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1. 发明授权

US07402399B2 Receptor tyrosine kinase signaling pathway analysis for diagnosis and therapy 有权
标题翻译：受体酪氨酸激酶信号通路分析诊断和治疗
公开(公告)号：US07402399B2
公开(公告)日：2008-07-22
申请号：US10963855
申请日：2004-10-13
申请人： Ali Mukherjeei , Mengxiang Tang , Harprit S. Pannu , Po-Ying Chan-Hui , Sharat Singh
发明人： Ali Mukherjeei , Mengxiang Tang , Harprit S. Pannu , Po-Ying Chan-Hui , Sharat Singh
IPC分类号： G01N33/53 , G01N33/533
CPC分类号： G01N33/74 , G01N33/5041 , G01N33/57492 , G01N33/6893 , G01N2333/485
摘要： The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明提供了通过测量受体二聚化和RTK途径特征的蛋白质 - 蛋白复合物或活化的效应蛋白的相对量来确定细胞样品或患者样品中受体酪氨酸激酶（RTK）途径的激活状态的方法。本发明还提供了使用这种状态信息来选择对途径特异性药物有反应的患者的方法，更具体地，涉及用于测量ErbB受体和受体复合物的方法，并使用这些信息来选择对ErbB途径特异性药物有反应的患者。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物组来实现，所述可释放分子标签对于在RTK活化中形成的一种或多种复合物的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

2. 发明申请

US20090011440A1 Receptor Tyrosine Kinase Signaling Pathway Analysis For Diagnosis And Therapy 审中-公开
标题翻译：受体酪氨酸激酶信号通路分析诊断和治疗
公开(公告)号：US20090011440A1
公开(公告)日：2009-01-08
申请号：US12176982
申请日：2008-07-21
申请人： Ali Mukherjee , Mengxiang Tang , Harprit S. Pannu , Po-Ying Chan-Hui , Sharat Singh
发明人： Ali Mukherjee , Mengxiang Tang , Harprit S. Pannu , Po-Ying Chan-Hui , Sharat Singh
IPC分类号： G01N33/574 , G01N33/53 , C12Q1/48
CPC分类号： G01N33/74 , G01N33/5041 , G01N33/57492 , G01N33/6893 , G01N2333/485
摘要： The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明提供了通过测量受体二聚化和RTK途径特征的蛋白质 - 蛋白复合物或活化的效应蛋白的相对量来确定细胞样品或患者样品中受体酪氨酸激酶（RTK）途径的激活状态的方法。本发明还提供了使用这种状态信息来选择对途径特异性药物有反应的患者的方法，更具体地，涉及用于测量ErbB受体和受体复合物的方法，并使用这些信息来选择对ErbB途径特异性药物有反应的患者。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物组来实现，所述可释放分子标签对于在RTK活化中形成的一种或多种复合物的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

3. 发明申请

US20050131006A1 Receptor tyrosine kinase signaling pathway analysis for diagnosis and therapy 有权
标题翻译：受体酪氨酸激酶信号通路分析诊断和治疗
公开(公告)号：US20050131006A1
公开(公告)日：2005-06-16
申请号：US10963855
申请日：2004-10-13
申请人： Ali Mukherjee , Mengxiang Tang , Harprit Pannu , Po-Ying Chan-Hui , Sharat Singh
发明人： Ali Mukherjee , Mengxiang Tang , Harprit Pannu , Po-Ying Chan-Hui , Sharat Singh
IPC分类号： A61B20060101 , A61K31/4745 , C12Q1/68 , G01N33/50 , G01N33/574 , G01N33/68 , G01N33/74
CPC分类号： G01N33/74 , G01N33/5041 , G01N33/57492 , G01N33/6893 , G01N2333/485
摘要： The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明提供了通过测量受体二聚化和RTK途径特征的蛋白质 - 蛋白复合物或活化的效应蛋白的相对量来确定细胞样品或患者样品中受体酪氨酸激酶（RTK）途径的激活状态的方法。本发明还提供了使用这种状态信息来选择对途径特异性药物有反应的患者的方法，更具体地，涉及用于测量ErbB受体和受体复合物的方法，并使用这些信息来选择对ErbB途径特异性药物有反应的患者。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物组来实现，所述可释放分子标签对于在RTK活化中形成的一种或多种复合物的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

