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51. 发明授权

US06890719B2 Fluorescence based biosensor 有权
公开(公告)号：US06890719B2
公开(公告)日：2005-05-10
申请号：US10144094
申请日：2002-05-10
申请人： Yi Lu , Juewen Liu
发明人： Yi Lu , Juewen Liu
IPC分类号： C12Q1/68 , C07H21/02 , C12M1/34 , C12P19/34 , G01N33/00
CPC分类号： C12Q1/68 , C12Q1/6825 , Y10S436/80 , Y10S977/924 , Y10T436/143333 , C12Q2565/501 , C12Q2563/137 , C12Q2521/337 , C12Q2541/101
摘要： A novel biosensor comprises at least one fluorophore and at least two quenchers, and is capable of selectively and specifically detecting the presence of an ion in the presence of other ions.

52. 发明授权

US06855496B2 Truncation SELEX method 失效
标题翻译：截断SELEX方法
公开(公告)号：US06855496B2
公开(公告)日：2005-02-15
申请号：US09907111
申请日：2001-07-17
申请人： Nikos Pagratis , Larry Gold , Timur Shtatland , Brenda Javornik
发明人： Nikos Pagratis , Larry Gold , Timur Shtatland , Brenda Javornik
IPC分类号： A61K31/70 , C07B61/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07H21/02 , C07H21/04 , C07K5/00 , C07K14/00 , C12N9/12 , C12N15/10 , C12N15/115 , C12P19/34 , C12Q1/37 , C12Q1/68 , C12Q1/70 , F02B75/02 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/569 , G01N33/68 , G01N33/76
CPC分类号： G01N33/6842 , A61K47/547 , A61K47/549 , B82Y5/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/001 , C12N9/1276 , C12N15/1048 , C12N15/115 , C12N2310/13 , C12N2310/322 , C12N2310/53 , C12Q1/37 , C12Q1/6811 , C40B40/00 , F02B2075/027 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , G01N33/76 , G01N2333/16 , G01N2333/163 , G01N2333/503 , G01N2333/575 , G01N2333/62 , G01N2333/8125 , G01N2333/96433 , G01N2333/96436 , G01N2333/96455 , G01N2333/96486 , G01N2333/966 , G01N2333/9726 , G01N2333/974 , G01N2333/976 , C12Q2541/101 , C12Q2525/101 , C12Q2521/301 , C12Q2525/155 , C12Q2521/501 , C12Q2521/107 , C12Q2521/319
摘要： This invention is directed to a method for identifying nucleic acid ligands by the SELEX method wherein the participation of fixed sequences is eliminated or minimized.
摘要翻译：本发明涉及通过SELEX方法鉴定核酸配体的方法，其中固定序列的参与被消除或最小化。

53. 发明申请

US20050009020A1 Microarray method for enriching dna fragments from complex mixtures 审中-公开
标题翻译：用于从复杂混合物中富集dna片段的微阵列方法
公开(公告)号：US20050009020A1
公开(公告)日：2005-01-13
申请号：US10474779
申请日：2002-04-11
申请人： Jurgen Distler
发明人： Jurgen Distler
IPC分类号： C12Q1/68 , C12Q1/6811 , C12Q1/6837 , C12P19/34
CPC分类号： C12Q1/6811 , C12Q1/6837 , C12Q2537/143 , C12Q2525/179 , C12Q2541/101
摘要： A method for the simultaneous, parallel, selective enrichment of different DNA segments which are obtained from different tissues by complex amplifications and have desired individual sequence properties is described. These properties of the DNA fragments, particularly the presence of 5-methylcytosines, can be identified by hybridization on DNA microarrays. The desired DNA fragments are enriched by several repetitions of the operating steps (hybridization, dehybridization and reamplification). The method combines the SELEX method with complex DNA arrays, which are used for the enrichment of DNA fragments. The sequence of the amplificates is then analyzed.
摘要翻译：描述了通过复合扩增从不同组织获得并具有期望的个体序列性质的不同DNA片段的同时，平行，选择性富集的方法。 DNA片段的这些性质，特别是5-甲基胞嘧啶的存在，可通过DNA微阵列杂交鉴定。通过几个重复的操作步骤（杂交，脱杂交和再扩增）来富集所需的DNA片段。该方法将SELEX方法与复杂DNA阵列结合，用于富集DNA片段。然后分析放大器的顺序。

