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11. 发明申请

US20120231462A1 ARTIFICIAL BASE PAIR CAPABLE OF FORMING SPECIFIC BASE PAIR 有权
标题翻译：人造基础配对形成特定基础对
公开(公告)号：US20120231462A1
公开(公告)日：2012-09-13
申请号：US13500635
申请日：2010-10-06
申请人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
IPC分类号： C12Q1/68 , C07K1/00 , G01N33/566 , C07H21/02 , C07H21/04
CPC分类号： C07H21/02 , C07H21/04 , C12Q1/6827 , C12Q1/6832 , C12Q2527/107 , C12Q2525/117
摘要： The present invention provides a double-stranded nucleic acid in which at least one nucleic acid strand includes an unnatural base that forms a self-complementary base pair or an unnatural base that forms a base pair with any natural base with substantially the same thermal stability. The present invention also provides a method of hybridizing a first nucleic acid strand with a second nucleic acid strand, wherein the first nucleic acid strand includes an unnatural base that forms a self-complementary base pair or an unnatural base that forms a base pair with any natural base with substantially the same thermal stability, and a method of applying the nucleic acid to SNP detection, a DNA chip, DNA/RNA computing, or an in vitro translation system. The present invention provides a method of introducing an unnatural base into a nucleic acid strand and thereby controlling the thermodynamic stability in hybridization of the nucleic acid strand.
摘要翻译：本发明提供双链核酸，其中至少一个核酸链包含形成自身互补碱基对的非天然碱基或与任何具有基本上相同热稳定性的天然碱形成碱基对的非天然碱基。本发明还提供了将第一核酸链与第二核酸链杂交的方法，其中所述第一核酸链包含形成自身互补碱基对的非天然碱基或与任意形成碱基对的非天然碱基具有基本上相同的热稳定性的天然碱基，以及将核酸应用于SNP检测，DNA芯片，DNA / RNA计算或体外翻译系统的方法。本发明提供了将非天然碱引入核酸链，从而控制核酸链杂交时的热力学稳定性的方法。

12. 发明授权

US08212014B2 Artificial base pairs and uses thereof 有权
标题翻译：人造碱基对及其用途
公开(公告)号：US08212014B2
公开(公告)日：2012-07-03
申请号：US11989840
申请日：2006-08-04
申请人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
IPC分类号： C07H21/00 , C07H21/02 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6816 , C12Q1/6844 , Y10T436/143333 , C12Q2563/107 , C12Q2525/101 , C12Q2525/117
摘要： The present invention provides nucleic acids based on novel artificial base pairing, as well as a preparation method and uses thereof.In the nucleic acids of the present invention, a nucleotide having a substituted or unsubstituted 2-formyl-1H-pyrrol-1-yl group as a base forms a base pair with a nucleotide having a 6-substituted 9H-purin-9-yl group as a base. The inventive method for preparing a nucleic acid comprises effecting transcription, reverse transcription or replication by using, as a template, a nucleic acid incorporating a nucleotide having a substituted or unsubstituted 2-formyl-1H-pyrrol-1-yl group as a base, so that the nucleotide having a 6-substituted 9H-purin-9-yl group is incorporated at a site complementary to the nucleotide having a substituted or unsubstituted 2-formyl-1H-pyrrol-1-yl group.
摘要翻译：本发明提供了基于新的人造碱基配对的核酸及其制备方法和用途。在本发明的核酸中，具有取代或未取代的2-甲酰基-1H-吡咯-1-基作为碱基的核苷酸与具有6-取代的9H-嘌呤-9-基的核苷酸形成碱基对集团为基地。用于制备核酸的本发明的方法包括通过使用掺入具有取代或未取代的2-甲酰基-1H-吡咯-1-基的核苷酸作为碱的核酸作为模板来实现转录，逆转录或复制，使得具有6-取代的9H-嘌呤-9-基的核苷酸掺入与具有取代或未取代的2-甲酰基-1H-吡咯-1-基的核苷酸互补的位点。