4. 发明申请

US20050130238A1 ErbB surface receptor complexes as biomarkers 审中-公开
标题翻译： ErbB表面受体复合物作为生物标志物
公开(公告)号：US20050130238A1
公开(公告)日：2005-06-16
申请号：US11041041
申请日：2005-01-21
申请人： Po-Ying Chan-Hui , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
发明人： Po-Ying Chan-Hui , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
IPC分类号： A61K31/275 , G01N33/53 , G01N33/542 , G01N33/567 , G01N33/574 , G01N33/68
CPC分类号： G01N33/542 , G01N33/57492 , G01N33/6803 , G01N33/6842 , G01N33/6872 , G01N2333/485 , G01N2333/49 , G01N2800/52
摘要： The invention is directed to a new class of biomarker in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of ErbB cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more types of receptor dimers. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明涉及包含ErbB细胞表面膜受体的二聚体的患者样品中的新一类生物标志物。在一个方面，本发明包括通过将这样的病症与在患者样品，特别是固定组织样品中直接测量的一种或多种ErbB细胞表面膜受体的二聚体的量相关联来确定疾病或健康状况的状态的方法。另一方面，本发明包括通过将样本细胞中的ErbB细胞表面膜受体的一种或多种二聚体的量的测量值与这样的状态相关联来确定来自个体的样品中癌症状态的方法，包括存在或不存在癌前状态，存在或不存在癌症状态，癌症预后或对治疗的反应性。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物来实现，所述组合化合物对于一种或多种类型的受体二聚体的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

5. 发明申请

US20100291594A1 ErbB Surface Receptor Complexes as Biomarkers 审中-公开
标题翻译： ErbB表面受体复合物作为生物标志物
公开(公告)号：US20100291594A1
公开(公告)日：2010-11-18
申请号：US12689144
申请日：2010-01-18
申请人： Po-Ying CHAN-HUI , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
发明人： Po-Ying CHAN-HUI , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
IPC分类号： G01N33/574
CPC分类号： G01N33/56905 , G01N33/6893
摘要： The invention is directed to a new class of biomarker in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of ErbB cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more types of receptor dimers. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明涉及包含ErbB细胞表面膜受体的二聚体的患者样品中的新一类生物标志物。在一个方面，本发明包括通过将这样的病症与在患者样品，特别是固定组织样品中直接测量的一种或多种ErbB细胞表面膜受体的二聚体的量相关联来确定疾病或健康状况的状态的方法。另一方面，本发明包括通过将样本细胞中的ErbB细胞表面膜受体的一种或多种二聚体的量的测量值与这样的状态相关联来确定来自个体的样品中癌症状态的方法，包括存在或不存在癌前状态，存在或不存在癌症状态，癌症预后或对治疗的反应性。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物来实现，所述组合化合物对于一种或多种类型的受体二聚体的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

6. 发明授权

US08247180B2 Measuring receptor homodimerization 有权
标题翻译：测量受体同二聚化
公开(公告)号：US08247180B2
公开(公告)日：2012-08-21
申请号：US12176245
申请日：2008-07-18
申请人： Sailaja Pidaparthi , Yining Shi , Rajiv Dua , Po-Ying Chan-Hui , Sharat Singh
发明人： Sailaja Pidaparthi , Yining Shi , Rajiv Dua , Po-Ying Chan-Hui , Sharat Singh
IPC分类号： G01N33/53 , G01N33/532 , G01N33/554 , C07K1/10 , C07K1/14
CPC分类号： G01N33/566 , G01N33/542 , G01N33/74 , G01N2333/71 , G01N2333/726 , Y10S436/824
摘要： The invention provides methods and kits for detecting and/or measuring receptor homodimers on a cell surface membrane. In one aspect, the methods employ pairs of probes comprising binding compounds and a cleaving probe, such that at least one binding compound binds specifically to the same epitope of a membrane-bound analyte as the cleaving probe. The binding compound includes one or more molecular tags attached through a cleavable linkage, and the cleaving probe includes a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to a homodimer of a cell surface molecules results in release of molecular tags from the binding compounds, providing a measure of formation of the homodimeric complex.
摘要翻译：本发明提供了用于在细胞表面膜上检测和/或测量受体同二聚体的方法和试剂盒。在一个方面，所述方法使用包含结合化合物和切割探针的探针对，使得至少一种结合化合物特异性结合作为切割探针的膜结合分析物的相同表位。结合化合物包括通过可切割键连接的一个或多个分子标签，并且切割探针包括切割诱导部分，其在限定的接近于其内时可切割连接。两个探针与细胞表面分子的同型二聚体的结合导致分子标签从结合化合物的释放，提供同二聚体复合物形成的量度。

7. 发明授权

US07648828B2 Methods for detecting receptor complexes comprising PI3K 有权
标题翻译：用于检测包含PI3K的受体复合物的方法
公开(公告)号：US07648828B2
公开(公告)日：2010-01-19
申请号：US11041073
申请日：2005-01-21
申请人： Po-Ying Chan-Hui , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
发明人： Po-Ying Chan-Hui , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
IPC分类号： G01N33/574
CPC分类号： G01N33/542 , G01N33/57492 , G01N33/6803 , G01N33/6842 , G01N33/6872 , G01N2333/485 , G01N2333/49 , G01N2800/52
摘要： The invention is directed to a new class of biomarker in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of ErbB cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more types of receptor dimers. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明涉及包含ErbB细胞表面膜受体的二聚体的患者样品中的新一类生物标志物。在一个方面，本发明包括通过将这样的病症与在患者样品，特别是固定组织样品中直接测量的一种或多种ErbB细胞表面膜受体的二聚体的量相关联来确定疾病或健康状况的状态的方法。另一方面，本发明包括通过将样本细胞中的ErbB细胞表面膜受体的一种或多种二聚体的量的测量值与这样的状态相关联来确定来自个体的样品中癌症状态的方法，包括存在或不存在癌前状态，存在或不存在癌症状态，癌症预后或对治疗的反应性。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物来实现，所述组合化合物对于一种或多种类型的受体二聚体的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

