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1. 发明授权

US5672695A Modified ribozymes 失效
标题翻译：改良的核酶
公开(公告)号：US5672695A
公开(公告)日：1997-09-30
申请号：US965411
申请日：1993-08-09
申请人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heidenreich
发明人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heidenreich
IPC分类号： A61K31/70 , A61K31/00 , A61K31/712 , A61K38/00 , A61K48/00 , A61P31/18 , C07H21/02 , C12N9/00 , C12N15/00 , C12N15/09 , C12N15/113 , C07H21/04 , C12Q1/68
CPC分类号： C12N15/1132 , C12N15/113 , A61K38/00 , C12N2310/121 , C12N2310/122 , C12N2310/315 , C12N2310/322
摘要： The claimed invention is drawn to RNA molecules with catalytic activity comprising at least one modified nucleoside having a modifier group replacing the hydroxy group at the 2'-position of the ribose sugar where the modifier group is an halo, amino, mono- or disubstituted amino, or an azido group.
摘要翻译： PCT No.PCT / EP91 / 01811 Sec。 371日期：1993年8月9日 102（e）日期1993年8月9日PCT 1991年9月23日PCT公布。公开号WO92 / 07065 日本1992年4月30日所要求保护的发明涉及具有催化活性的RNA分子，所述RNA分子包含至少一种具有修饰基团的修饰核苷酸，所述修饰核苷具有代替核糖2位的羟基，其中修饰基团是卤素，氨基，单或二取代的氨基或叠氮基。

2. 发明授权

US06890908B1 Modified ribozymes 失效
标题翻译：改良的核酶
公开(公告)号：US06890908B1
公开(公告)日：2005-05-10
申请号：US08936657
申请日：1997-09-24
申请人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heidenreich
发明人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heidenreich
IPC分类号： A61K31/70 , A61K31/00 , A61K31/712 , A61K38/00 , A61K48/00 , A61P31/18 , C07H21/02 , C12N9/00 , C12N15/00 , C12N15/09 , C12N15/113
CPC分类号： C12N15/1132 , A61K38/00 , C12N15/113 , C12N2310/121 , C12N2310/122 , C12N2310/315 , C12N2310/322
摘要： The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2′-position of the ribose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino and disubstituted amino groups, a process for the preparation of modified RNA molecules and the use of modified RNA molecules as therapeutic agents and biocatalysts.
摘要翻译：本发明涉及具有至少一种修饰核苷的催化活性的RNA分子，其中核糖2'-位的羟基被选自卤素，巯基，叠氮基，氨基，单取代的修饰基团氨基和二取代的氨基，制备修饰的RNA分子的方法和使用修饰的RNA分子作为治疗剂和生物催化剂。

3. 发明授权

US5817635A Modified ribozymes 失效
标题翻译：改良的核酶
公开(公告)号：US5817635A
公开(公告)日：1998-10-06
申请号：US434547
申请日：1995-05-04
申请人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heindenreich
发明人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heindenreich
IPC分类号： A61K38/00 , C12N15/113 , A61K48/00 , C12N15/85 , C12Q1/68
CPC分类号： C12N15/1132 , A61K38/00 , C12N2310/121 , C12N2310/122 , C12N2310/322
摘要： The claimed invention is drawn to RNA molecules with catalytic activity comprising at least one modified nucleoside having a modifier group replacing the hydroxy group at the 2'-position of the ribose sugar where the modifier group is an halo, amino, mono- or disubstituted amino, or an azido group, and methods of use in vivo.
摘要翻译：要求保护的发明涉及具有催化活性的RNA分子，所述RNA分子包含至少一种具有改性基团的修饰核苷，所述修饰核苷具有取代核糖2位的羟基，其中改性基是卤素，氨基，单或二取代的氨基，或叠氮基，以及在体内使用的方法。

