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41. 发明授权

US5723598A Encoded combinatorial chemical libraries 失效
公开(公告)号：US5723598A
公开(公告)日：1998-03-03
申请号：US665511
申请日：1996-06-18
申请人： Richard Lerner , Kim Janda , Sydney Brenner
发明人： Richard Lerner , Kim Janda , Sydney Brenner
IPC分类号： G01N33/53 , C07H21/00 , C07H21/04 , C07K14/00 , C12N15/09 , C12N15/10 , C12Q1/68 , C40B70/00
CPC分类号： C12N15/1075 , C07H21/00 , C12N15/1062 , B01J2219/00572 , C40B70/00
摘要： The present invention describes an encoded combinatorial chemical library comprised of a plurality of bifunctional molecules having both a chemical polymer and an identifier oligonucleotide sequence that defines the structure of the chemical polymer. Also described are the bifunctional molecules of the library, and methods of using the library to identify chemical structures within the library that bind to biologically active molecules in preselected binding interactions.

42. 发明授权

US5552278A DNA sequencing by stepwise ligation and cleavage 失效
标题翻译：通过逐步连接和切割进行DNA测序
公开(公告)号：US5552278A
公开(公告)日：1996-09-03
申请号：US280441
申请日：1994-07-25
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C12N15/09 , C12Q1/42 , C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6869 , C12Q1/6862 , C12Q1/6874 , Y02P20/582
摘要： The invention provides a method of nucleic acid sequence analysis based on repeated cycles of ligation to and cleavage of probes at the terminus of a target polynucleotide. At each such cycle one or more terminal nucleotides are identified and one or more nucleotides are removed from the end of the target polynucleotide, such that further cycles of ligation and cleavage can take place. At each cycle the target sequence is shortened by one or more nucleotides until the nucleotide sequence of the target polynucleotide is determined. The method obviates electrophoretic separation of similarly sized DNA fragments and eliminates the difficulties associated with the detection and analysis of spacially overlapping bands of DNA fragments in a gel, or like medium. The invention further obviates the need to generate DNA fragments from long single stranded templates with a DNA polymerase.
摘要翻译：本发明提供了基于在靶多核苷酸的末端连接和切割探针的重复循环的核酸序列分析方法。在每个这样的循环中，鉴定一个或多个末端核苷酸并从靶多核苷酸的末端去除一个或多个核苷酸，从而可以进一步进行连接和切割循环。在每个循环中，靶序列缩短一个或多个核苷酸，直到确定靶多核苷酸的核苷酸序列。该方法避免了类似大小的DNA片段的电泳分离，并消除了与凝胶或类似培养基中DNA片段的空间重叠带的检测和分析相关的困难。本发明进一步避免了用DNA聚合酶从长单链模板产生DNA片段的需要。

43. 发明授权

US08476018B2 Methods and compositions for tagging and identifying polynucleotides 有权
公开(公告)号：US08476018B2
公开(公告)日：2013-07-02
申请号：US13466883
申请日：2012-05-08
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12N15/1065 , C12N15/1093 , C12P19/34 , C12Q1/6827 , C12Q1/6837 , Y10T436/143333 , C12Q2565/514 , C12Q2563/179 , C12Q2537/143 , C12Q2525/191
摘要： The invention provides methods and compositions for attaching oligonucleotide tags to polynucleotides for the purpose of carrying out analytical assays in parallel and for decoding the oligonucleotide tags of polynucleotides selected in such assays. Words, or subunits, of oligonucleotide tags index submixtures in successively more complex sets of submixtures (referred to herein as “tiers” of submixtures) that a polynucleotide goes through while successive words are added to a growing tag. By identifying each word of an oligonucleotide tag, a series of submixtures is identified including the first submixture that contains only a single polynucleotide, thereby providing the identity of the selected polynucleotide. The analysis of the words of an oligonucleotide tag can be carried out in parallel, e.g. by specific hybridization of the oligonucleotide tag to its tag complement on an addressable array; or such analysis can be carried out serially by successive specific hybridizations of labeled word complements, or the like.

44. 发明授权

US08445205B2 Nucleic acid analysis using sequence tokens 有权
公开(公告)号：US08445205B2
公开(公告)日：2013-05-21
申请号：US13211113
申请日：2011-08-16
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C12Q1/68 , C07H21/00 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q2563/179 , C12Q2537/113 , C12Q2525/186
摘要： The present invention provides methods and compositions for tagging nucleic acid sequence fragments, e.g., a set of nucleic acid sequence fragments from a single genome, with one or more unique members of a collection of oligonucleotide tags, or sequence tokens, which, in turn, can be identified using a variety of readout platforms. As a general rule, a given sequence token is used once and only once in any tag sequence. In addition, the present invention also provides methods for using the sequence tokens to efficiently determine variations in nucleotide sequences in the associated nucleic acid sequence fragments.

