公开(公告)号：US06949347B2

公开(公告)日：2005-09-27

申请号：US10379965

申请日：2003-03-04

申请人： Sharat Singh ,  Po-Ying Chan-Hui

发明人： Sharat Singh ,  Po-Ying Chan-Hui

IPC分类号： G01N33/543 ,  G01N33/566 ,  G01N33/567 ,  G01N33/58 ,  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。

公开(公告)号：US20050079565A1

公开(公告)日：2005-04-14

申请号：US10916291

申请日：2004-08-10

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

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

IPC分类号： C12Q1/68 ,  G01N33/53 ,  G01N33/537 ,  G01N33/542 ,  G01N33/543 ,  G01N33/566

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。

公开(公告)号：US20090155818A1

公开(公告)日：2009-06-18

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

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。

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。

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。

公开(公告)号：US07402398B2

公开(公告)日：2008-07-22

申请号：US10946816

申请日：2004-09-22

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 ,  C07K16/00 ,  C07K1/10 ,  C07K1/14 ,  G01N33/533

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。

公开(公告)号：US07402397B2

公开(公告)日：2008-07-22

申请号：US10916291

申请日：2004-08-10

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 ,  G01N33/532 ,  G01N33/554 ,  C07K1/10 ,  C07K1/14

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.

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。

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。

公开(公告)号：US20050089940A1

公开(公告)日：2005-04-28

申请号：US10946816

申请日：2004-09-22

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： C12Q1/68 ,  G01N33/53 ,  G01N33/567

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。