4. 发明授权

US5698687A Modified ribozymls 失效
标题翻译：改良的核酶
公开(公告)号：US5698687A
公开(公告)日：1997-12-16
申请号：US434501
申请日：1995-05-04
申请人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heindenreich
发明人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David B. Olsen , David M. Williams , Olaf Heindenreich
IPC分类号： A61K31/70 , A61K31/00 , A61K31/712 , A61K38/00 , A61K48/00 , A61P31/18 , C07H21/02 , C12N9/00 , C12N15/00 , C12N15/09 , C12N15/113 , C07H21/04 , C07H21/00 , C12P19/34
CPC分类号： C12N15/1132 , C12N15/113 , A61K38/00 , C12N2310/121 , C12N2310/122 , C12N2310/315 , C12N2310/322
摘要： The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2'-position of the fibose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino, and disubstituted andno groups, a process for the preparation of modified KNA molecules and the use of modified KNA molecules as therapeutic agents and biocatalysts.
摘要翻译：本发明涉及具有至少一种修饰核苷的催化活性的RNA分子，其中纤维糖2位的羟基被选自卤素，巯基，叠氮基，氨基，单取代的修饰基团氨基和二取代和无基团，制备改性KNA分子的方法和使用修饰的KNA分子作为治疗剂和生物催化剂。

5. 发明申请

US20060036087A1 2'-deoxy-2'-fluoro modified RNA 审中-公开
标题翻译： 2'-脱氧-2'-氟修饰的RNA
公开(公告)号：US20060036087A1
公开(公告)日：2006-02-16
申请号：US10656270
申请日：2003-09-05
申请人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David Olsen , David Williams , Olaf Heindenreich
发明人： Fritz Eckstein , Wolfgang Pieken , Fritz Benseler , David Olsen , David Williams , Olaf Heindenreich
IPC分类号： C07H21/02
CPC分类号： C07H21/02 , B65G47/846
摘要： The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2′-position of the ribose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino and disubstituted amino groups, a process for the preparation of modified RNA molecules and the use of modified RNA molecules as therapeutic agents and biocatalysts.
摘要翻译：本发明涉及具有至少一种修饰核苷的催化活性的RNA分子，其中核糖2'-位的羟基被选自卤素，巯基，叠氮基，氨基，单取代的修饰基团氨基和二取代的氨基，制备修饰的RNA分子的方法和使用修饰的RNA分子作为治疗剂和生物催化剂。

6. 发明授权

US4145531A Process for producing 2'-substituted-D-ribofuranosyl purine compounds 失效
标题翻译：制备2 {40-取代-D-呋喃核糖基嘌呤化合物的方法
公开(公告)号：US4145531A
公开(公告)日：1979-03-20
申请号：US792077
申请日：1977-04-28
申请人： Fritz Eckstein , John Hobbs
发明人： Fritz Eckstein , John Hobbs
IPC分类号： C07H5/04 , C07H13/04 , C07H19/06 , C07H19/16 , C07H19/20
CPC分类号： C07H13/04 , C07H19/06 , C07H19/16 , C07H19/20 , C07H5/04
摘要： 2'-Substituted-D-ribofuranosyl purine compounds, especially 2'-azido-D-riuranosyl purine compounds, of the formula ##STR1## in which R.sub.1 is azide, amino, halogen or alkoxy, and R.sub.2 is the residue of a purine base and particularly a 9-adenyl group, a 7-guanyl group, or a 9-guanyl group (the waved lines in formula I above show that R.sub.2 can be bound in the .alpha.- or .beta.-configuration), Are prepared by a process comprising (a) reacting a uridine derivative with an alkali azide (when R.sub.1 is to be azide or, through further conversion, an amine group) or a halide (when R.sub.1 is halogen) or with an alkylating agent (when R.sub.1 is alkoxy); (b) transforming the resulting compound with hydrazine into the corresponding 2-deoxy-ribose; (c) converting the 2-deoxy-ribose into a 1-O-methylglucoside with methanol in the presence of a strong acid; (d) reacting the glucoside with acetic anhydride in a polar organic solvent to form a 1-O-methyl-ribose-3,5-diacetate; (e) converting the diacetate with acetic anhydride in glacial acetic acid, in the presence of a strong acid into a ribose-1,3,5-triacetate; (f) condensing the triacetate obtained with a purine base with a purine base in which any free primary amino group is protected by acylation in an organic solvent in the presence of a Lewis acid to form (after splitting the protective acyl group) the desired compound wherein R.sub.1 is azide, halogen or alkoxy; (g) optionally separating the product obtained into .alpha. and .beta. anomers; and (h) optionally reacting the said compound obtained in step (f), in which R.sub.1 is azido, with triphenylphosphine in saturated methanolic ammonia to yield the corresponding compound where R.sub.1 is amino.
摘要翻译： 2'-取代的D-呋喃核糖基嘌呤化合物，特别是其中R 1是叠氮基，氨基，卤素或烷氧基的式（Ⅰ）的2'-叠氮基-D-呋喃核糖嘌呤化合物，R2是嘌呤碱基，特别是9-腺苷基，7-脯氨酰基或9-脯氨酰基（上述式Ⅰ中的波浪表示R2可以以α-或β-构型结合），ARE制备一种包含（A）用碱性酰亚胺（当R1为叠氮化物或通过进一步转化为胺基）或卤化物（当R 1为卤素时）或与烷基化剂（当R 1为烷氧基时）反应尿苷衍生物的方法）; （B）将具有水合物的结果化合物转化为相应的2-脱氧赖氨酸; （C）在强酸存在下，用甲醇将2-脱氧蛋白转化成1-O-甲基葡糖苷; （D）在极性有机溶剂中用乙酸酐反应葡萄糖苷，形成1-O-甲基 - 核糖-3,5-二乙酸酯; （E）在强酸中存在于含有1,3,5-三硝基苯甲酸酯的柠檬酸中，使用乙酸酐转化为乙酸酐; （F）使用碱性基质获得的三苯乙烯与通过在有机溶剂中的有机溶剂中存在的路易斯酸形成（分解保护性酰基之后）所需化合物其中R1是叠氮基，卤素或烷氧基; （G）选择性地将产品分解为α和β异构体; 和（H）选择性地反应在步骤（F）中获得的化合物，其中R1是叠氮基，与饱和甲醇氨中的三苯基膦反应，得到其中R 1为氨基的相应化合物。

