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1. 发明申请

US20120219982A1 METHODS FOR SELECTING ACTIVE AGENTS FOR CANCER TREATMENT 审中-公开
标题翻译：选择活性剂用于癌症治疗的方法
公开(公告)号：US20120219982A1
公开(公告)日：2012-08-30
申请号：US13461079
申请日：2012-05-01
申请人： Zhibao Mi , Dave Gingrich , Mike Gabrin
发明人： Zhibao Mi , Dave Gingrich , Mike Gabrin
IPC分类号： C12Q1/02
CPC分类号： G01N33/5011 , G01N33/57415
摘要： The present invention provides methods for individualizing chemotherapy, and particularly methods for individualizing neoadjuvant chemotherapy. The present invention provides methods for predicting a cancer patient's response to neoadjuvant chemotherapy, including assessing the probability of a positive response upon treatment with candidate agents prior to surgery. In various aspects, the invention involves culturing a monolayer of malignant cells from an explant of a patient's biopsy specimen, such as a transcutaneous biopsy-sized specimen, and testing the malignant cells for resistance or sensitivity to one or a plurality of candidate agents for neoadjuvant therapy. In other aspects, the invention provides methods for accurately scoring and interpreting such assays, and discloses in vitro chemoresponse results that are predictive of a patient's pathological complete response (pCR) upon receiving the corresponding treatment regimen.
摘要翻译：本发明提供个体化化疗的方法，特别是个体化新辅助化疗的方法。本发明提供了预测癌症患者对新辅助化疗的反应的方法，包括评估在手术前用候选药物治疗时的阳性反应的可能性。在各个方面，本发明涉及从患者活组织检查样本例如经皮活组织检查大小的标本的外植体中培养单层恶性细胞，并测试恶性细胞对一种或多种新辅助药物的候选药物的抗性或敏感性治疗。在其他方面，本发明提供了用于准确评分和解释这些测定的方法，并且公开了在接受相应的治疗方案时预测患者病理学完全反应（pCR）的体外化学反应结果。

2. 发明申请

US20110238322A1 METHODS OF SIMULATING CHEMOTHERAPY FOR A PATIENT 审中-公开
标题翻译：模拟患者化疗的方法
公开(公告)号：US20110238322A1
公开(公告)日：2011-09-29
申请号：US13127337
申请日：2009-11-03
申请人： Nan Song
发明人： Nan Song
IPC分类号： G06F19/00
CPC分类号： G16H50/50 , G01N33/5011 , G01N33/502 , G01N33/574 , G01N2800/52 , G01N2800/7028 , G06F19/3481
摘要： The present invention provides methods for predicting or modeling a chemotherapy outcome for a given patient The method produces chemoresponse data, and presents the chemoresponse data in a clinically meaningful context such that the data can be meaningfully interpreted and evaluated in a clinical context The method of the invention involves correlating in vitro chemoresponse results for a particular patient with historical treatment outcomes Where a population of historical outcomes are matched to the patient by one or more clinical variables and such outcomes are matched to a potential treatment by the in vitro efficacy of the agent received, a meaningful simulation of the potential treatment for the patient can be constructed Simulations, such as survival curves, for a plurality of potential treatments may be generated and compared to contrast the estimated outcomes for several potential treatments, thereby providing the information desirable to design an individualized treatment regimen.
摘要翻译：本发明提供了用于预测或建模给定患者的化疗结果的方法。该方法产生化学响应数据，并在临床有意义的上下文中呈现化学反应数据，使得可以在临床上下文中有意义地解释和评估数据。发明涉及将特定患者的体外化学反应结果与历史治疗结果相关联，其中历史结果的群体通过一个或多个临床变量与患者匹配，并且这些结果与接受的药剂的体外功效的潜在治疗相匹配可以构建对患者的潜在治疗的有意义的模拟可以产生用于多个潜在治疗的模拟，例如存活曲线，并将其进行比较以对比几个潜在治疗的估计结果，从而提供所需的信息来设计个性化治疗 gimen

