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1. 发明申请

WO2010083463A9 METHODS OF DETERMINING PATIENT RESPONSE BY MEASUREMENT OF HER-2 EXPRESSION 审中-公开
标题翻译：通过测量HER-2表达来确定患者反应的方法
公开(公告)号：WO2010083463A9
公开(公告)日：2010-12-23
申请号：PCT/US2010021272
申请日：2010-01-15
申请人： LAB CORP AMERICA HOLDINGS , BATES MICHAEL , COOK JENNIFER W , DIEDRICH GUNDO , GOODMAN LAURIE , MUKHERJEE ALI , PARRY GORDON , SPERINDE JEFF , WILLIAMS STEPHEN JOHN
发明人： BATES MICHAEL , COOK JENNIFER W , DIEDRICH GUNDO , GOODMAN LAURIE , MUKHERJEE ALI , PARRY GORDON , SPERINDE JEFF , WILLIAMS STEPHEN JOHN
IPC分类号： G01N33/569
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。所述方法包括单独或与其它生物标志物（例如HER3标记物）结合存在或不存在HER2标记的样品的分析。在某些实例中，可以通过首先确定HER2阳性患者并随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。此外，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，确定治疗团的效果或分类病人以产生均匀组进行临床试验。

2. 发明申请

WO2010083470A1 METHODS OF DETERMINING PATIENT RESPONSE BY MEASUREMENT OF HER-3 审中-公开
标题翻译：通过测量HER-3测定患者反应的方法
公开(公告)号：WO2010083470A1
公开(公告)日：2010-07-22
申请号：PCT/US2010/021281
申请日：2010-01-15
申请人： LABORATORY CORPORATION OF AMERICA HOLDINGS , BATES, Michael , COOK, Jennifer W. , DIEDRICH, Gundo , GOODMAN, Laurie , MUKHERJEE, Ali , PARRY, Gordon , SPERINDE, Jeff , WILLIAMS, Stephen John
发明人： BATES, Michael , COOK, Jennifer W. , DIEDRICH, Gundo , GOODMAN, Laurie , MUKHERJEE, Ali , PARRY, Gordon , SPERINDE, Jeff , WILLIAMS, Stephen John
IPC分类号： G01N33/48 , G01N33/53
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。

3. 发明申请

WO2004091384A3 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：WO2004091384A3
公开(公告)日：2005-12-29
申请号：PCT/US2004009715
申请日：2004-03-30
申请人： ACLARA BIOSCIENCES INC , CHAN-HUI PO-YING , SALIMI-MOOSAVI HOSSEIN , SHI YINING , SINGH SHARAT , DUA RAJIV , MUKHERJEE ALI , PIDAPARTHI SAILAJA
发明人： CHAN-HUI PO-YING , SALIMI-MOOSAVI HOSSEIN , SHI YINING , SINGH SHARAT , DUA RAJIV , MUKHERJEE ALI , PIDAPARTHI SAILAJA
IPC分类号： A61B20060101 , C07K16/28 , C12N20060101 , C12Q3/00 , G01N33/542 , G01N33/543 , G01N33/574
CPC分类号： G01N33/57492 , C07K16/2863 , G01N33/542 , G01N2333/485 , 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。

4. 发明申请

WO2005019470A3 DETECTING AND PROFILING MOLECULAR COMPLEXES 审中-公开
公开(公告)号：WO2005019470A3
公开(公告)日：2005-03-03
申请号：PCT/US2004/025945
申请日：2004-08-10
申请人： ACLARA BIOSCIENCES, INC. , CHAN-HUI, Po-Ying , SINGH, Sharat , SALIMI-MOOSAVI, Hossein , SHI, Uining , MUKHERJEE, Ali , PIDAPARTHI, Sailaja , DUA, Rajiv
发明人： CHAN-HUI, Po-Ying , SINGH, Sharat , SALIMI-MOOSAVI, Hossein , SHI, Uining , MUKHERJEE, Ali , PIDAPARTHI, Sailaja , DUA, Rajiv
IPC分类号： C07K16/46
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.

5. 发明申请

WO2004092353A3 SURFACE RECEPTOR COMPLEXES AS BIOMARKERS 审中-公开
公开(公告)号：WO2004092353A3
公开(公告)日：2004-10-28
申请号：PCT/US2004/009717
申请日：2004-03-30
申请人： ACLARA BIOSCIENCES, INC. , CHAN-HUI, Po-Ying , SALIMI-MOOSAVI, Hossein , SHI, Yining , SINGH, Sharat , DUA, Rajiv , MUKHERJEE, Ali , PIDAPARTHI, Sailaja
发明人： CHAN-HUI, Po-Ying , SALIMI-MOOSAVI, Hossein , SHI, Yining , SINGH, Sharat , DUA, Rajiv , MUKHERJEE, Ali , PIDAPARTHI, Sailaja
IPC分类号： G01N33/543
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 release and separated from the assay mixture for analysis.

