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1. 发明授权

US5849482A Crosslinking oligonucleotides 失效
标题翻译：交联寡核苷酸
公开(公告)号：US5849482A
公开(公告)日：1998-12-15
申请号：US485611
申请日：1995-06-07
申请人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall , Charles R. Petrie , John C. Tabone , Gerald D. Hurst
发明人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall , Charles R. Petrie , John C. Tabone , Gerald D. Hurst
IPC分类号： A61K31/70 , A61K38/00 , A61K48/00 , A61P31/00 , A61P35/00 , C07H21/00 , C12N15/10 , C12N15/113 , C12Q1/68 , C07H21/04
CPC分类号： C12N15/113 , C07H21/00 , C12N15/102 , C12Q1/6839 , A61K38/00 , C12N2310/153 , C12N2310/311 , C12N2310/335 , C12N2310/3511
摘要： Oligonucleotides (ODNs) include a sequence that is complementary to a target sequence in single stranded RNA, or single or double stranded DNA, and an alkylating function which after hybridization alkylates the target sequence. ODNs adapted for alkylating single stranded RNA, such as messenger RNA, are complementary to the target sequence in the Watson Crick sense. ODNs adapted for alkylating double stranded DNA have at least two alkylating functions and are complementary to the target sequence in the Hoogsteen or reverse Hoogsteen sense. With these ODNs both strands of the target sequence are alkylated. A third class of ODNs have at least approximately 26 nucleotide units in a continous sequence which are complementary to the target sequence of double stranded DNA, and the alkylating function is covalently attached to a nucleotide unit in the continuous sequence. Alkylation or cross-linking with this class of ODNs occurs in the presence of a recombinase enzyme.
摘要翻译：寡核苷酸（ODN）包括与单链RNA或单链或双链DNA中的靶序列互补的序列，以及杂交后烷基化靶序列的烷基化功能。适用于烷基化单链RNA（如信使RNA）的ODN与Watson Crick意义上的靶序列互补。适于烷基化双链DNA的ODN具有至少两种烷基化功能，并且与Hoogsteen或反向Hoogsteen意义上的靶序列互补。使用这些ODN，靶序列的两条链被烷基化。第三类ODN在连续序列中具有至少约26个核苷酸单元，其与双链DNA的靶序列互补，并且烷基化功能以连续序列共价连接到核苷酸单元。与这类ODN的烷基化或交联发生在重组酶的存在下。

2. 发明授权

US5935830A Targeted mutagenesis in living cells using modified oligonucleotides 失效
公开(公告)号：US5935830A
公开(公告)日：1999-08-10
申请号：US827116
申请日：1997-03-26
申请人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall
发明人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall
IPC分类号： A61K31/70 , A61K38/00 , A61K48/00 , A61P31/00 , A61P35/00 , C07H21/00 , C12N15/10 , C12N15/113 , C12Q1/68 , C12N15/00 , C07H21/04
CPC分类号： C12N15/113 , C07H21/00 , C12N15/102 , C12Q1/6839 , A61K38/00 , C12N2310/153 , C12N2310/311 , C12N2310/335 , C12N2310/3511
摘要： A method for introducing a site-specific mutation into a target polynucleotide sequence is presented. The method involves the use of an oligonucleotide capable of binding to the target sequence, either by triplex formation (mediated by Hoogsteen, reverse Hoogsteen or equivalent base pairing) or by Watson/Crick base pairing (in the presence of a recombinase enzyme). The oligonucleotide of the invention is modified by the covalent attachment of one or more electrophilic groups. When a modified oligonucleotide is bound to its target sequence, the electrophilic group is able to interact with a nearby nucleotide in the target sequence, causing a modification to the nucleotide that results in a change in nucleotide sequence. Compositions used in the practice of the method are also disclosed.