3. 发明申请

US20110130302A1 BIOLOGICAL PATHWAYS ASSOCIATED WITH CHEMOTHERAPY OUTCOME FOR BREAST CANCER 审中-公开
标题翻译：与乳腺癌化疗相关的生物学途径
公开(公告)号：US20110130302A1
公开(公告)日：2011-06-02
申请号：US12957608
申请日：2010-12-01
申请人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
发明人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
IPC分类号： C40B30/04 , C12Q1/68 , C40B40/06
CPC分类号： C12Q1/6886 , C12Q2600/106
摘要： The present invention provides methods for preparing drug response and/or resistance profiles for breast tumor specimens, or cells derived therefrom. The drug response and/or resistance profiles are useful for determining effective chemotherapeutic agents for treatment of the tumor or cell to thereby individualize patient therapy. In other aspects, the invention provides a method for identifying a pathway or gene expression signature indicative of a breast cancer cell's sensitivity to a chemotherapeutic agent, which is useful for identifying a population response rate, or patient sub-population likely to respond to the drug candidate.
摘要翻译：本发明提供了用于制备用于乳腺肿瘤标本或由其衍生的细胞的药物反应和/或抗性谱的方法。药物反应和/或抗性谱可用于确定用于治疗肿瘤或细胞的有效化学治疗剂，从而个体化患者治疗。在其它方面，本发明提供了一种用于鉴定指示乳腺癌细胞对化学治疗剂的敏感性的途径或基因表达特征的方法，其可用于鉴定群体应答率，或可能对药物有反应的患者亚群候选人。

4. 发明申请

US20110129822A1 MULTI DRUG RESPONSE MARKERS FOR BREAST CANCER CELLS 审中-公开
标题翻译：多种药物对乳腺癌细胞的反应标记
公开(公告)号：US20110129822A1
公开(公告)日：2011-06-02
申请号：US12957604
申请日：2010-12-01
申请人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
发明人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/158
摘要： The present invention provides methods for preparing a gene expression profile of a breast cancer cell, tumor, or cell line, where the gene expression profile may be evaluated for one or more gene expression signatures indicative of multidrug resistance. The signature may be indicative of resistance to one or more chemotherapeutic agents selected from a Taxol (e.g., Docetaxel or Paclitaxel), an antibiotic (e.g., Doxorubicin or Epirubicin), an antimetabolite (e.g., Fluorouracil and/or Gemcitabine), and an alkylating agent (e.g., Cyclophosphamide). Generally, the gene expression profile contains the level of expression for a plurality of genes listed in FIGS. 3, 4, and/or 5. Gene expression profiles for evaluating multidrug resistance for ER positive and ER negative breast cancers are also provided.
摘要翻译：本发明提供了制备乳腺癌细胞，肿瘤或细胞系的基因表达谱的方法，其中基因表达谱可被评估表示多药耐药性的一种或多种基因表达特征。签名可以指示对一种或多种选自紫杉醇（例如多西紫杉醇或紫杉醇），抗生素（例如多柔比星或表柔比星），抗代谢药（例如氟尿嘧啶和/或吉西他滨）和化学治疗剂药剂（如环磷酰胺）。通常，基因表达谱包含图1和2中列出的多个基因的表达水平。还提供了评估ER阳性和ER阴性乳腺癌多药耐药性的基因表达谱。

5. 发明申请

US20100331210A1 METHODS AND SYSTEMS FOR EVALUATING THE SENSITIVITY OR RESISTANCE OF TUMOR SPECIMENS TO CHEMOTHERAPEUTIC AGENTS 审中-公开
标题翻译：用于评估肿瘤标本对化学治疗剂的敏感性或抗性的方法和系统
公开(公告)号：US20100331210A1
公开(公告)日：2010-12-30
申请号：US12791425
申请日：2010-06-01
申请人： Michael Gabrin , Kui Shen , Nan Song , Zhenyu Ding , David Gingrich
发明人： Michael Gabrin , Kui Shen , Nan Song , Zhenyu Ding , David Gingrich
IPC分类号： C40B30/06 , C12Q1/68 , C40B40/06
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： The present invention provides methods, systems, and kits for evaluating the sensitivity and/or resistance of tumor specimens to one or a combination of chemotherapeutic agents. Particularly, the invention provides malignant cell gene signatures that are predictive of a tumor's response to candidate chemotherapeutic regimens.
摘要翻译：本发明提供了用于评估肿瘤标本对化学治疗剂的一种或组合的敏感性和/或抗性的方法，系统和试剂盒。特别地，本发明提供可预测肿瘤对候选化疗方案的反应的恶性细胞基因特征。

