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1.发明授权公开(公告)号：US06210892B1
公开(公告)日：2001-04-03
申请号：US09277020
申请日：1999-03-26
申请人： C. Frank Bennett , Stanley T. Cooke , Muthiah Manoharan , Jacqueline R. Wyatt , Brenda F. Baker , Brett P. Monia , Susan M. Freier , Robert McKay , James G. Karras
发明人： C. Frank Bennett , Stanley T. Cooke , Muthiah Manoharan , Jacqueline R. Wyatt , Brenda F. Baker , Brett P. Monia , Susan M. Freier , Robert McKay , James G. Karras
IPC分类号： C12Q168
CPC分类号： C12N15/1135 , A61K38/00 , C12N2310/11 , C12N2310/315 , C12N2310/3181 , C12N2310/321 , C12N2310/3233 , C12N2310/334 , C12N2310/3341 , C12N2310/341 , C12N2310/345 , C12N2310/346 , Y02P20/582 , C12N2310/3525
摘要： The present invention provides compositions and methods for controlling the behavior of a cell, tissue or organism through antisense modulation of mRNA processing, using antisense compounds which does not support cleavage of the mRNA target.
摘要翻译： 本发明提供了使用不支持mRNA靶的切割的反义化合物来控制细胞，组织或生物体通过mRNA加工反义调节的行为的组合物和方法。
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2.发明申请公开(公告)号：US20120184031A1
公开(公告)日：2012-07-19
申请号：US13351511
申请日：2012-01-17
申请人： Brett P. Monia , Susan M. Freier , Muthiah Manoharan , William A. Gaarde , Richard H. Griffey , Eric E.` Swayze , C. Frank Bennett
发明人： Brett P. Monia , Susan M. Freier , Muthiah Manoharan , William A. Gaarde , Richard H. Griffey , Eric E.` Swayze , C. Frank Bennett
IPC分类号： C12N5/071
CPC分类号： C12N15/113 , A61K38/00 , C12N15/1137 , C12N2310/315 , C12N2310/318 , C12N2310/3181 , C12N2310/321 , C12N2310/322 , C12N2310/3233 , C12N2310/334 , C12N2310/3341 , C12N2310/345
摘要： The present invention provides compositions and methods for reducing levels of a preselected mRNA, using antisense compounds targeted to a splice site or a region up to 50 nucleobases upstream of an exon/intron junction on said mRNA. Preferably, said antisense compounds do not elicit RNAse H cleavage of the mRNA.
摘要翻译： 本发明提供了使用靶向剪接位点的反义化合物或在所述mRNA上的外显子/内含子结上游多达50个核碱基的区域来降低预选mRNA水平的组合物和方法。 优选地，所述反义化合物不引起mRNA的RNA酶H切割。
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公开(公告)号：US06784290B1
公开(公告)日：2004-08-31
申请号：US09575554
申请日：2000-05-22
IPC分类号： C07H2102
CPC分类号： C12N15/1135 , A61K38/00 , C07K14/82 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/3521 , C12N2310/3527 , C12N2310/3533 , C12Q2525/125 , C12N2310/3525
摘要： Compositions and methods are provided for the modulation of ras expression. Oligonucleotides are provided which are targeted to nucleic acids encoding human ras. Oligonucleotides specifically hybridizable with mRNA encoding human H-ras, Ki-ras and N-ras are provided. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. Methods are also disclosed for modulating ras gene expression in cells and tissues using the oligonucleotides provided, and for specific modulation of expression of activated ras. Methods for diagnosis, detection and treatment of conditions, or particular cancers, associated with ras are also disclosed.
