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91. 发明申请

US20030186260A1 Simple method of biologically evaluating natural and artificial chemicals by using dna injury index and apparatus therefor 审中-公开
标题翻译：通过使用dna损伤指数及其设备对天然和人造化学品进行生物评估的简单方法
公开(公告)号：US20030186260A1
公开(公告)日：2003-10-02
申请号：US10203553
申请日：2002-08-28
发明人： Atsushi Takaki
IPC分类号： C12Q001/68
CPC分类号： G01N33/52 , C12Q1/025 , C12Q1/68 , G01N33/5014 , C12Q2525/117 , C12Q2523/113 , C12Q2523/313
摘要： A biological evaluation method for rational and simply evaluating biological harmfulness or usefulness of a great number of natural and artificial chemicals, foods, etc. This method comprises adding a known amount of 2null-deoxyguanosine (dG) to a solution containing a test substance (drug, pesticide, functional food, etc.), optionally applying UV light and/or adding active oxygen generator, then quantifying 8-hydroxy-2null-deoxyguanosine (8OHdG) in the solution, and evaluating the toxicity or usefulness of the test substance according to the 8OhdG content (a higher 8OhdG content indicates a higher harmfulness of the test substance while a lower 8OhdG content indicates a lower harmfulness or an usefulness thereof). The invention also provide an apparatus for advantageously performing said biological evaluation method and an antioxidant preservative solution to be used in this apparatus.
摘要翻译：一种用于合理，简单地评估大量天然和人造化学品，食品等的生物有害性或有用性的生物学评估方法。该方法包括将已知量的2'-脱氧鸟苷（dG）加入到含有测试物质的溶液药物，农药，功能性食品等），任选地应用UV光和/或添加活性氧发生剂，然后定量溶液中的8-羟基-2'-脱氧鸟苷（8OHdG），并评估测试物质的毒性或有用性根据8OhdG含量（较高的8 OhdG含量表示测试物质的较高的有害性，而较低的8 OhdG含量表示较低的有害性或其有用性）。本发明还提供了用于有利地进行所述生物学评价方法的装置和用于该装置中的抗氧化防腐剂溶液。

92. 发明申请

US20030036058A1 Modified oligonucleotides and methods for determining the presence of a nucleic acid analyte in a sample 有权
标题翻译：用于测定样品中核酸分析物的存在的修饰的寡核苷酸和方法
公开(公告)号：US20030036058A1
公开(公告)日：2003-02-20
申请号：US09808558
申请日：2001-03-14
发明人： Michael M. Becker , Mehrdad Majlessi , Steven T. Brentano
IPC分类号： C12Q001/68 , C12P019/34
CPC分类号： C12Q1/6832 , C07H21/00 , C12Q1/6816 , C12Q1/6844 , C12Q1/686 , C12Q1/6865 , C12Q2563/131 , C12Q2563/113 , C12Q2525/101 , C12Q2525/117 , C12Q2527/107
摘要： The present invention concerns oligonucleotides containing one or more modified nucleotides which increase the binding affinity of the oligonucleotides to target nucleic acids having a complementary nucleotide base sequence. These modified oligonucleotides hybridize to the target sequence at a faster rate than unmodified oligonucleotides having an identical nucleotide base sequence. Such modified oligonucleotides include oligonucleotides containing at least one 2null-O-methylribofuranosyl moiety joined to a nitrogenous base. Oligonucleotides can be modified in accordance with the present invention to preferentially bind RNA targets. The present invention also concerns methods of using these modified oligonucleotides and kits containing the same.
摘要翻译：本发明涉及含有一个或多个修饰的核苷酸的寡核苷酸，其增加寡核苷酸与具有互补核苷酸碱基序列的靶核酸的结合亲和力。这些修饰的寡核苷酸以比具有相同核苷酸碱基序列的未修饰寡核苷酸更快的速率与靶序列杂交。这种修饰的寡核苷酸包括含有至少一个连接到含氮碱基的2'-O-甲基呋喃核糖基部分的寡核苷酸。可以根据本发明修饰寡核苷酸以优先结合RNA靶。本发明还涉及使用这些修饰的寡核苷酸的方法和含有该寡核苷酸的试剂盒。

