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公开(公告)号：US08945830B2
公开(公告)日：2015-02-03
申请号：US12859930
申请日：2010-08-20
申请人： James R. Heil , Daniel J. Schneider , Daniel T. Nieuwlandt , Sheri K. Wilcox , Dominic Zichi , Todd Gander , Bruce Eaton , Larry Gold
发明人： James R. Heil , Daniel J. Schneider , Daniel T. Nieuwlandt , Sheri K. Wilcox , Dominic Zichi , Todd Gander , Bruce Eaton , Larry Gold
CPC分类号： G01N33/54306 , C07B2200/11 , C12Q1/6832 , C12Q1/6834 , C12Q1/6837 , C40B40/00 , G01N33/58 , C12Q2537/101 , C12Q2525/205 , C12Q2523/313 , C12Q2525/161 , C12Q2565/514 , C12Q2565/101 , C12Q2541/101
摘要： The present disclosure describes methods, devices, reagents, and kits for the detection of one or more target molecules that may be present in a test sample. In one embodiment, a test sample is contacted with an aptamer that includes a tag and has a specific affinity for a target molecule. An aptamer affinity complex that includes an aptamer bound to its target molecule is allowed to form. If the test sample contains the target molecule, an aptamer affinity complex will generally form in the test sample. The aptamer affinity complex is optionally converted to an aptamer covalent complex that includes an aptamer covalently bound to its target molecule. The aptamer affinity complex (or optional aptamer covalent complex) can then be detected and/or quantified using any of a variety of methods known to one skilled in the art, including using a solid support, using mass spectrometry, and using quantitative polymerase chain reaction (Q-PCR).
摘要翻译： 本公开描述了用于检测可能存在于测试样品中的一种或多种靶分子的方法，装置，试剂和试剂盒。 在一个实施方案中，将测试样品与包含标签的适体接触并对靶分子具有特异性亲和力。 允许形成包含与其靶分子结合的适体的适体亲和复合体。 如果测试样品含有目标分子，通常将在测试样品中形成适体亲和复合体。 适体亲和复合物任选地转化为适体共价复合物，其包括与其靶分子共价结合的适体。 然后可以使用本领域技术人员已知的各种方法中的任一种检测和/或定量适体亲和复合物（或任选的适体共价复合物），包括使用固体支持物，使用质谱法和使用定量聚合酶链反应 （Q-PCR）。
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公开(公告)号：US20100317120A1
公开(公告)日：2010-12-16
申请号：US12859930
申请日：2010-08-20
申请人： James R. Heil , Daniel J. Schneider , Daniel T. Nieuwlandt , Sheri K. Wilcox , Dominic Zichi , Todd Gander , Bruce Eaton , Larry Gold
发明人： James R. Heil , Daniel J. Schneider , Daniel T. Nieuwlandt , Sheri K. Wilcox , Dominic Zichi , Todd Gander , Bruce Eaton , Larry Gold
IPC分类号： G01N33/68
CPC分类号： G01N33/54306 , C07B2200/11 , C12Q1/6832 , C12Q1/6834 , C12Q1/6837 , C40B40/00 , G01N33/58 , C12Q2537/101 , C12Q2525/205 , C12Q2523/313 , C12Q2525/161 , C12Q2565/514 , C12Q2565/101 , C12Q2541/101
摘要： The present disclosure describes methods, devices, reagents, and kits for the detection of one or more target molecules that may be present in a test sample. In one embodiment, a test sample is contacted with an aptamer that includes a tag and has a specific affinity for a target molecule. An aptamer affinity complex that includes an aptamer bound to its target molecule is allowed to form. If the test sample contains the target molecule, an aptamer affinity complex will generally form in the test sample. The aptamer affinity complex is optionally converted to an aptamer covalent complex that includes an aptamer covalently bound to its target molecule. The aptamer affinity complex (or optional aptamer covalent complex) can then be detected and/or quantified using any of a variety of methods known to one skilled in the art, including using a solid support, using mass spectrometry, and using quantitative polymerase chain reaction (Q-PCR).