3. 发明授权

US06312953B1 Bifunctional Crosslinking oligonucleotides adapted for linking to a target sequence of duplex DNA 失效
标题翻译：双功能交联寡核苷酸适于与双链DNA的靶序列连接
公开(公告)号：US06312953B1
公开(公告)日：2001-11-06
申请号：US08266949
申请日：1994-06-27
申请人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall
发明人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall
IPC分类号： C12Q168
CPC分类号： C07H21/00
摘要： Chemically modified oligonucleotides (ODNS) are complementary, either in the sense of the classic “four letter code” recognition motif, or in the sense required for triple strand formation based on the more limited “two letter code recognition motif”, to a target sequence of double stranded DNA of an invading cell, organism or pathogen, such as a virus, fungus, parasite, bacterium, malignant cell, or any duplex DNA which is desired to be broken into segments for the purpose of “mapping”. The ODNs have cross-linking agents covalently attached at least to two different sites of the ODN. Alternatively, the cross-linking agent which is attached to one site on the ODN has two cross-linking functionalities, and therefore in effect comprises two cross-linking agents. The cross-linking agent typically includes a linker arm (such as an alkyl, alkoxy, aminoalkyl or amidoalkyl chain) and a reactive group which, after triple strand formation with the target sequence of DNA, is capable of reacting with the target DNA to form a covalent bond therewith. Each cross-linking agent of the novel modified ODNs is capable of forming a covalent bond with the target DNA. As a result of the covalent bond formation between the modified ODN and both strands of the target DNA sequence, replication and expression of the target DNA sequence is inhibited. Alternatively the duplex DNA is selectively cleaved with enzymes or amino acids, at the alkylation sites for “mapping” or other investigative purposes.
摘要翻译：化学修饰的寡核苷酸（ODNS）在经典的“四字母代码”识别基序的意义上是互补的，或者在基于更有限的“双字母代码识别基序”的三链形成所需的意义上与目标序列的入侵细胞，生物体或病原体如病毒，真菌，寄生虫，细菌，恶性细胞或任何双链DNA的双链DNA，其为了“映射”的目的而被分解成片段。 ODN具有共价连接到ODN的至少两个不同位点的交联剂。或者，连接到ODN上的一个位点的交联剂具有两个交联官能团，因此实际上包含两种交联剂。交联剂通常包括连接臂（例如烷基，烷氧基，氨基烷基或酰氨基烷基链）和反应性基团，其在与DNA的靶序列形成三链后能够与靶DNA反应形成与其共价键。新型修饰的ODN的交联剂能与靶DNA形成共价键。由于修饰的ODN与目标DNA序列的两条链之间共价键的形成，靶DNA序列的复制和表达被抑制。或者，双链DNA在烷基化位点被选择性地用酶或氨基酸切割，用于“映射”或其它调查目的。

4. 发明授权

US6136601A Targeted mutagenesis in living cells using modified oligonucleotides 失效
标题翻译：使用修饰的寡核苷酸在活细胞中靶向诱变
公开(公告)号：US6136601A
公开(公告)日：2000-10-24
申请号：US827117
申请日：1997-03-26
申请人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall
发明人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall
IPC分类号： C07H21/00 , C12Q1/68 , C07H21/04
CPC分类号： C07H21/00 , C12Q1/6839
摘要： A method for introducing a site-specific mutation into a target polynucleotide sequence is presented. The method involves the use of an oligonucleotide capable of binding to the target sequence, either by triplex formation (mediated by Hoogsteen, reverse Hoogsteen or equivalent base pairing) or by Watson/Crick base pairing (in the presence of a recombinase enzyme). The oligonucleotide of the invention is modified by the covalent attachment of one or more electrophilic groups. When a modified oligonucleotide is bound to its target sequence, the electrophilic group is able to interact with a nearby nucleotide in the target sequence, causing a modification to the nucleotide that results in a change in nucleotide sequence. Compositions used in the practice of the method are also disclosed.
摘要翻译：提出了将位点特异性突变引入靶多核苷酸序列的方法。该方法包括通过三重形成（由Hoogsteen，逆Hoogsteen或等效碱基配对介导）或通过Watson / Crick碱基配对（在重组酶存在下）使用能够结合靶序列的寡核苷酸。本发明的寡核苷酸通过一个或多个亲电子基团的共价连接被修饰。当修饰的寡核苷酸与其靶序列结合时，亲电子基团能够与靶序列中的附近核苷酸相互作用，导致导致核苷酸序列变化的核苷酸修饰。还公开了在该方法的实践中使用的组合物。