54. 发明申请

US20050003380A1 Selective gene amplification 审中-公开
标题翻译：选择性基因扩增
公开(公告)号：US20050003380A1
公开(公告)日：2005-01-06
申请号：US10740133
申请日：2003-12-18
申请人： Helen Cohen , Bernie Kelly , Andrew Griffiths
发明人： Helen Cohen , Bernie Kelly , Andrew Griffiths
IPC分类号： C12N15/09 , C12N15/10 , C12Q1/68 , C12Q1/6811 , C12P19/34
CPC分类号： C12N15/1075 , C12N15/1058 , C12Q1/6811 , C12Q2541/101
摘要： A method is provided for selecting nucleric acids encoding gene product is in which the nucleic acid encoding the gene product is selectly and quantitatively amplified depending on the activity of the gene itself or the gene product. The method may, for example, be used in selecting gene products arising from in vitro evolution of molecular libraries.
摘要翻译：提供了选择编码基因产物的核酸的方法，其中编码基因产物的核酸根据基因本身或基因产物的活性被选择性并定量扩增。该方法可以例如用于选择由分子库的体外进化产生的基因产物。

55. 发明申请

US20040241731A1 Methods of producing nucleic acid ligands 失效
公开(公告)号：US20040241731A1
公开(公告)日：2004-12-02
申请号：US10818954
申请日：2004-04-06
申请人： GILEAD SCIENCES, INC.
发明人： Larry Gold , Craig Tuerk
IPC分类号： C12Q001/68 , C12P019/34
CPC分类号： B82Y5/00 , A61K38/00 , A61K47/547 , A61K47/549 , C07H21/00 , C07K7/22 , C07K14/001 , C07K14/005 , C07K14/72 , C12N9/1276 , C12N15/1048 , C12N15/1058 , C12N15/115 , C12N2310/13 , C12N2310/322 , C12N2310/53 , C12N2740/16222 , C12Q1/37 , C12Q1/6811 , C12Q1/703 , C40B40/00 , F02B2075/027 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , G01N33/6842 , G01N33/76 , G01N2333/16 , G01N2333/163 , G01N2333/503 , G01N2333/575 , G01N2333/62 , G01N2333/8125 , G01N2333/918 , G01N2333/96433 , G01N2333/96436 , G01N2333/96455 , G01N2333/96486 , G01N2333/966 , G01N2333/9726 , G01N2333/974 , G01N2333/976 , C12Q2541/101 , C12Q2525/101 , C12Q2525/301
摘要： The present invention includes methods for the identification and production of improved nucleic acid ligands based on the SELEX process. Also included are nucleic acid ligands to the HIV-RT protein identified according to the methods described therein.

56. 发明申请

US20040058884A1 Tenasin-C nucleic acid ligands 审中-公开
标题翻译：生物素-C核酸配体
公开(公告)号：US20040058884A1
公开(公告)日：2004-03-25
申请号：US10429176
申请日：2003-05-01
发明人： Brian Hicke , Stephen Warren , David Parma , Larry Gold
IPC分类号： A61K048/00 , C07H021/04
CPC分类号： C12N15/115 , A61K38/00 , A61K47/54 , A61K47/547 , A61K47/549 , A61K2123/00 , B82Y5/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/001 , C12N9/1276 , C12N15/1048 , C12N2310/13 , C12N2310/317 , C12N2310/3183 , C12N2310/321 , C12N2310/322 , C12N2310/3517 , C12N2310/53 , C12Q1/37 , C12Q1/6883 , C12Q2541/101 , C12Q2600/158 , C40B40/00 , F02B2075/027 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , G01N33/76 , G01N2333/16 , G01N2333/163 , G01N2333/503 , G01N2333/575 , G01N2333/62 , G01N2333/8125 , G01N2333/96433 , G01N2333/96455 , G01N2333/966 , G01N2333/9726 , G01N2333/974 , G01N2333/976 , C12N2310/3521
摘要： Methods are described for the identification and preparation of nucleic acid ligands to tenascin-C. Included in the invention are specific RNA ligands to tenascin-C identified by the SELEX method. Further included in the invention are methods for detecting the presence of a disease condition in a biological tissue in which tenascin-C is expressed.
摘要翻译：描述了用于鉴定和制备腱生蛋白-C的核酸配体的方法。包括在本发明中的是通过SELEX方法鉴定的腱生蛋白-C的特异性RNA配体。本发明还包括用于检测生物组织中存在腱生蛋白-C的疾病状况的方法。

