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1. 发明申请

WO2006054991A1 MAGNETIC ENRICHMENT OF CIRCULATING CELLS, FRAGMENTS AND DEBRIS FOR ENABLING HTS PROTEOMICS AND GENOMICS IN DISEASE DETECTION 审中-公开
标题翻译：循环细胞的磁性增殖，用于启动HTS预防和疾病感染的基因组的片段和修饰
公开(公告)号：WO2006054991A1
公开(公告)日：2006-05-26
申请号：PCT/US2004/038608
申请日：2004-11-17
申请人： IMMUNIVEST CORPORATION , DOYLE, Gerald, V. , O'HARA, Shawn, Mark , RUTNER, Herman
发明人： DOYLE, Gerald, V. , O'HARA, Shawn, Mark , RUTNER, Herman
IPC分类号： G01N33/574 , G01N33/567 , G01N33/566 , B03C1/00 , C07K16/00
CPC分类号： G01N33/574 , G01N33/5091
摘要： The methods and reagents described in this invention are used to analyze circulating tumor cells, clusters, fragments, and debris. Analysis is performed with a number of platforms, including flow cytometry, CellSpotter TM fluorescent microscopy imaging andmass spectrometric profiling. In addition to analyzing and enumerating morphologicaly classified cells by imaging, the presence of damaged cells and derived debris in magnetically enriched specimens has been shown to be an important “smoking gun” indicator of demised tumor cells. Described herein are improved methods to screen, diagnose and monitor disease based on intact circulating rare cells and associated fragments or debris. The present invention incorporates proteomic and genomic profiling of cellular debris in cancer cell analysis, either complementary to or independent of image cytometry. The technology provides diagnosis and prognostic tools in diseases such as cancer that incorporate not only detection and quantitation of intact circulating cells but also of cellular fragments and debris that bear generic cytoskeletal and/or tumor-specific markers. The presence of such markers reflects immune function in early disease and/or therapeutic effectiveness in later stages.
摘要翻译：本发明描述的方法和试剂用于分析循环肿瘤细胞，簇，碎片和碎片。使用许多平台进行分析，包括流式细胞术，CellSpotter TM荧光显微镜成像和质谱分析。除了通过成像分析和列举形态分类的细胞之外，磁性富集标本中损伤的细胞和衍生碎片的存在已经被证明是消除肿瘤细胞的重要的“吸烟枪”指标。本文描述了基于完整的循环稀有细胞和相关片段或碎片筛选，诊断和监测疾病的改进方法。本发明将细胞碎片的蛋白质组学和基因组分析结合在癌细胞分析中，与图像细胞计数的补充或独立。该技术在诸如癌症的疾病中提供了诊断和预后工具，其不仅包括完整的循环细胞的检测和定量，而且还包含具有通用细胞骨架和/或肿瘤特异性标志物的细胞碎片和碎片。这种标志物的存在反映早期疾病中的免疫功能和/或后期阶段的治疗有效性。

2. 发明申请

WO2006130737A1 A METHOD FOR ASSESSING METASTATIC CARCINOMAS FROM CIRCULATING ENDOTHELIAL CELLS AND DISSEMINATED TUMOR CELLS 审中-公开
标题翻译：从循环内皮细胞和分离的肿瘤细胞评估分化性癌的方法
公开(公告)号：WO2006130737A1
公开(公告)日：2006-12-07
申请号：PCT/US2006/021196
申请日：2006-06-01
申请人： IMMUNIVEST CORPORATION , CONNELLY, Mark, Carle , DOYLE, Gerald, V. , RAO, Galla, Chandra , TERSTAPPEN, Leon, W., M., M.
发明人： CONNELLY, Mark, Carle , DOYLE, Gerald, V. , RAO, Galla, Chandra , TERSTAPPEN, Leon, W., M., M.
IPC分类号： G06F19/00
CPC分类号： C12Q1/6886 , C12Q2600/106
摘要： A method for assessing cancer in test subjects is described based upon enumeration of circulating endothelial cells and/or disseminated tumor cells in a test subject. This method is used to quantify disseminated tumor cells. Correlations with circulating tumor cells provides prognostic information with high accuracy in assessing the risk of recurrence in patients with primary breast cancer.
摘要翻译：基于在测试对象中循环内皮细胞和/或扩散的肿瘤细胞的计数来描述用于评估测试受试者中的癌症的方法。该方法用于量化弥散性肿瘤细胞。与循环肿瘤细胞的相关性在准确评估原发性乳腺癌患者复发风险方面提供预后信息。