7. 发明授权

US06656731B1 Nucleic acid catalysts with endonuclease activity 失效
标题翻译：具有核酸内切酶活性的核酸催化剂
公开(公告)号：US06656731B1
公开(公告)日：2003-12-02
申请号：US09479005
申请日：2000-01-07
申请人： Fritz Eckstein , Janos Ludwig , Leonid Beigelman
发明人： Fritz Eckstein , Janos Ludwig , Leonid Beigelman
IPC分类号： C12N500
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/111 , C12N2310/121 , C12N2310/18
摘要： The present invention relates to nucleic acid molecules with new motifs having catalytic activity, methods of syntheses and uses thereof.
摘要翻译：本发明涉及具有催化活性的新基序的核酸分子，其合成方法及其应用。

8. 发明授权

US6121046A Synthetic antisense oligodeoxynucleotides targeted to human ache 失效
标题翻译：靶向人类疼痛的合成反义寡脱氧核苷酸
公开(公告)号：US6121046A
公开(公告)日：2000-09-19
申请号：US990065
申请日：1997-12-12
申请人： Hermona Soreq , Shlomo Seidman , Fritz Eckstein , Alon Friedman , Daniela Kaufer
发明人： Hermona Soreq , Shlomo Seidman , Fritz Eckstein , Alon Friedman , Daniela Kaufer
IPC分类号： C12N15/09 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P25/00 , A61P43/00 , C12N20060101 , C12N15/113 , C12Q1/68 , C07H21/04 , C12N15/00
CPC分类号： C12Y301/01007 , C12N15/1137 , A01K2217/05 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/53
摘要： A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-ODN) capable of selectively modulating human acetylcholinesterase (AChE) production and a composition comprising at least one AS-ODN as an active ingredient. A nuclease resistant antisense targeted against the splice junction in the AChE mRNA post-splice message is disclosed. The synthetic nuclease resistant AS-ODNs are capable of selectively modulating human AChE production in the central nervous system or capable of selectively reducing human AChE deposition of the neuromuscular junction. The present invention also provides a method to restore balanced cholinergic signalling in the brain and spinal cord or reduce AChE in the neuromuscular junction in patients in need of such treatment by administering to a patient in need of such treatment a therapeutically effective amount of at least one of the synthetic nuclease resistant AS-ODN capable of selectively modulating human AChE production.
摘要翻译：能够选择性调节人乙酰胆碱酯酶（AChE）产生的合成核酸酶抗性反义寡脱氧核苷酸（AS-ODN）和包含至少一种AS-ODN作为活性成分的组合物。公开了针对针对AChE mRNA剪接信号中的剪接连接的核酸酶抗性反义。合成的核酸酶抗性AS-ODN能够选择性调节中枢神经系统中的人AChE产生或者能够选择性地降低神经肌肉接头的人类AChE沉积。本发明还提供了一种在需要这种治疗的患者中恢复脑和脊髓中的平衡胆碱能信号传导或减少神经肌肉接头中的AChE的方法，其通过向需要这种治疗的患者施用治疗有效量的至少一种的能够选择性调节人AChE生产的合成核酸酶抗性AS-ODN。

