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1.发明授权Method of condensed cell slide preparation and detection of rarely occurring cells on microscope slides 失效缩小细胞载玻片制备方法和显微镜载片上罕见细胞的检测公开(公告)号：US07595874B1
公开(公告)日：2009-09-29
申请号：US11672794
申请日：2007-02-08
申请人： Vladimir M. Pelekhaty , Anatoliy Kachurin , William Warren , Kenneth Church , Heather Fahlenkamp , Russell Higbee
发明人： Vladimir M. Pelekhaty , Anatoliy Kachurin , William Warren , Kenneth Church , Heather Fahlenkamp , Russell Higbee
IPC分类号： G01J3/30
CPC分类号： G01N21/6458 , G01N1/36 , G01N15/1434 , G01N2201/104 , G01N2201/1045 , G01N2201/112 , G02B21/26 , G02B21/365
摘要： Detection of a rarely occurring event within one or more biological samples includes (a) processing each biological sample to provide a gellable liquid solution comprising concentrated biological sample and a flourochrome designed to associate with a rarely occurring event within the concentrated biological sample; (b) depositing the solution in a layer on a surface of a slide; and (c) scanning the solution on the slide with energy adapted to cause fluorescence of the flourochrome to detect potential instances of the rarely occurring event within the concentrated biological sample in the solution.
摘要翻译： 在一个或多个生物样品中检测到很少发生的事件包括（a）处理每个生物样品以提供包含浓缩的生物样品和设计成与浓缩的生物样品中罕见事件相关的荧光染料的可胶凝液体溶液; （b）将溶液沉积在载玻片表面上的层中; 和（c）用适于引起荧光色素的能量扫描载玻片上的溶液以检测溶液中浓缩的生物样品内很少发生的事件的潜在情况。
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公开(公告)号：US20070218054A1
公开(公告)日：2007-09-20
申请号：US11642938
申请日：2006-12-21
申请人： Selva Sukumar , Mohey Eldin El Shikh , John Tew , Guzman Sanchez-Schmitz , Donald Drake , Luis Mosquera , Eric Mishkin , Anatoly Kachurin , Russell Higbee , Conan Li , William Warren , Heather Fahlenkamp
发明人： Selva Sukumar , Mohey Eldin El Shikh , John Tew , Guzman Sanchez-Schmitz , Donald Drake , Luis Mosquera , Eric Mishkin , Anatoly Kachurin , Russell Higbee , Conan Li , William Warren , Heather Fahlenkamp
IPC分类号： A61K39/395 , G01N33/567 , C12P21/04 , C12N5/08
CPC分类号： C07K16/44 , C12N5/0639 , C12N5/0651 , C12N5/0697 , C12N2501/052 , C12N2501/21 , C12N2501/2304 , C12N2502/11 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/28 , C12N2503/04 , C12N2533/50 , C12N2533/54 , C12N2533/92 , C12N2535/10 , G01N33/5047 , G01N33/5076 , G01N33/5088
摘要： The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.
摘要翻译： 本发明将生发中心（GC）纳入三维（3D）工程组织构建体（ETC）中。 在一个实施方案中，我们已经将GC并入人造免疫系统（AIS）的设计中，以检查对疫苗和其他化合物的免疫应答。 体外GC的开发为AIS增加了功能，因为它能够在不使用人类受试者的情况下产生准确和可重复的人B淋巴细胞的体外人体液反应。 本发明还允许评估例如疫苗，过敏原和免疫原，以及对给定抗原特异性的人B细胞的活化，然后可以将其用于产生人抗体。 在本发明的一个实施方案中，通过将FDC和其他免疫细胞放置在3D ETC中来增强体外GC的功能; FDC在更长时间内看起来更有效（抗体产生持续长达约14天。
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3.发明申请Porous membrane device that promotes the differentiation of monocytes into dendritic cells 审中-公开促进单核细胞分化成树突状细胞的多孔膜装置公开(公告)号：US20070178076A1
公开(公告)日：2007-08-02
申请号：US11642926
申请日：2006-12-21
申请人： Donald Drake , David Moe , Conan Li , Heather Fahlenkamp , Guzman Sanchez-Schmitz , Russell Higbee , Robert Parkhill , William Warren
发明人： Donald Drake , David Moe , Conan Li , Heather Fahlenkamp , Guzman Sanchez-Schmitz , Russell Higbee , Robert Parkhill , William Warren
CPC分类号： C12N5/0639 , C12M23/12 , C12M23/20 , C12M25/02 , C12M25/14 , C12N2502/28 , C12N2503/00
摘要： Dendritic cells (DCs) for research and clinical applications are typically derived from purified blood monocytes that are cultured in a cocktail of cytokines for a week or more. Because it has been suggested that these cytokine-derived DCs may be deficient in some important immunological functions and might not accurately represent antigen-presenting cell (APC) populations found under physiologic conditions, there is a need for methods that allow the generation of DCs in a more physiologically relevant manner. The present invention comprises a simple and reliable technique for generating large numbers of highly purified DCs, based on a single migration of blood monocytes through endothelial cells that are cultured in, for example, a Transwell® device. The resultant APCs, harvested from the lower Transwell® chamber, resemble other in vitro-generated DC populations in their expression of major histocompatibility (MHC) and costimulatory molecules, ability to phagocytose foreign antigens, and capacity to trigger antigen-specific T cell responses.
