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1. 发明申请

WO2006052788A3 DETECTION OF ACTIVATION OF ENDOTHELIAL CELLS AS SURROGATE MARKER FOR ANGIOGENESIS 审中-公开
标题翻译：检测内源性细胞作为血管生成的标志物的活化
公开(公告)号：WO2006052788A3
公开(公告)日：2007-10-04
申请号：PCT/US2005040099
申请日：2005-11-04
申请人： MONOGRAM BIOSCIENCES INC , MOORE SEAN C , SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN , CAO LICHING , SPERINDE JEFF
发明人： MOORE SEAN C , SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN , CAO LICHING , SPERINDE JEFF
IPC分类号： G01N33/53 , C12Q1/24 , G01N33/541 , G01N33/557 , G01N33/58 , G01N33/96
CPC分类号： G01N33/5041 , G01N33/5064 , G01N33/5091 , G01N33/574 , G01N2333/515 , G01N2333/71 , G01N2800/52 , Y10S436/824
摘要： Methods, compositions and kits are provided for assessing angiogenesis through sensitive, direct detection of activation of endothelial cells at molecular levels. In general, activation of endothelial cells is detected by measuring the levels of cellular components and their protein complexes participating in a specific angiogenesis signaling pathway in endothelial cells. The methods can be used for assessing status of diseases associated with undesirable angiogenesis, such as the likelihood of developing the disease, presence or absence of the disease, prognosis of the disease and the likelihood of response or resistance to a particular anti-angiogenic therapy. The methods can also be used to guide the design of effective therapeutic regimens targeting a specific angiogenic signaling pathway, as well as in conjunction with therapeutic intervention of diseases or conditions associated with undesirable angiogenesis.
摘要翻译：提供了方法，组合物和试剂盒，用于通过敏感，直接检测分子水平的内皮细胞活化来评估血管发生。通常，通过测量参与内皮细胞中特异性血管生成信号传导途径的细胞成分及其蛋白质复合物的水平来检测内皮细胞的活化。该方法可用于评估与不期望的血管生成相关的疾病的状态，例如发展疾病的可能性，疾病的存在或不存在，疾病的预后以及对特定抗血管生成疗法的反应或抗性的可能性。该方法还可用于指导针对特定血管生成信号通路的有效治疗方案的设计，以及与不期望的血管发生相关的疾病或病症的治疗干预。

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

WO2004087887A2 INTRACELLULAR COMPLEXES AS BIOMARKERS 审中-公开
标题翻译：细胞内复合物作为生物标志物
公开(公告)号：WO2004087887A2
公开(公告)日：2004-10-14
申请号：PCT/US2004009805
申请日：2004-03-30
申请人： ACLARA BIOSCIENCES INC , SINGH SHARAT , BADAL M YOUSSOUF , JIN XUENGUANG , SALIMI-MOOSAVI HOSSEIN
发明人： SINGH SHARAT , BADAL M YOUSSOUF , JIN XUENGUANG , SALIMI-MOOSAVI HOSSEIN
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 provides a method for determining a disease status of a patient by measuring expression levels of selected intracellular complexes. In one aspect of the invention, the activation status of apoptotic pathways in a patient sample is determined by measuring relative amounts of protein-protein complexes that are characteristic of the apoptotic pathways. In particular, the invention provides a method of determining the activation status of the mitochondrial apoptotic pathway by simultaneously measuring relative amounts of complexes between 14-3-3 proteins and BAD proteins on the one hand and complexes of Bcl-2 proteins and BAD proteins on the other hand. 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 within apoptotic pathways. After binding molecular tags are released and separated from the assay mixture for analysis.
摘要翻译：本发明提供了一种通过测量所选细胞内复合物的表达水平来确定患者的疾病状态的方法。在本发明的一个方面，通过测量凋亡通路特征的蛋白质 - 蛋白质复合物的相对量来确定患者样品中凋亡途径的活化状态。特别地，本发明提供了一种通过同时测量14-3-3蛋白和BAD蛋白之间的复合物的相对量以及Bcl-2蛋白和BAD蛋白的复合物的相对量来确定线粒体凋亡途径的激活状态的方法另一方面。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在凋亡途径内形成的一种或多种复合物的多种组分是特异性的。结合分子标签后，从测定混合物中分离出分子标签进行分析。

