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公开(公告)号：US5886177A
公开(公告)日：1999-03-23
申请号：US669506
申请日：1996-08-08
IPC分类号： C07D295/08 , A61K31/40 , A61K31/403 , A61K31/404 , A61K31/70 , A61K31/7088 , A61P1/00 , A61P1/04 , A61P17/00 , A61P17/04 , A61P29/00 , A61P43/00 , C07B61/00 , C07C31/20 , C07C43/13 , C07C43/178 , C07C237/04 , C07C317/16 , C07C323/10 , C07C325/00 , C07C327/20 , C07C327/38 , C07C333/02 , C07D207/325 , C07D209/08 , C07D233/60 , C07D239/24 , C07D239/26 , C07D239/42 , C07D239/54 , C07D279/18 , C07D471/04 , C07D473/18 , C07D473/26 , C07D473/34 , C07F9/08 , C07F9/141 , C07F9/143 , C07F9/22 , C07F9/24 , C07F9/572 , C07F9/59 , C07F9/6503 , C07F9/6506 , C07F9/6509 , C07F9/6512 , C07F9/6521 , C07F9/6533 , C07F9/6547 , C07F9/6561 , C07H21/00 , C08G79/02 , C08G79/04 , C12Q1/68 , C07D237/00
CPC分类号： C07F9/143 , C07F9/2408 , C07F9/2429 , C07F9/5721 , C07F9/5728 , C07F9/591 , C07F9/65032 , C07F9/65038 , C07F9/65061 , C07F9/65121 , C07F9/65211 , C07F9/6533 , C07F9/65335 , C07F9/6547 , C07F9/6561 , C07F9/65616 , C07H21/00 , B01J2219/00592 , B01J2219/00695 , C07B2200/11
摘要： Novel ethylene glycol compounds bearing various functional groups are used to prepare oligomeric structures. The ethylene glycol monomers can be joined via standard phosphate linkages including phosphorothioate, phosphodiester, and phosphoramidate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.
摘要翻译： PCT No.PCT / US95 / 00449 Sec。 371日期：1996年8月8日 102（e）日期1996年8月8日PCT提交1995年1月11日PCT公布。 WO95 / 18820PC公报。 日期1995年7月13日使用具有各种官能团的新型乙二醇化合物来制备低聚结构。 乙二醇单体可以通过包括硫代磷酸酯，磷酸二酯和氨基磷酸酯键的标准磷酸键连接。 有用的官能团包括核碱基以及参与氢键的极性基团，疏水基团，离子基团，芳族基团和/或基团。
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公开(公告)号：US06001993A
公开(公告)日：1999-12-14
申请号：US768102
申请日：1996-12-16
摘要： The present invention provides methods of analyzing and evaluating phosphorus bearing monomeric units as to their suitability for use in preparing randomer oligomer libraries. The invention further provides methods for preparing such randomer oligomer libraries from the selected monomers.
摘要翻译： 本发明提供了分析和评价含磷单体单元在适用于制备兰德莫尔低聚物文库时的方法。 本发明还提供从所选择的单体制备这种兰定糖低聚物文库的方法。
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3.发明授权Phosphate linked oligomers formed of monomeric diols and processes for preparing same 失效由单体二醇形成的磷酸酯连接的低聚物及其制备方法公开(公告)号：US06448373B1
公开(公告)日：2002-09-10
申请号：US08179970
申请日：1994-01-11
IPC分类号： A61K3800
CPC分类号： C07H21/00 , B01J2219/00592 , B01J2219/00695 , C07B2200/11 , C07F9/143 , C07F9/2408 , C07F9/2429 , C07F9/572 , C07F9/5728 , C07F9/59 , C07F9/65031 , C07F9/65038 , C07F9/6506 , C07F9/6512 , C07F9/6521 , C07F9/6533 , C07F9/65335 , C07F9/6547 , C07F9/6561 , C07F9/65616
摘要： Novel ethylene glycol compounds bearing various functional groups are used to prepare oligomeric structures. The ethylene glycol monomers can be joined via standard phosphate linkages including phosphodiester and phosphorothioate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.
摘要翻译： 使用具有各种官能团的新型乙二醇化合物来制备低聚结构。 乙二醇单体可以通过包括磷酸二酯和硫代磷酸酯键的标准磷酸键连接。 有用的官能团包括核碱基以及参与氢键的极性基团，疏水基团，离子基团，芳族基团和/或基团。
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公开(公告)号：US06558633B1
公开(公告)日：2003-05-06
申请号：US08309925
申请日：1994-09-21
申请人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
发明人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
IPC分类号： C12M118
CPC分类号： B01L3/0268 , B01J19/0046 , B01J2219/00315 , B01J2219/00333 , B01J2219/00351 , B01J2219/00378 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00729 , C07B2200/11 , C07H21/00 , C07K1/047 , C12P19/34 , C40B40/06 , C40B40/10 , C40B60/14
摘要： Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.
摘要翻译： 提供化学反应装置，材料和方法用于化学物质和文库的可自动化，有效的合成。 根据优选实施方案，采用化学液滴产生和方向技术来制备化学物质的低聚物和文库。 还公开了适于高效合成使用和改进收集的反应组件。
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公开(公告)号：US06277334B1
公开(公告)日：2001-08-21
申请号：US09313403
申请日：1999-05-18
申请人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
发明人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
IPC分类号： B01L300
CPC分类号： B01L3/0268 , B01J19/0046 , B01J2219/00315 , B01J2219/00333 , B01J2219/00351 , B01J2219/00378 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00729 , C07B2200/11 , C07H21/00 , C07K1/047 , C12P19/34 , C40B40/06 , C40B40/10 , C40B60/14
摘要： Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.
