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1.发明授权Antisense inhibition of ras gene with chimeric and alternating oligonucleotides 有权用嵌合和交替寡核苷酸反义ras基因的抑制公开(公告)号：US06359124B1
公开(公告)日：2002-03-19
申请号：US09248386
申请日：1999-02-12
IPC分类号： C07H2102
CPC分类号： C12N15/1135 , C07H21/00 , C12N2310/315 , C12N2310/318 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/345 , C12N2310/346 , C12Q1/6876 , C12Q2600/158 , C12N2310/3525
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.
摘要翻译： 提供组合物和方法用于调节正常和活化形式的人ras基因的表达。 提供了具有与硫代磷酸酯或磷酸二酯键交替的亚甲基（甲基亚氨基）键的寡核苷酸。 提供另外的寡核苷酸，其具有与硫代磷酸酯或磷酸二酯键交替的亚甲基（甲基亚氨基）键的第一区域和具有硫代磷酸酯键的第二区域。 这样的寡核苷酸可用于诊断以及研究目的，包括用于诊断，检测和治疗由H-ras基因激活产生的病症的方法。
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2.发明授权Process for the synthesis of 2′-O-substituted pyrimidines and oligomeric compounds therefrom 失效用于合成2'-O-取代的嘧啶及其低聚化合物的方法公开(公告)号：US06222025B1
公开(公告)日：2001-04-24
申请号：US08894899
申请日：1998-01-07
申请人： Phillip Dan Cook , Yogesh S. Sanghvi , Kelly G. Sprankle , Bruce S. Ross , Rich H. Griffey , Robert H. Springer
发明人： Phillip Dan Cook , Yogesh S. Sanghvi , Kelly G. Sprankle , Bruce S. Ross , Rich H. Griffey , Robert H. Springer
IPC分类号： C07H1900
CPC分类号： C07H19/06 , C07H21/00 , Y02P20/55 , Y02P20/582
摘要： Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2′ and 5 positions. Monomeric sub-units having these modifications may be further modified at the 2 position. Improved processes for the synthesis of 2′-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2′-anhydropyrimidine nucleoside or a 2S,2′-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.
摘要翻译： 公开了寡核苷酸类似物，其中具有在2'和5位修饰的嘧啶单体亚单位。 具有这些修饰的单体子单元可以在2位进一步修饰。 还提供了用于合成2'-O-取代的嘧啶核苷的改进方法。 该方法的特征是在路易斯酸存在下，使用具有弱亲核试剂的2,2'-脱水嘧啶核苷或2S，2'-脱水嘧啶核苷进行烷基化。
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公开(公告)号：US5792844A
公开(公告)日：1998-08-11
申请号：US317289
申请日：1994-10-03
IPC分类号： C07D405/04 , C07D405/14 , C07F7/18 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00 , C07H21/02 , C07H21/04
CPC分类号： C07D405/04 , C07D405/14 , C07F7/1856 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds contain a selected nucleoside sequence wherein the nucleosides are covalently bound through linking groups that contain adjacent nitrogen atoms.
摘要翻译： 模仿和/或调节野生型核酸活性的新型化合物。 通常，化合物含有选择的核苷序列，其中核苷通过含有相邻氮原子的连接基团共价结合。
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4.发明授权Process for the synthesis of 2′-O-substituted pyrimidines and oligomeric compounds therefrom 失效用于合成2'-O-取代的嘧啶及其低聚化合物的方法公开(公告)号：US06642367B2
公开(公告)日：2003-11-04
申请号：US09747009
申请日：2000-12-22
申请人： Phillip Dan Cook , Yogesh S. Sanghvi , Kelly G. Sprankle , Bruce S. Ross , Rich H. Griffey , Robert H. Springer
发明人： Phillip Dan Cook , Yogesh S. Sanghvi , Kelly G. Sprankle , Bruce S. Ross , Rich H. Griffey , Robert H. Springer
IPC分类号： C07H1900
CPC分类号： C07H19/06 , C07H21/00 , Y02P20/55 , Y02P20/582
摘要： Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2′ and 5′ positions. Monomeric sub-units having these modifications may be further modified at the 2′ position. Improved processes for the synthesis of 2′-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2′-anhydropyrimidine nucleoside or a 2S,2′-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.
摘要翻译： 公开了寡核苷酸类似物，其中具有在2'和5'位置被修饰的嘧啶单体亚单位。 具有这些修饰的单体子单元可以在2'位置进一步修饰。 还提供了用于合成2'-O-取代的嘧啶核苷的改进方法。 该方法的特征是在路易斯酸存在下，使用具有弱亲核试剂的2,2'-脱水嘧啶核苷或2S，2'-脱水嘧啶核苷进行烷基化。
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5.发明授权Backbone modified oligonucleotide analogs and preparation thereof through radical coupling 失效骨架修饰的寡核苷酸类似物及其通过自由基偶联的制备
公开(公告)号：US5969118A
公开(公告)日：1999-10-19
申请号：US794493
申请日：1997-02-04
IPC分类号： C07D405/04 , C07D405/14 , C07F7/18 , C07H19/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00 , C07H21/02
CPC分类号： C07D405/04 , C07D405/14 , C07F7/1856 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Methods for preparing oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. In preferred embodiments, the methods involve radical coupling of 3'- and 5'-substituted or 5'- and 3'-subutituted nucleosidic synthons.