5. 发明授权

US06972328B2 Non-aggregating non-quenching oligomer comprising nucelotide analogs, method of synthesis and use thereof 有权
标题翻译：包含芥菜素类似物的非聚集性非猝灭寡聚物，其合成方法和用途
公开(公告)号：US06972328B2
公开(公告)日：2005-12-06
申请号：US10702007
申请日：2003-11-04
申请人： Alexander A. Gall , Igor V. Kutyavin , Nicolaas M. J. Vermeulen , Robert O. Dempcy
发明人： Alexander A. Gall , Igor V. Kutyavin , Nicolaas M. J. Vermeulen , Robert O. Dempcy
IPC分类号： G01N33/53 , A61K31/519 , A61K48/00 , C07D487/04 , C07H21/00 , C07H21/04 , C07K5/06 , C07K5/078 , C07K14/00 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N33/50 , G01N33/58 , C07H21/02
CPC分类号： C07D487/04 , A61K31/519 , C07H21/00 , C07K5/06026 , C07K5/06139 , C07K14/003 , C12Q1/6818 , C12Q1/6832 , C12Q2525/107 , C12Q2525/101
摘要： The invention provides compositions and methods for improved hybridization analysis utilizing DNA, RNA, PNA and chimeric oligomers in which one or more purine bases are substituted by a pyrazolo[5,4-d]pyrimidine or by a 7-deazapurine purine analogue. Reduced self-aggregation and reduced fluorescence quenching are obtained when the oligomers are used in various methods involving hybridization. Methods of synthesis, as well as novel synthetic precursors, are also provided.
摘要翻译：本发明提供使用DNA，RNA，PNA和嵌合寡聚物改进杂交分析的组合物和方法，其中一个或多个嘌呤碱基被吡唑并[5,4-d]嘧啶或7-脱氮嘌呤嘌呤类似物取代。当寡聚物以涉及杂交的各种方法使用时，获得了减少的自聚集和减少的荧光猝灭。还提供了合成方法，以及新型合成前体。

6. 发明授权

US06683173B2 Tm leveling methods 有权
标题翻译：调平方法
公开(公告)号：US06683173B2
公开(公告)日：2004-01-27
申请号：US10032307
申请日：2001-12-21
申请人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Michael J. Singer , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
发明人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Michael J. Singer , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
IPC分类号： C07H2104
CPC分类号： C07H21/00 , C07B2200/11 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H19/23 , C12Q1/6832 , C40B40/00 , G06F19/22 , C12Q2525/117
摘要： Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.
摘要翻译：提供了修饰的寡核苷酸，其含有选自未取代的和3-取代的吡唑并[3,4-d]嘧啶和5-取代的嘧啶的碱，并且任选具有连接的小沟结合剂和报道基团。

7. 发明授权

US06660845B1 Non-aggregating, non-quenching oligomers comprising nucleotide analogues; methods of synthesis and use thereof 有权
标题翻译：包含核苷酸类似物的非聚集性非猝灭性低聚物; 合成和使用方法
公开(公告)号：US06660845B1
公开(公告)日：2003-12-09
申请号：US09447936
申请日：1999-11-23
申请人： Alexander A. Gall , Igor V. Kutyavin , Nicolaas M. J. Vermeulen , Robert O. Dempcy
发明人： Alexander A. Gall , Igor V. Kutyavin , Nicolaas M. J. Vermeulen , Robert O. Dempcy
IPC分类号： C07H2100
CPC分类号： C07D487/04 , A61K31/519 , C07H21/00 , C07K5/06026 , C07K5/06139 , C07K14/003 , C12Q1/6818 , C12Q1/6832 , C12Q2525/107 , C12Q2525/101
摘要： The invention provides compositions and methods for improved hybridization analysis utilizing DNA, RNA, PNA and chimeric oligomers in which one or more purine bases are substituted by a pyrazolo[5,4-d]pyrimidine or by a 7-deazapurine purine analogue. Reduced self-aggregation and reduced fluorescence quenching are obtained when the oligomers are used in various methods involving hybridization. Methods of synthesis, as well as novel synthetic precursors, are also provided.
摘要翻译：本发明提供使用DNA，RNA，PNA和嵌合寡聚物改进杂交分析的组合物和方法，其中一个或多个嘌呤碱基被吡唑并[5,4-d]嘧啶或7-脱氮嘌呤嘌呤类似物取代。当寡聚物以涉及杂交的各种方法使用时，获得了减少的自聚集和减少的荧光猝灭。还提供了合成方法，以及新型合成前体。