93. 发明授权

US06506562B1 Allele frequency differences method for phenotype cloning 有权
标题翻译：等位基因频率差异法表型克隆
公开(公告)号：US06506562B1
公开(公告)日：2003-01-14
申请号：US09427104
申请日：1999-10-26
申请人： Sherman M. Weissman , Jon J. Jonsson
发明人： Sherman M. Weissman , Jon J. Jonsson
IPC分类号： C07H2104
CPC分类号： C12Q1/683 , C12Q1/6809 , C12Q2537/113 , C12Q2525/191 , C12Q2525/131 , C12Q2537/107 , C12Q2525/137 , C12Q2521/331 , C12Q2521/313 , C12Q2531/113 , C12Q2525/117
摘要： A general method is described for screening cDNAs, genes or genome segments to directly isolate and characterize sequences associated with particular phenotypes. In the case of the human genome, a simplification of the starting material is needed, and a specific method to generate highly polymorphic genome subsets for this purpose is presented. The general screening method identifies DNA sequences containing allele frequency differences when groups with dissimilar phenotypes are compared. The approach is based on mathematical principles of inequality. A change in the abundance ratio of homoduplexes of perfectly matched sequences to heteroduplexes of perfectly matched sequences, or, conversely, of mismatched homoduplexes to mismatched heteroduplexes, serves as an indicator of allele frequency difference.
摘要翻译：描述了筛选cDNA，基因或基因组片段以直接分离和表征与特定表型相关的序列的一般方法。在人类基因组的情况下，需要简化起始材料，并且提出了为此目的产生高度多态性基因组子集的具体方法。当比较具有不同表型的组时，一般筛选方法鉴定含有等位基因频率差异的DNA序列。这种方法是基于不平等的数学原理。完全匹配序列的同源双链体与完全匹配序列的异源双链体的丰度比的变化，或者相反地，将错配的同源双链体与错配的异源双链体的变化作为等位基因频率差异的指标。

94. 发明申请

US20020197618A1 Synthesis and amplification of unstructured nucleic acids for rapid sequencing 审中-公开
标题翻译：用于快速测序的非结构化核酸的合成和扩增
公开(公告)号：US20020197618A1
公开(公告)日：2002-12-26
申请号：US10052926
申请日：2002-01-16
发明人： Jeffrey R. Sampson
IPC分类号： C12Q001/68 , C12M001/34
CPC分类号： G01N33/48721 , C12Q1/6806 , C12Q1/6869 , C12Q2565/631 , C12Q2525/117 , C12Q2525/101 , C12Q2525/143 , C12Q2531/125
摘要： The present invention provides an improved method of nanopore sequencing by generating a nucleic acid molecule to be sequenced having tandem repeats of a sequence, and also having modified nucleotides which reduce the levels of secondary structure. The presence of tandemly repeated sequence and the absence of secondary structure increases the rate of sequencing and accuracy of sequences generated by nanopore sequencing.
摘要翻译：本发明通过产生具有序列的串联重复序列的待测序的核酸分子并且还具有降低二级结构水平的经修饰的核苷酸来提供纳米孔测序的改进方法。串联重复序列的存在和不存在二级结构增加了通过纳米孔测序产生的序列的测序速率和准确性。

95. 发明申请

US20020102586A1 Massive parallel method for decoding DNA and RNA 有权
标题翻译：用于解码DNA和RNA的大规模并行方法
公开(公告)号：US20020102586A1
公开(公告)日：2002-08-01
申请号：US09972364
申请日：2001-10-05
发明人： Jingyue Ju , Zengmin Li , John Robert Edwards , Yasuhiro Itagaki
IPC分类号： C12Q001/68 , C12P019/34
CPC分类号： C07H19/14 , C07B2200/11 , C07H19/10 , C07H21/00 , C12Q1/68 , C12Q1/686 , C12Q1/6869 , C12Q1/6872 , C12Q1/6874 , C12Q1/6876 , C12Q2525/117 , C12Q2535/101 , C12Q2535/122 , C12Q2563/107 , C40B40/00 , C12Q2565/501 , C12Q2525/186
摘要： This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap the nullOH group at the 3null-position of the deoxyribose.
摘要翻译：本发明提供了通过在聚合酶反应中将核苷酸类似物掺入DNA的生长链中之后检测核苷酸类似物的同一性来提供将核酸连接到固体表面和测序核酸的方法。本发明还提供核苷酸类似物，其包含通过可切割连接子连接至核苷酸类似物的独特标记，以及可脱氧化学基团以封端脱氧核糖3'-位上的-OH基团。

