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公开(公告)号：US08088908B2
公开(公告)日：2012-01-03
申请号：US11432304
申请日：2006-05-10
申请人： Mark A. Sherman , Anna M. Wu , Robert E. Reiter
发明人： Mark A. Sherman , Anna M. Wu , Robert E. Reiter
IPC分类号： C07H21/04
CPC分类号： C07K16/3069 , A61K2039/505 , C07K2317/24 , C07K2317/565
摘要： Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer patients, making it an ideal target for cancer immunotherapy. Murine monoclonal antibody 1G8 binds to PSCA with nanomolar affinity, but its efficacy as a therapeutic agent is limited by the generation of a HAMA response. The present invention discloses humanized 1G8 antibodies in which the majority of the mouse-derived epitopes have been removed. These humanized antibodies bind PSCA with high affinity and specificity, and have been shown to reduce human bladder tumor take in a nude mouse model. These characteristics make the humanized antibodies of the present invention attractive agents for the treatment and detection of tumors expressing PSCA.
摘要翻译： 前列腺干细胞抗原（PSCA）在大多数前列腺癌患者中表达，使其成为癌症免疫治疗的理想靶标。 鼠单克隆抗体1G8以纳摩尔亲和力结合PSCA，但其作为治疗剂的功效受到HAMA反应的产生的限制。 本发明公开了大部分小鼠来源的表位已被除去的人源化1G8抗体。 这些人源化抗体以高亲和力和特异性结合PSCA，并已显示可以减少人膀胱肿瘤的裸鼠模型。 这些特征使得本发明的人源化抗体用于治疗和检测表达PSCA的肿瘤的吸引剂。
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公开(公告)号：US08404817B2
公开(公告)日：2013-03-26
申请号：US13308783
申请日：2011-12-01
申请人： Mark A. Sherman , Anna M. Wu , Robert E. Reiter
发明人： Mark A. Sherman , Anna M. Wu , Robert E. Reiter
IPC分类号： C12P21/08
CPC分类号： C07K16/3069 , A61K2039/505 , C07K2317/24 , C07K2317/565
摘要： Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer patients, making it an ideal target for cancer immunotherapy. Murine monoclonal antibody 1G8 binds to PSCA with nanomolar affinity, but its efficacy as a therapeutic agent is limited by the generation of a HAMA response. The present invention discloses humanized 1G8 antibodies in which the majority of the mouse-derived epitopes have been removed. These humanized antibodies bind PSCA with high affinity and specificity, and have been shown to reduce human bladder tumor take in a nude mouse model. These characteristics make the humanized antibodies of the present invention attractive agents for the treatment and detection of tumors expressing PSCA.
摘要翻译： 前列腺干细胞抗原（PSCA）在大多数前列腺癌患者中表达，使其成为癌症免疫治疗的理想靶标。 鼠单克隆抗体1G8以纳摩尔亲和力结合PSCA，但其作为治疗剂的功效受到HAMA反应的产生的限制。 本发明公开了大部分小鼠来源的表位已被除去的人源化1G8抗体。 这些人源化抗体以高亲和力和特异性结合PSCA，并已显示可以减少人膀胱肿瘤的裸鼠模型。 这些特征使得本发明的人源化抗体用于治疗和检测表达PSCA的肿瘤的吸引剂。
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公开(公告)号：US09701754B1
公开(公告)日：2017-07-11
申请号：US12788477
申请日：2010-05-27
CPC分类号： C07K16/30 , A61K39/39558 , A61K2039/505 , C07K16/00 , C07K16/3007 , C07K16/46 , C07K2317/626 , C07K2317/64 , C07K2317/90 , C07K2319/00
摘要： The present invention provides recombinant antibody fragments which include a variable domain which has been modified by the addition of a tail sequence to its C-terminal end. The tail sequence comprises a terminal cysteine residue and an amino acid spacer and does not substantially affect the fragment's target-binding affinity. The present invention also provides pharmaceutical compositions comprising the described antibody fragments and a pharmaceutically acceptable carrier and methods of delivering an agent to cells of interest in a subject using the fragments as delivery vehicles. The invention further provides compositions comprising the described antibody fragments for the in vitro detection and measurement of target molecules which bind to the fragments and method of determining the presence or amount of such targets in a biological sample by contacting the sample with such compositions.