6. 发明申请

WO2004092353A2 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：WO2004092353A2
公开(公告)日：2004-10-28
申请号：PCT/US2004009717
申请日：2004-03-30
申请人： ACLARA BIOSCIENCES INC , CHAN-HUI PO-YING , SALIMI-MOOSAVI HOSSEIN , SHI YINING , SINGH SHARAT , DUA RAJIV , MUKHERJEE ALI , PIDAPARTHI SAILAJA
发明人： CHAN-HUI PO-YING , SALIMI-MOOSAVI HOSSEIN , SHI YINING , SINGH SHARAT , DUA RAJIV , MUKHERJEE ALI , PIDAPARTHI SAILAJA
IPC分类号： A61B20060101 , C07K16/28 , C12N20060101 , C12Q3/00 , G01N33/542 , G01N33/543 , G01N33/574 , C12N
CPC分类号： G01N33/57492 , C07K16/2863 , G01N33/542 , G01N2333/485 , G01N2800/52
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 release 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，将分子标签从测定混合物中释放并分离以进行分析。

7. 发明申请

WO2005037071A3 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用于诊断和治疗
公开(公告)号：WO2005037071A3
公开(公告)日：2007-06-07
申请号：PCT/US2004033815
申请日：2004-10-13
申请人： MONOGRAM BIOSCIENCES INC , MUKHERJEE ALI , TANG MENGXIANG , PANNU HARPRIT S , CHAN-HUI PO-YING , SINGH SHARAT
发明人： MUKHERJEE ALI , TANG MENGXIANG , PANNU HARPRIT S , CHAN-HUI PO-YING , SINGH SHARAT
IPC分类号： G01N33/567 , A61B20060101 , A61K31/4745 , C12Q1/68 , G01N33/50 , G01N33/543 , G01N33/566 , 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 - 蛋白质复合物或活化的效应物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。

8. 发明申请

WO2006084018A3 METHODS FOR DETERMINING RESPONSIVENESS TO CANCER THERAPY 审中-公开
标题翻译：确定对癌症治疗的反应的方法
公开(公告)号：WO2006084018A3
公开(公告)日：2006-09-21
申请号：PCT/US2006003660
申请日：2006-02-01
申请人： MONOGRAM BIOSCIENCES INC , TANG MENGXIANG , CAO LICHING , DUA RAJIV , MUKHERJEE ALI , PANNU HERJIT , PANNU JAGRUP , SHI YINING , TAN YUPING , SINGH SHARAT , CHAPPEY COLOMBE
发明人： TANG MENGXIANG , CAO LICHING , DUA RAJIV , MUKHERJEE ALI , PANNU HERJIT , PANNU JAGRUP , SHI YINING , TAN YUPING , SINGH SHARAT , CHAPPEY COLOMBE
IPC分类号： C12Q1/68 , G01N33/567
CPC分类号： G01N33/57484 , G01N33/5748 , G01N2333/82
摘要： In certain aspects, the present invention provides methods and compositions for determining whether a cancer cells is likely to respond to treatment with a Her 1 -acting agent. In one aspect, the invention provides a method for determining whether a cancer cell is likely to respond to treatment with a Her 1 -acting agent, comprising detecting on the cancer cell at least about 600 Her 1 -Her 1 dimers, wherein the presence of the at least about 600 Her 1 -Her 1 dimers indicates that the cancer is likely to respond to treatment with the Her 1 -acting agent. In another aspect, the invention provides a method for determining whether a cancer cell is likely to respond to treatment with a Her 1 -acting agent, comprising detecting on a cell of the cancer at least about 600 Her 1 -Her 1 dimers, at least about 1000 Herl-Her2 dimers, and fewer than about 1000 Her2-Her3 dimers, wherein the presence of the at least about 600 Her 1 -Her 1 dimers, the at least about 1000 Herl-Her2 dimers, and the fewer than about 1000 Her2-Her3 dimers indicates that the cancer cell is likely to respond to treatment with the Her 1 -acting agent. 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：在某些方面，本发明提供了用于确定癌细胞是否可能响应Her 1作用剂治疗的方法和组合物。在一个方面，本发明提供了用于确定癌细胞是否可能对用Her 1作用剂治疗有反应的方法，包括在癌细胞上检测至少约600个Her 1 --Her 1二聚体，其中存在该至少约600个Her 1 -Her 1二聚体表明癌症可能对用Her 1作用剂治疗有反应。另一方面，本发明提供了用于确定癌细胞是否可能响应用Her 1作用剂治疗的方法，包括在癌细胞上检测至少约600个Her 1 --Her 1二聚体，至少约1000个Her1-Her2二聚体和少于约1000个Her2-Her3二聚体，其中所述至少约600个Her1-Her1二聚体，所述至少约1000个Her1-Her2二聚体和少于约1000个Her2 -Her3二聚体表明癌细胞可能对Her-1作用剂的治疗有反应。优选地，本发明的方法通过使用具有对一种或多种类型的受体二聚体的多种组分特异的可释放分子标签的结合化合物组来实施。结合后，分子标签被释放并从测定混合物中分离出来用于分析。

