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11. 发明授权

US09725713B1 In vitro selection with expanded genetic alphabets 有权
公开(公告)号：US09725713B1
公开(公告)日：2017-08-08
申请号：US14082800
申请日：2013-11-18
申请人： Steven A Benner , Zunyi Yang
发明人： Steven A Benner , Zunyi Yang
IPC分类号： C12Q1/68 , C12N15/10
CPC分类号： C12N15/1048 , C12Q1/6811 , C12Q2521/345 , C12Q2525/117 , C12Q2525/205
摘要： This invention provides for products and processes for binding to a preselected target, where the process involves contacting this target to an oligonucleotide molecule that contains one or more “non-standard” nucleotides, which are nucleotide analogs that, when incorporated into oligonucleotides (DNA or RNA, collectively xNA), present to a complementary strand in a Watson-Crick pairing geometry a pattern of hydrogen bonds that is different from the pattern presented by adenine, guanine, cytosine, and uracil. This disclosure provides an example where such an oligonucleotide molecule contains a single 2-amino-8-(1′-β-D-2′-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)one and a single 6-amino-5-nitro-3-(1′-β-D-2′-deoxyribofuranosyl)-2(1H)-pyridone, and where the target is a cell, and is obtained by a process of in vitro selection.

12. 发明授权

US09315842B2 Helicase dependent amplification of DNA molecules using nucleotide analogs 有权
标题翻译：使用核苷酸类似物的DNA分子的螺旋酶依赖性扩增
公开(公告)号：US09315842B2
公开(公告)日：2016-04-19
申请号：US13970111
申请日：2013-08-19
申请人： Steven A Benner , Zunyi Yang
发明人： Steven A Benner , Zunyi Yang
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12P19/34 , C12Q1/6844 , C12Q1/6853 , C12Q2521/513 , C12Q2525/101 , C12Q2525/117 , C12Q2521/101
摘要： This invention covers processes for the isothermal amplification of DNA molecules having a preselected sequence. It is based on the unexpected discovery that primers having, at some positions, adenine substituted by 2-aminopurine or diaminopurine, guanine by inosine, thymine by 2-thiothymine, and cytosine by N4-ethylcytosine (“SAMRS nucleotides”) were accepted by enzymes used in the standard helicase-dependent amplification (HDA). Further unexpected was the discovery that target nucleotides are efficiently amplified in an HDA-like process (hereinafter abbreviated as simply HDA) using substituted primers. Also discovered was the diminution of spurious products through the use of SAMRS-substituted primers.
摘要翻译：本发明涉及具有预选序列的DNA分子的等温扩增方法。基于意想不到的发现，在某些位置，由2-氨基嘌呤或二氨基嘌呤取代的腺嘌呤，由肌苷引起的鸟嘌呤，2-硫代胸腺嘧啶的胸腺嘧啶和N4-乙基胞嘧啶的胞嘧啶（“SAMRS核苷酸”）的引物被酶用于标准解旋酶依赖性扩增（HDA）。进一步意外的是，使用取代的引物，以HDA样方法（以下简称为HDA）有效扩增靶核苷酸。还发现通过使用SAMRS取代的引物减少杂质产物。

13. 发明授权

US09062336B1 Recombinase-based amplification with substitute nucleotides 有权
标题翻译：用替代核苷酸进行基于重组酶的扩增
公开(公告)号：US09062336B1
公开(公告)日：2015-06-23
申请号：US13789022
申请日：2013-03-07
申请人： Steven A Benner , Nidhi Sharma
发明人： Steven A Benner , Nidhi Sharma
IPC分类号： C12P19/34
CPC分类号： C12P19/34 , C12Q1/6844 , C12Q2521/507 , C12Q2525/101 , C12Q2537/157
摘要： This invention covers methods for isothermal amplification of DNA. It is based on the unexpected discovery that primers having, at some positions, adenine substituted by 2-aminopurine or diaminopurine, guanine by inosine, thymine by 2-thiothymine, and cytosine by N4-ethylcytosine (“substituted primers”) were accepted by enzymes used in the standard recombinase polymerase assay (RPA). Further unexpected was the discovery that target nucleotides are efficiently amplified in an RPA-like process (hereinafter abbreviated as simply RPA) using substituted primers. RPA-like processes were also discovered to amplify target DNA with substituted primers tagged with oligonucleotides incorporating nucleotides from an artificially expanded genetic information system (AEGIS).
摘要翻译：本发明涵盖了DNA等温扩增的方法。基于意想不到的发现，在某些位置，由2-氨基嘌呤或二氨基嘌呤取代的腺嘌呤，肌苷中的鸟嘌呤，2-硫代胸腺嘧啶的胸腺嘧啶和由N-4-乙基胞嘧啶（“取代的引物”）的胞嘧啶的引物被酶接受用于标准重组酶聚合酶测定（RPA）。更令人意想不到的是，使用取代的引物，在RPA样过程（以下简称为RPA）中有效扩增靶核苷酸。还发现了类似RPA的过程，用来自人工扩增的遗传信息系统（AEGIS）的核苷酸的寡核苷酸标记的取代的引物扩增靶DNA。