8. 发明授权

US07715989B2 Systems and methods for predicting oligonucleotide melting temperature (TmS) 有权
标题翻译：用于预测寡核苷酸融合温度（TmS）的系统和方法
公开(公告)号：US07715989B2
公开(公告)日：2010-05-11
申请号：US10176972
申请日：2002-06-18
申请人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Michael J. Singer , Karen M. Singer, legal representative , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
发明人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Michael J. Singer , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
IPC分类号： G01N33/48
CPC分类号： G06F19/20 , C07B2200/11 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H19/23 , C07H21/00 , C12Q1/6813 , C12Q1/6827 , C12Q1/6858 , C12Q2600/156 , C40B40/00 , G06F19/22 , C12Q2563/173 , C12Q2527/107 , C12Q2525/117 , C12Q2525/197 , C12Q2541/101 , C12Q2535/125
摘要： Software systems and methods for predicting the melting temperature (Tm) and other characteristics of oligonucleotides, including modified oligonucleotides. Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.
摘要翻译：用于预测寡核苷酸的融解温度（Tm）和其他特征的软件系统和方法，包括修饰的寡核苷酸。提供了修饰的寡核苷酸，其含有选自未取代的和3-取代的吡唑并[3,4-d]嘧啶和5-取代的嘧啶的碱，并且任选具有连接的小沟结合剂和报道基团。

9. 发明授权

US07045610B2 Modified oligonucleotides for mismatch discrimination 有权
标题翻译：用于错配鉴别的修饰寡核苷酸
公开(公告)号：US07045610B2
公开(公告)日：2006-05-16
申请号：US09796988
申请日：2001-02-28
申请人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Michael J. Singer , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
发明人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Michael J. Singer , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04 , C12P19/34 , G01N31/00
CPC分类号： C07H19/06 , C07B2200/11 , C07H19/10 , C07H19/16 , C07H19/20 , C07H19/23 , C07H21/00 , C12Q1/6832 , C40B40/00 , G06F19/22 , C12Q2525/117
摘要： Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.
摘要翻译：提供了修饰的寡核苷酸，其含有选自未取代的和3-取代的吡唑并[3,4-d]嘧啶和5-取代的嘧啶的碱，并且任选具有连接的小沟结合剂和报道基团。

10. 发明授权

US07751982B2 TM leveling methods 有权
标题翻译： TM调平方法
公开(公告)号：US07751982B2
公开(公告)日：2010-07-06
申请号：US10672429
申请日：2003-09-26
申请人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
发明人： Robert O. Dempcy , Alexander A. Gall , Sergey G. Lokhov , Irina A. Afonina , Igor V. Kutyavin , Nicolaas M. J. Vermeulen
IPC分类号： G06F19/00 , C12Q1/68
CPC分类号： C07H21/00 , C07B2200/11 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H19/23 , C12Q1/6832 , C40B40/00 , G06F19/22 , C12Q2525/117
摘要： Methods for designing an oligonucleotide sequence having a selected duplex stability are provided wherein the oligonucleotide portion comprises at least one modified base selected from universal bases, unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally having attached minor groove binders and reporter groups.
摘要翻译：提供了设计具有所选双链体稳定性的寡核苷酸序列的方法，其中寡核苷酸部分包含至少一个选自通用碱基，未取代的和3-取代的吡唑并[3,4-d]嘧啶和5-取代的嘧啶的修饰碱基，附有小沟结合物和记者组。

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