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1. 发明授权

US5688687A Bioreactor for mammalian cell growth and maintenance 失效
标题翻译：用于哺乳动物细胞生长和维持的生物反应器
公开(公告)号：US5688687A
公开(公告)日：1997-11-18
申请号：US478622
申请日：1995-06-07
申请人： Bernhard O. Palsson , R. Douglas Armstrong , James Maluta
发明人： Bernhard O. Palsson , R. Douglas Armstrong , James Maluta
IPC分类号： C12M3/04 , C12M1/36 , C12M3/06 , C12M3/00
CPC分类号： C12M41/48 , C12M23/42 , C12M41/14
摘要： A bioreactor for the ex vivo maintenance and growth of mammalian cells includes a disposable, self contained cell cassette, a system manager, an incubator unit matable with a plurality of the cassettes and a processor unit. The cell cassette includes a substantially circular cell growth chamber defined between a substantially planar cell bed and a gas permeable, liquid impervious membrane. A media inlet enters the cell growth chamber communicates at a radially central portion of the cell bed. A plurality of media outlets are radially outwardly spaced from the media inlet by a distance sufficient for cell growth to occur between the inlet and the outlets. The outlets are substantially equiangularly circumferentially spaced about the cell growth chamber.
摘要翻译：用于哺乳动物细胞的离体维持和生长的生物反应器包括一次性的，独立的细胞盒，系统管理器，可与多个盒子配合的培养箱单元和处理器单元。细胞盒包括基本上圆形的细胞生长室，其限定在基本上平面的细胞床和透气的液体不可渗透的膜之间。介质入口进入细胞生长室，在细胞床的径向中心部分连通。多个介质出口与介质入口径向向外间隔开一定距离，足以在入口和出口之间发生细胞生长。出口基本上等角地围绕细胞生长室周向间隔开。

2. 发明授权

US5635386A Methods for regulating the specific lineages of cells produced in a human hematopoietic cell culture 失效
标题翻译：调节人类造血细胞培养物中产生的细胞特异性谱系的方法
公开(公告)号：US5635386A
公开(公告)日：1997-06-03
申请号：US334011
申请日：1994-11-02
申请人： Bernhard O. Palsson , R. Douglas Armstrong , Michael F. Clarke , Stephen G. Emerson
发明人： Bernhard O. Palsson , R. Douglas Armstrong , Michael F. Clarke , Stephen G. Emerson
IPC分类号： A61F2/16 , A61K48/00 , C07K14/535 , C07K14/54 , C07K14/705 , C12M1/34 , C12M3/02 , C12M3/06 , C12N5/02 , C12N5/078 , C12N5/0787 , C12N5/0789 , C12N15/85 , C12N15/867 , C12N5/00
CPC分类号： C07K14/5403 , C07K14/535 , C07K14/5412 , C07K14/705 , C12N15/85 , C12N15/86 , C12N5/0641 , C12N5/0642 , C12N5/0647 , A61K48/00 , C12N2500/34 , C12N2501/125 , C12N2501/14 , C12N2501/22 , C12N2501/23 , C12N2501/39 , C12N2502/1394 , C12N2502/99 , C12N2740/10043
摘要： Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium. The disclosed culture conditions afford improved methods for bone marrow transplantation.
摘要翻译：提供体外人干细胞分裂和/或优化人类造血祖细胞培养物和/或增加人基质细胞的代谢或GM-CSF分泌或IL-6分泌的方法，包括培养基条件和/或公开了一种用于测定物质或病症对人类造血细胞群体的影响和/或消耗人类造血细胞群体的恶性细胞或T细胞和B细胞含量的方法。所述方法依赖于在液体培养基中培养人类干细胞和/或人类造血祖细胞和/或人类基质细胞，所述液体培养基以每毫升培养物1ml培养基的速率连续或周期性地更换，优选灌注每24-48小时左右，并且除去代谢产物并补充耗尽的营养物质，同时保持培养物在生理上可接受的条件下。任选地，将生长因子加入到培养基中。所公开的培养条件提供了改进的骨髓移植方法。