13. 发明授权

US08030478B2 Method for nucleic acid replication and novel artificial base pairs 有权
标题翻译：核酸复制方法和新型人造碱基对
公开(公告)号：US08030478B2
公开(公告)日：2011-10-04
申请号：US12096517
申请日：2006-12-07
申请人： Ichiro Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Shigeyuki Yokoyama
IPC分类号： C07H21/00
CPC分类号： C12P19/34 , C07H19/04 , C07H21/00 , C12Q1/6844 , C12Q2525/101 , C12Q2525/117 , C12Q2525/113
摘要： The present invention relates to a method for nucleic acid replication and novel artificial base pairs.The method of the present invention for nucleic acid replication is characterized in that a deoxyribonucleoside 5′-triphosphate, in which the hydroxyl group of phosphoric acid at the γ-position is substituted with a group selected from the group consisting of an amino group, a methylamino group, a dimethylamino group, a mercapto group and a fluoro group, is used as a substrate during replication reaction. The novel artificial base pairs of the present invention are characterized in that 7-(2-thienyl)-imidazo[4,5-b]pyridine (Ds) or an analog thereof forms a base pair with pyrrole-2-carbaldehyde (Pa) or an analog thereof.
摘要翻译：本发明涉及核酸复制的方法和新的人造碱基对。用于核酸复制的本发明的方法的特征在于，其中在γ-位上的磷酸的羟基被选自下列的基团取代的脱氧核糖核苷5'-三磷酸：氨基，甲基氨基，二甲基氨基，巯基和氟基在复制反应期间用作底物。本发明的新型人造碱基对的特征在于7-（2-噻吩基） - 咪唑并[4,5-b]吡啶（Ds）或其类似物与吡咯-2-甲醛（Pa）形成碱基对，或其类似物。

14. 发明授权

US07615628B2 Imidazopyridine derivatives 有权
标题翻译：咪唑并吡啶衍生物
公开(公告)号：US07615628B2
公开(公告)日：2009-11-10
申请号：US11795554
申请日：2006-01-17
申请人： Ichiro Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Shigeyuki Yokoyama
IPC分类号： C07H19/00 , C07H19/22
CPC分类号： C07H19/052
摘要： The present invention relates to a novel imidazo[4,5-b]pyridine derivative compound represented by Formula (I) and a pharmaceutically acceptable salt thereof. The present invention also relates to a method for preparing the above compound. The present invention further relates to a pharmaceutical composition comprising the above compound. The above compound has growth inhibitory activity on cancer cells, and this effect is dissociated from growth inhibitory activity on normal cells. This indicates that the compound is useful as a novel anticancer agent.
摘要翻译：本发明涉及由式（I）表示的新的咪唑并[4,5-b]吡啶衍生物及其药学上可接受的盐。本发明还涉及制备上述化合物的方法。本发明还涉及包含上述化合物的药物组合物。上述化合物对癌细胞具有生长抑制活性，并且这种作用与对正常细胞的生长抑制活性解离。这表明该化合物可用作新的抗癌剂。

