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21. 发明授权

US07771963B2 Methods for determining efficacy of chemotherapeutic agents 有权
标题翻译：确定化疗药效的方法
公开(公告)号：US07771963B2
公开(公告)日：2010-08-10
申请号：US12244463
申请日：2008-10-02
申请人： Paul L. Kornblith
发明人： Paul L. Kornblith
IPC分类号： C12Q1/24
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观地确定特定患者的最佳治疗或药剂。具体的方法创新，如组织样品制备技术使这种方法实际上和理论上有用。通过使细胞的均匀样品经受各种各样的活性剂（及其浓度），可以确定用于治疗特定患者的最有希望的药剂和浓度。

22. 发明授权

US07112415B2 Method of preparing cell cultures from biological specimens for assaying a response to an agent 有权
标题翻译：从生物标本制备细胞培养物以测定对试剂的反应的方法
公开(公告)号：US07112415B2
公开(公告)日：2006-09-26
申请号：US11073931
申请日：2005-03-08
申请人： Paul L. Kornblith
发明人： Paul L. Kornblith
IPC分类号： C12Q1/02
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated. The tissue sample technique of the present invention is also useful in assaying expression and/or secretion of various markers, factors or antigens present on or produced by the cultured cells for diagnostic purposes and for using such expression to monitor the applicability of certain candidate therapeutic or chemotherapeutic agents and the progress of treatment with those agents.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观识别。一个特别重要的组织样品制备技术是组织样品的粘性多细胞颗粒的初始制备。对于关于癌症治疗的测定，考虑了两阶段评估，其中研究给定抗癌剂的急性细胞毒性和长期抑制作用。本发明的组织样本技术还可用于测定出于诊断目的存在于培养细胞上或由培养细胞产生的各种标志物，因子或抗原的表达和/或分泌，并且用于使用这种表达来监测某些候选治疗剂或化学治疗剂和用这些药物治疗的进展。

23. 发明申请

US20050202411A1 Precise efficacy assay methods for active agents including chemotherapeutic agents 有权
标题翻译：包括化学治疗剂在内的活性剂的精确效力测定方法
公开(公告)号：US20050202411A1
公开(公告)日：2005-09-15
申请号：US11081827
申请日：2005-03-17
申请人： Paul Kornblith
发明人： Paul Kornblith
IPC分类号： G01N33/48 , A61K45/00 , A61P17/02 , A61P31/00 , A61P35/00 , A61P37/02 , C12N5/10 , G01N33/15 , G01N33/50 , G01N33/574 , C12Q1/00
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample, rather than enzymatically dissociated cell suspensions or preparations, for initial tissue culture monolayer preparation. With respect to the culturing of malignant cells, for example, it is believed (without any intention of being bound by the theory) that by maintaining the malignant cells within a multicellular particulate of the originating tissue, growth of the malignant cells themselves is facilitated versus the overgrowth of fibroblasts or other cells which tends to occur when suspended tumor cells are grown in culture. Practical monolayers of cells may thus be formed to enable meaningful screening of a plurality of treatments and/or agents. Growth of cells is monitored to ascertain the time to initiate the assay and to determine the growth rate of the cultured cells; sequence and timing of drug addition is also monitored and optimized. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观地确定特定患者的最佳治疗或药剂。具体的方法创新，如组织样品制备技术使这种方法实际上和理论上有用。一个特别重要的组织样品制备技术是用于初始组织培养单层制备的组织样品的粘性多细胞颗粒的初始制备，而不是酶解离的细胞悬浮液或制剂。关于恶性细胞的培养，例如，认为（不意在被理论束缚），通过将恶性细胞维持在原始组织的多细胞颗粒中，恶性细胞本身的生长有助于相对于当在培养物中培养悬浮的肿瘤细胞时倾向于发生的成纤维细胞或其它细胞的过度生长。因此，可以形成细胞的实用单层以使得能够有意义地筛选多个处理和/或试剂。监测细胞的生长以确定引发测定的时间并确定培养细胞的生长速率; 药物添加的顺序和时间也被监测和优化。通过使细胞的均匀样品经受各种各样的活性剂（及其浓度），可以确定用于治疗特定患者的最有希望的药剂和浓度。对于关于癌症治疗的测定，考虑了两阶段评估，其中研究给定抗癌剂的急性细胞毒性和长期抑制作用。

24. 发明申请

US20050202410A1 Precise efficacy assay methods for active agents inlcluding chemotherapeutic agents 有权
标题翻译：包括化学治疗剂的活性剂的精确效力测定方法
公开(公告)号：US20050202410A1
公开(公告)日：2005-09-15
申请号：US11073931
申请日：2005-03-08
申请人： Paul Kornblith
发明人： Paul Kornblith
IPC分类号： G01N33/48 , A61K45/00 , A61P17/02 , A61P31/00 , A61P35/00 , A61P37/02 , C12N5/10 , G01N33/15 , G01N33/50 , C12Q1/00
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated. The tissue sample technique of the present invention is also useful in assaying expression and/or secretion of various markers, factors or antigens present on or produced by the cultured cells for diagnostic purposes and for using such expression to monitor the applicability of certain candidate therapeutic or chemotherapeutic agents and the progress of treatment with those agents.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观识别。一个特别重要的组织样品制备技术是组织样品的粘性多细胞颗粒的初始制备。对于关于癌症治疗的测定，考虑了两阶段评估，其中研究给定抗癌剂的急性细胞毒性和长期抑制作用。本发明的组织样本技术还可用于测定出于诊断目的存在于培养细胞上或由培养细胞产生的各种标志物，因子或抗原的表达和/或分泌，并且用于使用这种表达来监测某些候选治疗剂或化学治疗剂和用这些药物治疗的进展。