摘要翻译： 提供了具有改善的核酸酶抗性和改进的细胞摄取的寡核苷酸类似物的制备方法。 在优选的实施方案中，所述方法包括3'-和5'-取代或5'-和3'-取代的核苷合成子的自由基偶联。
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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：US5808023A
公开(公告)日：1998-09-15
申请号：US335046
申请日：1994-11-07
IPC分类号： A61K47/48 , C07D405/04 , C07D405/14 , C07F7/18 , C07H19/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
CPC分类号： C07H19/06 , A61K31/70 , A61K47/48092 , C07D405/04 , C07D405/14 , C07F7/1856 , C07H19/04 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids are provided. The novel compounds have modified internucleoside linkages which preferably replace naturally-occurring phosphodiester-5'-methylene linkages with four atom linking groups. Preferred linkages have structures such as, for example, CH.sub.2 --R.sub.A --NR.sub.1 --CH.sub.2, CH.sub.2 --NR.sub.1 --R.sub.A --CH.sub.2, R.sub.A --NR.sub.1 --CH.sub.2 --CH.sub.2, CH.sub.2 --CH.sub.2 --NR.sub.1 --R.sub.A, CH.sub.2 --CH.sub.2 --R.sub.A --NR.sub.1, or NR.sub.1 --R.sub.A --CH.sub.2 --CH.sub.2 where R.sub.A is O or NR.sub.2. These linkages are prepared from appropriately functionalized nucleosides and oligonucleotides.
摘要翻译： 提供了模拟和/或调节野生型核酸活性的新型化合物。 新化合物具有修饰的核苷间键，其优选用四个原子连接基团取代天然存在的磷酸二酯-5'-亚甲基键。 优选的连接键具有例如CH 2 -R RA-NR 1 -CH 2，CH 2 -NR 1 -RA-CH 2，RA-NR 1 -CH 2 -CH 2，CH 2 -CH 2 -NR 11-RA，CH 2 -CH 2 -RA-NR 1， 或NR1-RA-CH2-CH2，其中RA是O或NR2。 这些连接是由适当官能化的核苷和寡核苷酸制备的。
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公开(公告)号：US06214551B1
公开(公告)日：2001-04-10
申请号：US09123572
申请日：1998-07-27
IPC分类号： C12Q168
CPC分类号： A61K31/70 , A61K47/59 , A61K47/605 , C07D405/04 , C07D405/14 , C07F7/1804 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds contain a selected nucleoside sequence wherein the nucleosides are covalently bound through linking groups that contain adjacent nitrogen atoms.
摘要翻译： 模仿和/或调节野生型核酸活性的新型化合物。 通常，化合物含有选择的核苷序列，其中核苷通过含有相邻氮原子的连接基团共价结合。
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9.发明授权Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions 失效具有嘧啶核苷酸（S）的具有2'-5个取代基的低聚化合物
公开(公告)号：US06166197A
公开(公告)日：2000-12-26
申请号：US398901
申请日：1995-03-06
CPC分类号： C07H19/06 , C07H21/00 , Y02P20/582
摘要： Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2' and 5 positions. Monomeric sub-units having these modifications may be further modified at the 2 position.
摘要翻译： 公开了寡核苷酸类似物，其中具有在2'和5位修饰的嘧啶单体亚单位。 具有这些修饰的单体子单元可以在2位进一步修饰。
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公开(公告)号：US6121433A
公开(公告)日：2000-09-19
申请号：US669300
申请日：1996-08-08
IPC分类号： A61K47/48 , A61K49/00 , C07D405/04 , C07D405/14 , C07F7/18 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00 , C08G73/02 , C08G75/30 , C12N15/113 , C12Q1/68 , C07H19/00 , C07H21/02 , C07H21/04 , A01N43/04
CPC分类号： A61K31/70 , A61K47/48192 , A61K49/0006 , C07D405/04 , C07D405/14 , C07F7/1856 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00 , C08G73/02 , C08G75/30 , C12N15/113 , C12N15/1137 , C12Q1/68 , C12Y113/11012 , C12N2310/318
摘要： Novel compounds and libraries of compounds based on nitrogen atoms that are joined together with spanner groups include "letters" i.e., functional groups, that are attached to the nitrogen atoms, to the spanner groups or to both the nitrogen atoms and the spanner groups to render the compounds and libraries of such compounds with diverse properties.
摘要翻译： PCT No.PCT / US95 / 00350 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。 公开号WO95 / 18623 日期1995年7月13日新的化合物和基于与氮原子连接在一起的扳手组合物的文库包括连接到氮原子的官能团，即扳手组或氮原子和 扳手组以使具有不同性质的这些化合物的化合物和文库。
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