8. 发明申请

US20090111127A1 Surface Receptor Complexes as Biomarkers 审中-公开
标题翻译：表面受体复合物作为生物标志物
公开(公告)号：US20090111127A1
公开(公告)日：2009-04-30
申请号：US11866293
申请日：2007-10-02
申请人： Po-Ying Chan-Hui , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
发明人： Po-Ying Chan-Hui , Rajiv Dua , Ali Mukherjee , Sailaja Pidaparthi , Hossein Salimi-Moosavi , Yining Shi , Sharat Singh
IPC分类号： G01N33/574 , C12Q1/02 , G01N33/53
CPC分类号： G01N33/57492 , G01N33/542 , G01N2333/485
摘要： The invention is directed to a new class of biomarker in patient samples comprising dimers of cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more types of receptor dimers. After binding, molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明涉及包含细胞表面膜受体二聚体的患者样品中的新一类生物标志物。在一个方面，本发明包括通过将这样的病症与在患者样品，特别是固定组织样品中直接测量的一种或多种细胞表面膜受体的二聚体的量相关联来确定疾病或健康状况的状态的方法。另一方面，本发明包括通过将样本细胞中的一种或多种细胞表面膜受体的二聚体的量的测量值与这样的状态相关联来确定来自个体的样品中癌症的状态的方法，包括存在或不存在癌前状态，癌症状态的存在或不存在，癌症的预后或对治疗的反应性。优选地，本发明的方法通过使用具有可释放分子标签的结合化合物来实现，所述组合化合物对于一种或多种类型的受体二聚体的多种组分是特异性的。结合后，分离标签被释放并与测定混合物分离，用于分析。

9. 发明授权

US07105308B2 Detecting receptor oligomerization 有权
标题翻译：检测受体低聚
公开(公告)号：US07105308B2
公开(公告)日：2006-09-12
申请号：US10623057
申请日：2003-07-17
申请人： Po-Ying Chan-Hui , Yining Shi , Sailaja Pidaparthi , Rajiv Dua , Sharat Singh
发明人： Po-Ying Chan-Hui , Yining Shi , Sailaja Pidaparthi , Rajiv Dua , Sharat Singh
IPC分类号： G01N33/53
CPC分类号： G01N33/566 , G01N33/542 , G01N2333/71 , G01N2333/726
摘要： Methods are provided for detecting formation of oligomeric complexes of molecules on the surface of cell membranes. These methods employ pairs of tagged probes and cleaving probes, each of which binds specificly to a cell surface molecule. The tagged probe includes a molecular tag that is linked to a first binding compound through a cleavable linkage, and the cleaving probe includes a second binding agent and a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to cell surface molecules that have formed an oligomeric complex results in release of the molecular tag from the binding compound, providing a measure of formation of the complex.
摘要翻译：提供了用于检测细胞膜表面上分子的寡聚复合物的形成的方法。这些方法采用成对的标记探针和切割探针，每个探针和细胞表面分子都特异性地结合。标记的探针包括通过可切割键连接到第一结合化合物的分子标签，并且所述切割探针包括第二结合剂和切割诱导部分，其在限定的接近于其内时可切割连接。两个探针与形成寡聚复合物的细胞表面分子的结合导致分子标签从结合化合物的释放，提供复合物形成的量度。

10. 发明申请

US20060166282A1 Methods and compositions for screening cell binding molecules 审中-公开
标题翻译：用于筛选细胞结合分子的方法和组合物
公开(公告)号：US20060166282A1
公开(公告)日：2006-07-27
申请号：US10520230
申请日：2003-07-09
申请人： Sharat Singh , Po-Ying Chan-Hui , Hrair Kirakossian
发明人： Sharat Singh , Po-Ying Chan-Hui , Hrair Kirakossian
IPC分类号： G01N33/567
CPC分类号： G01N33/502 , C07H21/02 , C07H21/04 , G01N27/44726 , G01N33/5008 , G01N33/5011 , G01N33/569 , G01N2550/00
摘要： Ligands, such as antibodies, are screened for binding to cell surface moieties such as receptors. Multiple cell types and/or binding ligands can be screened simultaneously in multiplexed assays. The screening assays employ membrane-anchored electrophoretic probes for detection of binding of the ligand to the cell surface.
摘要翻译：对诸如抗体的配体进行筛选以结合细胞表面部分例如受体。多重细胞类型和/或结合配体可以在多重测定中同时筛选。筛选测定使用膜锚定电泳探针来检测配体与细胞表面的结合。

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