15. 发明申请

US20140194320A1 METHOD FOR PREPARING NUCLEIC ACID APTAMER 审中-公开
标题翻译：制备核酸APTAMER的方法
公开(公告)号：US20140194320A1
公开(公告)日：2014-07-10
申请号：US14237645
申请日：2012-08-08
申请人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
IPC分类号： C12N15/115 , C12Q1/68
CPC分类号： G01N33/543 , A61K31/7105 , C12N15/1048 , C12N15/115 , C12N2310/16 , C12N2320/13 , C12N2320/30 , C12N2330/30 , C12Q1/6834 , G01N33/5308 , G01N2333/47 , G01N2333/4703
摘要： An object of the present invention is to develop and provide a method for efficiently and conveniently producing a nucleic acid aptamer, particularly, a DNA aptamer, having high specificity for and high binding activity against a target substance. The present invention provides a method for producing a nucleic acid aptamer, comprising: a complex formation step of mixing a single-stranded nucleic acid library with a target substance in a solution to form a complex of a single-stranded nucleic acid and the target substance; an immobilization step of mixing the solution after the preceding step with a solid-phase support to immobilize the complex onto the solid-phase support via connector(s) adsorbed on the target substance and/or the solid-phase support; a recovery step of recovering the complex immobilized on the solid-phase support from the solution; an amplification step of recovering the single-stranded nucleic acid from the complex, followed by amplification by a nucleic acid amplification method; and a single-stranded nucleic acid preparation step of converting the double-stranded nucleic acids obtained in the amplification step into single strands and then forming an intramolecular conformation.
摘要翻译：本发明的目的是开发和提供一种有效且方便地制备对靶物质具有高特异性和高结合活性的核酸适体，特别是DNA适体。本发明提供了一种生产核酸适配体的方法，包括：在溶液中将单链核酸文库与目标物质混合以形成单链核酸与靶物质的复合物的复合物形成步骤 ; 固定步骤，将上述步骤之后的溶液与固相支持物混合，以通过吸附在目标物质和/或固相载体上的连接器将复合物固定在固相载体上; 从溶液中回收固定在固相载体上的络合物的回收步骤; 从复合物中回收单链核酸，然后用核酸扩增法扩增的扩增步骤; 以及将扩增步骤中得到的双链核酸转化为单链然后形成分子内构象的单链核酸制备步骤。

16. 发明授权

US08426569B2 DNA capable of being amplified by PCR with high selectivity and high efficiency 有权
标题翻译：能够通过PCR以高选择性和高效率扩增的DNA
公开(公告)号：US08426569B2
公开(公告)日：2013-04-23
申请号：US12934066
申请日：2009-03-31
申请人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
IPC分类号： C07H21/02 , C07H21/00 , C07H19/044 , C07H19/052
CPC分类号： C07H21/04 , C12Q1/6806 , C12Q1/6844 , C12Q1/6853 , C12Q1/6869 , C12Q2525/101 , C12Q2525/117
摘要： The present invention relates to unnatural base pairs of Ds (a 7-(2 thienyl)-3H-imidazo[4,5-b]pyridine-3-yl group) and a Pa derivative (a 2-nitro-1H-pyrrole-1-yl group bearing a substituent having a π-electron system attached at position 4) that can be replicated with high selectivity/high efficiency, and methods for replicating nucleic acids containing the unnatural base pairs. The present invention also relates to methods for incorporating an unnatural base bearing a functional substituent attached thereto into DNA by a nucleic acid replication reaction. The present invention also relates to methods for replicating and selectively collecting a nucleic acid containing an unnatural base pair from a nucleic acid pool. The present invention also relates to methods for determining a sequence of natural bases in the proximity of an unnatural base in DNA for achieving highly efficient and highly selective replication of a nucleic acid containing the unnatural base.
摘要翻译：本发明涉及Ds（7-（2噻吩基）-3H-咪唑并[4,5-b]吡啶-3-基）和Pa衍生物（2-硝基-1H-吡咯-2-基）带有具有连接在位置4上的π电子系统的取代基的1-基团）可以以高选择性/高效率复制，以及用于复制含有非天然碱基对的核酸的方法。本发明还涉及通过核酸复制反应将具有连接到其上的功能性取代基的非天然碱掺入DNA中的方法。本发明还涉及用于从核酸池复制和选择性收集含有非天然碱基对的核酸的方法。本发明还涉及用于确定DNA中非天然碱基附近的天然碱基序列的方法，以实现含有非天然碱的核酸的高效和高选择性复制。