3. 发明授权

US6096532A Processor apparatus for use in a system for maintaining and growing biological cells 失效
标题翻译：用于维持和生长生物细胞的系统中的处理器装置
公开(公告)号：US6096532A
公开(公告)日：2000-08-01
申请号：US921847
申请日：1997-09-02
申请人： R. Douglas Armstrong , James Maluta , David W. Roecker
发明人： R. Douglas Armstrong , James Maluta , David W. Roecker
IPC分类号： C12M3/02
CPC分类号： C12M27/16 , C12M23/42 , C12M23/54 , C12M41/00 , C12M41/48
摘要： A processor apparatus is disclosed, for conditioning a portable cassette as part of a process in which biological cells contained within a sterilizable cell growth chamber of the cassette are maintained and grown ex vivo, without exposing the cells to the external environment. The processor apparatus includes a support configured to removably receive the portable cassette and to be movable in a controlled manner, and it further includes a flow control actuator engageable with a media flow path of the portable cassette, which communicates with the cell growth chamber. The processor apparatus further includes a controller that controls the flow control actuator and the support, such that a quantity of growth medium is selectively delivered to the cell growth chamber, such that the cassette is moved in a manner that properly distributes the biological cells throughout the chamber, and such that biological cells are harvested from the cell growth chamber, all without exposing the chamber and the media flow path to the external environment. The processor apparatus also may be configured to retrieve data from, and to store data to, an updatable memory device carried on the portable cassette.
摘要翻译：公开了一种处理器装置，用于调节便携式盒式磁带，作为其中包含在盒的可灭菌细胞生长室内的生物细胞离体维持和生长的过程的一部分，而不将细胞暴露于外部环境。所述处理器装置包括支撑件，其构造成可拆卸地容纳所述便携式盒并可受控地移动，并且还包括可与所述便携式盒的介质流动路径接合的流量控制致动器，所述介质流动路径与所述电池生长室连通。处理器装置还包括控制器，其控制流量控制致动器和支撑件，使得一定量的生长培养基被选择性地递送到细胞生长室，使得盒以适当地分布生物细胞的方式移动并且使得从细胞生长室收获生物细胞，所有这些都不会暴露室和介质流动路径到外部环境。处理器装置还可以被配置为从便携式盒带上携带的可更新存储装置检索数据并将数据存储到其中。

4. 发明授权

US5985653A Incubator apparatus for use in a system for maintaining and growing biological cells 失效
标题翻译：用于维持和生长生物细胞的系统中的孵化器装置
公开(公告)号：US5985653A
公开(公告)日：1999-11-16
申请号：US999593
申请日：1997-06-24
申请人： R. Douglas Armstrong , James Maluta , David W. Roecker
发明人： R. Douglas Armstrong , James Maluta , David W. Roecker
IPC分类号： C12M1/38 , C12M3/00 , C12M3/06 , C12C1/00
CPC分类号： C12M41/00 , C12M23/42 , C12M23/54
摘要： An incubator apparatus is disclosed, for conditioning a portable cassette such that biological cells contained within a cell growth chamber of the cassette are maintained and grown ex vivo, without exposing the cells to the external environment. The incubator apparatus includes first and second receptacles sized and configured to removably receive first and second casings, respectively, of the portable cassette, and it further includes first and second temperature regulators that regulate the temperatures of the respective first and second receptacles to prescribed values. In addition, the incubator apparatus includes a mechanical interface that is engaged by the portable cassette's first and second casings when they are received in their corresponding receptacles, and this mechanical interface controls the transport of growth media and a gas through the cassette's cell growth chamber, without exposing the cell growth chamber to the external environment. The incubator apparatus also is configured to retrieve data from, and to store data to, an updatable memory device carried on the cassette.
摘要翻译：公开了一种用于调节便携式盒的培养器装置，使得包含在盒的细胞生长室内的生物细胞在体外保持和生长，而不将细胞暴露于外部环境。培养箱装置包括第一和第二容器，其尺寸和构造分别可拆卸地容纳便携式盒子的第一和第二壳体，并且还包括将相应的第一和第二容器的温度调节到规定值的第一和第二温度调节器。此外，培养箱装置包括机械接口，当它们被容纳在其相应的容器中时，其被便携式盒的第一和第二壳体接合，并且该机械界面控制生长介质和气体通过盒的细胞生长室的传送，而不会将细胞生长室暴露于外部环境。培养箱装置还被配置为从盒上携带的可更新存储装置检索数据并将数据存储到其中。