摘要翻译： 提供了ras表达调控的组成和方法。 提供了靶向编码人ras的核酸的寡核苷酸。 提供与编码人H-ras，Ki-ras和N-ras的mRNA特异性杂交的寡核苷酸。 这样的寡核苷酸可用于治疗和诊断以及用于研究目的。 还公开了使用所提供的寡核苷酸调节细胞和组织中的ras基因表达以及用于特异性调节活化的ras表达的方法。 还公开了与ras有关的病症或特定癌症的诊断，检测和治疗方法。
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公开(公告)号：US6117848A
公开(公告)日：2000-09-12
申请号：US128494
申请日：1998-08-03
IPC分类号： C12N15/09 , A61K31/70 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P35/00 , C07H21/04 , C07K14/82 , C12Q1/68 , C07H21/02
CPC分类号： C07K14/82 , A61K38/00 , C12N2310/322 , C12N2310/3521 , C12N2310/3527 , C12N2310/3533 , C12Q2525/125
摘要： Compositions and methods are provided for the modulation of ras expression. Oligonucleotides are provided which are targeted to nucleic acids encoding human ras. Oligonucleotides specifically hybridizable with mRNA encoding human H-ras, Ki-ras and N-ras are provided. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. Methods are also disclosed for modulating ras gene expression in cells and tissues using the oligonucleotides provided, and for specific modulation of expression of activated ras. Methods for diagnosis, detection and treatment of conditions associated with ras are also disclosed.
摘要翻译： 提供了ras表达调控的组成和方法。 提供了靶向编码人ras的核酸的寡核苷酸。 提供与编码人H-ras，Ki-ras和N-ras的mRNA特异性杂交的寡核苷酸。 这样的寡核苷酸可用于治疗和诊断以及用于研究目的。 还公开了使用所提供的寡核苷酸调节细胞和组织中的ras基因表达以及用于特异性调节活化的ras表达的方法。 还公开了与ras相关的病症的诊断，检测和治疗方法。
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公开(公告)号：US5872242A
公开(公告)日：1999-02-16
申请号：US889296
申请日：1997-07-08
IPC分类号： C12N15/09 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P35/00 , C07K14/82 , C12N15/113 , C07H21/04 , C12P19/34 , C12Q1/68
CPC分类号： C12N15/1135 , C07K14/82 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/333 , C12N2310/3521 , C12N2310/3527 , C12N2310/3533 , C12Q2525/125
摘要： Compositions and methods are provided for the modulation of ras expression. Oligonucleotides are provided which are targeted to nucleic acids encoding human ras. Oligonucleotides specifically hybridizable with mRNA encoding human H-ras, Ki-ras and N-ras are provided. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. Methods are also disclosed for modulating ras gene expression in cells and tissues using the oligonucleotides provided, and for specific modulation of expression of activated ras. Methods for diagnosis, detection and treatment of conditions associated with ras are also disclosed.
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公开(公告)号：US08604183B2
公开(公告)日：2013-12-10
申请号：US10701007
申请日：2003-11-04
申请人： Charles Allerson , Balkrishen Bhat , Anne B. Eldrup , Muthiah Manoharan , Richard H. Griffey , Brenda F. Baker , Eric E. Swayze
发明人： Charles Allerson , Balkrishen Bhat , Anne B. Eldrup , Muthiah Manoharan , Richard H. Griffey , Brenda F. Baker , Eric E. Swayze
CPC分类号： C07H21/00 , C07H21/04 , C12N15/111 , C12N15/113 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2310/343 , C12N2310/3521 , C12N2310/3533 , C12N2320/51
摘要： The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
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7.发明授权2′-substituted oligomeric compounds and compositions for use in gene modulations 有权2'-取代的寡聚化合物和用于基因调节的组合物公开(公告)号：US07919612B2
公开(公告)日：2011-04-05
申请号：US10701316
申请日：2003-11-04
申请人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
发明人： Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke , Thazha P. Prakash
CPC分类号： C12N15/113 , A61K38/00 , C07H21/00 , C12N9/22 , C12N15/1135 , C12N2310/311 , C12N2310/312 , C12N2310/314 , C12N2310/315 , C12N2310/316 , C12N2310/318 , C12N2310/3181 , C12N2310/321 , C12N2310/322 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , C12N2310/346 , Y02A50/395 , Y02P20/582 , C12N2310/3527 , C12N2310/3525 , C12N2310/3521
摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′ substituent group on a sugar moiety that is not H or OH. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide of the oligomer has a modified sugar and/or backbone modification.
