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1. 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。

2. 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。

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. 再颁专利

USRE44437E1 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：USRE44437E1
公开(公告)日：2013-08-13
申请号：US13352705
申请日：2012-01-18
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： G01N33/542 , 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。

6. 发明申请

US20050170439A1 Methods for Detecting Receptor Complexes Comprising PI3K 有权
标题翻译：检测包含PI3K的受体复合物的方法
公开(公告)号：US20050170439A1
公开(公告)日：2005-08-04
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： 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： Abstract of the Disclosure 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：摘要揭示本发明涉及一种包含ErbB细胞表面膜受体二聚体的患者样品中的一类新生物标志物。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的状态的方法，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。

7. 发明申请

US20080187948A1 ERBB HETERODIMERS AS BIOMARKERS 审中-公开
标题翻译： ERBB HETERODIMERS作为生物标记
公开(公告)号：US20080187948A1
公开(公告)日：2008-08-07
申请号：US11965659
申请日：2007-12-27
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： C12Q1/02 , G01N33/50
CPC分类号： G01N33/542 , G01N33/57492 , G01N2333/485
摘要： A method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more heterodimers of ErbB, or Her, cell surface membrane receptors measured directly in a patient sample is described. 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 heterodimers 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：描述了通过将这样的条件与直接在患者样品中测量的ErbB或Her的细胞表面膜受体的一个或多个异源二聚体的量相关联来确定疾病状态或健康状况的方法。本发明包括通过将样品细胞中ErbB细胞表面膜受体的一个或多个异源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本中癌症的状态的方法，包括存在或不存在前体 - 癌症状态，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。

8. 发明申请

US20050170438A1 Methods for Detecting Receptor Complexes Comprising PDGFR 审中-公开
标题翻译：检测包含PDGFR的受体复合物的方法
公开(公告)号：US20050170438A1
公开(公告)日：2005-08-04
申请号：US11041029
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： Abstract of the Disclosure 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：摘要揭示本发明涉及一种包含ErbB细胞表面膜受体二聚体的患者样品中的一类新生物标志物。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。

9. 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。

10. 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。

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