96. 发明申请

US20020072095A1 Process for controlling contamination of nucleic acid amplification reactions 有权
标题翻译：控制核酸扩增反应污染的方法
公开(公告)号：US20020072095A1
公开(公告)日：2002-06-13
申请号：US09782516
申请日：2001-02-14
申请人： Invitrogen Corporation,
发明人： James L. Hartley , Mark Berninger
IPC分类号： C12P019/34 , C12Q001/68
CPC分类号： C12Q1/6848 , C12Q1/6853 , C12Q1/708 , Y10S435/81 , C12Q2525/117 , C12Q2521/531 , C12Q2531/113 , C12Q2525/186 , C12Q2531/137 , C12Q2521/301 , C12Q2537/137 , C12Q2525/101
摘要： This invention relates to a method of incorporating an exo-sample nucleotide into the amplified product strands resulting from a nucleic acid amplification process. Once the product strands have been obtained and analyzed (e.g., by hybridization, Southern blot, etc.), the exo-sample strands can be selectively destroyed by acting on the incorporated exo-sample nucleotide. Two embodiments are presented. In a first embodiment, the exo-sample nucleotide is incorporated by carrying out the amplification reaction in the presence of an excess of exo-sample nucleotide triphosphate. In a second embodiment, the exo-sample nucleotide is incorporated by carrying out the amplification reaction in the presence of an oligonucleotide which has, as part of its sequence, one or more exo-sample nucleotides.
摘要翻译：本发明涉及将外切样品核苷酸掺入由核酸扩增过程产生的扩增产物链中的方法。一旦获得并分析了产物链（例如通过杂交，Southern印迹等），可以通过作用于外加的外切核苷酸来选择性地破坏外部样品链。呈现两个实施例。在第一个实施方案中，通过在过量样品核苷酸三磷酸的存在下进行扩增反应来引入外切核苷酸。在第二个实施方案中，通过在寡核苷酸的存在下进行扩增反应来引入外切核苷酸，所述寡核苷酸作为其序列的一部分，具有一个或多个外切核苷酸。

97. 发明申请

US20010031483A1 Primer-mediated polynucleotide synthesis and manipulation techniques 审中-公开
标题翻译：引物介导的多核苷酸合成和操作技术
公开(公告)号：US20010031483A1
公开(公告)日：2001-10-18
申请号：US09795965
申请日：2001-02-28
申请人： Stratagene
发明人： Joseph A. Sorge , Kerstien A. Padgett
IPC分类号： C12P001/00 , C07K001/00 , C07K014/00 , C07K017/00 , C12Q001/68
CPC分类号： C12N15/66 , C12N15/10 , C12Q1/686 , C12Q2525/131 , C12Q2525/117
摘要： The invention provides improved techniques for conveniently manipulating polynucleotides of interest without the need to rely upon the presence of naturally occurring restriction sites. Additionally, using the methods and primers of the invention, one may synthesize a polynucleotide of interest in a form which is easily and directionally cloned into a DNA sequence of choice without necessarily introducing extraneous nucleotides in the final polynucleotide product. The methods of the invention employ releasable primers that comprise a recognition site for a releasing enzyme joined to a region for annealing to the polynucleotide template of interest. Polynucleotide sequences of interest are synthesized using one or more synthesis primers, wherein at least one of the primers is a releasable primer. After synthesis, the synthesis product is cleaved by a releasing enzyme. In a preferred embodiment of the invention, inhibitory base analogs are incorporated in the synthesis product to protect against the formation of unwanted internal cleavage products. In another embodiment of the invention, at least one of the releasable primers is bound to an immobilizing solid phase support so as to produce immobilized synthesis products that may be conveniently released by a releasing enzyme. Another aspect of the invention is to provide releasable primers and kits for performing the subject methods. Typically, such kits may comprise a releasing enzyme and one or more reagents for performing a polynucleotide synthesis reaction, preferably a cyclic amplification reaction.
摘要翻译：本发明提供了用于方便地操作感兴趣的多核苷酸的改进的技术，而不需要依赖天然存在的限制性位点的存在。另外，使用本发明的方法和引物，人们可以以容易且定向克隆到选择的DNA序列中的形式合成感兴趣的多核苷酸，而不必在最终多核苷酸产物中引入外来核苷酸。本发明的方法使用可释放的引物，其包含连接到用于退火的感兴趣的多核苷酸模板的区域的释放酶的识别位点。使用一种或多种合成引物合成感兴趣的多核苷酸序列，其中至少一种引物是可释放引物。合成后，合成产物被释放酶切割。在本发明的优选实施方案中，将抑制性碱基类似物掺入合成产物中以防止形成不需要的内部裂解产物。在本发明的另一个实施方案中，至少一个可释放的引物与固定的固相载体结合，以产生可通过释放酶方便地释放的固定的合成产物。本发明的另一方面是提供用于实施本发明方法的可释放的底漆和试剂盒。通常，这样的试剂盒可以包含释放酶和用于进行多核苷酸合成反应的一种或多种试剂，优选循环扩增反应。

