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    ErbB surface receptor complexes as biomarkers
    1.
    发明申请
    ErbB surface receptor complexes as biomarkers 审中-公开
    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。

    Methods for detecting receptor complexes comprising PI3K
    3.
    再颁专利
    Methods for detecting receptor complexes comprising PI3K 有权
    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。

    Receptor Tyrosine Kinase Signaling Pathway Analysis For Diagnosis And Therapy
    7.
    发明申请
    Receptor Tyrosine Kinase Signaling Pathway Analysis For Diagnosis And Therapy 审中-公开
    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。

    Detecting and Profiling Molecular Complexes
    8.
    发明申请
    Detecting and Profiling Molecular Complexes 审中-公开
    检测和分析分子复合物

    公开(公告)号：US20090011432A1

    公开(公告)日：2009-01-08

    申请号：US12177049

    申请日：2008-07-21

    申请人： Po-Ying Chan-Hui ,  Sharat Singh ,  Hossein Salimi-Moosavi ,  Hasan Tahir ,  Gerald J. Wallweber ,  Hrair Kirakosssian ,  Tracy J. Matray

    发明人： Po-Ying Chan-Hui ,  Sharat Singh ,  Hossein Salimi-Moosavi ,  Hasan Tahir ,  Gerald J. Wallweber ,  Hrair Kirakosssian ,  Tracy J. Matray

    IPC分类号： G01N33/53 ,  G01N33/573

    CPC分类号： G01N33/542 ,  G01N33/566 ,  G01N2333/71 ,  G01N2333/726 ,  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。

    Multiplex analysis using membrane-bound sensitizers
    9.
    发明授权
    Multiplex analysis using membrane-bound sensitizers 失效
    使用膜结合敏化剂的多重分析

    公开(公告)号：US07217531B2

    公开(公告)日：2007-05-15

    申请号：US11214234

    申请日：2005-08-27

    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： G01N33/53

    CPC分类号： G01N33/58 ,  G01N33/54306 ,  G01N33/566 ,  G01N33/567 ,  G01N33/582 ,  Y10T436/10

    摘要： The present invention is directed to methods and compositions for determining the presence, absence, and/or amounts of one or more membrane-associated analytes in a sample. In accordance with the invention, binding compounds derivatized with releasable molecular tags specifically bind to selected membrane-associated analytes, after which the molecular tags are released upon activation of cleavage moieties, or sensitizers, anchored in the same membrane as the membrane-associated analytes. The released molecular tags are then identified by their distinct separation and detection characteristics.

    摘要翻译： 本发明涉及用于确定样品中一种或多种膜相关分析物的存在，不存在和/或量的方法和组合物。 根据本发明，用可释放分子标签衍生化的结合化合物特异性地结合选定的膜相关分析物，之后分子标签在激活切割部分或在与膜相关分析物相同的膜中锚定的敏化剂时被释放。 然后通过它们独特的分离和检测特征鉴定释放的分子标签。

    Profiling frequencies of receptor heterodimers
    10.
    发明授权
    Profiling frequencies of receptor heterodimers 有权
    受体异源二聚体的分布频率

    公开(公告)号：US07135300B2

    公开(公告)日：2006-11-14

    申请号：US10830543

    申请日：2004-04-22

    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。