5. 发明授权

US5312900A 23K protein with binding specificity for queuine 失效
标题翻译： 23K蛋白具有对奎宁的结合特异性
公开(公告)号：US5312900A
公开(公告)日：1994-05-17
申请号：US681889
申请日：1991-04-08
申请人： R. Douglas Armstrong
发明人： R. Douglas Armstrong
IPC分类号： A61K38/00 , C07K14/47 , C07K15/00 , C07K3/18
CPC分类号： C07K14/47 , A61K38/00 , Y10S530/851
摘要： The invention generally relates to the discovery of a 23 kD protein, designated herein as Queb, that has specific binding affinity for the purine base Queuine. The invention particularly relates to polypeptides having specific binding reactivity with Queuine and methods of using such polypeptides to purify Queuine and Queuine-containing substances. The invention also relates to antibodies having specific reactivity with Queuine or Queb. Methods for determining the presence and concentration of Queuine and Queb are also provided as well as methods for the diagnosis of a pathological disease or prognosis of a patient having a disease associated with Queuine, Queuine-containing substances such as Queuine-tRNA, or Queb. Kits useful for performing the methods of the present invention are also provided.
摘要翻译：本发明通常涉及对嘌呤碱基奎因具有特异性结合亲和力的23kD蛋白质（本文称为Queb）的发现。本发明特别涉及对Queuine具有特异性结合反应性的多肽以及使用这些多肽来净化Queuine和Queuine的物质的方法。本发明还涉及具有与Queuine或Queb具有特异反应性的抗体。还提供了用于确定Queuine和Queb的存在和浓度的方法，以及用于诊断具有与Queuine，Queuine-tRNA或Queb等含奎因的物质相关的疾病的患者的病理疾病或预后的方法。还提供了用于执行本发明的方法的试剂盒。

6. 发明授权

US06238908B1 Apparatus and method for maintaining and growth biological cells 失效
标题翻译：用于维持和生长生物细胞的装置和方法
公开(公告)号：US06238908B1
公开(公告)日：2001-05-29
申请号：US08999853
申请日：1997-06-24
申请人： R. Douglas Armstrong , James Maluta , David W. Roecker
发明人： R. Douglas Armstrong , James Maluta , David W. Roecker
IPC分类号： C12M136
CPC分类号： C12M23/42 , C12M23/54 , C12M41/00
摘要： An apparatus and related method are disclosed, for receiving, maintaining and growing biological cells ex vivo within a portable cassette, without exposing the cells to the external environment. The portable cassette is used in combination with a processor instrument that facilitates an initial inoculation of the cassette with cells of the kind to be grown and subsequently distributes those cells in a predetermined pattern (e.g., uniformly) throughout a cell growth chamber. Thereafter, the portable cassette is used in combination with an incubator instrument that incubates the cell growth chamber so that the cells are optimally expanded. The same processor instrument then is used to harvest the expanded cells from the portable cassette. Both instruments are configured to condition the portable cassette during stages of the cell growth process, without disturbing the cassette's sterile system. In addition, an updatable memory device associated with the cassette stores significant information about the cassette and its condition during the various steps of the cell growth process. Such information is useful both for subsequent archival purposes and for facilitating a resumption of the cell growth process in the event of any instrument failure or significant alarm condition.
摘要翻译：公开了一种装置和相关方法，用于在便携式盒式磁带内离体接收，维持和增长生物细胞，而不将细胞暴露于外部环境。便携式盒式磁带与处理器仪器组合使用，其便于初始接种具有待生长种类细胞的盒，并随后将细胞以预定图案（例如，均匀地）分布在整个细胞生长室中。此后，便携式盒与孵化器一起使用，该培养器将培养细胞生长室，使得细胞被最佳地扩大。然后使用相同的处理器乐器从便携式盒式磁带收获扩展的单元。两个仪器被配置为在细胞生长过程的阶段期间调节便携式盒，而不会干扰盒的无菌系统。此外，与盒相关联的可更新存储器件在细胞生长过程的各个步骤期间存储关于盒及其状况的重要信息。这样的信息对于随后的归档目的是有用的，并且在任何仪器故障或显着的警报状况的情况下有助于恢复细胞生长过程。