45. 发明申请

US20100216125A1 NUCLEIC ACID ANALYSIS USING SEQUENCE TOKENS 有权
标题翻译：使用序列昆虫的核酸分析
公开(公告)号：US20100216125A1
公开(公告)日：2010-08-26
申请号：US12428229
申请日：2009-04-22
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C12Q1/68 , C12P19/34 , C12M1/34
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q2563/179 , C12Q2537/113 , C12Q2525/186
摘要： The present invention provides methods and compositions for tagging nucleic acid sequence fragments, e.g., a set of nucleic acid sequence fragments from a single genome, with one or more unique members of a collection of oligonucleotide tags, or sequence tokens, which, in turn, can be identified using a variety of readout platforms. As a general rule, a given sequence token is used once and only once in any tag sequence. In addition, the present invention also provides methods for using the sequence tokens to efficiently determine variations in nucleotide sequences in the associated nucleic acid sequence fragments.
摘要翻译：本发明提供了用于标记核酸序列片段的方法和组合物，例如，来自单个基因组的一组核酸序列片段，与寡核苷酸标签或序列标记的集合的一个或多个唯一成员，可以使用各种读出平台来识别。作为一般规则，给定的序列令牌在任何标签序列中使用一次且仅一次。此外，本发明还提供了使用序列令牌有效地确定相关核酸序列片段中的核苷酸序列变异的方法。

46. 发明授权

US07365179B2 Multiplexed analytical platform 有权
标题翻译：复用分析平台
公开(公告)号：US07365179B2
公开(公告)日：2008-04-29
申请号：US10934617
申请日：2004-09-02
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C12N15/11 , C07H21/04
CPC分类号： C12Q1/6837 , C12Q2563/179
摘要： The invention provides a system and reagents for carrying out multiplexed analytical measurements using the hybridization of oligonucleotide tags to addressable solid phase supports to obtain simultaneous readouts from hundreds to tens of thousands of reactions. In one aspect of the invention, analyte interaction moieties, such as oligonucleotide probes, are produced that are each labeled with a unique synthesis tag constructed from a set of two-nucleotide “words.” During or after an assay, the synthesis tags are converted to hybridization tags that are used in the readout step. Hybridization tags are constructed to maximize discrimination in the readout. Hybridization tags of the invention are preferably constructed from oligonucleotide “words” selected from a minimally cross-hybridizing set using combinatorial synthesis techniques. In a further aspect, discrimination in the readout is enhanced by employing hybridization tags that are constructed with words having the “comma-less” property and by minimizing or eliminating extraneous nucleic acids associated with the hybridization tag during a readout step.
摘要翻译：本发明提供了一种系统和试剂，用于使用寡核苷酸标签与可寻址固相载体的杂交来进行多重分析测量，以获得从数百到数万个反应的同时读数。在本发明的一个方面，产生分析物相互作用部分，例如寡核苷酸探针，每个标记有由一组两核苷酸“单词”构成的唯一合成标签。在测定期间或之后，将合成标签转化为在读出步骤中使用的杂交标签。构建杂交标签以最大化读出中的区分。本发明的杂交标签优选由使用组合合成技术的从最小交叉杂交组中选出的寡核苷酸“词”构建。在另一方面，通过使用由具有“无逗号”性质的词组构成的杂交标签，以及通过在读出步骤期间最小化或消除与杂交标签相关的外来核酸来增强阅读中的鉴别。

47. 发明授权

US07282370B2 System and apparatus for sequential processing of analytes 有权
标题翻译：用于顺序处理分析物的系统和设备
公开(公告)号：US07282370B2
公开(公告)日：2007-10-16
申请号：US11207443
申请日：2005-08-18
申请人： John Bridgham , Kevin Corcoran , George Golda , Michael C. Pallas , Sydney Brenner
发明人： John Bridgham , Kevin Corcoran , George Golda , Michael C. Pallas , Sydney Brenner
IPC分类号： G01N21/76 , G01N21/00 , G01N37/00
CPC分类号： G01N21/253 , B01J2219/00274 , B01L3/5027 , B01L3/502715 , B01L3/502761 , B01L2200/0647 , B01L2200/10 , B01L2300/0877 , B01L2400/0403 , B01L2400/0475 , B01L2400/0622 , B01L2400/0644 , G01N2015/144 , G01N2015/1452 , G01N2035/00158 , Y10S435/81 , Y10T436/13 , Y10T436/143333
摘要： An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside of a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array. A key feature of the invention is the correlation of the sequence of optical signals generated by each microparticle in the planar array during the analytical process.
摘要翻译：提供了一种用于同时分析锚定到微粒的多个分析物的装置和系统。每个具有单一类型分析物的均匀群体的微粒被布置为在流动室内部基本上固定的平面阵列，其中分析过程的步骤通过将一系列处理试剂通过流体系统递送到微粒进行，微处理器控制。响应于这样的处理步骤，在每个微粒的表面产生光信号，其特征在于微粒携带的分析物与递送的处理试剂之间的相互作用。通过收集和记录由平面阵列中的所有微粒产生的光学信号的图像来同时分析多个分析物。本发明的一个关键特征是在分析过程中由平面阵列中的每个微粒产生的光信号序列的相关性。