57. 发明申请

US20030162216A1 Nucleic acid ligand diagnostic biochip 有权
标题翻译：核酸配体诊断生物芯片
公开(公告)号：US20030162216A1
公开(公告)日：2003-08-28
申请号：US10375487
申请日：2003-02-27
申请人： SomaLogic, Inc.
发明人： Larry Gold , Dominic A. Zichi
IPC分类号： C12Q001/68 , G01N033/53 , G01N033/542 , C12M001/34
CPC分类号： C12Q1/6839 , C07B2200/11 , C12Q1/6834 , C12Q1/6837 , C40B40/00 , Y10S977/924 , C12Q2565/514 , C12Q2565/101 , C12Q2541/101 , C12Q2525/205
摘要： A nucleic acid ligand nullbiochipnull is disclosed, consisting of a solid support to which one or more specific nucleic acid ligands is attached in a spatially defined manner. Each nucleic acid ligand binds specifically and avidly to a particular target molecule contained within a test mixture, such as a bodily fluid. The target molecules include, but are not limited to, proteins (cellular, viral, bacterial, etc.) hormones, sugars, metabolic byproducts, cofactor, and intermediates, drugs, and toxins. Contacting the test mixture with the biochip leads to the binding of a target molecule to its cognate nucleic acid ligand. The biochip may then be contacted with a reagent(s) that reacts covalently with proteins and not with nucleic acids. Each protein target in the test mixture may then detected by detecting the presence of the reagent at the appropriate address on the biochip.
摘要翻译：公开了一种核酸配体“生物芯片”，其由以空间限定的方式连接一个或多个特定核酸配体的固体支持物组成。每个核酸配体特异性地并且强烈地结合到测试混合物（例如体液）中所含的特定靶分子。靶分子包括但不限于蛋白质（细胞，病毒，细菌等）激素，糖，代谢副产物，辅因子和中间体，药物和毒素。将测试混合物与生物芯片接触导致靶分子与其同源核酸配体的结合。然后生物芯片可以与与蛋白质共价反应的试剂与不与核酸反应的试剂接触。然后可以通过检测生物芯片上适当地址处的试剂的存在来检测测试混合物中的每个蛋白质靶标。

58. 发明授权

US06528639B2 Base-modified enzymatic nucleic acid 失效
公开(公告)号：US06528639B2
公开(公告)日：2003-03-04
申请号：US09034113
申请日：1998-03-03
申请人： Nassim Usman , Leonid Beigelman , James McSwiggen , Alex Karpeisky
发明人： Nassim Usman , Leonid Beigelman , James McSwiggen , Alex Karpeisky
IPC分类号： C07H2104
CPC分类号： C07K14/005 , C07H19/06 , C07H21/00 , C12N15/113 , C12N15/85 , C12N15/86 , C12N2310/12 , C12N2310/121 , C12N2310/122 , C12N2310/123 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/334 , C12N2310/335 , C12N2310/336 , C12N2310/3521 , C12N2310/3531 , C12N2310/3533 , C12N2310/3535 , C12N2770/00022 , C12N2770/28122 , C12Q1/6811 , C12Q1/701 , C12Q2541/101 , C12Q2521/337
摘要： Method to produce a more active ribozyme by introducing a modified base into a substrate binding arm of the ribozyme or its catalytic core.

59. 发明授权

US06503715B1 Nucleic acid ligand diagnostic biochip 有权
标题翻译：核酸配体诊断生物芯片
公开(公告)号：US06503715B1
公开(公告)日：2003-01-07
申请号：US09723394
申请日：2000-11-28
申请人： Larry Gold , Dan Drolet , Dom Zichi , Sumedha Jayasena , Steve Creighton , Stanley Gill
发明人： Larry Gold , Dan Drolet , Dom Zichi , Sumedha Jayasena , Steve Creighton , Stanley Gill
IPC分类号： C12Q168
CPC分类号： C12Q1/6839 , C07B2200/11 , C12Q1/6834 , C12Q1/6837 , C40B40/00 , Y10S977/924 , C12Q2565/514 , C12Q2565/101 , C12Q2541/101 , C12Q2525/205
摘要： A Nucleic acid ligand “Biochip” is disclosed, consisting of a solid support to which one or more specific Nucleic acid ligands is attached in a spatially defined manner. Each Nucleic acid ligand binds specifically and avidly to a particular Target molecule contained within a Test mixture, such as a Bodily fluid. The Target molecules include, but are not limited to, proteins (cellular, viral, bacterial, etc.) hormones, sugars, metabolic byproducts, cofactor, and intermediates, drugs, and toxins. Contacting the Test mixture with the Biochip leads to the binding of a Target molecule to its cognate Nucleic acid ligand. Binding of Target to the Nucleic acid ligand results in a detectable change at each specific location on the Biochip. The detectable change can include, but is not limited to, a change in fluorescence, or a change in a physical parameter, such as electrical conductance or refractive index, at each location on the Biochip. The Biochip will then be read by a device, such as a fluorescence scanner or a surface plasmon resonance detector, that can measure the magnitude of the change at each location on the Biochip. The location of the change reveals what Target molecule has been detected, and the magnitude of the change indicates how much of it is present. The combination of these two pieces of information will yield diagnostic and prognostic medical information when signal patterns are compared with those obtained from Bodily fluids of individuals with diagnosed disorders (FIG. 1). In principle, the Biochip could be used to test any chemically complex mixture provided that Nucleic acid ligands to components suspected of being present in the mixture are attached to the Biochip. Thus, the Nucleic acid ligand Biochip will have a wider use in environmental testing, etc.
摘要翻译：披露了一种核酸配体“生物芯片”，由一种或多种特定的核酸配体以空间限定的方式连接的固体支持物组成。每个核酸配体特异性地和特异性地结合到包含在测试混合物例如体液内的特定靶分子。靶分子包括但不限于蛋白质（细胞，病毒，细菌等）激素，糖，代谢副产物，辅因子和中间体，药物和毒素。将测试混合物与Biochip接触导致Target分子与其同源核酸配体的结合。靶向核酸配体的结合在Biochip上的每个特定位置产生可检测的变化。可检测的变化可以包括但不限于在生物芯片上的每个位置的荧光的变化或物理参数的变化，例如电导率或折射率。然后，生物芯片将被诸如荧光扫描仪或表面等离子体共振检测器的装置读取，该检测器可以测量Biochip上每个位置的变化幅度。变化的位置揭示了目标分子被检测到的，变化的大小表明它有多少存在。当将信号模式与从具有诊断障碍的个体的体液获得的信号模式进行比较时，这两条信息的组合将产生诊断和预后的医学信息（图1）。原则上，生物芯片可以用于测试任何化学复合物混合物，只要核酸配体与怀疑存在于混合物中的组分连接在Biochip上即可。因此，核酸配体生物芯片将在环境测试等方面有更广泛的应用。