7. 发明授权

US06228635B1 Portable cell growth cassette for use in maintaining and growing biological cells 失效
标题翻译：用于维持和生长生物细胞的便携式细胞生长盒
公开(公告)号：US06228635B1
公开(公告)日：2001-05-08
申请号：US08999996
申请日：1997-06-24
申请人： R. Douglas Armstrong , James Maluta , David W. Roecker
发明人： R. Douglas Armstrong , James Maluta , David W. Roecker
IPC分类号： C12M136
CPC分类号： C12M23/54 , C12M23/42 , C12M41/00
摘要： A portable cassette is disclosed, for receiving, maintaining and growing biological cells ex vivo, without exposing the cells to the external environment. The portable cassette is used in combination with a succession of instruments, to inoculate the cassette's cell growth chamber with cells, to then incubate the chamber so that the cells are optimally expanded, and finally to harvest the expanded cells. Each instrument is configured to condition the portable cassette during a stage of the cell growth process, without disturbing the cassette's sterile system. In addition, an updatable memory device associated with the cassette stores significant information about the cassette and its condition during the various steps of the cell growth process. Such information is useful both for subsequent archival purposes and for facilitating a resumption of the cell growth process in the event of any instrument failure or significant alarm condition.
摘要翻译：公开了一种便携式盒，用于从体外接收，维持和生长生物细胞，而不将细胞暴露于外部环境。便携式盒与一系列仪器组合使用，用细胞接种盒式细胞生长室，然后孵育室，使细胞最佳扩增，最后收获扩大的细胞。每个仪器被配置为在细胞生长过程的阶段调节便携式盒，而不会干扰盒的无菌系统。此外，与盒相关联的可更新存储器件在细胞生长过程的各个步骤期间存储关于盒及其状况的重要信息。这样的信息对于随后的归档目的是有用的，并且在任何仪器故障或显着的警报状况的情况下有助于恢复细胞生长过程。

8. 发明授权

US06667034B2 METHODS FOR REGULATING THE SPECIFIC LINEAGES OF CELLS PRODUCED IN A HUMAN HEMATOPOIETIC CELL CULTURE, METHODS FOR ASSAYING THE EFFECT OF SUBSTANCES ON LINEAGE-SPECIFIC CELL PRODUCTION, AND CELL COMPOSITIONS PRODUCED BY THESE CULTURES 失效
公开(公告)号：US06667034B2
公开(公告)日：2003-12-23
申请号：US08857594
申请日：1997-05-16
申请人： Bernhard O. Palsson , R. Douglas Armstrong , Michael F. Clarke , Stephen G. Emerson
发明人： Bernhard O. Palsson , R. Douglas Armstrong , Michael F. Clarke , Stephen G. Emerson
IPC分类号： A01N6300
CPC分类号： C07K14/5403 , A61K48/00 , C07K14/535 , C07K14/5412 , C07K14/705 , C12N5/0641 , C12N5/0642 , C12N5/0647 , C12N15/85 , C12N15/86 , C12N2500/34 , C12N2501/125 , C12N2501/14 , C12N2501/22 , C12N2501/23 , C12N2501/39 , C12N2502/1394 , C12N2502/99 , C12N2740/10043
摘要： Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium. The disclosed culture conditions afford improved methods for bone marrow transplantation.

