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1. 发明专利

JP2009271087A Detection of the receptor oligomerization 审中-公开
标题翻译：检测受体低聚
公开(公告)号：JP2009271087A
公开(公告)日：2009-11-19
申请号：JP2009188699
申请日：2009-08-17
申请人： Aclara Biosciences Inc , アクララバイオサイエンシーズ, インコーポレイテッド
发明人： CHAN-HUI PO-YING , SHI YINING , PIDAPARTHI SAILAJA , DUA RAJIV , SINGH SHARAT
IPC分类号： G01N33/53 , C12Q1/68 , G01N20060101 , G01N27/447 , G01N33/483 , G01N33/542 , G01N33/543 , G01N33/556 , G01N33/566 , G01N33/567 , G01N33/68
CPC分类号： G01N33/566 , G01N33/542 , G01N2333/71 , G01N2333/726
摘要： PROBLEM TO BE SOLVED: To provide a method of detecting formation of oligomer complexes of molecules on surfaces of cell membranes. SOLUTION: This method employs pairs of tagged probes and cleaving probes, each of which binds specifically 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 two probes to cell surface molecules that have formed an oligomeric complex results in release of the molecular tag from the binding compound, and providing measure of formation of the complex. COPYRIGHT: (C)2010,JPO&INPIT
摘要翻译：待解决的问题：提供检测细胞膜表面上分子的低聚物复合物的形成的方法。解决方案：该方法采用成对的标记探针和切割探针，每个探针和切割探针都与细胞表面分子特异性结合。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。两个探针与形成低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，并提供复合物形成的测量。版权所有（C）2010，JPO＆INPIT

2. 发明申请

WO2005019470A2 DETECTING AND PROFILING MOLECULAR COMPLEXES 审中-公开
标题翻译：检测和分析分子配合物
公开(公告)号：WO2005019470A2
公开(公告)日：2005-03-03
申请号：PCT/US2004025945
申请日：2004-08-10
申请人： ACLARA BIOSCIENCES INC , CHAN-HUI PO-YING , SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN
发明人： CHAN-HUI PO-YING , SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN
IPC分类号： C07K16/46 , C12N7/02 , C12Q20060101 , G01N33/53 , G01N33/542 , G01N33/566 , C12Q
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（特别是蛋白质）复合物形成的方法。在一个方面，提供了对复合物中的第一种蛋白质特异的切割探针和对复合物中的一种或多种第二蛋白质特异的一种或多种结合化合物。在结合后，诱导裂解探针产生活性物质，例如单线态氧，其仅在裂解探针的局部区域中裂解连接至结合化合物的分子标签。释放的分子标签与测定混合物分离并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。

3. 发明申请

WO03006947A3 CELL-SCREENING ASSAY AND COMPOSITION 审中-公开
标题翻译：细胞筛选测定和组成
公开(公告)号：WO03006947A3
公开(公告)日：2003-05-08
申请号：PCT/US0221339
申请日：2002-07-05
申请人： ACLARA BIOSCIENCES INC , SINGH SHARAT , CHAN-HUI PO-YING
发明人： SINGH SHARAT , CHAN-HUI PO-YING
IPC分类号： G01N33/50 , G01N33/58 , C12Q1/66 , C07H21/02 , C07H21/04 , C12N9/12 , C12P21/06 , G01N27/26
CPC分类号： G01N33/5023 , G01N33/5008 , G01N33/581
摘要： The present invention discloses methods for multiplexed cellular assays. The methods can be used for a simultaneous quantitation of transcription levels from multiple promoters, multiple drugs, or for monitoring effects on multiple protein-protein interactions. These methods make use of reporter gene constructs that couple a single reporter enzyme coding sequence with one or more promoter regions, and a set of probes that are subject to degradation by the reporter enzyme, producing a set of reporters that can be separated from each other by differences in their mobilities. Multiplexed assays are achieved by combining a set of cell populations, wherein each population contains a distinct reporter gene construct and a distinct probe. Various treatments are then carried out on the mixture of cells. Treatments that induce transcription from specific promoters will cause synthesis of the reporter enzyme in that particular cell population, leading to degradation of the corresponding probe. The generation of specific reporters is determined by electrophoresis, or other means of measuring mobility, and is correlated with an effect of the treatment on transcription from a defined promoter.
摘要翻译：本发明公开了用于多路复用细胞分析的方法。该方法可用于同时定量多种启动子，多种药物的转录水平，或用于监测对多种蛋白质 - 蛋白质相互作用的影响。这些方法利用将单个报道酶编码序列与一个或多个启动子区偶联的报道基因构建体和一组受到报道酶降解的探针，产生一组可以彼此分离的报道分子通过其流动性的差异。通过组合一组细胞群实现复合测定，其中每个群包含独特的报道基因构建体和独特的探针。然后对细胞混合物进行各种处理。诱导特定启动子转录的处理将引起该特定细胞群中报道酶的合成，导致相应探针的降解。特定报道分子的产生通过电泳或其他测量流动性的手段来确定，并与治疗对来自确定的启动子的转录的影响相关。

