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1. 发明授权

US07759471B2 Monomer compositions for the synthesis of RNA, methods of synthesis, and methods of deprotection 有权
标题翻译：用于合成RNA的单体组合物，合成方法和脱保护方法
公开(公告)号：US07759471B2
公开(公告)日：2010-07-20
申请号：US11388112
申请日：2006-03-23
申请人： Douglas J. Dellinger , Zoltan Timar , Agnieszka Sierzchala , Geraldine Dellinger , Marvin H. Caruthers
发明人： Douglas J. Dellinger , Zoltan Timar , Agnieszka Sierzchala , Geraldine Dellinger , Marvin H. Caruthers
IPC分类号： C07H19/00 , C07H19/067 , C07H19/167 , C07H21/02
CPC分类号： C07H19/12 , C07H19/16 , C07H21/02
摘要： Nucleotide monomers, polynucleotides, methods of making each, methods of deprotecting each, and the like are disclosed herein.
摘要翻译：本文公开了核苷酸单体，多核苷酸，制备方法，各自的脱保护方法等。

2. 发明申请

US20080206851A1 Methods and compositions for RNA synthesis 审中-公开
标题翻译：用于RNA合成的方法和组合物
公开(公告)号：US20080206851A1
公开(公告)日：2008-08-28
申请号：US11713424
申请日：2007-02-28
申请人： Douglas J. Dellinger , Geraldine F. Dellinger , Marvin H. Caruthers
发明人： Douglas J. Dellinger , Geraldine F. Dellinger , Marvin H. Caruthers
IPC分类号： C07H21/02 , C12M1/34
CPC分类号： C07H21/02 , Y02P20/55
摘要： In some embodiments, the present disclosure relates to new phosphoramidite compositions, that have Silyl-containing carbonate or thiocarbonate or ether as 5′-hydroxyl protecting groups useful fo the syntheis of RNA, and in particular for the synthesis of long sequences of RNA (e.g., >50 mer). In some embodiments, there are provided methods for simultaneous oxidation of the internucleoside phosphate triester linkages and removal of the 5′-hydroxyl-protecting group, making this process a new 2-step RNA synthesis, that involves the use of peroxyanions in combination with fluoride anions.
摘要翻译：在一些实施方案中，本公开涉及新的亚磷酰胺组合物，其具有含有甲硅烷基的碳酸酯或硫代碳酸酯或醚作为用于RNA合成的5'-羟基保护基，特别是用于合成长序列的RNA（例如，> 50 mer）。在一些实施方案中，提供了同时氧化核苷磷酸三酯键并除去5'-羟基保护基团的方法，使该方法成为新的2步RNA合成，其涉及使用过氧阴离子与氟化物阴离子

3. 发明授权

US07417139B2 Method for polynucleotide synthesis 失效
标题翻译：多核苷酸合成方法
公开(公告)号：US07417139B2
公开(公告)日：2008-08-26
申请号：US10652054
申请日：2003-08-30
申请人： Douglas J Dellinger , Agnieszka B. Sierzchala , Marvin H Caruthers , Geraldine F Dellinger
发明人： Douglas J Dellinger , Agnieszka B. Sierzchala , Marvin H Caruthers , Geraldine F Dellinger
IPC分类号： C07H21/00
CPC分类号： C07H21/00 , Y02P20/55
摘要： Methods of forming an internucleotide bond are disclosed. Such methods find use in synthesis of polynucleotides. The method involves contacting a functionalized support with a precursor having an exocyclic amine triaryl methyl protecting group under conditions and for a time sufficient to result in internucleotide bond formation. The functionalized support includes a solid support, a triaryl methyl linker group, and a nucleoside moiety having a reactive site hydroxyl, the nucleoside moiety attached to the solid support via the triaryl methyl linker group. In particular embodiments, the precursor has the structure: wherein: O and H represent oxygen and hydrogen, respectively R1 is hydrido, hydroxyl, protected hydroxyl, lower alkyl, modified lower alkyl, or alkoxy, one of R2 or R3 is a hydroxyl protecting group; and the other of R2 or R3 is a reactive group capable of reacting with the reactive site hydroxyl, Base is a heterocyclic base having an exocyclic amine group, and Tram is the exocyclic amine triaryl methyl protecting group.
摘要翻译：公开了形成核苷酸间键的方法。这些方法可用于多核苷酸的合成。该方法包括使官能化载体与具有环外胺三芳基甲基保护基团的前体在足以导致形成核苷酸键的条件下进行接触。官能化载体包括固体支持物，三芳基甲基连接基团和具有反应性位点羟基的核苷部分，所述核苷部分通过三芳基甲基连接基团连接到固体支持物上。在具体实施方案中，前体具有以下结构：其中：O和H分别表示氧和氢，R 1为氢，羟基，保护的羟基，低级烷基，经修饰的低级烷基或烷氧基，R2或R3中的一个为羟基保护基 ; R2或R3中的另一个是能够与反应性位点羟基反应的反应性基团，碱是具有环外胺基的杂环基，Tram是环外胺三芳基甲基保护基。

