公开(公告)号：US20100233732A1

公开(公告)日：2010-09-16

申请号：US12688766

申请日：2010-01-15

申请人： Michael Bates ,  Jennifer W. Cook ,  Gundo Diedrich ,  Laurie Goodman ,  Ali Mukherjee ,  Gordon Parry ,  Jeff Sperinde ,  Stephen J. Williams

发明人： Michael Bates ,  Jennifer W. Cook ,  Gundo Diedrich ,  Laurie Goodman ,  Ali Mukherjee ,  Gordon Parry ,  Jeff Sperinde ,  Stephen J. Williams

IPC分类号： G01N33/574

CPC分类号： G01N33/57415 ,  G01N33/57492 ,  G01N2333/71 ,  G01N2800/52

摘要： Methods are provided for determining or otherwise assessing the response of a patient to treatment, in particular, to cancer treatment. The methods include the analysis of samples for the presence or the absence of HER2 markers alone or in conjunction with other biomarkers, such as HER3 markers. In certain examples, the probable time to progression can be determined by first determining HER2 positive patients and then further stratifying by using the presence or the absence of a second biomarker (e.g, HER3 markers). In addition, the data can be used to track a patient's response to a treatment regimen, assessing the expected success of treating a patient using a particular regiment, determining the effects of a treatment regiment or for categorizing a patient in order to create a homogenous group for a clinical trial.

摘要翻译： 提供了用于确定或以其他方式评估患者对治疗，特别是癌症治疗的反应的方法。 这些方法包括单独或与其他生物标志物（如HER3标记物）结合存在或不存在HER2标记物的样品分析。 在某些实例中，可以通过首先确定HER2阳性患者，然后通过使用第二生物标志物（例如HER3标记）的存在或不存在进一步分层来确定进展的可能时间。 另外，数据可用于跟踪患者对治疗方案的反应，评估使用特定团治疗患者的预期成功率，确定治疗方案的效果或为了分类患者以创建均质组 进行临床试验。

公开(公告)号：US08349574B2

公开(公告)日：2013-01-08

申请号：US12688798

申请日：2010-01-15

申请人： Michael Bates ,  Ali Mukherjee ,  Gordon Parry ,  Jeff Sperinde ,  Jennifer W. Cook ,  Gundo Diedrich ,  Laurie Goodman ,  Stephen J. Williams

发明人： Michael Bates ,  Ali Mukherjee ,  Gordon Parry ,  Jeff Sperinde ,  Jennifer W. Cook ,  Gundo Diedrich ,  Laurie Goodman ,  Stephen J. Williams

IPC分类号： G01N33/574 ,  G01N33/53 ,  G01N33/567

CPC分类号： G01N33/57415 ,  C07K16/28 ,  C07K16/32 ,  G01N33/574 ,  G01N2333/47 ,  G01N2333/71 ,  G01N2800/52

摘要： The invention provides methods of measuring and/or quantifying the presence and/or amount of Her-3 and/or Her-3 in a complex in a sample. The invention also provides antibodies specific for Her-3.

摘要翻译： 本发明提供了测量和/或定量样品中复合物中Her-3和/或Her-3的存在和/或量的方法。 本发明还提供对Her-3特异的抗体。

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。

公开(公告)号：US08198031B2

公开(公告)日：2012-06-12

申请号：US11717760

申请日：2007-03-12

申请人： Po-Ying Chan-Yui ,  Sharat Singh ,  Hossein Salimi-Moosavi ,  Yining Shi ,  Sailaja Pidaparthi ,  Rajiv Dua ,  Ali Mukherjee

发明人： Po-Ying Chan-Yui ,  Sharat Singh ,  Hossein Salimi-Moosavi ,  Yining Shi ,  Sailaja Pidaparthi ,  Rajiv Dua ,  Ali Mukherjee

IPC分类号： G01N33/53 ,  G01N33/532 ,  G01N33/554 ,  C07K1/10 ,  C07K1/14

CPC分类号： G01N33/566 ,  G01N33/542 ,  Y10S436/824

摘要： Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.

摘要翻译： 提供了用于检测样品（例如细胞或组织裂解物）中分子复合物（特别是蛋白质）的形成的方法。 在一个方面，提供了对复合物中的第一种蛋白质特异性的切割探针和一种或多种特异于复合物中的一种或多种第二种蛋白质的结合化合物。 在结合时，诱导切割探针以产生仅在切割探针的局部区域中切割附着于结合化合物的分子标签的活性物质，例如单线态氧。 将释放的分子标签与测定混合物和彼此分离，以提供与复合物中存在的蛋白质的数量和类型相关的读数。

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。

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。

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。

公开(公告)号：US20080233602A1

公开(公告)日：2008-09-25

申请号：US11717760

申请日：2007-03-12

申请人： Po-Ying Chan-Yui ,  Sharat Singh ,  Hossein Salimi-Mossavi ,  Yining Shi ,  Sailaja Pidaparthi ,  Rajiv Dua ,  Ali Mukherjee

发明人： Po-Ying Chan-Yui ,  Sharat Singh ,  Hossein Salimi-Mossavi ,  Yining Shi ,  Sailaja Pidaparthi ,  Rajiv Dua ,  Ali Mukherjee

IPC分类号： C12Q1/48 ,  G01N33/00 ,  G01N33/536

CPC分类号： G01N33/566 ,  G01N33/542 ,  Y10S436/824

摘要： Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.

摘要翻译： 提供了用于检测样品（例如细胞或组织裂解物）中分子复合物（特别是蛋白质）的形成的方法。 在一个方面，提供了对复合物中的第一种蛋白质特异性的切割探针和一种或多种特异于复合物中的一种或多种第二种蛋白质的结合化合物。 在结合时，诱导切割探针以产生仅在切割探针的局部区域中切割附着于结合化合物的分子标签的活性物质，例如单线态氧。 将释放的分子标签与测定混合物和彼此分离，以提供与复合物中存在的蛋白质的数量和类型相关的读数。

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。

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。