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公开(公告)号：US20090176977A1
公开(公告)日：2009-07-09
申请号：US12162142
申请日：2007-01-29
IPC分类号： C07H21/02
摘要： The current invention provides oligonucleotides which comprise a dinucleotide consisting of a 5′ locked nucleic acid (LNA), a phosphorothioate internucleoside linkage bond to a 3′ RNA or RNA analogue. The dinucleotide reduces the strength of hybridization of the oligonucleotide to a complementary nucleic acid target. The modification can be used to modulate hybridisation properties in both single stranded oligonucleotides and in double stranded siRNA complexes, particularly in oligonucleotides where the use of LNA results in excessively strong hybridisation properties.
摘要翻译： 本发明提供了包含由5'锁定核酸（LNA），与3'RNA或RNA类似物的硫代磷酸核苷间键合键的二核苷酸的寡核苷酸。 二核苷酸降低寡核苷酸与互补核酸靶的杂交强度。 该修饰可用于调节单链寡核苷酸和双链siRNA复合物中的杂交性质，特别是在使用LNA导致过强的杂交性质的寡核苷酸中。
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公开(公告)号：US6117973A
公开(公告)日：2000-09-12
申请号：US805411
申请日：1997-02-24
申请人： Hans-Georg Batz , Henrik Frydenlund Hansen , Henrik Orum , Troels Koch , Gary B. Shuster , Bruce A. Armitage
发明人： Hans-Georg Batz , Henrik Frydenlund Hansen , Henrik Orum , Troels Koch , Gary B. Shuster , Bruce A. Armitage
CPC分类号： C07H21/00 , C07K14/003 , C12Q1/6818 , Y10S435/81
摘要： New electron transfer moiety labeled nucleic acid analogue probes are provided that can be used in methods for determining nucleic acids in a sample. The new probes can be prepared using novel monomer subunits in a chemical synthesis route. The nucleic acids can be determined by binding the probe molecules to the nucleic acid and inducing electron transfer within the complex formed. The occurrence of the electron transfer is determined as a measure of the nucleic acid.
摘要翻译： 提供了新的电子转移部分标记的核酸类似物探针，其可用于测定样品中核酸的方法。 可以在化学合成途径中使用新型单体亚单位制备新的探针。 核酸可以通过将探针分子与核酸结合并在形成的复合物内诱导电子转移来确定。 电子转移的发生被确定为核酸的量度。
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公开(公告)号：US06225052B1
公开(公告)日：2001-05-01
申请号：US08975894
申请日：1997-11-21
申请人： Hans-Georg Batz , Henrik Frydenlund Hansen , Henrik Orum , Troels Koch , Gary B. Schuster , Bruce A. Armitage , Danith Ly
发明人： Hans-Georg Batz , Henrik Frydenlund Hansen , Henrik Orum , Troels Koch , Gary B. Schuster , Bruce A. Armitage , Danith Ly
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07K14/003 , C12Q1/6818 , Y10S435/81
摘要： New electron transfer moiety labeled nucleic acid analogue probes are provided that can be used in methods for determining nucleic acids in a sample. The new probes can be prepared using novel monomer subunits in a chemical synthesis route. The nucleic acids can be determined by binding the probe molecules to the nucleic acid and inducing electron transfer within the complex formed. The occurrence of the electron transfer is determined as a measure of the nucleic acid.
摘要翻译： 提供了新的电子转移部分标记的核酸类似物探针，其可用于测定样品中核酸的方法。 可以在化学合成途径中使用新型单体亚单位制备新的探针。 核酸可以通过将探针分子与核酸结合并在形成的复合物内诱导电子转移来确定。 电子转移的发生被确定为核酸的量度。
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公开(公告)号：US20080249039A1
公开(公告)日：2008-10-09
申请号：US10587775
申请日：2005-01-28
申请人： Joacim Elmen , Claes Wahlestedt , Zicai Liang , Henrik Orum , Troels Koch
发明人： Joacim Elmen , Claes Wahlestedt , Zicai Liang , Henrik Orum , Troels Koch
IPC分类号： A61K31/7105 , C07H21/04
CPC分类号： C07H21/04 , C12N15/111 , C12N15/113 , C12N2310/14 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2320/51
摘要： The present invention is directed to modified siRNA which are significantly impaired in their ability to support cleavage of mRNA when incorporated into a RISC complex. Such modified siRNA may be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the modified siRNA comprises a sense strand and an antisense strand, wherein the sense strand contains a modified RNA nucleotide in at least one of positions 8-14, calculated from the 5′-end.