17. 发明申请

US20110053782A1 NOVEL DNA CAPABLE OF BEING AMPLIFIED BY PCR WITH HIGH SELECTIVITY AND HIGH EFFICIENCY 有权
标题翻译：通过PCR具有高选择性和高效率扩增的新型DNA
公开(公告)号：US20110053782A1
公开(公告)日：2011-03-03
申请号：US12934066
申请日：2009-03-31
申请人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
IPC分类号： C40B20/00 , C12P19/34 , C07H21/00
CPC分类号： C07H21/04 , C12Q1/6806 , C12Q1/6844 , C12Q1/6853 , C12Q1/6869 , C12Q2525/101 , C12Q2525/117
摘要： The present invention relates to unnatural base pairs of Ds (a 5-amino-7-(2-thienyl)-3H-imidazo[4,5-b]pyridine-3-yl group) and a Pa derivative (a 2-nitro-1H-pyrrole-1-yl group bearing a substituent having a π-electron system attached at position 4) that can be replicated with high selectivity/high efficiency, and methods for replicating nucleic acids containing the unnatural base pairs. The present invention also relates to methods for incorporating an unnatural base bearing a functional substituent attached thereto into DNA by a nucleic acid replication reaction. The present invention also relates to methods for replicating and selectively collecting a nucleic acid containing an unnatural base pair from a nucleic acid pool. The present invention also relates to methods for determining a sequence of natural bases in the proximity of an unnatural base in DNA for achieving highly efficient and highly selective replication of a nucleic acid containing the unnatural base.
摘要翻译：本发明涉及Ds（5-氨基-7-（2-噻吩基）-3H-咪唑并[4,5-b]吡啶-3-基）和Pa衍生物（2-硝基具有可以以高选择性/高效率复制的位置4上连接的＆pgr-电子系统的取代基的-1H-吡咯-1-基以及用于复制含有非天然碱基对的核酸的方法。本发明还涉及通过核酸复制反应将具有连接到其上的功能性取代基的非天然碱掺入DNA中的方法。本发明还涉及用于从核酸池复制和选择性收集含有非天然碱基对的核酸的方法。本发明还涉及用于确定DNA中非天然碱基附近的天然碱基序列的方法，以实现含有非天然碱的核酸的高效和高选择性复制。

18. 发明申请

US20100285598A1 Novel Artificial Base Pairs and Uses Thereof 有权
标题翻译：新型人造基础对及其用途
公开(公告)号：US20100285598A1
公开(公告)日：2010-11-11
申请号：US11989840
申请日：2006-08-04
申请人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Michiko Hirao , Shigeyuki Yokoyama
IPC分类号： G01N33/00 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6816 , C12Q1/6844 , Y10T436/143333 , C12Q2563/107 , C12Q2525/101 , C12Q2525/117
摘要： The present invention provides nucleic acids based on novel artificial base pairing, as well as a preparation method and uses thereof.In the nucleic acids of the present invention, a nucleotide having a substituted or unsubstituted 2-formyl-1H-pyrrol-1-yl group as a base forms a base pair with a nucleotide having a 6-substituted 9H-purin-9-yl group as a base. The inventive method for preparing a nucleic acid comprises effecting transcription, reverse transcription or replication by using, as a template, a nucleic acid incorporating a nucleotide having a substituted or unsubstituted 2-formyl-1H-pyrrol-1-yl group as a base, so that the nucleotide having a 6-substituted 9H-purin-9-yl group is incorporated at a site complementary to the nucleotide having a substituted or unsubstituted 2-formyl-1H-pyrrol-1-yl group.
摘要翻译：本发明提供了基于新的人造碱基配对的核酸及其制备方法和用途。在本发明的核酸中，具有取代或未取代的2-甲酰基-1H-吡咯-1-基作为碱基的核苷酸与具有6-取代的9H-嘌呤-9-基的核苷酸形成碱基对集团为基地。用于制备核酸的本发明的方法包括通过使用掺入具有取代或未取代的2-甲酰基-1H-吡咯-1-基的核苷酸作为碱的核酸作为模板来实现转录，逆转录或复制，使得具有6-取代的9H-嘌呤-9-基的核苷酸掺入与具有取代或未取代的2-甲酰基-1H-吡咯-1-基的核苷酸互补的位点。