3. 发明申请

WO2006104474A2 A METHOD FOR PREDICTING PROGRESSION FREE AND OVERALL SURVIVAL AT EACH FOLLOW-UP TIME POINT DURING THERAPY OF METASTATIC BREAST CANCER PATIENTS USING CIRCULATING TUMOR CELLS 审中-公开
标题翻译：在使用循环肿瘤细胞的成人乳腺癌患者治疗期间的每个后续时间点上预测免疫进展和整体存活的方法
公开(公告)号：WO2006104474A2
公开(公告)日：2006-10-05
申请号：PCT/US2005/008602
申请日：2005-03-14
申请人： IMMUNIVEST CORPORATION , ALLARD, Jeffrey, W. , DOYLE, Gerald, V. , HAYES, Daniel, F. , MILLER, Michael, Craig , TERSTAPPEN, Leon, W., M., M.
发明人： ALLARD, Jeffrey, W. , DOYLE, Gerald, V. , HAYES, Daniel, F. , MILLER, Michael, Craig , TERSTAPPEN, Leon, W., M., M.
IPC分类号： C12Q1/68
CPC分类号： G01N33/574
摘要： A cancer test having prognostic utility in predicting time to disease progression, overall survival, and response to therapy in patients with MBC based upon the presence and number of CTC’s. The Cell Spotter® System is used to enumerate CTC’s in blood. The system immunomagnetically concentrates epithelial cells, fluorescently labels the cells and identifies and quantifies CTC’s. The absolute number of CTC’s detected in the peripheral blood tumor load is, in part, a factor in prediction of survival, time to progression, and response to therapy. The mean time to survival of patients depended upon a threshold number of (5) CTC'’ per 7.5 ml of blood. Detection of CTC’s in metastatic cancer represents a novel prognostic factor in patients with metastatic cancers, suggests a biological role for the presence of tumor cells in the blood, and indicates that the detection of CTC’s could be considered an appropriate surrogate marker for prospective therapeutic clinical trials.
摘要翻译：基于CTC的存在和数量，一种具有预测用于预测疾病进展时间，总体存活和对MBC患者的治疗反应的癌症测试。 CellSpotter®系统用于列举血液中的四氯化碳。该系统免疫磁性浓缩上皮细胞，荧光标记细胞，识别和定量CTC。在外周血肿瘤负荷中检测到的四氯化碳的绝对数量部分是预测生存期，进展时间和治疗反应的因素。患者生存的平均时间取决于每7.5毫升血液的阈值数（5）CTC“。在转移性癌症中检测CTC代表转移癌患者的新型预后因素，表明血液中肿瘤细胞存在的生物学作用，并且表明CTC检测可被认为是前瞻性治疗性临床试验的适当替代标记。

4. 发明申请

WO2006020936A2 A METHOD FOR ASSESSING DISEASE STATES BY PROFILE ANALYSIS OF ISOLATED CIRCULATING ENDOTHELIAL CELLS 审中-公开
标题翻译：通过剖析分离的循环内皮细胞的分析来评估疾病状态的方法
公开(公告)号：WO2006020936A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/028862
申请日：2005-08-12
申请人： IMMUNIVEST CORPORATION , CONNELLY, Mark, Carle , DOYLE, Gerald, V. , RAO, Galla, Chandra , TERSTAPPEN, Leon, W., M., M.
发明人： CONNELLY, Mark, Carle , DOYLE, Gerald, V. , RAO, Galla, Chandra , TERSTAPPEN, Leon, W., M., M.
IPC分类号： C12Q1/00
CPC分类号： G01N33/6893 , G01N2800/32
摘要： Elevated number of Circulating Endothelial Cells (CEC) have been implicated in disease conditions associated with the formation or destruction of blood vessels such as acute coronary syndrome, thrombocytopenic purpura, sickle cell disease, sepsis, lupus, nephrotic syndromes, rejection of organ transplants, surgical trauma and cancer. This invention provides a method for assessing the levels of CEC which vary between different studies using a sensitive enrichment, imaging, and enumberation analysis. CD146 is one of the most specific endotheliumassociated cell-surface antigens which can be used in image cytometry. CEC analysis provides an essential tool in prognostic/diagnostic evaluation in the clinic.
摘要翻译：循环内皮细胞数量增加已涉及与血管形成或破坏相关的疾病状况，如急性冠状动脉综合征，血小板减少性紫癜，镰状细胞病，败血症，狼疮，肾病综合征，器官移植排斥，外科手术创伤和癌症。本发明提供了一种用于评估使用敏感浓缩，成像和启发分析的不同研究之间变化的CEC水平的方法。 CD146是可用于图像细胞计数的最具体的内皮细胞相关细胞表面抗原之一。 CEC分析为诊所的预后/诊断评估提供了重要的工具。