9. 发明申请

WO2006084018A2 METHODS FOR DETERMINING RESPONSIVENESS TO CANCER THERAPY 审中-公开
标题翻译：用于确定对癌症治疗的反应的方法
公开(公告)号：WO2006084018A2
公开(公告)日：2006-08-10
申请号：PCT/US2006/003660
申请日：2006-02-01
申请人： MONOGRAM BIOSCIENCES, INC. , TANG, Mengxiang , CAO, Liching , DUA, Rajiv , MUKHERJEE, Ali , PANNU, Herjit , PANNU, Jagrup , SHI, Yining , TAN, Yuping , SINGH, Sharat , CHAPPEY, Colombe
发明人： TANG, Mengxiang , CAO, Liching , DUA, Rajiv , MUKHERJEE, Ali , PANNU, Herjit , PANNU, Jagrup , SHI, Yining , TAN, Yuping , SINGH, Sharat , CHAPPEY, Colombe
IPC分类号： C12Q1/68
CPC分类号： G01N33/57484 , G01N33/5748 , G01N2333/82
摘要： In certain aspects, the present invention provides methods and compositions for determining whether a cancer cells is likely to respond to treatment with a Her 1 -acting agent. In one aspect, the invention provides a method for determining whether a cancer cell is likely to respond to treatment with a Her 1 -acting agent, comprising detecting on the cancer cell at least about 600 Her 1 -Her 1 dimers, wherein the presence of the at least about 600 Her 1 -Her 1 dimers indicates that the cancer is likely to respond to treatment with the Her 1 -acting agent. In another aspect, the invention provides a method for determining whether a cancer cell is likely to respond to treatment with a Her 1 -acting agent, comprising detecting on a cell of the cancer at least about 600 Her 1 -Her 1 dimers, at least about 1000 Herl-Her2 dimers, and fewer than about 1000 Her2-Her3 dimers, wherein the presence of the at least about 600 Her 1 -Her 1 dimers, the at least about 1000 Herl-Her2 dimers, and the fewer than about 1000 Her2-Her3 dimers indicates that the cancer cell is likely to respond to treatment with the Her 1 -acting agent. 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：在某些方面，本发明提供了用于确定癌细胞是否可能对Her 1处理剂的治疗有反应的方法和组合物。一方面，本发明提供了一种用于确定癌细胞是否可能对Her1处理剂起反应的方法，包括在癌细胞上检测至少约600个Her 1 -Her 1二聚体，其中存在至少约600个Her 1 -Her 1二聚体表明癌症可能对她用1代谢剂的治疗有反应。在另一方面，本发明提供了一种用于确定癌细胞是否可能对Her 1处理剂有反应的方法，包括至少检测至少约600个Her 1 -Her 1二聚体的癌细胞约1000个Herl-Her2二聚体和少于约1000个Her2-Her3二聚体，其中存在至少约600个Her1-Her2二聚体，至少约1000个Her1-Her2二聚体，以及少于约1000个Her2-Her2二聚体 -Her3二聚体表明癌细胞很可能对Her1处理剂有反应。优选地，通过使用具有对一种或多种类型的受体二聚体的多种成分特异的可释放分子标签的组合化合物来实现本发明的方法。结合后，将分子标签从测定混合物中释放并分离出来进行分析。

10. 发明申请

WO2010083463A1 METHODS OF DETERMINING PATIENT RESPONSE BY MEASUREMENT OF HER-2 EXPRESSION 审中-公开
标题翻译：通过测量HER-2表达来确定患者反应的方法
公开(公告)号：WO2010083463A1
公开(公告)日：2010-07-22
申请号：PCT/US2010/021272
申请日：2010-01-15
申请人： LABORATORY CORPORATION OF AMERICA HOLDINGS , BATES, Michael , COOK, Jennifer, W. , DIEDRICH, Gundo , GOODMAN, Laurie , MUKHERJEE, Ali , PARRY, Gordon , SPERINDE, Jeff , WILLIAMS, Stephen John
发明人： BATES, Michael , COOK, Jennifer, W. , DIEDRICH, Gundo , GOODMAN, Laurie , MUKHERJEE, Ali , PARRY, Gordon , SPERINDE, Jeff , WILLIAMS, Stephen John
IPC分类号： G01N33/569
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的反应，特别是对癌症治疗的反应的方法。所述方法包括分析样品中单独存在或不存在HER2标记或与其他生物标记如HER3标记结合的情况。在某些实例中，进展的可能时间可通过首先确定HER2阳性患者然后通过使用第二生物标志物（例如HER3标志物）的存在或不存在来进一步分层来确定。此外，数据可用于追踪患者对治疗方案的反应，评估使用特定团体治疗患者的预期成功率，确定治疗团的效果或对患者进行分类以创建均质组进行临床试验。

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