摘要翻译： 本公开描述了用于检测可能存在于测试样品中的一种或多种靶分子的方法，装置，试剂和试剂盒。 在一个实施方案中，将测试样品与包含标签的适体接触并对靶分子具有特异性亲和力。 允许形成包含与其靶分子结合的适体的适体亲和复合体。 如果测试样品含有目标分子，通常将在测试样品中形成适体亲和复合体。 适体亲和复合物任选地转化为适体共价复合物，其包括与其靶分子共价结合的适体。 然后可以使用本领域技术人员已知的各种方法中的任一种检测和/或定量适体亲和复合物（或任选的适体共价复合物），包括使用固体支持物，使用质谱法和使用定量聚合酶链反应 （Q-PCR）。
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公开(公告)号：US08975026B2
公开(公告)日：2015-03-10
申请号：US13382493
申请日：2010-07-09
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold , Thale C. Jarvis , Jeffrey D. Carter
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold , Thale C. Jarvis , Jeffrey D. Carter
IPC分类号： C12N15/115
CPC分类号： C12N15/1048 , C12N15/115 , C12N2310/16 , C12Q1/6811 , G01N33/5308 , C12Q2525/117 , C12Q2525/205 , C12Q2541/101
摘要： The present disclosure describes the identification and use of aptamers and photoaptamers having slower dissociation rate constants than those obtained using previously described methods. Specifically, the present disclosure describes methods for the identification and use of aptamers to one or more targets within a histological or cytological sample, which have slow rates of dissociation. The aptamers may be used to assess localization, relative density, and presence or absence of one or more targets in cytological and histological samples. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. The aptamers may also be used to introduce target specific signal moieties. In addition to target identification, the aptamers may be used to amplify signal generation through a variety of methods.
摘要翻译： 本公开描述了具有比使用先前描述的方法获得的那些更快的解离速率常数的适配体和光致抗体的鉴定和使用。 具体地，本公开描述了用于鉴定和使用适配体到组织学或细胞学样品中的一种或多种目标的方法，其具有缓慢的解离速率。 适配体可用于评估细胞学和组织学样品中的一种或多种靶标的定位，相对密度和存在或不存在。 可以选择对于样品收集的给定疾病状态的特异性和诊断性的靶标。 适体也可以用于引入目标特异性信号部分。 除目标识别之外，适体可用于通过各种方法放大信号产生。
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公开(公告)号：US07964356B2
公开(公告)日：2011-06-21
申请号：US12499967
申请日：2009-07-09
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
CPC分类号： C12N15/1048 , C12Q1/6811 , C12Q2525/205
摘要： The present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. This invention relates to the field of diagnostic histology, cytology, histopathology, and cytopathology methods and reagents for the detection of various disease states. More specifically, the invention relates to the use of aptamers in histologic, cytologic, histopathic, and/or cytopathic diagnostic methods. Aptamers may be provided that react with specific target molecules contained within a histological or cytological sample. Aptamers may be used to assess localization, relative density, and presence or absence of one or more target. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. Aptamers may be used to introduce target specific signal moieties. Antigen retrieval methods may be applied to the sample prior to reaction with the specific aptamer/s to improve interaction of the aptamer and target within the sample. Or aptamers may be developed for the specific target that eliminates the need for the antigen retrieval process. In addition to target identification, aptamers may be used to amplify signal generation through a variety of methods.