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公开(公告)号：US20120283418A1
公开(公告)日：2012-11-08
申请号：US13554306
申请日：2012-07-20
IPC分类号： C07K16/00
CPC分类号： C07K16/30 , A61K39/39558 , A61K2039/505 , C07K16/00 , C07K16/3007 , C07K16/46 , C07K2317/626 , C07K2317/64 , C07K2317/90 , C07K2319/00
摘要： The present invention provides recombinant antibody fragments which include a variable domain which has been modified by the addition of a tail sequence to its C-terminal end. The tail sequence comprises a terminal cysteine residue and an amino acid spacer and does not substantially affect the fragment's target-binding affinity. The present invention also provides pharmaceutical compositions comprising the described antibody fragments and a pharmaceutically acceptable carrier and methods of delivering an agent to cells of interest in a subject using the fragments as delivery vehicles. The invention further provides compositions comprising the described antibody fragments for the in vitro detection and measurement of target molecules which bind to the fragments and method of determining the presence or amount of such targets in a biological sample by contacting the sample with such compositions.
摘要翻译： 本发明提供重组抗体片段，其包括通过向其C末端添加尾序列而被修饰的可变结构域。 尾序列包含末端半胱氨酸残基和氨基酸间隔基，并且基本上不影响片段的靶结合亲和力。 本发明还提供包含所述抗体片段和药学上可接受的载体的药物组合物，以及使用片段作为递送载体将试剂递送至受试者感兴趣的细胞的方法。 本发明还提供了包含所述抗体片段的组合物，用于体外检测和测量结合片段的靶分子，以及通过使样品与这些组合物接触来确定生物样品中这些靶的存在或量的方法。
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公开(公告)号：US07776330B2
公开(公告)日：2010-08-17
申请号：US11861093
申请日：2007-09-25
IPC分类号： A61K39/395 , C12P21/04 , C12P21/08 , C07K16/00
CPC分类号： C07K16/3007 , A61K2039/505 , C07K16/32 , C07K16/465 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/626 , C07K2317/92 , C12N15/1089 , G01N33/574
摘要： Embodiments of the present invention utilize a more efficient CDR grafting technique to generate humanized versions of the T84.66 antibody. The technique used to generate these antibodies utilizes crystallographic structural data to select an immunoglobulin framework having maximum structural overlap with a non-human donor molecule. This technique was used to develop humanized T84.66 antibodies exhibiting in vitro binding affinity and specificity for carcinoembryonic antigen (CEA) nearly identical to that of T84.66 and the ability to specifically target tumors expressing CEA in vivo.
摘要翻译： 本发明的实施方案利用更有效的CDR移植技术来产生人源化版本的T84.66抗体。 用于产生这些抗体的技术利用晶体结构数据来选择与非人供体分子具有最大结构重叠的免疫球蛋白框架。 该技术用于开发显示与T84.66几乎完全相同的癌胚抗原（CEA）的体外结合亲和性和特异性的人源化T84.66抗体，并且具体靶向体内表达CEA的肿瘤的能力。
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公开(公告)号：US09765155B2
公开(公告)日：2017-09-19
申请号：US13554306
申请日：2012-07-20
IPC分类号： A61K39/00 , C07K16/46 , C07K16/00 , C07K16/30 , A61K39/395
CPC分类号： C07K16/30 , A61K39/39558 , A61K2039/505 , C07K16/00 , C07K16/3007 , C07K16/46 , C07K2317/626 , C07K2317/64 , C07K2317/90 , C07K2319/00
摘要： The present invention provides recombinant antibody fragments which include a variable domain which has been modified by the addition of a tail sequence to its C-terminal end. The tail sequence comprises a terminal cysteine residue and an amino acid spacer and does not substantially affect the fragment's target-binding affinity. The present invention also provides pharmaceutical compositions comprising the described antibody fragments and a pharmaceutically acceptable carrier and methods of delivering an agent to cells of interest in a subject using the fragments as delivery vehicles. The invention further provides compositions comprising the described antibody fragments for the in vitro detection and measurement of target molecules which bind to the fragments and method of determining the presence or amount of such targets in a biological sample by contacting the sample with such compositions.
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公开(公告)号：US07273608B2
公开(公告)日：2007-09-25
申请号：US11077978
申请日：2005-03-11
IPC分类号： A61K39/00
CPC分类号： C07K16/3007 , A61K2039/505 , C07K16/32 , C07K16/465 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/626 , C07K2317/92 , C12N15/1089 , G01N33/574
摘要： Embodiments of the present invention utilize a more efficient CDR grafting technique to generate humanized versions of the T84.66 antibody. The technique used to generate these antibodies utilizes crystallographic structural data to select an immunoglobulin framework having maximum structural overlap with a non-human donor molecule. This technique was used to develop humanized T84.66 antibodies exhibiting in vitro binding affinity and specificity for carcinoembryonic antigen (CEA) nearly identical to that of T84.66 and the ability to specifically target tumors expressing CEA in vivo.