摘要翻译： 用于研究和临床应用的树突状细胞（DC）通常衍生自在细胞因子混合物中培养一周或更长时间的纯化血液单核细胞。 由于已经提出这些细胞因子衍生的DC可能在一些重要的免疫功能上有缺陷，并且可能不能准确地代表在生理条件下发现的抗原呈递细胞（APC）群体，所以需要一种允许在 更生理相关的方式。 本发明包括一种用于产生大量高度纯化的DC的简单可靠的技术，其基于通过在例如Transwell装置中培养的内皮细胞的血液单核细胞的单次迁移。 从较低的Transwell室收获的所得APC在其主要组织相容性（MHC）和共刺激分子的表达，吞噬外来抗原的能力和触发抗原特异性T细胞的能力方面类似于其它体外产生的DC群体 回应。
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公开(公告)号：US20070141552A1
公开(公告)日：2007-06-21
申请号：US11594171
申请日：2006-11-08
申请人： William Warren , Robert Parkhill , Michael Nguyen , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Russell Higbee , Donald Drake , Anatoly Kachurin , David Moe
发明人： William Warren , Robert Parkhill , Michael Nguyen , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Russell Higbee , Donald Drake , Anatoly Kachurin , David Moe
CPC分类号： G01N33/5088 , G01N33/5047
摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.
摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人造免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。
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公开(公告)号：US20050282148A1
公开(公告)日：2005-12-22
申请号：US11116234
申请日：2005-04-28
申请人： William Warren , Heather Fahlenkamp , Russell Higbee , Anatoly Kachurin , Conan Li , Mike Nguyen , Robert Parkhill , Guzman Sanchez-Schmitz , Darrell Irvine , Gwendalyn Randolph , Nir Hacohen , Bruce Torbett
发明人： William Warren , Heather Fahlenkamp , Russell Higbee , Anatoly Kachurin , Conan Li , Mike Nguyen , Robert Parkhill , Guzman Sanchez-Schmitz , Darrell Irvine , Gwendalyn Randolph , Nir Hacohen , Bruce Torbett
CPC分类号： G01N33/5008 , C12N5/0697 , C12N5/0698 , C12N2501/21 , C12N2502/094 , C12N2502/11 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1157 , C12N2502/1192 , C12N2502/1323 , C12N2502/28 , C12N2503/04 , C12N2513/00 , C12N2531/00 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5088 , G01N2500/10
摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interaction with the immune system.
摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人工免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。
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6.发明申请Controlling dendritic cell maturation state in the lymphoid tissue equivalent of an artificial immune system 有权控制人造免疫系统的淋巴组织等效的树突状细胞成熟状态公开(公告)号：US20070015136A1
公开(公告)日：2007-01-18
申请号：US11471514
申请日：2006-06-21
申请人： Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Darrell Irvine , William Warren , Donald Drake
发明人： Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Darrell Irvine , William Warren , Donald Drake
CPC分类号： C12N5/0639 , C12N5/0651 , C12N5/0697 , C12N2501/21 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/28 , C12N2503/04 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5047
摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.
摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人造免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。
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公开(公告)号：US20060275270A1
公开(公告)日：2006-12-07
申请号：US11375128
申请日：2006-03-15
申请人： William Warren , Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Donald Drake , John Tew
发明人： William Warren , Guzman Sanchez-Schmitz , Russell Higbee , Heather Fahlenkamp , Donald Drake , John Tew
CPC分类号： C12N5/0697 , C12N2501/21 , C12N2502/094 , C12N2502/11 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/1323 , C12N2502/28 , C12N2503/04 , C12N2533/50 , C12N2533/54 , C12N2533/92 , C12N2535/10 , G01N33/5044 , G01N33/564
摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with pathogens and vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.
摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的病原体和疫苗相互作用的正常组织。 人造免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。
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公开(公告)号：US20070026392A1
公开(公告)日：2007-02-01
申请号：US11453003
申请日：2006-06-15
申请人： William Warren , Russell Higbee , Eric Mishkin , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Michael Rivard
发明人： William Warren , Russell Higbee , Eric Mishkin , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Michael Rivard
IPC分类号： C12Q1/70 , G01N33/567 , C12N5/08 , C12N5/06
CPC分类号： C12M21/08 , C12M25/14 , C12M35/08 , C12N5/0697 , C12N2501/21 , C12N2502/091 , C12N2502/094 , C12N2502/11 , C12N2502/28 , C12N2502/30 , C12N2503/04 , C12N2531/00 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5044 , G01N33/5064 , G01N33/5082 , G01N33/5088 , G01N2800/24
摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising a three-dimensional matrix comprising lymphoid tissue, a three-dimensional matrix comprising epithelial and/or endothelial cells, and diseased cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.
摘要翻译： 本发明涉及人造免疫系统的制备方法。 人造免疫系统包括细胞培养物，其包含包含淋巴组织的三维基质，包含上皮和/或内皮细胞的三维基质和患病细胞。 本发明的人造免疫系统可用于疫苗，佐剂，免疫治疗候选物，化妆品，药物，生物制剂和其它化学品的体外试验。
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公开(公告)号：US20060270029A1
公开(公告)日：2006-11-30
申请号：US11375033
申请日：2006-03-15
申请人： William Warren , Robert Parkhill , Michael Nguyen , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Russell Higbee , Donald Drake , Anatoly Kachurin , David Moe
发明人： William Warren , Robert Parkhill , Michael Nguyen , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Russell Higbee , Donald Drake , Anatoly Kachurin , David Moe
CPC分类号： C12N5/0697 , B01L3/5027 , C12N2501/21 , C12N2502/094 , C12N2502/11 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/28 , C12N2503/02 , C12N2503/04 , C12N2531/00 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5082 , G01N33/5088
摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.
摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人造免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。
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公开(公告)号：US08298823B2
公开(公告)日：2012-10-30
申请号：US12730899
申请日：2010-03-24
申请人： William L. Warren , Robert Parkhill , Michael N. Nguyen , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Russell Higbee , Donald Drake, III , Anatoly Kachurin , David Moe
发明人： William L. Warren , Robert Parkhill , Michael N. Nguyen , Guzman Sanchez-Schmitz , Heather Fahlenkamp , Russell Higbee , Donald Drake, III , Anatoly Kachurin , David Moe
CPC分类号： C12N5/0697 , B01L3/5027 , C12N2501/21 , C12N2502/094 , C12N2502/11 , C12N2502/1107 , C12N2502/1114 , C12N2502/1121 , C12N2502/1192 , C12N2502/28 , C12N2503/02 , C12N2503/04 , C12N2531/00 , C12N2533/50 , C12N2533/54 , C12N2535/10 , G01N33/5082 , G01N33/5088
摘要： The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.
摘要翻译： 本发明涉及构建综合人造免疫系统的方法，其包括适当的体外细胞和组织构建体或其等同物以模拟与哺乳动物中的疫苗相互作用的正常组织。 人造免疫系统可用于测试疫苗候选物在体外的功效，因此可用于加速疫苗开发和测试与免疫系统的药物和化学相互作用。
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