14. 发明授权

US08389703B1 Ribonucleoside analogs with novel hydrogen bonding patterns 有权
标题翻译：具有新型氢键模式的核糖核苷类似物
公开(公告)号：US08389703B1
公开(公告)日：2013-03-05
申请号：US13287169
申请日：2011-11-02
申请人： Steven A. Benner , Hyo-Joong Kim
发明人： Steven A. Benner , Hyo-Joong Kim
IPC分类号： C07H19/048 , C07H21/00 , C07H21/02
CPC分类号： C07D405/04 , C12P19/34
摘要： This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with nucleotide analogs that present the donor-donor-acceptor, hydrogen bonding patterns on pyrimidine analogs, and especially those that are analogs of ribonucleotides, including protected ribonucleotides suitable for phosphoramidite-based synthesis of RNA. The heterocycles on these nucleoside analogs are aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.
摘要翻译：本发明涉及包含非标准核碱基类似物的核苷，核苷酸和寡核苷酸类似物，其被定义为与互补链中的配对核碱基类似物呈现氢键图案的不同于腺嘌呤，鸟嘌呤，胞嘧啶和胸腺嘧啶。本发明特别涉及呈现供体 - 供体受体的核苷酸类似物，嘧啶类似物上的氢键型，特别是涉及核糖核苷酸类似物的核苷酸类似物，包括适合于基于亚磷酰胺的RNA合成的受保护的核糖核苷酸。这些核苷类似物上的杂环是在标准嘧啶（包括硝基，氰基和羧酸衍生物）中具有连接到类似于环的5位的位置的吸电子基团的氨基吡啶酮。

15. 发明申请

US20110319298A1 Differential detection of single nucleotide polymorphisms 审中-公开
公开(公告)号：US20110319298A1
公开(公告)日：2011-12-29
申请号：US12311982
申请日：2009-04-21
申请人： Steven A. Benner , Shuichi Hoshika , Nicole Leal
发明人： Steven A. Benner , Shuichi Hoshika , Nicole Leal
IPC分类号： C40B50/06 , C07H21/00
CPC分类号： C12Q1/6855 , C12Q1/6853 , C12Q1/6858 , C12Q2521/301 , C12Q2525/121 , C12Q2525/179 , C12Q2525/186 , C12Q2525/191 , C12Q2525/204 , C12Q2535/122 , C12Q2535/125 , C12Q2563/131
摘要： This patent application claims processes and compositions of matter that enable the discovery of single nucleotide polymorphisms (SNPs) that distinguish the genomes of two individual organisms in the same species, as well as that distinguish the paternal and maternal genetic inheritance of a single individual, as well as distinguish the genomes of cells in special tissues (e.g. cancer tissues) within an individual from the genomes of the standard cells in the same individuals, as well as the SNPs that are discovered using these processes and compositions. Two steps are essential to the invention disclosed in this application. The first step provides four sets of primers, which are designated “T-extendable”, “A-extendable”, “C-extendable”, and “G-extendable”. These primers, when targeted against a reference genome as a template, add (respectively) T, A, C, and G to their 3′-ends in a template-directed primer extension reaction. The second step presents these four primer sets, separately, to a sample of the target genome DNA under conditions where they bind to their complementary segments within the target DNA. Once bound, members of each primer set serve as primers for a template-directed primer extension reaction using the target genome as the template. If the template from the target genome presents the same templating nucleotide for the first nucleotide added in the extension reaction as the reference genome, then the T-extendable, A-extendable, C-extendable, and G-extendable primers will be extended (respectively) by T, A, C, and G. If, however, the template from the target genome presents a nucleotide different from the reference genome, then the T-extendable, A-extendable, C-extendable, and G-extendable primers will be extended (respectively) by not T, not A, not C, and not G (referred to here as “3N” or “3”, to indicate the other three nucleotides, where which of the other three is understood by context). In these cases, the primers have discovered a SNP, a difference between the target and reference genomes. Then, the T-extendable, A-extendable, C-extendable, and G-extendable primers that add (respectively) not-T, not-A, not-C, and not-G are separated or made otherwise physically distinct (through, for example, the use of irreversible terminators, such as 2′,3′-dideoxynucleosides) from those that added T, A, C, and G (respectively). Those that added T, A, C, and G (respectively) did not discover a SNP, and are discarded. The primers that added “not-T”, “not-A”, “not-C”, and “not-G” discovered a SNP, and presented in a mixture enriched (relative to those primers that did not discover a SNP) in a useful deliverable. Following these steps, the SNPs discoveries are realized by sequencing the extracted species. The information obtained from this sequencing allows the identification of the locus of the SNP in the in silico genome.