60. 发明授权

US06482594B2 Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands 失效
标题翻译：配体通过指数富集的系统演化：核酸配体的选择
公开(公告)号：US06482594B2
公开(公告)日：2002-11-19
申请号：US09882246
申请日：2001-06-14
申请人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
发明人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
IPC分类号： C12Q168
CPC分类号： G01N33/76 , A61K47/547 , A61K47/549 , B82Y5/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/001 , C12N9/1276 , C12N15/1048 , C12N15/115 , C12N2310/13 , C12N2310/322 , C12N2310/53 , C12Q1/37 , C12Q1/6811 , C12Q1/703 , C40B40/00 , F02B2075/027 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , G01N2333/163 , G01N2333/575 , G01N2333/62 , G01N2333/8125 , G01N2333/96433 , G01N2333/96455 , G01N2333/966 , G01N2333/9726 , G01N2333/974 , G01N2333/976 , C12Q2541/101 , C12Q2523/313
摘要： Methods to obtain nucleic acid ligands that photocrosslink to target molecules associated with a disease state are provided. The methods presented are variations on the photoSELEX methods for obtaining nucleic acid ligands. In one method, a candidate mixture of photocrosslinkable nucleic acids is contacted with a biological substance obtained from a source associated with a disease state suspected of containing a target molecule to form nucleic acid-target molecule complexes, the complexes are irradiated to form crosslinked complexes, the photocrosslinked complexes are partitioned from the remainder of the candidate mixture; and the nucleic acid ligands that photocrosslink to molecule are retained. These nucleic acids are then contacted with a second biological substance of the same type as the first, but obtained from a source not associated with a disease state. This removes nucleic acids with affinity to molecules that are not associated with the disease state. In another method, photocrosslinkable nucleic acids are not incorporated in the initial candidate mixture, but rather are incorporated in an enriched candidate mixture obtained by contacting a biological substance associated with a disease state containing a target molecule to form nucleic acid-target molecule complexes, partitioning the complexes away from the candidate mixture.
摘要翻译：提供了获得与疾病状态相关的靶分子光交联的核酸配体的方法。所提出的方法是用于获得核酸配体的photoSELEX方法的变化。在一种方法中，光可交联核酸的候选混合物与从怀疑含有靶分子的疾病状态的来源获得的生物物质接触以形成核酸 - 靶分子复合物，照射复合物以形成交联的复合物，将光致交联复合物与候选混合物的其余部分分隔开; 并保留与分子光交联的核酸配体。然后将这些核酸与与第一种相同类型的第二生物物质接触，但从不与疾病状态相关的来源获得。这样就可以去除与疾病状态无关的分子的亲和力的核酸。在另一种方法中，光可交联核酸不并入初始候选混合物中，而是掺入通过使与含有靶分子的疾病状态相关的生物物质接触形成核酸 - 靶分子复合物，分配远离候选混合物的复合物。

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