摘要翻译： 本发明涉及修饰的siRNA，当掺入到RISC复合物中时，其显着损害其支持mRNA切割的能力。 这样的修饰的siRNA可用作治疗剂，例如治疗各种癌症形式。 更具体地，修饰的siRNA包含有义链和反义链，其中有义链含有从5'-末端计算的位置8-14中的至少一个中的修饰的RNA核苷酸。
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公开(公告)号：US20070191294A1
公开(公告)日：2007-08-16
申请号：US10550152
申请日：2004-03-22
申请人： Joacim Elmen , Claes Wahlestedt , Zicai Liang , Anders Sorensen , Henrik Orum , Troels Koch
发明人： Joacim Elmen , Claes Wahlestedt , Zicai Liang , Anders Sorensen , Henrik Orum , Troels Koch
IPC分类号： A61K48/00 , A61K31/7072 , A61K31/704 , A61K38/14 , A61K31/337 , A61K38/09
CPC分类号： C12N15/1131 , A61K38/00 , A61K38/09 , A61K38/2013 , A61K38/212 , A61K38/31 , C12N15/111 , C12N15/1135 , C12N2310/14 , C12N2310/315 , C12N2310/3231 , C12N2310/3233 , C12N2310/3341 , C12N2310/53 , C12N2320/51 , C12N2330/30 , Y02A50/465 , A61K2300/00
摘要： The present invention is directed to novel double-stranded short interfering (siRNA) analogues comprising locked nucleic acid (LNA) monomers. Such compounds induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). The compounds disclosed herein has improved properties compared to non-modified siRNAs and may, accordingly, be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the present invention is directed to siRNA analogues comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogues comprise at least one locked nucleic acid (LNA) monomer.
摘要翻译： 本发明涉及包含锁定核酸（LNA）单体的新型双链短干扰（siRNA）类似物。 这种化合物通过称为RNA干扰（RNAi）的方法在许多生物体中诱导序列特异性的转录后基因沉默。 本文公开的化合物与未修饰的siRNA相比具有改善的性质，因此可用作治疗剂，例如用于治疗各种癌症形式。 更具体地，本发明涉及包含有义链和反义链的siRNA类似物，其中每条链包含12-35个核苷酸，并且其中siRNA类似物包含至少一个锁定核酸（LNA）单体。
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6.发明授权公开(公告)号：US08580756B2
公开(公告)日：2013-11-12
申请号：US12532532
申请日：2008-03-19
申请人： Jens Bo Rode Hansen , Henrik Orum , Henrik Frydenlund Hansen , Ellen Marie Straarup , Niels Fisker Nielsen , Maj Hedtjärn
发明人： Jens Bo Rode Hansen , Henrik Orum , Henrik Frydenlund Hansen , Ellen Marie Straarup , Niels Fisker Nielsen , Maj Hedtjärn
CPC分类号： C12N15/1136 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2320/51
摘要： The invention provides LNA gapmer oligomers of between 10-20 nucleobases in length, which have a total of 1-3 phosphodiester internucleoside linkages. Such oligomers have been found to have superior bioavailability and have also been found to selectively accumulate in kidney cells.
摘要翻译： 本发明提供长度为10-20个核碱基的LNA gapmer寡聚体，其具有总共1-3个磷酸二酯核苷间键。 已经发现这样的低聚物具有优异的生物利用度，并且也被发现选择性地积累在肾细胞中。
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公开(公告)号：US06346378B2
公开(公告)日：2002-02-12
申请号：US09086726
申请日：1998-05-29
IPC分类号： C12Q168
CPC分类号： C07K14/003 , C07H21/00 , C12Q1/6813
摘要： A nucleic acid analog comprising a polymeric strand which includes a sequence of ligands bound to a backbone made up of linked backbone moieties, which analog is capable of hybridization to a nucleic acid of complementary sequence, further comprising a chelating moiety capable of binding at least one metal ion by chelation.