98. 发明授权

US06232462B1 Reduction of nonspecific hybridization by using novel base-pairing schemes 失效
标题翻译：通过使用新的碱基配对方案减少非特异性杂交
公开(公告)号：US06232462B1
公开(公告)日：2001-05-15
申请号：US09115566
申请日：1998-07-14
申请人： Mark L. Collins , Thomas Horn , Patrick J Sheridan , Brian D. Warner , Michael S. Urdea
发明人： Mark L. Collins , Thomas Horn , Patrick J Sheridan , Brian D. Warner , Michael S. Urdea
IPC分类号： C07H2100
CPC分类号： C12N15/113 , C07H19/16 , C07H19/20 , C07H21/00 , C12N2310/322 , C12N2310/336 , C12Q1/68 , C12Q1/6811 , C12Q1/6813 , C12Q1/682 , C12Q1/6832 , C12Q1/6837 , C12Q2527/107 , C12Q2525/117 , C12Q2525/113
摘要： Methods are provided for substantially reducing background signals encountered in nucleic acid hybridization assays. The method is premised on the elimination or significant reduction of the phenomenon of nonspecific hybridization, so as to provide a detectable signal which is produced only in the presence the target polynucleotide of interest. In addition, a novel method for the chemical synthesis of isoguanosine or 2′-deoxy-isoguanosine is provided. The invention also has applications in antisense and aptamer therapeutics and drug discovery.
摘要翻译：提供了用于基本上减少在核酸杂交测定中遇到的背景信号的方法。该方法的前提是消除或显着降低非特异性杂交的现象，从而提供仅在存在目标目的多核苷酸的情况下产生的可检测信号。另外，提供了一种用于化学合成异鸟嘌呤或2'-脱氧 - 异鸟嘌呤的新方法。本发明还可应用于反义和适体治疗剂和药物发现。

99. 发明授权

US06190865B1 Method for characterizing nucleic acid molecules 失效
标题翻译：表征核酸分子的方法
公开(公告)号：US06190865B1
公开(公告)日：2001-02-20
申请号：US08534799
申请日：1995-09-27
申请人： Jerome J. Jendrisak , Leslie M. Hoffman , Robert E. Smith
发明人： Jerome J. Jendrisak , Leslie M. Hoffman , Robert E. Smith
IPC分类号： C12Q168
CPC分类号： C12Q1/6869 , C12Q1/6848 , C12Q2525/119 , C12Q2525/117 , C12Q2521/531 , C12Q2525/101
摘要： A method of characterizing a nucleic acid molecule is disclosed. The method comprises synthesizing DNA in the presence of a reaction mixture comprising a nucleic acid template, a primer molecule, an enzyme that extends the primer so that a DNA molecule may be synthesized, four canonical deoxynucleoside triphosphates and at least one non-canonical deoxynucleoside triphosphate. The non-canonical deoxynucleoside triphosphate is incorporated into the synthesized DNA in place of a portion of only one canonical deoxynucleoside triphosphate. The synthesized DNA is treated with an N-glycosylase that excises a base portion of the non-canonical deoxynucleoside triphosphate from the synthesized DNA. The DNA is then treated in such a manner that the phosphodiester backbone of the DNA is broken at the abasic site, thus creating at least two DNA fragments. The fragments are separated according to size.
摘要翻译：公开了表征核酸分子的方法。该方法包括在包含核酸模板，引物分子，延伸引物以使得可以合成DNA分子的酶的反应混合物存在下合成DNA，四种典型脱氧核苷三磷酸和至少一种非标准脱氧核苷三磷酸。将非标准脱氧核苷三磷酸引入合成的DNA中代替仅一个典型脱氧核苷三磷酸的一部分。合成的DNA用从合成的DNA中切除非标准脱氧核苷三磷酸的碱基的N-糖基化酶处理。然后以这样的方式处理DNA，使得DNA的磷酸二酯骨架在脱碱基位点断裂，从而产生至少两个DNA片段。碎片根据大小分离。

100. 发明申请

US20180274024A1 DESIGN AND SYNTHESIS OF NOVEL DISULFIDE LINKER BASED NUCLEOTIDES AS REVERSIBLE TERMINATORS FOR DNA SEQUENCING BY SYNTHESIS 审中-公开
公开(公告)号：US20180274024A1
公开(公告)日：2018-09-27
申请号：US15763364
申请日：2016-09-28
申请人： Jingyue Ju , Xiaoxu Li , Xin Chen , Zengmin Li , Shiv Kumar , Shundi Shi , Cheng Guo , Jianyi Ren , Min-Kang Hsieh , Minchen Chien , Chuanjuan Tao , Ece Erturk , Sergey Kalachikov , James J. Russo
发明人： Jingyue Ju , Xiaoxu Li , Xin Chen , Zengmin Li , Shiv Kumar , Shundi Shi , Cheng Guo , Jianyi Ren , Min-Kang Hsieh , Minchen Chien , Chuanjuan Tao , Ece Erturk , Sergey Kalachikov , James J. Russo
IPC分类号： C12Q1/6869 , C07H19/20 , C07H19/10 , C07H19/14
CPC分类号： C12Q1/6869 , C07H19/10 , C07H19/14 , C07H19/20 , C12Q2525/117 , C12Q2563/107
摘要： Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof in the sequencing of a nucleic acid.

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