deloggio , Thomas Erdenberger , Kenneth P. Clapp , Richard Damren , Parrish M. Galliher , Patrick Guertin , Jiyoung Lee , Michael Fisher
摘要： Disclosed is a single-use bioreactor bag design providing substantially equivalent maximum shear rate at the impeller tip and average or bulk shear rate over a range of power per unit working volume and rpm needed for bioculture processing. The uniformity in shear profile of the bag design providing a unique advantage when used as a scale-down or scale-up platform. Also disclosed is a linearly scalable, single-use, bioreactor system for use in carrying out a scalable biomanufacturing process, the system comprising two single-use bioreactor bags of different volumes, wherein the ratio H/D of the height of the working volume H to the diameter D of the tank, or of the bag is equal to about 1.5, and the bulk shear in each of the bags is substantially constant. The disclosed small scale system models larger scale systems from both a shear/scalability/performance basis and also from a validation and regulatory basis. In summary, the 10L bioreactor system disclosed provides for “linear scalability” by using the same or substantially simulating the same vessel geometry, gas sparging system, impeller shape and type, polymer composition of the flexible bag/components, process control system, and shear rates as larger 50-5000 L systems.
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公开(公告)号：US09499781B2
公开(公告)日：2016-11-22
申请号：US13434345
申请日：2012-03-29
申请人： Richard Damren , Colin Touhey , Thomas Erdenberger , Michael Fisher , Geoffrey L. Hodge , Patrick M. Guertin , Parrish M. Galliher
发明人： Richard Damren , Colin Touhey , Thomas Erdenberger , Michael Fisher , Geoffrey L. Hodge , Patrick M. Guertin , Parrish M. Galliher
CPC分类号： C12M29/26 , B01D5/0042 , B01D5/0093 , B01D46/4263 , B01D53/265 , C12M23/28 , C12M29/04 , C12M41/12
摘要： Disclosed herein is a system and method for condensing moisture in a moist gas stream entering a bioreactor or leaving a bioreactor, forming a dry gas stream for entering or leaving the bioreactor.
摘要翻译： 本文公开了一种用于冷凝进入生物反应器或离开生物反应器的湿气流中的水分的系统和方法，形成用于进入或离开生物反应器的干燥气流。
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公开(公告)号：US09109193B2
公开(公告)日：2015-08-18
申请号：US12124039
申请日：2008-05-20
CPC分类号： C12M29/10 , B01D29/13 , C12M23/14 , C12M23/26 , C12M23/48 , C12M27/02 , C12M27/20 , C12M29/00 , C12M29/18 , C12M47/10
摘要： Systems and methods for containing and manipulating liquids, including vessels and unit operations or components of cell culture, cell containment, bioreactor, and/or pharmaceutical manufacturing systems, are provided. In certain embodiments, such vessels and unit operations are directed to continuous perfusion reactor or bioreactor systems and may include one or more disposable components. For instance, in one aspect, a system includes an apparatus in the form of a bioreactor for harvesting cells which produce one or more products. The apparatus may include a disposable, collapsible bag adapted for containing a liquid, the collapsible bag in fluid communication with a liquid-solids (e.g., cell) separation device. For example, an outlet of the collapsible bag may be connected to an inlet of the separation device, and an outlet of the separation device may be connected to an inlet of the collapsible bag for recycle. Accordingly, after separating the cells from the liquid in the separation device, the cells can be flowed back into the collapsible bag where they can be re-harvested. Meanwhile, product contained in the liquid can be collected in a separate container. The efficiency of product formation in such a system may be enhanced by using mixing systems described herein.