4. 发明授权

US07385050B2 Cleavable linker for polynucleotide synthesis 有权
标题翻译：用于多核苷酸合成的可切割接头
公开(公告)号：US07385050B2
公开(公告)日：2008-06-10
申请号：US10652063
申请日：2003-08-30
申请人： Douglas J Dellinger , Geraldine F Dellinger , Marvin H Caruthers
发明人： Douglas J Dellinger , Geraldine F Dellinger , Marvin H Caruthers
IPC分类号： C07H21/00 , C07H19/10 , C07H19/20
CPC分类号： C07H21/04
摘要： Functionalized supports for polynucleotide synthesis are disclosed. The supports have linker moieties that are stable to conditions used in polynucleotide synthesis, but may be cleaved to release synthesized polynucleotides from the support. Methods of making the functionalized supports and methods of using are also disclosed. In particular embodiments of methods of making the functionalized supports, a solid support, on which an available reactive group is bound, is contacted with a reagent having the structure (I) Phos-Cgp-Trl-Cgp′Nucl (I) wherein the groups are defined as follows: Phos is a reactive phosphorus group capable of specifically reacting with an available reactive group on the support, Trl is a triaryl methyl linker group having three aryl groups, each bound to a central methyl carbon, at least one of said three aryl groups having one or more substituents, Cgp is a linking group linking the reactive phosphorus group and the triaryl methyl linker group, or is a bond linking the reactive phosphorus group and the triaryl methyl linker group, Nucl is a nucleoside moiety, wherein the nucleoside moiety is optionally part of a polynucleotide moiety, and Cgp′ is a linking group linking the nucleoside moiety and the triaryl methyl linker group, or is a bond linking the nucleoside moiety and the triaryl methyl linker group. In typical embodiments, the solid support is contacted with the reagent having the structure (I) under conditions and for a time sufficient to result in a functionalized support having a nucleoside moiety bound to the solid support via a triaryl methyl linker group.
摘要翻译：公开了用于多核苷酸合成的官能化载体。载体具有对于多核苷酸合成中使用的条件稳定的接头部分，但可被切割以从载体释放合成的多核苷酸。还公开了制备官能化载体的方法和使用方法。在制备官能化载体的方法的具体实施方案中，在其上结合有可用的反应性基团的固体支持体与具有结构（I）的试剂接触<？in-line-formula description =“In-Line Formulas” end =“lead”？> Phos-Cgp-Trl-Cgp'Nucl（I）<？in-line-formula description =“In-line Formulas”end =“tail”？>其中定义如下：Phos 是能够与载体上可用的反应性基团特异性反应的活性磷基团，Tr1是具有三个芳基的三芳基甲基连接基团，每个芳基与中心甲基碳结合，所述三个芳基中的至少一个具有一个或多个取代基，Cgp是连接反应性磷基团和三芳基甲基连接基团的连接基团，或者是连接反应性磷基团和三芳基甲基连接基团的键，Nuc1是核苷部分，其中核苷部分任选地是多核苷酸部分，Cgp'是连接基团核苷核苷部分和三芳基甲基连接基团，或是连接核苷部分和三芳基甲基连接基团的键。在典型的实施方案中，固体支持物与具有结构（I）的试剂在足以导致具有通过三芳基甲基连接基团与固体支持物结合的核苷部分的官能化载体的条件下接触。