9. 发明授权

US06127173A Nucleic acid catalysts with endonuclease activity 失效
标题翻译：具有核酸内切酶活性的核酸催化剂
公开(公告)号：US06127173A
公开(公告)日：2000-10-03
申请号：US159274
申请日：1998-09-22
申请人： Fritz Eckstein , Paul A. Heaton , Narendra K. Vaish
发明人： Fritz Eckstein , Paul A. Heaton , Narendra K. Vaish
IPC分类号： C12N15/09 , A61K31/7105 , A61K38/00 , C12N5/10 , C12N9/16 , C12N15/113 , C12Q1/68 , C12N5/00 , C12N15/00 , C12P19/34
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/111 , C12N2310/121 , C12N2310/18
摘要： Nucleic acid molecules with new motifs having catalytic activity, methods of synthesis, and use thereof are also described.
摘要翻译：还描述了具有催化活性的新基序的核酸分子，合成方法及其应用。

10. 发明授权

US6110742A Synthetic antisense oligodeoxynucleotides targeted to AChE 失效
标题翻译：靶向AChE的合成反义寡脱氧核苷酸
公开(公告)号：US6110742A
公开(公告)日：2000-08-29
申请号：US850347
申请日：1997-05-02
申请人： Hermona Soreq , Shlomo Seidman , Fritz Eckstein
发明人： Hermona Soreq , Shlomo Seidman , Fritz Eckstein
IPC分类号： A61K31/137 , A61K31/138 , A61K31/46 , A61K38/00 , A61K38/46 , C12N15/113 , C07H21/04 , A61K48/00 , C12N15/00 , C12Q1/68
CPC分类号： C12N15/1137 , A61K31/137 , A61K31/138 , A61K31/46 , C12Y301/01007 , C12Y301/01008 , A01K2217/05 , C12N2310/111 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/53
摘要： A synthetic nuclease resistant antisense oligodeoxynucleotide (AS-OND) capable of selectively modulating human acetylcholinesterase production in the central nervous system is provided. In an embodiment the antisense oligodeoxynucleotide can be selected from5'ACGCTTTCTTGAGGC 3' SEQ ID No:1, or - 5'GGCACCCTGGGCAGC 3' SEQ ID No:2. The present invention also discloses a pharmaceutical or medical composition comprising as active ingredient at least one synthetic nuclease resistant antisense oligodeoxynucleotide capable of selectively modulating human acetylcholinesterase production in the central nervous system in a physiologically acceptable carrier or diluent. The present invention also provides a method to restore balanced cholinergic signaling in the brain in patients in need of such treatment comprising administering to a patient in need of such treatment a therapeutically effective amount of at least one of a synthetic nuclease resistant antisense oligodeoxynucleotide capable of selectively modulating human acetylcholinesterase production in the central nervous system in a physiologically acceptable carrier.
摘要翻译：提供了能够选择性调节中枢神经系统中的人乙酰胆碱酯酶生成的合成核酸酶抗性反义寡脱氧核苷酸（AS-OND）。在一个实施方案中，反义寡脱氧核苷酸可以选自5'ACGCTTTCTTGAGGC 3'SEQ ID No：1或 - - 5'GGCACCCTGGGCAGC 3'SEQ ID No：2。 - 本发明还公开了一种药物或医药组合物，其包含至少一种能够在生理上可接受的载体或稀释剂中在中枢神经系统中选择性调节人乙酰胆碱酯酶产生的合成核酸酶抗性反义寡脱氧核苷酸作为活性成分。本发明还提供一种在需要这种治疗的患者中恢复脑中平衡胆碱能信号传导的方法，包括向需要这种治疗的患者施用治疗有效量的至少一种能够选择性地合成核酸酶抗性反义寡脱氧核苷酸在生理上可接受的载体中调节中枢神经系统中的人乙酰胆碱酯酶的产生。

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