4. 发明专利

AT442589T 未知
公开(公告)号：AT442589T
公开(公告)日：2009-09-15
申请号：AT03771670
申请日：2003-07-17
申请人： ACLARA BIOSCIENCES INC
发明人： CHAN-HUI PO-YING , SHI YINING , PIDAPARTHI SAILAJA , DUA RAJIV , SINGH SHARAT
IPC分类号： G01N33/53 , G01N33/542 , C12Q1/68 , G01N20060101 , G01N27/447 , G01N33/483 , G01N33/543 , G01N33/556 , G01N33/566 , G01N33/567 , G01N33/68
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.

5. 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。

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. 发明专利

AU2003259175A1 DETECTING RECEPTOR OLIGOMERIZATION 未知
公开(公告)号：AU2003259175A1
公开(公告)日：2004-02-16
申请号：AU2003259175
申请日：2003-07-17
申请人： ACLARA BIOSCIENCES INC
发明人： DUA RAJIV , SINGH SHARAT , CHAN-HUI PO-YING , SHI YINING , PIDAPARTHI SAILAJA
IPC分类号： G01N33/53 , C12Q1/68 , G01N20060101 , G01N27/447 , G01N33/483 , G01N33/542 , G01N33/543 , G01N33/556 , G01N33/566 , G01N33/567 , G01N33/68
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.

8. 发明专利

CA2475516A1 MULTIPLEX ANALYSIS USING MEMBRANE-BOUND SENSITIZERS 未知
公开(公告)号：CA2475516A1
公开(公告)日：2003-09-18
申请号：CA2475516
申请日：2003-03-04
申请人： ACLARA BIOSCIENCES INC
发明人： CHAN-HUI PO-YING , SINGH SHARAT
IPC分类号： G01N33/543 , G01N33/566 , G01N33/567 , G01N33/58 , C12Q1/00 , C12M1/00 , G01N27/00
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.

9. 发明申请

WO2004011900A3 DETECTING RECEPTOR OLIGOMERIZATION 审中-公开
标题翻译：检测受体低聚
公开(公告)号：WO2004011900A3
公开(公告)日：2004-06-10
申请号：PCT/US0322611
申请日：2003-07-17
申请人： ACLARA BIOSCIENCES INC
发明人： CHAN-HUI PO-YING , SHI YINING , PIDAPARTHI SAILAJA , DUA RAJIV , SINGH SHARAT
IPC分类号： G01N33/53 , C12Q1/68 , G01N20060101 , G01N27/447 , G01N33/483 , G01N33/542 , G01N33/543 , G01N33/556 , G01N33/566 , G01N33/567 , G01N33/68
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与第一结合化合物连接的分子标签，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。

10. 发明专利

AU2004229348A1 ErbB surface receptor complexes as biomarkers 未知
公开(公告)号：AU2004229348A1
公开(公告)日：2004-10-28
申请号：AU2004229348
申请日：2004-03-30
申请人： ACLARA BIOSCIENCES INC
发明人： SHI YINING , CHAN-HUI PO-YING , DUA RAJIV , PIDAPARTHI SAILAJA , MUKHERJEE ALI , SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN
IPC分类号： A61B20060101 , C07K16/28 , C12N20060101 , C12Q3/00 , G01N33/542 , G01N33/543 , G01N33/574

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