5. 发明申请

WO2008063371A2 IMAGING OF ACTIVATED VASCULAR ENDOTHELIUM USING IMMUNOMAGNETIC MRI CONTRAST AGENTS 审中-公开
标题翻译：使用免疫组化MRI对比剂激活血管内皮细胞的成像
公开(公告)号：WO2008063371A2
公开(公告)日：2008-05-29
申请号：PCT/US2007/023048
申请日：2007-11-01
申请人： IMMUNIVEST CORPORATION , DOYLE, Gerald, V.
发明人： DOYLE, Gerald, V.
IPC分类号： A61K49/16
CPC分类号： A61K49/1875 , A61K49/16 , A61K49/1869 , B82Y5/00
摘要： lmmunomagnetic nanoparticles are used as a contrast agent for enhancing medical diagnostic imaging such as magnetic resonance imaging (MRI). The present invention is directed to methods of making targeted MRI contrast agents from immunomagnetic particles, and to methods of using such MRI contrast agents. Typically, such targeted MRI contrast agents provide enhanced relaxivity, improved signal-to-noise, targeting ability, and resistance to agglomeration. Methods of making such MRI contrast agents typically afford better control over particle size, and methods of using such MRI contrast agents typically can afford enhanced blood clearance rates and distribution. The ability to use the contrast agents im MRI provides a tool in the diagnosis and treatment of several disease states.
摘要翻译：使用无磁性纳米粒子作为增强医学诊断成像如磁共振成像（MRI）的造影剂。本发明涉及从免疫磁性颗粒制备靶向MRI造影剂的方法，以及使用这种MRI造影剂的方法。通常，这种靶向MRI造影剂提供增强的舒张度，改善的信噪比，靶向能力和抵抗聚集。制备这种MRI造影剂的方法通常能够更好地控制粒度，并且使用这种MRI造影剂的方法通常可以提供增强的血液清除率和分布。使用造影剂im MRI的能力提供了诊断和治疗几种疾病状态的工具。

6. 发明申请

WO2010047682A1 MONITORING SERIAL CHANGS IN CIRCULATING BREAST CANCER CELLS IN MICE 审中-公开
标题翻译：监测循环乳腺癌细胞系列的变化
公开(公告)号：WO2010047682A1
公开(公告)日：2010-04-29
申请号：PCT/US2008/080430
申请日：2008-10-20
申请人： VERIDEX, LLC , DOYLE, Gerald, V.
发明人： DOYLE, Gerald, V.
IPC分类号： G01N33/574
CPC分类号： G01N33/57492
摘要： The CellTracks® System provides a system to enumerate CTCs in blood. The system immunomagnetically concentrates epithelial cells, fluorescently labels the cells and identifies and quantifies CTCs. The absolute number of CTCs detected in the peripheral blood tumor load is, in part, a factor in prediction of survival, time to progression, and response to therapy. Pre-clinical studies of circulating tumor cells (CTCs) have been limited by the inability to repetitively monitor CTCs in animal models. The present invention provides a method to enumerate CTCs in blood samples obtained from living mice, using a protocol similar to an in vitro diagnostic system for quantifying CTCs in patients. Accordingly, this technology can be adapted for serial monitoring of CTCs in mouse xenograft tumor models of human breast cancer.
摘要翻译： CellTracks®系统提供了一个系统来列举血液中的四氯化碳。该系统免疫磁性浓缩上皮细胞，荧光标记细胞并识别和量化CTC。在外周血肿瘤负荷中检测到的CTC的绝对数量部分地是预测存活时间，进展时间和对治疗反应的因素。循环肿瘤细胞（CTC）的临床前研究受到动物模型中不能重复监测CTC的限制。本发明提供了一种使用类似于用于定量患者中的CTC的体外诊断系统的方案来列举从活小鼠获得的血液样品中的CTC的方法。因此，该技术可适用于人类乳腺癌小鼠异种移植肿瘤模型中CTC的连续监测。

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