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    • 5. 发明申请
    • METHODS OF ENZYMATIC DISCRIMINATION ENHANCEMENT AND SURFACE-BOUND DOUBLE-STRANDED DNA
    • 酶切鉴定增强和表面双重双链DNA的方法
    • US20120164693A1
    • 2012-06-28
    • US11950213
    • 2007-12-04
    • David J. LockhartMark S. CheeDirk VetterMartin Digglemann
    • David J. LockhartMark S. CheeDirk VetterMartin Digglemann
    • C12P19/34C40B40/06C40B30/04
    • C12N15/1093B01J19/0046B01J2219/00529B01J2219/00608B01J2219/00612B01J2219/00626B01J2219/0063B01J2219/00659B01J2219/00722C07B2200/11C07H21/00C12Q1/6827C12Q1/683C12Q1/6837C12Q1/6874C40B40/06C40B80/00G01N33/5308G01N33/551
    • Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.
    • 用于区分完全互补的杂交体与通过一个或多个碱基对不同的那些的方法和在固体支持物上的单分子双链寡核苷酸的文库。 在一个实施方案中,本发明提供了使用核酸酶处理来提高高密度寡核苷酸阵列上杂交信号质量的方法。 在另一个实施方案中,本发明提供了使用连接反应来提高高密度寡核苷酸阵列上杂交信号质量的方法。 在另一个实施方案中,本发明提供了在固体支持物上的单分子或分子间双链寡核苷酸的文库。 这些文库在药物发现中可用于筛选许多生物样品,用于双链寡核苷酸与肽,蛋白质,药物和RNA之间的特异性相互作用。 在相关方面,本发明提供了在固体支持物上的构象限制探针的文库。 使用双链寡核苷酸作为脚手架,探针的运动和灵活性受到限制。 探针也可用于与药物发现和诊断相关的各种筛选程序。 本发明还提供了制备和筛选上述文库的方法。
    • 7. 发明申请
    • CO-LOCALIZATION AFFINITY ASSAYS
    • 共定位亲和力测定
    • US20110245101A1
    • 2011-10-06
    • US13079878
    • 2011-04-05
    • Mark S. CheeIgor A. KozlovAnita D. WentworthStephanie J. Kosakovsky Pond
    • Mark S. CheeIgor A. KozlovAnita D. WentworthStephanie J. Kosakovsky Pond
    • C40B30/04
    • G01N33/6845G01N2458/10
    • The invention provides a new assay format for high throughput molecular binding studies at a single molecule level. The invention enables creation of binding event identifiers in a highly parallel way. Individual binding events occur between two agents of a binding pair, e.g., a protein-based binding pair or a binding pair comprising a protein and a chemical moiety. The binding event identifier created through the binding of the two binding agents is unique to that pair, and identification of the binding event identifier is indicative of the binding of these specific may be assessed through a readout that is digital in nature. The invention enables very large sets of thousands or more of different binding agents or potential binding agents to be assayed simultaneously, resolving millions or more of potential interactions, and distinguishing specific interactions from those that are less specific.
    • 本发明提供了在单一分子水平上用于高通量分子结合研究的新的测定形式。 本发明能够以高度并行的方式创建绑定事件标识符。 个体结合事件发生在结合对的两个试剂之间,例如基于蛋白质的结合对或包含蛋白质和化学部分的结合对。 通过两个绑定代理的绑定而创建的绑定事件标识符对于该对是唯一的,并且绑定事件标识符的标识指示可以通过本质上是数字的读出来评估这些特定的绑定。 本发明使得能够同时测定成千上万或更多种不同结合剂或潜在的结合剂的非常大的组,解决数百万或更多的潜在相互作用,并且将特异性相互作用与不太具体的相互作用区分开来。