4. 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。

5. 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。

6. 发明申请

WO2005045058A3 DETECTING HUMAN ANTI-THERAPEUTIC ANTIBODIES 审中-公开
标题翻译：检测人体抗病毒抗体
公开(公告)号：WO2005045058A3
公开(公告)日：2005-12-08
申请号：PCT/US2004035079
申请日：2004-10-25
申请人： ACLARA BIOSCIENCES INC , SALIMI-MOOSAVI HOSSEIN , KIRAKOSSIAN HRAIR , SINGH SHARAT
发明人： SALIMI-MOOSAVI HOSSEIN , KIRAKOSSIAN HRAIR , SINGH SHARAT
IPC分类号： C12Q20060101 , G01N27/26 , G01N33/53 , G01N33/537 , G01N33/543 , G01N33/68 , G01N33/94
CPC分类号： G01N33/6854 , G01N33/94
摘要： The invention provides a method for detecting the presence of anti-therapeutic antibody antibodies in a patient being treated with a therapeutic antibody. In one aspect of the invention, the invention is implemented by the following steps: (i) providing a first therapeutic antibody having a molecular tag attached thereto by a cleavable linkage, the molecular tag having one or more predetermined separation characteristics; (ii) providing a second therapeutic antibody having a cleavage-inducing moiety attached thereto, the cleavage-inducing moiety having an effective proximity; (iii) combining in an assay mixture the sample, the first therapeutic antibody, and the second therapeutic antibody under condition such that the first and second therapeutic antibodies form a complex with an anti-therapeutic antibody wherein the cleavable linkage of the first therapeutic antibody is within the effective proximity of the cleavage-inducing moiety of the second therapeutic antibody and molecular tags are released; and (iv) separating from the assay mixture and detecting the released molecular tags to determine the presence or absence of anti-therapeutic antibodies in the sample.
摘要翻译：本发明提供了用于检测正在用治疗性抗体治疗的患者中抗 - 治疗性抗体抗体的存在的方法。在本发明的一个方面中，通过以下步骤实施本发明：（i）提供具有通过可切割连接与其连接的分子标签的第一治疗性抗体，所述分子标签具有一种或多种预定分离特征; （ii）提供具有与其连接的切割诱导部分的第二种治疗性抗体，所述切割诱导部分具有有效的接近性; （iii）在使得第一和第二治疗性抗体与抗治疗性抗体形成复合物的条件下，在测定混合物中组合样品，第一治疗性抗体和第二治疗性抗体，其中第一治疗性抗体的可切割的连接是在第二治疗性抗体的切割诱导部分的有效接近范围内并释放分子标签; 和（iv）从测定混合物中分离并检测释放的分子标签以确定样品中是否存在抗治疗性抗体。

7. 发明申请

WO02095356A3 METHODS AND COMPOSITIONS FOR ANALYZING PROTEINS 审中-公开
标题翻译：分析蛋白质的方法和组合物
公开(公告)号：WO02095356A3
公开(公告)日：2004-12-23
申请号：PCT/US0216098
申请日：2002-05-21
申请人： ACLARA BIOSCIENCES INC , SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN , TAHIR SYED HASAN , WALLWEBER GERALD J , KIRAKOSSIAN HRAIR , MATRAY TRACY J , HERNANDEZ VINCENT S
发明人： SINGH SHARAT , SALIMI-MOOSAVI HOSSEIN , TAHIR SYED HASAN , WALLWEBER GERALD J , KIRAKOSSIAN HRAIR , MATRAY TRACY J , HERNANDEZ VINCENT S
IPC分类号： G01N33/483 , G01N21/78 , G01N27/447 , G01N33/53 , G01N33/536 , G01N33/68
CPC分类号： G01N33/6842 , C07K16/00 , C07K2317/40 , G01N33/582 , G01N33/6803
摘要： Methods, compositions and kits are disclosed for determining one or more target polypeptides in a sample where the target polypeptides have undergone a post-translational modification. A mixture comprising the sample and a first reagent comprising a cleavage-inducing moiety and a first binding agent for a binding site on a target polypeptide is subjected to conditions under which binding of respective binding moieties occurs. The binding site is the result of post-translational modification activity involving the target polypeptide. The method may be employed to determine the target polypeptide itself. In another embodiment the presence and/or amount of the target polypeptide is related to the presence and/or amount and/or activity of an agent such as an enzyme involved in the post-translational modification of the target polypeptide. The interaction between the first binding agent and the binding site brings the cleavage-inducing moiety into close proximity to a cleavable moiety, which is associated with the polypeptide and is susceptible to cleavage only when in proximity to the cleavage-inducing moiety. In this way, an electrophoretic tag for each of the polypeptides may be released. Released electrophoretic tags are separated and the presence and/or amount of the target polypeptides are determined based on the corresponding electrophoretic tags.
摘要翻译：公开了用于确定样品中一种或多种靶多肽已经经历了翻译后修饰的方法，组合物和试剂盒。包含样品和包含切割诱导部分和用于靶多肽上的结合位点的第一结合剂的第一试剂的混合物经受各自结合部分的结合发生的条件。结合位点是涉及靶多肽的翻译后修饰活性的结果。该方法可用于确定靶多肽本身。在另一个实施方案中，靶多肽的存在和/或量与试剂例如涉及靶多肽的翻译后修饰的酶的存在和/或量和/或活性有关。第一结合剂和结合位点之间的相互作用使切割诱导部分紧密接近与多肽相关的可切割部分，并且仅在接近切割诱导部分时易于切割。以这种方式，可以释放每个多肽的电泳标签。分离出释放的电泳标签，并且基于相应的电泳标签确定靶多肽的存在和/或量。

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