摘要翻译： 本公开描述了用于产生具有比使用先前的SELEX和photoSELEX方法获得的解离速率常数更慢的适体和光催化剂的方法。 本公开进一步描述了具有比使用现有方法获得的那些更快的解离速率常数的适体和光致抗体。 本发明涉及用于检测各种疾病状态的诊断组织学，细胞学，组织病理学和细胞病理学方法和试剂领域。 更具体地，本发明涉及适配体在组织学，细胞学，组织病理学和/或细胞病变诊断方法中的用途。 可以提供与包含在组织学或细胞学样品中的特定靶分子反应的适配子。 可以使用适配器来评估定位，相对密度以及一个或多个靶的存在或不存在。 可以选择对于样品收集的给定疾病状态的特异性和诊断性的靶标。 适配子可用于引入目标特异性信号部分。 抗原检索方法可以在与特异性适体反应之前应用于样品，以改善样品中适体和靶标的相互作用。 或者可以针对特定靶标开发适配体，从而消除对抗原检索过程的需要。 除目标识别之外，适体可用于通过各种方法放大信号产生。
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公开(公告)号：US07947447B2
公开(公告)日：2011-05-24
申请号：US12175434
申请日：2008-07-17
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
CPC分类号： C12N15/115 , C12N9/6429 , C12N15/1048 , C12N2310/16 , C12N2310/314 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/334 , C12N2310/335 , C12N2310/336 , C12N2330/31 , C12Q1/6811 , C12Q1/6816 , C12Q1/6832 , C12Q1/6834 , G01N33/5308 , G01N33/58 , C12Q2525/205 , C12Q2565/514 , C12Q2525/161 , C12Q2537/101 , C12Q2523/313
摘要： The present disclosure describes improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules. Specifically, the present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. In addition, the disclosure describes aptamer constructs that include a variety of functionalities, including a cleavable element, a detection element, and a capture or immobilization element.
摘要翻译： 本公开描述了用于产生能够结合靶分子的适配体的改进的SELEX方法，以及用于产生能够结合和共价交联靶分子的光反应性适体的改进的photoSELEX方法。 具体地，本公开描述了用于生产具有比使用先前的SELEX和photoSELEX方法获得的解离速率常数更慢的适体和光致抗体的方法。 本公开进一步描述了具有比使用现有方法获得的那些更快的解离速率常数的适体和光致抗体。 此外，本公开描述了包括多种功能的适体构建体，包括可切割元件，检测元件和捕获或固定元件。
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公开(公告)号：US08975388B2
公开(公告)日：2015-03-10
申请号：US13113261
申请日：2011-05-23
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
CPC分类号： C12N15/115 , C12N9/6429 , C12N15/1048 , C12N2310/16 , C12N2310/314 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/334 , C12N2310/335 , C12N2310/336 , C12N2330/31 , C12Q1/6811 , C12Q1/6816 , C12Q1/6832 , C12Q1/6834 , G01N33/5308 , G01N33/58 , C12Q2525/205 , C12Q2565/514 , C12Q2525/161 , C12Q2537/101 , C12Q2523/313
摘要： The present disclosure describes improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules. Specifically, the present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. In addition, the disclosure describes aptamer constructs that include a variety of functionalities, including a cleavable element, a detection element, and a capture or immobilization element.
摘要翻译： 本公开描述了用于产生能够结合靶分子的适配体的改进的SELEX方法，以及用于产生能够结合和共价交联靶分子的光反应性适体的改进的photoSELEX方法。 具体地，本公开描述了用于生产具有比使用先前的SELEX和photoSELEX方法获得的解离速率常数更慢的适体和光致抗体的方法。 本公开进一步描述了具有比使用现有方法获得的那些更快的解离速率常数的适配体和光致抗体。 此外，本公开描述了包括多种功能的适体构建体，包括可切割元件，检测元件和捕获或固定元件。
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公开(公告)号：US20090004667A1
公开(公告)日：2009-01-01
申请号：US12175434
申请日：2008-07-17
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
CPC分类号： C12N15/115 , C12N9/6429 , C12N15/1048 , C12N2310/16 , C12N2310/314 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/334 , C12N2310/335 , C12N2310/336 , C12N2330/31 , C12Q1/6811 , C12Q1/6816 , C12Q1/6832 , C12Q1/6834 , G01N33/5308 , G01N33/58 , C12Q2525/205 , C12Q2565/514 , C12Q2525/161 , C12Q2537/101 , C12Q2523/313
摘要： The present disclosure describes improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules. Specifically, the present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. In addition, the disclosure describes aptamer constructs that include a variety of functionalities, including a cleavable element, a detection element, and a capture or immobilization element.