9. 发明授权

US6048721A Bioreactor for mammalian cell growth and maintenance 失效
标题翻译：用于哺乳动物细胞生长和维持的生物反应器
公开(公告)号：US6048721A
公开(公告)日：2000-04-11
申请号：US939489
申请日：1997-09-29
申请人： R. Douglas Armstrong , James Maluta , David Roecker
发明人： R. Douglas Armstrong , James Maluta , David Roecker
IPC分类号： C12M3/04 , C12M1/36 , C12M3/06 , C12M3/00
CPC分类号： C12M41/48 , C12M23/42 , C12M41/14
摘要： A bioreactor for the ex vivo maintenance and growth of mammalian cells includes a disposable, self contained cell cassette, a system manager, an incubator unit matable with a plurality of the cassettes and a processor unit. The cell cassette includes a substantially circular cell growth chamber defined between a substantially planar cell bed and a gas permeable, liquid impervious membrane. A media inlet enters the cell growth chamber communicates at a radially central portion of the cell bed. A plurality of media outlets are radially outwardly spaced from the media inlet by a distance sufficient for cell growth to occur between the inlet and the outlets. The outlets are substantially equiangularly circumferentially spaced about the cell growth chamber.
摘要翻译：用于哺乳动物细胞的离体维持和生长的生物反应器包括一次性的，独立的细胞盒，系统管理器，可与多个盒子配合的培养箱单元和处理器单元。细胞盒包括基本上圆形的细胞生长室，其限定在基本上平面的细胞床和透气的液体不可渗透的膜之间。介质入口进入细胞生长室，在细胞床的径向中心部分连通。多个介质出口与介质入口径向向外间隔开一定距离，足以在入口和出口之间发生细胞生长。出口基本上等角地围绕细胞生长室周向间隔开。

10. 发明授权

US5994129A Portable cassette for use in maintaining and growing biological cells 失效
标题翻译：用于维持和生长生物细胞的便携式盒式磁带
公开(公告)号：US5994129A
公开(公告)日：1999-11-30
申请号：US889848
申请日：1997-07-08
申请人： R. Douglas Armstrong , James Maluta , David W. Roecker
发明人： R. Douglas Armstrong , James Maluta , David W. Roecker
IPC分类号： C12M1/38 , C12M3/00 , C12M3/06 , C12M1/36
CPC分类号： C12M23/42 , C12M23/54 , C12M41/00
摘要： A portable cassette is disclosed, for use in receiving, maintaining and growing biological cells ex vivo without exposing the cells to the external environment. The portable cassette is used in combination with a processor instrument that facilitates an initial inoculation of the cassette with cells of the kind to be grown and to distribute those cells in a predetermined pattern (e.g., uniformly) throughout a cell growth chamber. Thereafter, the portable cassette is used in combination with an incubator instrument that incubates the cell growth chamber so that the cells are optimally expanded. The same processor instrument then is used to harvest the expanded cells from the portable cassette. Both instruments are configured to condition the portable cassette during stages of the cell growth process, without disturbing the cassette's sterile system.
摘要翻译：公开了便携式盒式磁带，用于离子体接收，维持和生长生物细胞而不将细胞暴露于外部环境。便携式盒与处理器仪器组合使用，其便于初始接种具有待种植种类细胞的盒，并将细胞以预定图案（例如，均匀地）分布在整个细胞生长室中。此后，便携式盒与孵化器一起使用，该培养器将培养细胞生长室，使得细胞被最佳地扩大。然后使用相同的处理器乐器从便携式盒式磁带收获扩展的单元。两个仪器被配置为在细胞生长过程的阶段期间调节便携式盒，而不会干扰盒的无菌系统。

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