摘要翻译： 本发明的实施方案利用更有效的CDR移植技术来产生人源化版本的T84.66抗体。 用于产生这些抗体的技术利用晶体结构数据来选择与非人供体分子具有最大结构重叠的免疫球蛋白框架。 该技术用于开发显示与T84.66几乎完全相同的癌胚抗原（CEA）的体外结合亲和性和特异性的人源化T84.66抗体，并且具体靶向体内表达CEA的肿瘤的能力。
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公开(公告)号：US5351195A
公开(公告)日：1994-09-27
申请号：US30859
申请日：1993-03-12
申请人： Mark A. Sherman
发明人： Mark A. Sherman
IPC分类号： G05B19/418 , G06Q10/00 , G06F15/46
CPC分类号： G05B19/41885 , G06Q10/04 , G06Q10/06 , G05B2219/31385 , G05B2219/31386 , G05B2219/31388 , G05B2219/32237 , G05B2219/32262 , G05B2219/32264 , G05B2219/32265 , G05B2219/32364 , G05B2219/42137 , Y02P90/20 , Y02P90/26
摘要： The batch size of materials required for each process within a workstation based on a given shipment schedule, as well as the values of several other workstation variables that are determinative of workstation and factory performance are determined. With this information, the user of the invention may schedule production for the factory or spot and prioritize workstations requiring the most improvement, and determine the character and quantity of improvement.
摘要翻译： 基于给定的出货计划，工作站内每个过程所需的材料的批量大小以及确定工作站和工厂性能的其他几个工作站变量的值被确定。 利用该信息，本发明的用户可以为工厂或现场安排生产并优先处理需要最大改进的工作站，并确定改进的特性和数量。
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公开(公告)号：US5195041A
公开(公告)日：1993-03-16
申请号：US384292
申请日：1989-07-24
申请人： Michael L. George , Mark A. Sherman
发明人： Michael L. George , Mark A. Sherman
IPC分类号： G05B19/418 , G06Q10/04 , G06Q10/06
CPC分类号： G06Q10/04 , G05B19/41885 , G06Q10/06 , G05B2219/31385 , G05B2219/31386 , G05B2219/31388 , G05B2219/32237 , G05B2219/32262 , G05B2219/32264 , G05B2219/32265 , G05B2219/32364 , G05B2219/42137 , Y02P90/20 , Y02P90/26
摘要： The invention determines the batch size of materials required for each process within a workstation based on a given shipment schedule, as well as the values of several other workstation variables that are determinative of workstation and factory performance. With this information, the user of the invention may schedule production for the factory or spot and prioritize workstations requiring the most improvement, and determine the character and quantity of improvement.
摘要翻译： 本发明基于给定的出货计划确定工作站内每个过程所需的材料的批量大小，以及确定工作站和工厂性能的其他几个工作站变量的值。 利用该信息，本发明的用户可以为工厂或现场安排生产并优先处理需要最大改进的工作站，并确定改进的特性和数量。
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10.发明授权Method for determining and eliminating the drivers of non-value added cost due to product complexity and process parameters 有权确定和消除由于产品复杂性和工艺参数导致的非增值成本驱动因素的方法公开(公告)号：US06993492B2
公开(公告)日：2006-01-31
申请号：US10705498
申请日：2003-11-10
IPC分类号： G06F17/60
CPC分类号： G06Q10/06 , G06Q10/06375 , G06Q10/087 , G06Q30/0202
摘要： A method for measuring and reducing the cost of complexity in producing products or providing a service by comparing selected non-value added steps in the manufacturing or service process with the number of different products or services provided, so as to provide the non-value added cost of the product or service for various selected complexities. The number of products required to be processed or held in inventory for a particular demand, or the number of different specific services required for a particular demand of the service is determined by comparing the number of different product part numbers, or service categories offered, with selected non-value added steps in the respective processes. Mathematical analyses are derived from equations of motion of process improvement including the first derivative of process velocity.
摘要翻译： 一种通过将制造或服务过程中选定的非增值步骤与所提供的不同产品或服务的数量进行比较来测量和降低生产产品或提供服务的复杂性成本的方法，以便提供非附加值 针对各种复杂性的产品或服务的成本。 通过将提供的不同产品部件号或提供的服务类别的数量与所提供的服务类别的数量进行比较，确定针对特定需求需要处理或保存在库存中的产品数量，或服务的特定需求所需的不同特定服务的数量 在各个进程中选择的非增值步骤。 数学分析得自流程改进运动方程，包括过程速度的一阶导数。
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