5. 发明授权

US06630581B2 Monomers for solid phase synthesis of oligonucleotides using carbonate protecting groups and alpha-effect nucleophile deprotection 有权
标题翻译：使用碳酸酯保护基团和α-效应亲核体脱保护剂固相合成寡核苷酸的单体
公开(公告)号：US06630581B2
公开(公告)日：2003-10-07
申请号：US09756991
申请日：2001-01-08
申请人： Douglas J. Dellinger , Marvin H. Caruthers , Jason R. Betley
发明人： Douglas J. Dellinger , Marvin H. Caruthers , Jason R. Betley
IPC分类号： C07H2100
CPC分类号： C07H19/10 , C07B2200/11 , C07H19/20 , C07H21/00 , C07H21/04 , C40B40/06 , C40B50/14 , Y02P20/55
摘要： The invention provides a method for synthesizing oligonucleotides using carbonate protection of hydroxyl groups and nucleophilic deprotection reagents. The deprotection reagents irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage, and can be used in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides. Reagents and kits for carrying out the aforementioned method are provided as well.
摘要翻译：本发明提供了使用碳酸酯保护羟基和亲核脱保护试剂合成寡核苷酸的方法。脱保护试剂不可逆地切割碳酸酯保护基，同时氧化核苷酸亚磷酸三酯键，并可用于中性至弱碱性pH的水溶液中。该方法不需要单独的脱保护和氧化步骤，并且由于不需要使用酸去除保护基团，所以避免了酸诱导的去血。可以使用荧光或其它容易检测的碳酸酯保护基团，使得能够监测寡核苷酸合成期间的各个反应步骤。本发明在寡核苷酸的高度平行，微尺度合成中特别有用。还提供了用于实施上述方法的试剂和试剂盒。

6. 发明授权

US5962291A Metal dependent catalytic antibodies and method for producing the same 失效
标题翻译：金属依赖性催化抗体及其制备方法
公开(公告)号：US5962291A
公开(公告)日：1999-10-05
申请号：US949220
申请日：1997-10-10
申请人： Darla A. Graff , Marvin H. Caruthers , Jeffrey W. Jacobs
发明人： Darla A. Graff , Marvin H. Caruthers , Jeffrey W. Jacobs
IPC分类号： C12N9/00 , C12N5/12
CPC分类号： C12N9/0002
摘要： The present invention relates to catalytic antibodies and a method for producing the same wherein a host is immunized using an "antigen chelate" or more specifically a stable compound capable of chelating metal ions. The immune response mounted in response to the antigen chelate produces antibodies that are capable of binding both a substrate and a metal ion, thus achieving a metal cofactor assisted reaction.
摘要翻译：本发明涉及催化抗体及其制备方法，其中使用“抗原螯合物”或更具体地是能够螯合金属离子的稳定化合物免疫宿主。响应于抗原螯合物而安装的免疫应答产生能够结合底物和金属离子两者的抗体，从而实现金属辅因子辅助反应。

7. 发明授权

US5684148A Nucleoside thiophosphoramidites 失效
标题翻译：核苷硫代亚磷酰胺
公开(公告)号：US5684148A
公开(公告)日：1997-11-04
申请号：US442705
申请日：1995-05-17
申请人： Marvin H. Caruthers , Wolfgang K. D. Brill , Eric Yau , Michael Ma , John Nielsen
发明人： Marvin H. Caruthers , Wolfgang K. D. Brill , Eric Yau , Michael Ma , John Nielsen
IPC分类号： C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04
CPC分类号： C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04
摘要： The present invention relates to new and useful nucleoside thiophosphoroamidites and polynucleotide phosphorodithioate compounds as well as the processes whereby these compounds may be used for synthesizing new mononucleotides and polynucleotides having phosphorothioate and phosphorodithioate internucleotide linkages.
摘要翻译：本发明涉及新的和有用的核苷硫代亚磷酰胺和多核苷酸二硫代磷酸酯化合物以及这些化合物可用于合成新的单核苷酸和具有硫代磷酸酯和二硫代磷酸酯核苷酸间键的多核苷酸的方法。

