公开(公告)号：US20090104221A1

公开(公告)日：2009-04-23

申请号：US12167689

申请日：2008-07-03

申请人： Mohey Eldin Moustafa El Shikh ,  Rania El Sayed ,  Andras K. Szakal ,  John G. Tew ,  Donald R. Drake, III ,  Vaughan Wittman ,  Jennifer Eatrides ,  William L. Warren

发明人： Mohey Eldin Moustafa El Shikh ,  Rania El Sayed ,  Andras K. Szakal ,  John G. Tew ,  Donald R. Drake, III ,  Vaughan Wittman ,  Jennifer Eatrides ,  William L. Warren

IPC分类号： A61K39/00 ,  C12Q1/02 ,  C12P21/00

CPC分类号： G01N33/5052 ,  A61K39/00 ,  A61K2039/545 ,  A61K2039/55505 ,  A61K2039/6012 ,  A61K2039/6056 ,  C07K16/4283 ,  C12N5/0639 ,  C12N2503/02 ,  G01N33/5044 ,  G01N33/505 ,  G01N33/5082

摘要： The present invention comprises the use of follicular dendritic cells (FDCs) or FDC-like cells to generate FDC-dependent, but T cell-independent, B cell responses to T cell-dependent antigens, with antigen-specific and polyclonal antibody production in ˜48 h. In another embodiment, a germinal center (GC) lymphoid tissue equivalent (LTE) was used to generate antigen-specific IgM, followed by switching to IgG. The GC LTE model can be used in vaccine assessment. Dual forms of immunogen were used in the GC LTE and in vivo. Dual immunogens resulted in rapid, specific IgM responses and enhanced IgG responses. This vaccine design approach can be used, for example, to provide rapid IgM protection (˜24-48 h) and high-affinity IgG more quickly in people moving to areas with endemic disease, or in people with T cell insufficiencies, who can be immunized to rapidly generate protective IgM.

摘要翻译： 本发明包括使用滤泡树突状细胞（FDC）或FDC样细胞来产生FDC依赖但与T细胞无关的B细胞对T细胞依赖性抗原的应答，其中抗原特异性和多克隆抗体产生在〜 48小时。 在另一个实施方案中，使用生发中心（GC）淋巴组织等同物（LTE）产生抗原特异性IgM，随后切换至IgG。 GC LTE模型可用于疫苗评估。 免疫原的双重形式用于GC LTE和体内。 双重免疫原导致快速，特异性IgM反应和增强的IgG反应。 例如，这种疫苗设计方法可以用于在移动到地方性疾病地区的人群中或在具有T细胞功能不足的人群中提供快速的IgM保护（〜24-48小时）和高亲和力IgG 免疫以快速产生保护性IgM。

公开(公告)号：US08962319B2

公开(公告)日：2015-02-24

申请号：US13289024

申请日：2011-11-04

申请人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

发明人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

IPC分类号： C12N5/00 ,  C12N5/02 ,  G01N33/50 ,  C12N5/0781 ,  C12N5/0783 ,  C12N5/0784 ,  C12N5/071

CPC分类号： G01N33/5052 ,  C12N5/0635 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0697 ,  C12N2500/90 ,  C12N2501/21 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2510/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/505 ,  G01N33/5088

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic 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。 人造免疫系统包括包含T细胞，B细胞和抗原引发的树突状细胞的细胞培养物。 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。

公开(公告)号：US08071373B2

公开(公告)日：2011-12-06

申请号：US11453046

申请日：2006-06-15

申请人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

发明人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

IPC分类号： C12N5/00 ,  C12N5/08

CPC分类号： G01N33/5052 ,  C12N5/0635 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0697 ,  C12N2500/90 ,  C12N2501/21 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2510/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/505 ,  G01N33/5088

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic 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。 人造免疫系统包括包含T细胞，B细胞和抗原引发的树突状细胞的细胞培养物。 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。

公开(公告)号：US08247226B2

公开(公告)日：2012-08-21

申请号：US13167115

申请日：2011-06-23

申请人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

发明人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

IPC分类号： C12N5/00 ,  C12N5/02

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。

公开(公告)号：US08003385B2

公开(公告)日：2011-08-23

申请号：US12707563

申请日：2010-02-17

申请人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

发明人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

IPC分类号： C12N5/06 ,  C12N5/02

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.