25. 发明授权

US06900027B1 Method for preparing cell cultures from biological specimens for chemotherapeutic and other assays 失效
标题翻译：从化学治疗和其他测定的生物标本制备细胞培养物的方法
公开(公告)号：US06900027B1
公开(公告)日：2005-05-31
申请号：US09040161
申请日：1998-03-17
申请人： Paul L. Kornblith
发明人： Paul L. Kornblith
IPC分类号： G01N33/48 , A61K45/00 , A61P17/02 , A61P31/00 , A61P35/00 , A61P37/02 , C12N5/10 , G01N33/15 , G01N33/50 , C12Q1/02
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. The system includes the initial preparation of cohesive multicellular particulates of the tissue sample, rather than enzymatically dissociated cell suspensions or preparations, for initial tissue culture monolayer preparation. Practical monolayers of cells may thus be formed to enable meaningful screening of a plurality of treatments and/or agents. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观地确定特定患者的最佳治疗或药剂。该系统包括用于初始组织培养单层制备的组织样品的粘性多细胞颗粒的初始制备，而不是酶解离的细胞悬浮液或制剂。因此，可以形成细胞的实用单层以使得能够有意义地筛选多个处理和/或试剂。通过使细胞的均匀样品经受各种各样的活性剂（及其浓度），可以确定用于治疗特定患者的最有希望的药剂和浓度。对于关于癌症治疗的测定，考虑了两阶段评估，其中研究给定抗癌剂的急性细胞毒性和长期抑制作用。

26. 发明授权

US08236489B2 Chemo-sensitivity assays using tumor cells exhibiting persistent phenotypic characteristics 有权
标题翻译：使用表现出持久表型特征的肿瘤细胞的化学敏感性测定
公开(公告)号：US08236489B2
公开(公告)日：2012-08-07
申请号：US12622022
申请日：2009-11-19
申请人： Michael Gabrin , Stacey Brower , Sean McDonald , Holly Gallion , Payal Nanavati , Shara Dawn Rice , Anuja Chattopadhyay
发明人： Michael Gabrin , Stacey Brower , Sean McDonald , Holly Gallion , Payal Nanavati , Shara Dawn Rice , Anuja Chattopadhyay
IPC分类号： G01N33/574 , G01N33/577 , C12N5/02 , C12N5/06 , C12N5/09 , C12Q1/00
CPC分类号： G01N33/57407 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136
摘要： The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring the progression of an individual patient malignancy. The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring and for identifying cellular and secreted markers, for screening cells to detect phenotypic and genotypic drift and for predicting chemotherapeutic response of patient tumor cells to at least one therapeutic agent. The assays, methods, tools and systems discussed herein also represent an improved and unified system for monitoring and for screening multiple pharmaceutical agents for efficacy and long term effect as to a specific patient.
摘要翻译：本文讨论的测定，方法，工具和系统表示改进和统一的系统，用于监测个体患者恶性肿瘤的进展。本文讨论的测定，方法，工具和系统表示改进和统一的系统，用于监测和鉴定细胞和分泌标记物，用于筛选细胞以检测表型和基因型漂移，并用于预测患者肿瘤细胞对至少一种治疗剂的化疗反应。本文所讨论的测定法，方法，工具和系统也表示改进和统一的系统，用于监测和筛选多种药剂，用于特定患者的功效和长期效果。

27. 发明授权

US08058025B2 Methods for determining efficacy of chemotherapeutic agents 有权
标题翻译：确定化疗药效的方法
公开(公告)号：US08058025B2
公开(公告)日：2011-11-15
申请号：US12828665
申请日：2010-07-01
申请人： Paul L. Kornblith
发明人： Paul L. Kornblith
IPC分类号： C12Q1/24
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观地确定特定患者的最佳治疗或药剂。具体的方法创新，如组织样品制备技术使这种方法实际上和理论上有用。通过使细胞的均匀样品经受各种各样的活性剂（及其浓度），可以确定用于治疗特定患者的最有希望的药剂和浓度。