8. 发明授权

US4973679A Process for oligonucleo tide synthesis using phosphormidite intermediates 失效
标题翻译：使用亚磷酰胺中间体进行寡核苷酸合成的方法
公开(公告)号：US4973679A
公开(公告)日：1990-11-27
申请号：US909070
申请日：1986-09-18
申请人： Marvin H. Caruthers , Serge L. Beaucage
发明人： Marvin H. Caruthers , Serge L. Beaucage
IPC分类号： C07H21/00
CPC分类号： C07H21/00
摘要： A new class of nucleoside phosphoramidites which are relatively stable to permit isolation thereof and storage at room temperature. The phosphoramidites are derivatives of saturated secondary amines.
摘要翻译：一类新的核苷亚磷酰胺，其相对稳定以允许其在室温下分离并储存。亚磷酰胺是饱和仲胺的衍生物。

9. 发明申请

US20120238737A1 THIOCARBON-PROTECTING GROUPS FOR RNA SYNTHESIS 有权
标题翻译：用于RNA合成的THIOCARBON保护组
公开(公告)号：US20120238737A1
公开(公告)日：2012-09-20
申请号：US13485592
申请日：2012-05-31
申请人： Douglas J. Dellinger , Agnieszka Sierzchala , John Turner , Joel Myerson , Zoltan Kupihar , Fernando Ferreira , Marvin H. Caruthers , Geraldine F. Dellinger
发明人： Douglas J. Dellinger , Agnieszka Sierzchala , John Turner , Joel Myerson , Zoltan Kupihar , Fernando Ferreira , Marvin H. Caruthers , Geraldine F. Dellinger
IPC分类号： C07H1/00 , C07H19/20 , C07H21/02 , C07H19/10
CPC分类号： C07H19/073 , C07H13/12 , C07H19/16 , C07H21/02 , Y02P20/55
摘要： Aspects of the invention include 2′ protected nucleoside monomers that are protected at the 2′ site with thiocarbon protecting groups. Thiocarbon protecting groups of interest include thiocarbonate, thionocarbonate, dithiocarbonate groups, as well as thionocarbamate protecting groups. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.
摘要翻译：本发明的方面包括2'受保护的核苷单体，其在2'位置被硫代保护基团保护。感兴趣的硫代碳保护基包括硫代碳酸酯，硫代碳酸酯，二硫代碳酸酯基，以及硫羰氨基保护基。本发明的方面还包括包含本发明的保护基团的核酸以及使用本发明的保护基合成核酸的方法。

10. 发明申请

US20090082554A1 Thiocarbonate linkers for polynucleotides 有权
标题翻译：多核苷酸的硫代碳酸酯接头
公开(公告)号：US20090082554A1
公开(公告)日：2009-03-26
申请号：US11903821
申请日：2007-09-24
申请人： Douglas J. Dellinger , Zoltan Timar , Joel Myerson , Geraldine Dellinger , Marvin H. Caruthers
发明人： Douglas J. Dellinger , Zoltan Timar , Joel Myerson , Geraldine Dellinger , Marvin H. Caruthers
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04
CPC分类号： C07H21/00 , C07H21/02 , C07H21/04
摘要： In various embodiments of the invention, novel compositions having a polynucleotide bound to a substrate via a cleavable linker are provided, and methods of cleaving a polynucleotide from a substrate are provided.
摘要翻译：在本发明的各种实施方案中，提供了具有通过可切割连接子与底物结合的多核苷酸的新型组合物，并提供了从底物切割多核苷酸的方法。

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