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6.发明授权Chemical reaction apparatus for performing multiple reaction on a surface and collecting the product 失效用于在表面上进行多次反应并收集产品的化学反应装置
公开(公告)号：US5925732A
公开(公告)日：1999-07-20
申请号：US778876
申请日：1997-01-02
申请人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
发明人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
IPC分类号： B01J19/00 , B01L3/02 , C07B61/00 , C07H21/00 , C07K1/04 , C12P19/34 , C40B40/06 , C40B40/10 , C40B60/14 , G01N33/53 , C12Q1/68
CPC分类号： B01L3/0268 , B01J19/0046 , C07H21/00 , C07K1/047 , C12P19/34 , B01J2219/00315 , B01J2219/00333 , B01J2219/00351 , B01J2219/00378 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00729 , C07B2200/11 , C40B40/06 , C40B40/10 , C40B60/14
摘要： Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.
摘要翻译： 提供化学反应装置，材料和方法用于化学物质和文库的可自动化，有效的合成。 根据优选实施方案，采用化学液滴产生和方向技术来制备化学物质的低聚物和文库。 还公开了适于高效合成使用和改进收集的反应组件。
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公开(公告)号：US5587471A
公开(公告)日：1996-12-24
申请号：US179972
申请日：1994-01-11
申请人： Phillip D. Cook , David J. Ecker , Oscar L. Acevedo , Peter Davis
发明人： Phillip D. Cook , David J. Ecker , Oscar L. Acevedo , Peter Davis
摘要： The present invention provides methods of analyzing and evaluating phosphorus bearing monomeric units as to their suitability for use in preparing randomer oligomer libraries. The invention further provides methods for preparing such randomer oligomer libraries from the selected monomers.
摘要翻译： 本发明提供了分析和评价含磷单体单元在适用于制备兰德莫尔低聚物文库时的方法。 本发明还提供从所选择的单体制备这种兰定糖低聚物文库的方法。
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8.发明授权公开(公告)号：US06262241B1
公开(公告)日：2001-07-17
申请号：US08383666
申请日：1995-02-03
申请人： Phillip Dan Cook , David J. Ecker , Charles John Guinosso , Oscar Leobardo Acevedo , Andrew Kawasaki , Kandasamy Ramasamy
发明人： Phillip Dan Cook , David J. Ecker , Charles John Guinosso , Oscar Leobardo Acevedo , Andrew Kawasaki , Kandasamy Ramasamy
IPC分类号： C12Q168
CPC分类号： C12N15/113 , A61K38/00 , A61K47/51 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C12N9/0069 , C12N15/1131 , C12N15/1132 , C12N15/1133 , C12N15/1135 , C12N15/1137 , C12N15/1138 , C12N2310/3125 , C12N2310/315 , C12N2310/318 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/336 , C12N2310/3521 , C12N2310/3523 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533 , C12Q1/68 , C12Y113/11012
摘要： Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferrably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferrably accomplished. Therapeutics, diagnostics and research methods and also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.
摘要翻译： 公开了调节RNA和DNA活性的组合物和方法。 根据优选实施方案，制备包含靶向和反应部分的反义组合物。 优选使用通过骨架糖键切割或通过碱改性而作用或通过磷酸酯键断裂的反应性部分。 根据本发明的某些实施方案，提高寡核苷酸的药效学和药代动力学性质的组也是有用的。 通过组合物与靶RNA的杂交形成的反应性或非反应性官能团的递送也是优选的。 治疗，诊断和研究方法也被披露。 合成核苷和核苷片段也可用于制备用于这些目的的寡核苷酸和寡核苷酸类似物。
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公开(公告)号：US5965722A
公开(公告)日：1999-10-12
申请号：US848840
申请日：1997-04-30
IPC分类号： C12N15/09 , A61K31/7125 , A61K48/00 , A61P35/00 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/1135 , C07H21/00 , C12Q1/6876 , C12N2310/315 , C12N2310/318 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/345 , C12N2310/346 , C12Q2600/158
摘要： Compositions and methods are provided for the modulation of expression of the human ras gene in both the normal and activated forms. Oligonucleotides are provided that have methylene(methylimino) linkages alternating with phosphorothioate or phosphodiester linkages. Further oligonucleotides are provide that have a first region having a methylene(methylimino) linkage alternating with a phosphorothioate or phosphodiester linkage and a second region having phosphorothioate linkages. Such oligonucleotides can be used for diagnostics as well as for research purposes including methods for diagnosis, detection and treatment of conditions arising from the activation of the H-ras gene.
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公开(公告)号：US08377897B2
公开(公告)日：2013-02-19
申请号：US11237063
申请日：2005-09-28
申请人： Ching-Leou Teng , Phillip Dan Cook , Lloyd Tillman , Gregory E. Hardee , David J. Ecker , Muthiah Manoharan
发明人： Ching-Leou Teng , Phillip Dan Cook , Lloyd Tillman , Gregory E. Hardee , David J. Ecker , Muthiah Manoharan
CPC分类号： A61K48/0008 , A61K9/0014 , A61K9/0031 , A61K9/107 , A61K9/1075 , A61K38/00 , A61K47/12 , A61K47/28 , A61K48/00 , A61K48/0025 , A61K48/0041 , C12N15/113 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3521 , C12N2310/3527 , C12N2310/3525
摘要： The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes. The compositions and methods of the invention are utilized to effect the oral, buccal, rectal or vaginal administration of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic, palliative or prophylactic purposes.
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