摘要翻译： 包含聚合物链的核酸类似物，其包含与由连接的主链部分构成的主链结合的配体序列，该类似物能够与互补序列的核酸杂交，还包含能够结合至少一个 金属离子螯合。
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8.发明授权Methods of capturing nucleic acid analogs and nucleic acids on a solid support 失效在固体支持物上捕获核酸类似物和核酸的方法
公开(公告)号：US5843663A
公开(公告)日：1998-12-01
申请号：US653607
申请日：1996-05-24
IPC分类号： G01N33/53 , C07H21/00 , C07K14/00 , C08G69/00 , C08G75/00 , C08G75/30 , C09K3/00 , C12Q1/68 , G01N33/569
CPC分类号： C07K14/003 , C07H21/00 , C12Q1/6813
摘要： A nucleic acid analog comprising a polymeric strand which includes a sequence of ligands bounds to a backbone made up of linked backbone moieties, which analog is capable of hybridization to a nucleic acid of complementary sequence, further comprising a chelating moiety capable of binding at least one metal ion by chelation.
摘要翻译： 包含聚合物链的核酸类似物，其包含与由连接的主链部分构成的主链结合的配体序列，该类似物能够与互补序列的核酸杂交，还包含能够结合至少一个 金属离子螯合。
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9.发明申请Splice Switching Oligomers for TNF Superfamily Receptors and their Use in Treatment of Disease 审中-公开用于TNF超家族受体的接头开关寡聚体及其在治疗疾病中的应用公开(公告)号：US20090264353A1
公开(公告)日：2009-10-22
申请号：US11875277
申请日：2007-10-19
申请人： Henrik Orum , Peter L. Sazani
发明人： Henrik Orum , Peter L. Sazani
IPC分类号： A61K38/17 , A61K31/70 , A61K31/7052 , C07H19/00 , C07K14/47 , C07H21/02 , C12N15/85 , C12N5/10 , C12P21/02 , A61P29/00
CPC分类号： C07H21/04 , A61K38/00 , C07H19/00 , C07H21/02 , C07K14/7151 , C12N2799/025 , C12N2799/026 , Y02A50/463
摘要： The present invention relates to compositions and methods for preparing splice variants of TNFalpha receptor (TNFR) in vivo or in vitro, and the resulting TNFR protein variants. Such variants may be prepared by controlling the splicing of pre-mRNA molecules and regulating protein expression with splice switching oligonucleotides or splice switching oligomers (SSOs). The preferred SSOs according to the invention target exon 7 or 8 of TNFR1 (TNFRSF1A) or TNFR2 (TNFRSF1A) pre-mRNA, typically resulting in the production of TNFR variants which comprise a deletion in part or the entire exon 7 or 8 respectfully. SSOs targeting exon 7 are found to result in a soluble form of the TNFR, which has therapeutic benefit for treatment of inflammatory diseases. The SSO's are characterized in that they are substantially incapable or incapable of recruiting RNaseH.
摘要翻译： 本发明涉及用于在体内或体外制备TNFα受体（TNFR）的剪接变体的组合物和方法，以及所得的TNFR蛋白质变体。 可以通过控制前mRNA分子的剪接和用剪接切换寡核苷酸或剪接切换寡聚体（SSO）调节蛋白质表达来制备这些变体。 根据本发明的优选SSO靶向TNFR1（TNFRSF1A）或TNFR2（TNFRSF1A）前mRNA的外显子7或8，通常导致在部分或全部外显子7或8中包含缺失的TNFR变体的产生。 发现针对外显子7的SSOs产生可溶形式的TNFR，其具有治疗炎性疾病的治疗益处。 SSO的特点是它们基本上无能力或不能招募RNaseH。
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公开(公告)号：US09364495B2
公开(公告)日：2016-06-14
申请号：US13503189
申请日：2010-10-20
IPC分类号： C07H21/04 , C07H21/02 , A61K48/00 , C12N15/85 , A61K31/712 , C12N15/113
CPC分类号： A61K31/712 , A61K9/0053 , C12N15/113 , C12N15/1136 , C12N2310/11 , C12N2310/113 , C12N2310/315 , C12N2310/3231 , C12N2310/3341 , C12N2320/30
摘要： The invention provides for LNA oligomers, for the treatment of a metabolic or liver disorder, wherein the LNA oligomer is administered orally in a unit dose of less than 50 mgs/kg, wherein the LNA oligomer is administered in the presence of a penetration (permeation) enhancer.
摘要翻译： 本发明提供用于治疗代谢或肝病症的LNA寡聚体，其中所述LNA低聚物以小于50mg / kg的单位剂量口服给药，其中所述LNA低聚物在渗透（渗透 ）增强剂。
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