6. 发明申请

US20100330613A1 METHODS FOR DETERMINING EFFICACY OF CHEMOTHERAPEUTIC AGENTS 有权
标题翻译：用于测定化学药剂效能的方法
公开(公告)号：US20100330613A1
公开(公告)日：2010-12-30
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： C12Q1/06 , 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. 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。

7. 发明申请

US20100311084A1 METHODS FOR PREDICTING A PATIENT'S RESPONSE TO EGFR INHIBITORS 审中-公开
标题翻译：方法预防患者对EGFR抑制剂的反应
公开(公告)号：US20100311084A1
公开(公告)日：2010-12-09
申请号：US12795286
申请日：2010-06-07
申请人： Stacey Brower , Shara D. Rice , Theresa R. Cassino , Lahari Sakhamuri , Heather M. Buechel , Lauren M. Hancher
发明人： Stacey Brower , Shara D. Rice , Theresa R. Cassino , Lahari Sakhamuri , Heather M. Buechel , Lauren M. Hancher
IPC分类号： G01N33/574
CPC分类号： G01N33/5091 , G01N33/574 , G01N2333/485 , G01N2800/52
摘要： The present invention provides methods for individualizing chemotherapy for cancer treatment, and particularly for evaluating a patient's responsiveness to one or more epidermal growth factor receptor (EGFR) inhibitors prior to treatment with such agents. Particularly, the invention provides an in vitro chemoresponse assay for predicting a patient's response to a monoclonal EGFR antibody, such as cetuximab. The method generally comprises culturing malignant cells from a patient's specimen (e.g., biopsy specimen), contacting the cultured cells with a monoclonal EGFR antibody that is a candidate treatment for the patient, and evaluating the cultured cells for a response to the drug. In certain embodiments, monolayer(s) of malignant cells are cultured from explants prepared by mincing tumor tissue, and the cells of the monolayer are suspended and plated for chemosenstivity testing. The in vitro response to the drug as determined by the method of the invention is correlative with the patient's in vivo response upon receiving the monoclonal EGFR antibody during chemotherapeutic treatment (e.g., in combination with other standardized or individualized chemotherapeutic regimen).
摘要翻译：本发明提供了用于个体化癌症治疗化学疗法的方法，特别是用于评估患者在用这些药物治疗之前对一种或多种表皮生长因子受体（EGFR）抑制剂的反应性。特别地，本发明提供了用于预测患者对单克隆EGFR抗体如西妥昔单抗的应答的体外化学应答测定。该方法通常包括从患者标本（例如活检标本）培养恶性细胞，使培养的细胞与作为患者候选治疗的单克隆EGFR抗体接触，并评价培养细胞对药物的应答。在某些实施方案中，从通过切割肿瘤组织制备的外植体培养恶性细胞的单层，并将单层细胞悬浮并铺板以进行化学敏感性测试。通过本发明的方法确定的对药物的体外应答与在化疗期间接受单克隆EGFR抗体（例如，与其他标准化或个体化化学治疗方案组合）时患者体内应答相关。

8. 发明申请

US20100143948A1 CHEMO-SENSITIVITY ASSAYS USING TUMOR CELLS EXHIBITING PERSISTENT PHENOTYPIC CHARACTERISTICS 有权
标题翻译：使用肿瘤细胞的化学敏感性测定显示出不同的PHENOTYPIC特性
公开(公告)号：US20100143948A1
公开(公告)日：2010-06-10
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
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。

9. 发明授权

US07678552B2 Method for selecting therapeutic agents for cancer treatment 有权
标题翻译：选择癌症治疗药物的方法
公开(公告)号：US07678552B2
公开(公告)日：2010-03-16
申请号：US12208076
申请日：2008-09-10
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. 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。

10. 发明授权

US07642048B2 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：US07642048B2
公开(公告)日：2010-01-05
申请号：US11785984
申请日：2007-04-23
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： C12N5/02 , C12N5/06 , C12Q1/00 , C12N5/08
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。

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