摘要翻译： 本公开描述了用于产生能够结合靶分子的适配体的改进的SELEX方法，以及用于产生能够结合和共价交联靶分子的光反应性适体的改进的photoSELEX方法。 具体地，本公开描述了用于生产具有比使用先前的SELEX和photoSELEX方法获得的解离速率常数更慢的适体和光致抗体的方法。 本公开进一步描述了具有比使用现有方法获得的那些更快的解离速率常数的适体和光致抗体。 此外，本公开描述了包括多种功能的适体构建体，包括可切割元件，检测元件和捕获或固定元件。
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公开(公告)号：US20120115752A1
公开(公告)日：2012-05-10
申请号：US13382493
申请日：2010-07-09
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold , Thale C. Jarvis , Jeffrey D. Carter
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold , Thale C. Jarvis , Jeffrey D. Carter
CPC分类号： C12N15/1048 , C12N15/115 , C12N2310/16 , C12Q1/6811 , G01N33/5308 , C12Q2525/117 , C12Q2525/205 , C12Q2541/101
摘要： The present disclosure describes the identification and use of aptamers and photoaptamers having slower dissociation rate constants than those obtained using previously described methods. Specifically, the present disclosure describes methods for the identification and use of aptamers to one or more targets within a histological or cytological sample, which have slow rates of dissociation. The aptamers may be used to assess localization, relative density, and presence or absence of one or more targets in cytological and histological samples. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. The aptamers may also be used to introduce target specific signal moieties. In addition to target identification, the aptamers may be used to amplify signal generation through a variety of methods.
摘要翻译： 本公开描述了具有比使用先前描述的方法获得的那些更快的解离速率常数的适配体和光致抗体的鉴定和使用。 具体地，本公开描述了用于鉴定和使用适配体到组织学或细胞学样品中的一种或多种目标的方法，其具有缓慢的解离速率。 适配体可用于评估细胞学和组织学样品中的一种或多种靶标的定位，相对密度和存在或不存在。 可以选择对于样品收集的给定疾病状态的特异性和诊断性的靶标。 适体也可以用于引入目标特异性信号部分。 除目标识别之外，适体可用于通过各种方法放大信号产生。
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公开(公告)号：US08404830B2
公开(公告)日：2013-03-26
申请号：US12969239
申请日：2010-12-15
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
CPC分类号： C12Q1/6811 , C12Q2525/205
摘要： The present disclosure is directed to the field of nucleic acid chemistry, specifically to 5-position modified uridines, as well as, oligonucleotides comprising said 5-position modified uridines. The present disclosure describes methods for producing aptamers comprising said 5-position modified uridines that are capable of binding to target molecules.
摘要翻译： 本公开涉及核酸化学领域，具体涉及5位修饰的尿苷，以及包含所述5位修饰的尿苷的寡核苷酸。 本公开描述了用于产生适合物的方法，其包含能够结合靶分子的所述5位修饰的尿苷。
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公开(公告)号：US20110245479A1
公开(公告)日：2011-10-06
申请号：US13113261
申请日：2011-05-23
申请人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
发明人： Dominic Zichi , Sheri K. Wilcox , Chris Bock , Daniel J. Schneider , Bruce Eaton , Larry Gold
CPC分类号： C12N15/115 , C12N9/6429 , C12N15/1048 , C12N2310/16 , C12N2310/314 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/334 , C12N2310/335 , C12N2310/336 , C12N2330/31 , C12Q1/6811 , C12Q1/6816 , C12Q1/6832 , C12Q1/6834 , G01N33/5308 , G01N33/58 , C12Q2525/205 , C12Q2565/514 , C12Q2525/161 , C12Q2537/101 , C12Q2523/313
摘要： The present disclosure describes improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules. Specifically, the present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. In addition, the disclosure describes aptamer constructs that include a variety of functionalities, including a cleavable element, a detection element, and a capture or immobilization element.
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