摘要翻译： 提供了用于容纳和操纵液体的系统和方法，包括容器和单元操作或细胞培养物，细胞容纳物，生物反应器和/或药物制造系统的组分。 在某些实施方案中，这样的容器和单元操作涉及连续灌注反应器或生物反应器系统，并且可以包括一个或多个一次性组件。 例如，一方面，系统包括生物反应器形式的装置，用于收集产生一种或多种产品的细胞。 该装置可以包括适于容纳液体的一次性可折叠袋，该可折叠袋与液体 - 固体（例如，池）分离装置流体连通。 例如，可折叠袋的出口可以连接到分离装置的入口，并且分离装置的出口可以连接到可折叠袋的入口以用于再循环。 因此，在分离装置中的液体分离细胞后，细胞可以流回到可收缩的袋子中，在那里它们可以被再次收获。 同时，包含在液体中的产品可以收集在单独的容器中。 通过使用本文所述的混合系统可以提高这种系统中产物形成的效率。
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公开(公告)号：US20130200005A1
公开(公告)日：2013-08-08
申请号：US13879354
申请日：2011-10-14
申请人： Scott A. Mangiacotti , Parrish M. Galliher , Joseph J. Arduino , Michael Fisher , John J. Vicalvi, JR. , Joseph Makowiecki
发明人： Scott A. Mangiacotti , Parrish M. Galliher , Joseph J. Arduino , Michael Fisher , John J. Vicalvi, JR. , Joseph Makowiecki
IPC分类号： B01D61/22
CPC分类号： B01D61/22 , B01D61/145 , B01D2311/08 , B01D2311/25 , B01D2313/18 , B01D2313/20 , B01D2313/243 , B01D2313/58 , B01D2315/16 , B01D2317/08 , B01D2319/06 , C02F1/444 , C02F2209/005 , C02F2209/02 , C02F2209/03 , C02F2209/05 , C02F2209/11 , C02F2209/40 , B01D2311/04
摘要： A disposable filtration system can include a disposable filter housing having an ultrafiltration filter contained therein. The disposable filtration system can further include a feed inlet and retentate outlet in fluid communication on one side of the filter and a permeate conduit on the other side of the filter for withdrawing permeate that passes through the filter. The system can include at least one disposable pressure control valve in fluid communication with either the retentate outlet or the permeate conduit and configured to regulate the pressure within the housing.
摘要翻译： 一次性过滤系统可以包括其中包含超滤过滤器的一次性过滤器壳体。 一次性过滤系统还可以包括在过滤器的一侧处流体连通的进料入口和滞留物出口，以及在过滤器的另一侧的渗透管道，用于抽出通过过滤器的渗透物。 该系统可以包括至少一个一次性压力控制阀，其与渗余物出口或渗透物导管流体连通，并被配置成调节壳体内的压力。
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公开(公告)号：US20090035856A1
公开(公告)日：2009-02-05
申请号：US12124039
申请日：2008-05-20
CPC分类号： C12M29/10 , B01D29/13 , C12M23/14 , C12M23/26 , C12M23/48 , C12M27/02 , C12M27/20 , C12M29/00 , C12M29/18 , C12M47/10
摘要： Systems and methods for containing and manipulating liquids, including vessels and unit operations or components of cell culture, cell containment, bioreactor, and/or pharmaceutical manufacturing systems, are provided. In certain embodiments, such vessels and unit operations are directed to continuous perfusion reactor or bioreactor systems and may include one or more disposable components. For instance, in one aspect, a system includes an apparatus in the form of a bioreactor for harvesting cells which produce one or more products. The apparatus may include a disposable, collapsible bag adapted for containing a liquid, the collapsible bag in fluid communication with a liquid-solids (e.g., cell) separation device. For example, an outlet of the collapsible bag may be connected to an inlet of the separation device, and an outlet of the separation device may be connected to an inlet of the collapsible bag for recycle. Accordingly, after separating the cells from the liquid in the separation device, the cells can be flowed back into the collapsible bag where they can be re-harvested. Meanwhile, product contained in the liquid can be collected in a separate container. The efficiency of product formation in such a system may be enhanced by using mixing systems described herein.
摘要翻译： 提供了用于容纳和操纵液体的系统和方法，包括容器和单元操作或细胞培养物，细胞容纳物，生物反应器和/或药物制造系统的组分。 在某些实施方案中，这样的容器和单元操作涉及连续灌注反应器或生物反应器系统，并且可以包括一个或多个一次性组件。 例如，一方面，系统包括生物反应器形式的装置，用于收集产生一种或多种产品的细胞。 该装置可以包括适于容纳液体的一次性可折叠袋，该可折叠袋与液体 - 固体（例如，池）分离装置流体连通。 例如，可折叠袋的出口可以连接到分离装置的入口，并且分离装置的出口可以连接到可折叠袋的入口以用于再循环。 因此，在分离装置中的液体分离细胞后，细胞可以流回到可收缩的袋子中，在那里它们可以被再次收获。 同时，包含在液体中的产品可以收集在单独的容器中。 通过使用本文所述的混合系统可以提高这种系统中产物形成的效率。
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