16. 发明授权

US11168106B1 Synthesis and stabilization of nicotinamide ribose and its derivatives 有权
公开(公告)号：US11168106B1
公开(公告)日：2021-11-09
申请号：US16160189
申请日：2018-10-15
申请人： Hyo-Joong Kim , Steven A Benner , Ion Mircesti Scorei
发明人： Hyo-Joong Kim , Steven A Benner , Ion Mircesti Scorei
IPC分类号： C07H19/048 , C07H1/02
摘要： Nicotinamide ribose has many applications, including as a dietary supplement. This invention convers a process to prepare nicotinamide ribose it in its phosphorylated form. The instant invention is based on the discovery that nicotinamide ribose phosphate emerges in stable form by direct reaction of ribose-1,2-cyclic phosphate. It is based on the further conversion of the phosphorylated nicotinamide ribose product to unphosphorylated nicotinamide ribose upon treatment with an enzymatic phosphatase, most preferably in buffer containing borate. It is based on the further discovery that compositions of nicotinamide ribose with borate slow the decomposition of nicotinamide ribose, and therefore is more useful than compositions of nicotinamide ribose without borate.

17. 发明申请

US20210238643A1 Enzymatic Processes for Synthesizing RNA Containing Certain Non-Standard Nucleotides 有权
公开(公告)号：US20210238643A1
公开(公告)日：2021-08-05
申请号：US17188248
申请日：2021-03-01
申请人： Nicole A Leal , Steven A Benner
发明人： Nicole A Leal , Steven A Benner
IPC分类号： C12P19/34 , C07H21/02
摘要： This invention relates to nucleotide analogs and their derivatives (termed non-standard nucleotides) that, when incorporated into DNA and RNA, expand the number of nucleotides beyond the four found in standard DNA and RNA. The invention further relates to enzymatic processes that incorporate those non-standard nucleotide analogs into oligonucleotide products using the corresponding triphosphate derivatives. The RNA polymerases of the instant invention transcribe DNA containing nonstandard nucleotides to give RNA containing nonstandard nucleotides, where certain of those nucleotides have nucleobases that do not present electron density to the minor groove.

18. 发明授权

US10513704B2 Binding and catalytic molecules built from L-DNA with added nucleotides 有权
公开(公告)号：US10513704B2
公开(公告)日：2019-12-24
申请号：US15639336
申请日：2017-06-30
申请人： Steven A Benner
发明人： Steven A Benner
IPC分类号： C12N15/115 , C12P19/34 , C12Q1/6811
摘要： This invention provides for processes for binding to and/or chemically transforming a preselected target, where the process involves contacting said target to an oligonucleotide molecule that contains one or more “non-standard” nucleotides, which are nucleotide analogs that, when incorporated into oligonucleotides (DNA or RNA, collectively xNA), present to a pattern of hydrogen bonds that is different from the pattern presented by adenine, guanine, cytosine, and uracil. This disclosure provides an example where such an oligonucleotide molecule is built from both D- and L-mirror image carbohydrates in the backbone. It also provides a process for obtaining these binders and/or transformers by a laboratory in vitro selection process that exploits rolling circle amplification rather than the polymerase chain reaction.

19. 发明授权

US10415088B1 In vivo conversion of nucleosides in plasmid DNA 有权
公开(公告)号：US10415088B1
公开(公告)日：2019-09-17
申请号：US15997325
申请日：2018-06-04
申请人： Steven A Benner , Zunyi Yang
发明人： Steven A Benner , Zunyi Yang
IPC分类号： C12Q1/68 , C12Q1/6869 , C12P19/34 , C12Q1/6844 , C07H21/04
摘要： Disclosed are processes that use DNA polymerases to extend primers annealed to templates, wherein a standard nucleotide in the template guiding the extension directs the incorporation of a nonstandard nucleotide analog into the product duplex opposite that standard template nucleotide, and processes wherein a nonstandard nucleotide in the template guiding the extension directs the incorporation of a standard nucleotide analog opposite the nonstandard template nucleotide. Conditions, including the pH of the mixture where the primer extension is done and the composition of triphosphate mixtures where the primary extensions done, are disclosed.

20. 发明申请

US20180265537A1 Nucleoside Triphosphates with Stable Aminoxy Groups 审中-公开
公开(公告)号：US20180265537A1
公开(公告)日：2018-09-20
申请号：US15460475
申请日：2017-03-16
申请人： Steven A. Benner
发明人： Steven A. Benner
IPC分类号： C07H19/10
CPC分类号： C07H19/10 , C07H19/20
摘要： This invention claims aqueous compositions that comprise triphosphates of 2′-deoxynucleoside derivatives that have, instead of a 3′-OH moiety, a 3′-ONH2 moiety; wherein said compositions contain less than 0.5 mole percent contaminating triphosphate having a 3′-OH moiety, as well as processes for providing such compositions. The compositions further must contain insubstantial amounts of hydroxylamine.

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