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1. 发明授权

US5691316A Cyclodextrin cellular delivery system for oligonucleotides 失效
公开(公告)号：US5691316A
公开(公告)日：1997-11-25
申请号：US341522
申请日：1994-11-17
申请人： Sudhir Agrawal , Qiuyan Zhao , Ivan Habus
发明人： Sudhir Agrawal , Qiuyan Zhao , Ivan Habus
IPC分类号： A61K47/48 , A61K48/00 , C07H21/02 , C07H21/04 , C08B37/16
CPC分类号： B82Y5/00 , A61K47/48969
摘要： Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.

2. 发明授权

US5616565A Cyclodextrin cellular delivery system for oligonucleotides 失效
标题翻译：寡核苷酸的环糊精细胞递送系统
公开(公告)号：US5616565A
公开(公告)日：1997-04-01
申请号：US480834
申请日：1995-06-07
申请人： Sudhir Agrawal , Qiuyan Zhao , Ivan Habus
发明人： Sudhir Agrawal , Qiuyan Zhao , Ivan Habus
IPC分类号： A61K47/48 , A61K48/00
CPC分类号： B82Y5/00 , A61K47/48969
摘要： Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.
摘要翻译：公开了包含与环糊精复合的寡核苷酸的组合物。寡核苷酸可以与环糊精非共价结合。或者，寡核苷酸可与与环糊精非共价结合的金刚烷共价络合。还公开了增强寡核苷酸的细胞摄取和细胞内浓度的方法，增加寡核苷酸在细胞中的溶解度的方法，以及治疗细胞用于病毒感染或预防病毒感染的方法。

3. 发明授权

US5605890A Cyclodextrin cellular delivery system for oligonucleotides 失效
公开(公告)号：US5605890A
公开(公告)日：1997-02-25
申请号：US480833
申请日：1995-06-07
申请人： Sudhir Agrawal , Qiuyan Zhao , Ivan Habus
发明人： Sudhir Agrawal , Qiuyan Zhao , Ivan Habus
IPC分类号： A61K47/48 , A61K48/00 , C12N7/06
CPC分类号： B82Y5/00 , A61K47/48969
摘要： Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.

4. 发明授权

US5912332A Affinity-based purification of oligonucleotides using soluble multimeric oligonucleotides 失效
标题翻译：使用可溶性多聚寡核苷酸的亲和纯化寡核苷酸
公开(公告)号：US5912332A
公开(公告)日：1999-06-15
申请号：US690300
申请日：1996-07-26
申请人： Sudhir Agrawal , Ivan Habus , Ekambar R. Kandimalla
发明人： Sudhir Agrawal , Ivan Habus , Ekambar R. Kandimalla
IPC分类号： C07H1/06 , C07H21/00 , C12Q1/68
CPC分类号： C07H21/00 , C07H1/06
摘要： The present invention provides novel compounds and methods for purifying oligonucleotides. The compounds according to the invention are multimeric oligonucleotides comprising a multimerization domain for inducing multimeric oligonucleotide aggregation, a hybridization domain that is complementary to a target oligonucleotide whose isolation is desired, and a linker domain connecting the multimerization domain and the hybridization domain. Other compounds of the invention comprise dendrimers having oligonucleotides with hybridization domains linked thereto.The methods of the invention comprise contacting the compounds of the invention with a solution containing a target oligonucleotide whose purification is desired. The target oligonucleotide hybridizes to the hybridization domain of the inventive compounds, thereby forming an aggregate. Synthetic failure sequences (N-1, N-2, etc.) and other oligonucleotides not complementary to the hybridization domain do not hybridize with the hybridization domain of the compounds and remain free in solution. Conventional size exclusion chromatography or small pore filter membranes are then used to separate the aggregate (and hence target oligonucleotide) from the other oligonucleotides. The aggregate is denatured and the target oligonucleotide separated once again by size exclusion chromatography or with a small pore filter membrane.
摘要翻译：本发明提供了用于纯化寡核苷酸的新型化合物和方法。根据本发明的化合物是多聚寡核苷酸，其包含用于诱导多聚寡核苷酸聚集的多聚化结构域，与需要分离的靶寡核苷酸互补的杂交结构域和连接多聚化结构域和杂交结构域的连接体结构域。本发明的其它化合物包含具有与其连接的杂交结构域的寡核苷酸的树枝状大分子。本发明的方法包括使本发明的化合物与含有需要纯化的靶寡核苷酸的溶液接触。靶寡核苷酸与本发明化合物的杂交结构域杂交，从而形成聚集体。合成失败序列（N-1，N-2等）和与杂交结构域不互补的其他寡核苷酸不与化合物的杂交结构域杂交并且在溶液中保持游离。然后使用常规尺寸排阻色谱法或小孔过滤膜将聚集体（因此靶寡核苷酸）与其他寡核苷酸分离。聚集体变性，并且目标寡核苷酸再次通过尺寸排阻色谱法或用小孔滤膜分离。

5. 发明授权

US06605708B1 Building blocks with carbamate internucleoside linkages and oligonucleotides derived therefrom 失效
标题翻译：具有氨基甲酸酯核苷间键的构建块和衍生自其的寡核苷酸
公开(公告)号：US06605708B1
公开(公告)日：2003-08-12
申请号：US08098945
申请日：1993-07-28
申请人： Ivan Habus , Sudhir Agrawal
发明人： Ivan Habus , Sudhir Agrawal
IPC分类号： C07H2100
CPC分类号： C07H21/00
摘要： The invention provides synthons containing a novel carbamate internucleoside linkage, methods for using such synthons to make oligonucleotides containing such novel carbamate linkages, and oligonucleotides containing such novel carbamate linkages.
摘要翻译：本发明提供了含有新的氨基甲酸酯核苷间键的合成子，使用这种合成子制备含有这种新型氨基甲酸酯键的寡核苷酸的方法，以及含有这种新型氨基甲酸酯键的寡核苷酸。