19. 发明申请

US20090286247A1 Novel nucleic acid base pair 审中-公开
标题翻译：新型核酸碱基对
公开(公告)号：US20090286247A1
公开(公告)日：2009-11-19
申请号：US12459794
申请日：2009-07-07
申请人： Ichiro Hirao , Masahide Ishikawa , Tsuyoshi Fujihara , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Masahide Ishikawa , Tsuyoshi Fujihara , Shigeyuki Yokoyama
IPC分类号： C12Q1/68 , C07H21/00 , C12P19/34 , C07K1/00 , C12N1/00
CPC分类号： C07H11/04 , C07H19/207 , C07H21/00 , C12N15/11 , C12P21/02
摘要： A novel artificial nucleic acid base pair which is obtained by forming a selective base pair by introducing a group having steric hindrance (preferably a group having steric hindrance and static repulsion and a stacking effect) and can be recognized by a polymerase such as DNA polymerase; a novel artificial gene; and a method of designing nucleic acid bases so as to form a selective base pair with the use of steric hindrance, static repulsion and stacking effect at the base moiety of the nucleic acid. An artificial nucleic acid comprising these bases; a process for producing the same; a codon containing the same; a nucleic acid molecule containing the same; a process for producing a non-natural gene by using the same; a process for producing a novel protein by using the above nucleic acid molecule or non-natural gene, and the like.
摘要翻译：通过引入具有空间位阻的基团（优选具有空间位阻和静电排斥和堆叠效应的基团）形成选择性碱基对而获得的新型人造核酸碱基对，可以通过聚合酶如DNA聚合酶识别; 一种新型人工基因; 以及设计核酸碱基以在核酸的碱基部分上使用空间位阻，静电排斥和堆叠效应形成选择性碱基对的方法。包含这些碱的人造核酸; 其制造方法; 含有相同的密码子; 含有该核酸分子的核酸分子; 通过使用该方法生产非天然基因的方法; 通过使用上述核酸分子或非天然基因来生产新型蛋白质的方法等。

20. 发明授权

US07101992B1 Nucleic acid base pair 有权
标题翻译：核酸碱基对
公开(公告)号：US07101992B1
公开(公告)日：2006-09-05
申请号：US09787196
申请日：2000-07-14
申请人： Ichiro Hirao , Masahide Ishikawa , Tsuyoshi Fujihara , Shigeyuki Yokoyama
发明人： Ichiro Hirao , Masahide Ishikawa , Tsuyoshi Fujihara , Shigeyuki Yokoyama
IPC分类号： C07H21/00 , C07H19/16 , C07H19/048
CPC分类号： C07H11/04 , C07H19/207 , C07H21/00 , C12N15/11 , C12P21/02
摘要： A novel artificial nucleic acid base pair which is obtained by forming a selective base pair by introducing a group having steric hindrance (preferably a group having steric hindrance and static repulsion and a stacking effect) and can be recognized by a polymerase such as DNA polymerase; a novel artificial gene; and a method of designing nucleic acid bases so as to form a selective base pair with the use of steric hindrance, static repulsion and stacking effect at the base moity of the nucleic acid. An artificial nucleic acid comprising these bases; a process for producing the same; a codon containing the same; a nucleic acid molecule containing the same; a process for producing a non-natural gene by using the same; a process for producing a novel protein by using the above nucleic acid molecule or non-natural gene, and the like.
摘要翻译：通过引入具有空间位阻的基团（优选具有空间位阻和静电排斥和堆叠效应的基团）形成选择性碱基对而获得的新型人造核酸碱基对，可以通过聚合酶如DNA聚合酶识别; 一种新型人工基因; 以及设计核酸碱基的方法，以便在核酸的基础上使用空间位阻，静电排斥和堆叠效应形成选择性碱基对。包含这些碱的人造核酸; 其制造方法; 含有相同的密码子; 含有该核酸分子的核酸分子; 通过使用该方法生产非天然基因的方法; 通过使用上述核酸分子或非天然基因来生产新型蛋白质的方法等。

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