公开(公告)号：US08697371B2

公开(公告)日：2014-04-15

申请号：US13288401

申请日：2011-11-03

申请人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

发明人： William L. Warren ,  Donald Drake, III ,  Janice Moser ,  Inderpal Singh ,  Haifeng Song ,  Eric Mishkin ,  John G. Tew

IPC分类号： G01N33/567 ,  C12N5/00 ,  C12N5/08

CPC分类号： G01N33/5052 ,  C12N5/0635 ,  C12N5/0636 ,  C12N5/0639 ,  C12N5/0697 ,  C12N2500/90 ,  C12N2501/21 ,  C12N2502/1107 ,  C12N2502/1114 ,  C12N2502/1121 ,  C12N2502/28 ,  C12N2503/04 ,  C12N2510/04 ,  C12N2531/00 ,  C12N2533/50 ,  C12N2533/54 ,  C12N2535/10 ,  G01N33/505 ,  G01N33/5088

摘要： The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic 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。 人造免疫系统包括包含T细胞，B细胞和抗原引发的树突状细胞的细胞培养物。 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。

公开(公告)号：US08669105B2

公开(公告)日：2014-03-11

申请号：US13167131

申请日：2011-06-23

申请人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

发明人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Conan Li ,  Anatoly M. Kachurin ,  Russell Higbee ,  Heather Fahlenkamp ,  Eric Mishkin ,  William L. Warren

IPC分类号： C12N5/00 ,  C12N5/02

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。

公开(公告)号：US08003387B2

公开(公告)日：2011-08-23

申请号：US11642938

申请日：2006-12-21

申请人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Eric Mishkin ,  Anatoly M. Kachurin ,  Russell Higbee ,  Conan Li ,  William L. Warren ,  Heather Fahlenkamp

发明人： Selva Sukumar ,  Mohey Eldin M. El Shikh ,  John G. Tew ,  Guzman Sanchez-Schmitz ,  Donald Drake, III ,  Luis Mosquera ,  Eric Mishkin ,  Anatoly M. Kachurin ,  Russell Higbee ,  Conan Li ,  William L. Warren ,  Heather Fahlenkamp

IPC分类号： C12N5/08 ,  C12N5/00 ,  C12N5/02

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。

公开(公告)号：US07855074B2

公开(公告)日：2010-12-21

申请号：US11116234

申请日：2005-04-28

申请人： William L. Warren ,  Heather Fahlenkamp ,  Russell Higbee ,  Anatoly Kachurin ,  Conan Li ,  Mike Nguyen ,  Robert Parkhill ,  Guzman Sanchez-Schmitz ,  Darrell J. Irvine ,  Gwendalyn J. Randolph ,  Nir Hacohen ,  Bruce Torbett

发明人： William L. Warren ,  Heather Fahlenkamp ,  Russell Higbee ,  Anatoly Kachurin ,  Conan Li ,  Mike Nguyen ,  Robert Parkhill ,  Guzman Sanchez-Schmitz ,  Darrell J. Irvine ,  Gwendalyn J. Randolph ,  Nir Hacohen ,  Bruce Torbett

IPC分类号： C12N5/08

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。

公开(公告)号：US6140157A

公开(公告)日：2000-10-31

申请号：US129588

申请日：1998-08-05

申请人： William L. Warren ,  Karel J. R. Vanheusden ,  Daniel M. Fleetwood ,  Roderick A. B. Devine

发明人： William L. Warren ,  Karel J. R. Vanheusden ,  Daniel M. Fleetwood ,  Roderick A. B. Devine

IPC分类号： G11C11/22 ,  G11C13/04 ,  H01L21/30 ,  H01L29/792 ,  H01L21/00

CPC分类号： H01L21/263 ,  G11C11/22 ,  G11C13/04 ,  G11C13/048 ,  H01L21/3003 ,  H01L29/792

摘要： An electrically written memory element utilizing the motion of protons within a dielectric layer surrounded by layers on either side to confine the protons within the dielectric layer with electrode means attached to the surrounding layers to change the spatial position of the protons within the dielectric layer. The device is preferably constructed as a silicon-silicon dioxide-silicon layered structure with the protons being introduced to the structure laterally through the exposed edges of the silicon dioxide layer during a high temperature anneal in an atmosphere containing hydrogen gas. The device operates at low power, is preferably nonvolatile, is radiation tolerant, and is compatible with convention silicon MOS processing for integration with other microelectronic elements on the same silicon substrate. With the addition of an optically active layer, the memory element becomes an electrically written, optically read optical memory element.

摘要翻译： 一种电子写入的存储元件，其利用在由两侧上的层围绕的电介质层内的质子的运动，以将质子限制在电介质层内，电极装置连接到周围层，以改变电介质层内质子的空间位置。 该装置优选构造为硅 - 二氧化硅 - 硅层状结构，其中在包含氢气的气氛中的高温退火期间，质子通过二氧化硅层的暴露边缘横向引入该结构。 该器件以低功率工作，优选是非易失性的，具有耐辐射性，并且与常规硅MOS处理兼容，用于与同一硅衬底上的其它微电子元件集成。 通过添加光学活性层，存储元件变成电学写入的光学读取光学存储元件。