28. 发明申请

US20090042221A1 PRECISE EFFICACY ASSAY METHODS FOR ACTIVE AGENTS INCLUDING CHEMOTHERAPEUTIC AGENTS 有权
标题翻译：包括化学治疗剂在内的活性药剂的精确效能测定方法
公开(公告)号：US20090042221A1
公开(公告)日：2009-02-12
申请号：US12244463
申请日：2008-10-02
申请人： Paul L. KORNBLITH
发明人： Paul L. KORNBLITH
IPC分类号： G01N33/567
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample, rather than enzymatically dissociated cell suspensions or preparations, for initial tissue culture monolayer preparation. With respect to the culturing of malignant cells, for example, it is believed (without any intention of being bound by the theory) that by maintaining the malignant cells within a multicellular particulate of the originating tissue, growth of the malignant cells themselves is facilitated versus the overgrowth of fibroblasts or other cells which tends to occur when suspended tumor cells are grown in culture. Practical monolayers of cells may thus be formed to enable meaningful screening of a plurality of treatments and/or agents. Growth of cells is monitored to ascertain the time to initiate the assay and to determine the growth rate of the cultured cells; sequence and timing of drug addition is also monitored and optimized. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观地确定特定患者的最佳治疗或药剂。具体的方法创新，如组织样本制备技术使这种方法实际上和理论上有用。一个特别重要的组织样品制备技术是用于初始组织培养单层制备的组织样品的粘性多细胞颗粒的初始制备，而不是酶解离的细胞悬浮液或制剂。关于恶性细胞的培养，例如，认为（不意在被理论束缚），通过将恶性细胞维持在原始组织的多细胞颗粒中，恶性细胞本身的生长有助于相对于当在培养物中培养悬浮的肿瘤细胞时倾向于发生的成纤维细胞或其它细胞的过度生长。因此，可以形成细胞的实用单层以使得能够有意义地筛选多个处理和/或试剂。监测细胞的生长以确定引发测定的时间并确定培养细胞的生长速率; 药物添加的顺序和时间也被监测和优化。通过使细胞的均匀样品经受各种各样的活性剂（及其浓度），可以确定用于治疗特定患者的最有希望的药剂和浓度。对于关于癌症治疗的测定，考虑了两阶段评估，其中研究给定抗癌剂的急性细胞毒性和长期抑制作用。

29. 发明授权

US06933129B1 Method for culturing and assaying cells 失效
标题翻译：培养和测定细胞的方法
公开(公告)号：US06933129B1
公开(公告)日：2005-08-23
申请号：US09039957
申请日：1998-03-16
申请人： Paul L. Kornblith
发明人： Paul L. Kornblith
IPC分类号： G01N33/48 , A61K45/00 , A61P17/02 , A61P31/00 , A61P35/00 , A61P37/02 , C12N5/10 , G01N33/15 , G01N33/50 , C12Q1/02
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated. The tissue sample technique of the present invention is also useful in assaying expression and/or secretion of various markers, factors or antigens present on or produced by the cultured cells for diagnostic purposes and for using such expression to monitor the applicability of certain candidate therapeutic or chemotherapeutic agents and the progress of treatment with those agents.
摘要翻译：用于筛选多种候选治疗剂或化学治疗剂以用于特定患者的改进的系统，其中来自患者的组织样品被收获，培养和分别暴露于多种治疗和/或治疗剂，用于客观识别。一个特别重要的组织样品制备技术是组织样品的粘性多细胞颗粒的初始制备。对于关于癌症治疗的测定，考虑了两阶段评估，其中研究给定抗癌剂的急性细胞毒性和长期抑制作用。本发明的组织样本技术还可用于测定出于诊断目的存在于培养细胞上或由培养细胞产生的各种标志物，因子或抗原的表达和/或分泌，并且用于使用这种表达来监测某些候选治疗剂或化学治疗剂和用这些药物治疗的进展。

30. 发明授权

US06887680B2 Method for preparing cell cultures from biological specimens for chemotherapeutic and other assays 有权
公开(公告)号：US06887680B2
公开(公告)日：2005-05-03
申请号：US10205887
申请日：2002-07-26
申请人： Paul L. Kornblith
发明人： Paul L. Kornblith
IPC分类号： G01N33/48 , A61K45/00 , A61P17/02 , A61P31/00 , A61P35/00 , A61P37/02 , C12N5/10 , G01N33/15 , G01N33/50 , C12Q1/02
CPC分类号： G01N33/5044 , G01N33/5011 , G01N33/5014 , G01N2800/52
摘要： An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. One particularly important tissue sample preparation technique is the initial preparation of cohesive multicellular particulates of the tissue sample, rather than enzymatically dissociated cell suspensions or preparations, for initial tissue culture monolayer preparation. With respect to the culturing of malignant cells, for example, it is believed (without any intention of being bound by the theory) that by maintaining the malignant cells within a multicellular particulate of the originating tissue, growth of the malignant cells themselves is facilitated versus the overgrowth of fibroblasts or other cells which tends to occur when suspended tumor cells are grown in culture. Practical monolayers of cells may thus be formed to enable meaningful screening of a plurality of treatments and/or agents. Growth of cells is monitored to ascertain the time to initiate the assay and to determine the growth rate of the cultured cells; sequence and timing of drug addition is also monitored and optimized. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined. For assays concerning cancer treatment, a two-stage evaluation is contemplated in which both acute cytotoxic and longer term inhibitory effect of a given anti-cancer agent are investigated.

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