48. 再颁专利

USRE39793E1 Compositions for sorting polynucleotides 有权
标题翻译：用于分选多核苷酸的组合物
公开(公告)号：USRE39793E1
公开(公告)日：2007-08-21
申请号：US09366081
申请日：1999-08-02
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C07H19/00 , C07H21/02 , C07H21/04 , C12Q1/68 , C12N15/09
CPC分类号： B01J19/0046 , B01J2219/005 , B01J2219/00572 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00648 , B01J2219/00659 , B01J2219/00722 , C07H21/00 , C12N15/10 , C12N15/1034 , C12N15/1065 , C12Q1/6809 , C12Q1/6816 , C12Q1/6827 , C12Q1/6834 , C12Q1/6837 , C12Q1/6855 , C12Q1/6874 , C40B40/06 , C40B70/00 , C40B80/00 , C12Q2565/518 , C12Q2563/107 , C12Q2563/185 , C12Q2525/191 , C12Q2565/519 , C12Q2521/501 , C12Q2565/501 , C12Q2521/313 , C12Q2525/161 , C12Q2523/101 , C12Q2525/185 , C12Q2565/514 , C12Q2563/131 , C12Q2561/125
摘要： The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention each consist of a plurality of subunits 3 to 6 nucleotides in length selected from a minimally cross-hybridizing set. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports. This embodiment provides a readily automated system for manipulating and sorting polynucleotides, particularly useful in large-scale parallel operations, such as large-scale DNA sequencing, mRNA fingerprinting, and the like, wherein many target polynucleotides or many segments of a single target polynucleotide are sequenced simultaneously.
摘要翻译：本发明提供了通过使用寡核苷酸标签来跟踪，鉴定和/或分类分子的分类或亚群的方法。本发明的寡核苷酸标签每个由选自最小交叉杂交组的长度为3至6个核苷酸的多个亚单位组成。最小交叉杂交组的亚基形成具有两个或更多个错配的双链体或三链体，同一组的任何其他亚基的互补体。在特定实施方案中可用的寡核苷酸标签的数量取决于每个标签的亚单位的数目和子单元的长度。本发明的一个重要方面是使用寡核苷酸标签通过将与多核苷酸连接的标签与其固相载体上的互补序列特异性杂交来分选多核苷酸。该实施方案提供了用于操纵和分选多核苷酸的容易自动化系统，特别可用于大规模并行操作，例如大规模DNA测序，mRNA指纹图谱等，其中单个靶多核苷酸的许多靶多核苷酸或多个片段是同时排序。

49. 发明申请

US20060051876A1 System and apparatus for sequential processing of analytes 有权
公开(公告)号：US20060051876A1
公开(公告)日：2006-03-09
申请号：US11207443
申请日：2005-08-18
申请人： John Bridgham , Kevin Corcoran , George Golda , Michael Pallas , Sydney Brenner
发明人： John Bridgham , Kevin Corcoran , George Golda , Michael Pallas , Sydney Brenner
IPC分类号： G01N33/50
CPC分类号： G01N21/253 , B01J2219/00274 , B01L3/5027 , B01L3/502715 , B01L3/502761 , B01L2200/0647 , B01L2200/10 , B01L2300/0877 , B01L2400/0403 , B01L2400/0475 , B01L2400/0622 , B01L2400/0644 , G01N2015/144 , G01N2015/1452 , G01N2035/00158 , Y10S435/81 , Y10T436/13 , Y10T436/143333
摘要： An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside of a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array. A key feature of the invention is the correlation of the sequence of optical signals generated by each microparticle in the planar array during the analytical process.

50. 发明授权

US06884612B2 Lambdoid bacteriophage vectors for expression of foreign proteins 失效
标题翻译：用于表达外源蛋白的羊类噬菌体载体
公开(公告)号：US06884612B2
公开(公告)日：2005-04-26
申请号：US08852020
申请日：1997-05-06
申请人： Ichiro Maruyama , Hiroko Maruyama , Sydney Brenner
发明人： Ichiro Maruyama , Hiroko Maruyama , Sydney Brenner
IPC分类号： C12N9/38 , C12N15/62 , C12N15/73 , C07H21/04 , C12N15/00 , C12N15/11 , C12P21/06
CPC分类号： C07K14/005 , C07K2319/00 , C07K2319/01 , C07K2319/20 , C07K2319/61 , C07K2319/735 , C12N9/2471 , C12N15/1037 , C12N15/62 , C12N15/73 , C12N2795/10322 , C12Y302/01023 , C40B40/02
摘要： Lambdoid phage comprising a matrix of proteins encapsulating a genome encoding first and second polypeptides of an autogenously assembling receptor and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a lambdoid phage tail protein matrix anchor domain fused to at least one of the polypeptides.
摘要翻译：包含蛋白质基质的蛋白质包含蛋白质基质，所述蛋白质基因组编码自身组装受体的第一和第二多肽，以及由第一和第二多肽组成的受体，所述受体通过与至少一个融合的羊链蛋白噬菌体尾蛋白基质锚结构域表面整合到基质中的多肽。

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