摘要翻译： 提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶 核酸，并且第一或第二寡聚体中的至少一种包括修饰的糖和/或骨架修饰。 在一些实施方案中，修饰是糖部分上不是H或OH的2'取代基。 还提供低聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一个核苷酸 低聚物具有修饰的糖和/或骨架修饰。
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8.发明授权2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations 有权2'-氟取代低聚化合物和用于基因调控的组合物公开(公告)号：US07812149B2
公开(公告)日：2010-10-12
申请号：US10700689
申请日：2003-11-04
申请人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
发明人： Thazha P. Prakash , Brenda F. Baker , Anne B. Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric E. Swayze , Stanley T. Crooke
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/346 , C12N2310/3521 , C12N2310/3533 , C12N2310/531 , C12N2320/51
摘要： Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2′-F substituent group on a sugar moiety. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a modified sugar and/or backbone modification.
摘要翻译： 提供包含第一和第二寡聚体的组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与选定的靶互补并能够与选定的靶 核酸，并且第一或第二寡聚体中的至少一种包括修饰的糖和/或骨架修饰。 在一些实施方案中，修饰是糖部分上的2'-F取代基。 还提供寡聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一种核苷 低聚物具有修饰的糖和/或骨架修饰。
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9.发明授权Compositions comprising alternating 2′-modified nucleosides for use in gene modulation 有权包含交替的2'-修饰核苷的组合物用于基因调控公开(公告)号：US09150605B2
公开(公告)日：2015-10-06
申请号：US10860265
申请日：2004-06-03
申请人： Charles Allerson , Balkrishen Bhat , Anne B. Eldrup , Muthiah Manoharan , Richard H. Griffey , Brenda F. Baker , Eric E. Swayze
发明人： Charles Allerson , Balkrishen Bhat , Anne B. Eldrup , Muthiah Manoharan , Richard H. Griffey , Brenda F. Baker , Eric E. Swayze
IPC分类号： C07H21/02 , C07H21/00 , C07H21/04 , C12N15/11 , C12N15/113
CPC分类号： C12N15/113 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/111 , C12N2310/14 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2320/30 , C12N2320/51
摘要： The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
摘要翻译： 本发明提供包含至少一种包含交替基序的低聚化合物并且还包括与核酸靶互补的区域的组合物。 该组合物可用于靶向选定的核酸分子并调节一个或多个基因的表达。 在优选的实施方案中，本发明的组合物与靶RNA的一部分杂交导致靶RNA的正常功能丧失。 本发明还提供了调节基因表达的方法。
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10.发明授权Compositions comprising alternating 2'-modified nucleosides for use in gene modulation 有权包含交替的2'-修饰核苷的组合物用于基因调控公开(公告)号：US09150606B2
公开(公告)日：2015-10-06
申请号：US11054848
申请日：2005-02-09
申请人： Charles Allerson , Balkrishen Bhat , Anne B. Eldrup , Muthiah Manoharan , Richard H. Griffey , Brenda F. Baker , Eric E. Swayze
发明人： Charles Allerson , Balkrishen Bhat , Anne B. Eldrup , Muthiah Manoharan , Richard H. Griffey , Brenda F. Baker , Eric E. Swayze
IPC分类号： C07H21/02
CPC分类号： C07H21/02
摘要： The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
摘要翻译： 本发明提供包含至少一种包含交替基序的低聚化合物并且还包括与核酸靶互补的区域的组合物。 该组合物可用于靶向选定的核酸分子并调节一个或多个基因的表达。 在优选的实施方案中，本发明的组合物与靶RNA的一部分杂交导致靶RNA的正常功能丧失。 本发明还提供了调节基因表达的方法。
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