6. 发明授权

US06509459B1 Base protecting groups and rapid process for oligonucleotide synthesis 失效
标题翻译：碱基保护基和寡核苷酸合成的快速过程
公开(公告)号：US06509459B1
公开(公告)日：2003-01-21
申请号：US08846303
申请日：1997-04-30
申请人： Sudhir Agrawal , Radhakrishnan P. Iyer , Ivan Habus , Dong Yu
发明人： Sudhir Agrawal , Radhakrishnan P. Iyer , Ivan Habus , Dong Yu
IPC分类号： C07H2100
CPC分类号： C07H21/00 , C07H19/10 , C07H19/16 , C07H19/20 , Y02P20/55
摘要： The invention provides new processes for synthesizing oligonucleotides that allow for deprotection of the oligonucleotide under more rapid and/or more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups. The invention also provides oligonucleotides containing any of a variety of base labile functionalities and methods for using such oligonucleotides.
摘要翻译：本发明提供了合成寡核苷酸的新方法，其允许寡核苷酸在比现有方法更快和/或更温和的条件下脱保护。本发明还提供了在寡核苷酸合成条件下稳定但可被除去的核苷碱基保护基在比现有保护基更温和的条件下，以及具有这种碱保护基的核苷合成子。本发明还提供了含有各种碱不稳定功能的寡核苷酸的寡核苷酸和使用这些寡核苷酸的方法。

7. 发明授权

US6140482A Primary phosphoramidate internucleoside linkages and oligonucleotides containing the same 失效
标题翻译：初级氨基磷酸核苷间核苷键和含有其的寡核苷酸
公开(公告)号：US6140482A
公开(公告)日：2000-10-31
申请号：US519318
申请日：1995-08-25
申请人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal
发明人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal
IPC分类号： C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00
CPC分类号： C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00
摘要： The invention provides new primary phosphoramidate internucleoside linkages that are less sterically constrained than existing phosphoramidate linkages, as well as oligonucleotides containing such linkages and processes for making and methods for using such oligonucleotides.
摘要翻译：本发明提供了比现有氨基磷酸酯键更少的空间限制的新的初级氨基磷酸酯核苷间键，以及含有这种连接的寡核苷酸和制备方法以及使用这种寡核苷酸的方法。

8. 发明授权

US5614622A 5-pentenoyl moiety as a nucleoside-amino protecting group, 4-pentenoyl-protected nucleotide synthons, and related oligonucleotide syntheses 失效
标题翻译： 5-戊烯酰基部分作为核苷 - 氨基保护基，4-戊烯酰基保护的核苷酸合成子和相关的寡核苷酸合成
公开(公告)号：US5614622A
公开(公告)日：1997-03-25
申请号：US518921
申请日：1995-08-24
申请人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal
发明人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal
IPC分类号： C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H19/06
CPC分类号： C07H19/16 , C07H19/10 , C07H19/20 , C07H21/00 , Y02P20/55
摘要： The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotide under more mild conditions than existing methods. The invention further provides a nucleoside base protective group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protective groups, as well as nucleoside synthons having such base protective groups.
摘要翻译：本发明提供了合成寡核苷酸的新方法，其允许寡核苷酸在比现有方法更温和的条件下脱保护。本发明还提供了在寡核苷酸合成条件下稳定但可在比现有保护基更温和的条件下除去的核苷碱基保护基以及具有这种碱性保护基的核苷合成子。

9. 发明授权

US06531589B1 Base protecting groups and synthons for oligonucleotide synthesis 失效
标题翻译：用于寡核苷酸合成的碱基保护基和合成子
公开(公告)号：US06531589B1
公开(公告)日：2003-03-11
申请号：US08598320
申请日：1996-02-08
申请人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal , Nan-Hui Ho
发明人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal , Nan-Hui Ho
IPC分类号： C07H2100
CPC分类号： C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , Y02P20/55
摘要： The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.
摘要翻译：本发明提供了合成寡核苷酸的新方法，其允许在比现有方法更温和的条件下对寡核苷酸进行脱保护。本发明还提供了在寡核苷酸合成条件下稳定但可在比现有保护基更温和的条件下除去的核苷碱保护基，以及具有这种碱保护基的核苷合成子。

10. 发明授权

US5962674A Synthesis of oligonucleotides containing alkylphosphonate internucleoside linkages 失效
标题翻译：含有烷基膦酸酯核苷间键的寡核苷酸的合成
公开(公告)号：US5962674A
公开(公告)日：1999-10-05
申请号：US606915
申请日：1996-02-26
申请人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal
发明人： Radhakrishnan P. Iyer , Theresa Devlin , Ivan Habus , Dong Yu , Sudhir Agrawal
IPC分类号： C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00
CPC分类号： C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , Y02P20/55
摘要： The invention provides new reagents and an improved process for synthesizing oligonucleotides that contain methylphosphonate internucleoside linkages. The reagents and process utilize a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups.
摘要翻译：本发明提供新的试剂和用于合成含有甲基膦酸核苷间键的寡核苷酸的改进方法。试剂和方法利用在寡核苷酸合成条件下稳定的核苷碱基保护基，但可以在比现有保护基更温和的条件下除去。

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