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101. 发明授权

US07695902B2 Oligoribonucleotides and ribonucleases for cleaving RNA 失效
标题翻译：用于切割RNA的寡核糖核苷酸和核糖核酸酶
公开(公告)号：US07695902B2
公开(公告)日：2010-04-13
申请号：US10078949
申请日：2002-02-20
申请人： Stanley T. Crooke
发明人： Stanley T. Crooke
IPC分类号： C12Q1/68 , C07H21/02 , C12N5/00
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： Oligomeric compounds including oligoribonucleotides and oligoribonucleosides are provided that have subsequences of 2′-pentoribofuranosyl nucleosides that activate dsRNase. The oligoribonucleotides and oligoribonucleosides can include substituent groups for increasing binding affinity to complementary nucleic acid strand as well as substituent groups for increasing nuclease resistance. The oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics. Also included in the invention are mammalian ribonucleases, i.e., enzymes that degrade RNA, and substrates for such ribonucleases. Such a ribonuclease is referred to herein as a dsRNase, wherein “ds” indicates the RNase's specificity for certain double-stranded RNA substrates. The artificial substrates for the dsRNases described herein are useful in preparing affinity matrices for purifying mammalian ribonuclease as well as non-degradative RNA-binding proteins.
摘要翻译：提供了包含寡核糖核苷酸和寡核糖核苷的寡聚化合物，其具有激活dsRNase的2'-戊二呋呋糖基核苷的亚序列。寡核糖核苷酸和寡核糖核苷可以包括用于增加对互补核酸链的结合亲和力的取代基以及用于增加核酸酶抗性的取代基。寡聚化合物可用于诊断和其他研究目的，用于调节生物体中的蛋白质的表达，以及用于诊断，检测和治疗对寡核苷酸治疗剂敏感的其它病症。本发明还包括哺乳动物核糖核酸酶，即降解RNA的酶和这种核糖核酸酶的底物。这样的核糖核酸酶在本文中称为dsRNase，其中“ds”表示RNase对某些双链RNA底物的特异性。本文所述的dsR酶的人造底物可用于制备用于纯化哺乳动物核糖核酸酶以及非降解性RNA结合蛋白的亲和基质。

102. 发明申请

US20100069472A1 COMPOSITIONS AND THEIR USES DIRECTED TO HUNTINGTIN 审中-公开
标题翻译：组合物及其与HUNTINGTIN有关的用途
公开(公告)号：US20100069472A1
公开(公告)日：2010-03-18
申请号：US12618470
申请日：2009-11-13
申请人： Gene Hung , Janet M. Leeds , C. Frank Bennett , Susan M. Freier
发明人： Gene Hung , Janet M. Leeds , C. Frank Bennett , Susan M. Freier
IPC分类号： A61K31/7088 , C07H21/04 , A61P25/28
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/111 , C12N2310/31 , C12N2310/315 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2310/3231 , C12N2310/33 , C12N2310/3341 , C12N2310/335 , C12N2310/341 , C12N2310/346 , C12N2320/30 , C12N2310/3525
摘要： Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's disease progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntingtin's disease in an individual susceptible to Huntingtin's Disease. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.
摘要翻译：本文公开了用于调节细胞，组织或动物中亨廷丁氏蛋白的表达的化合物，组合物和方法。还提供了使用靶向亨廷顿汀的反义化合物减慢或预防亨廷顿病进展的方法。另外提供的方法是延缓或预防在亨廷顿病易感的个体中亨廷顿病发病的方法。还提供了所公开的化合物和组合物在制备用于治疗疾病和病症的药物中的用途。

103. 发明申请

US20100056606A1 Combination therapy using budesonide and antisense oligonucleotide targeted to IL4-receptor alpha 审中-公开
标题翻译：使用针对IL4受体α的布地奈德和反义寡核苷酸的联合治疗
公开(公告)号：US20100056606A1
公开(公告)日：2010-03-04
申请号：US12066633
申请日：2006-10-03
申请人： James G. Karras , Susan Gregory
发明人： James G. Karras , Susan Gregory
IPC分类号： A61K31/7088
CPC分类号： C12N15/1138 , A61K31/573 , A61K31/58 , A61K31/7088 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2320/31 , A61K2300/00 , C12N2310/3525
摘要： Provided herein is a method for reducing the amount of steroid required for the prevention, amelioration and/or treatment of pulmonary inflammation and/or airway hyperresponsiveness, comprising administration of the steroid and an oligonucleotide targeted to IL-4R alpha. Also described is a method for the prevention, amelioration and/or treatment of pulmonary inflammation and/or airway hyperresponsiveness comprising administration of a corticosteroid and an oligonucleotide targeted to IL-4R alpha. Further provided are compositions comprising a corticosteroid and an IL-4R alpha targeted antisense oligonucleotide.
摘要翻译：本文提供的是减少预防，改善和/或治疗肺部炎症和/或气道高反应性所需类固醇的量的方法，包括给予类固醇和靶向IL-4Rα的寡核苷酸。还描述了一种预防，改善和/或治疗肺部炎症和/或气道高反应性的方法，包括给予皮质类固醇和靶向IL-4Rα的寡核苷酸。还提供了包含皮质类固醇和IL-4Rα靶向反义寡核苷酸的组合物。

104. 发明授权

US07666854B2 Bis-modified bicyclic nucleic acid analogs 有权
标题翻译：双改性双环核酸类似物
公开(公告)号：US07666854B2
公开(公告)日：2010-02-23
申请号：US12331226
申请日：2008-12-09
申请人： Punit P. Seth , Eric E. Swayze
发明人： Punit P. Seth , Eric E. Swayze
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C07H21/00 , C07H7/02 , C07H9/04 , C07H13/04 , C07H15/18 , C07H17/02 , C07H19/04 , C07H19/06 , C07H19/16 , C07H23/00
摘要： The present disclosure describes bis-modified bicyclic nucleosides and oligomeric compounds that can be prepared comprising at least one of these bis-modified bicyclic nucleosides. More particularly, the bis-modified bicyclic nucleosides have at least one substituent group at the 5′-methylene and on the bridge methylene and can be chiral. These bis-modified bicyclic nucleosides are expected to be useful for enhancing one or more property of oligomeric compounds including for example enhancing nuclease resistance.
摘要翻译：本公开描述了可以制备的双改性双环核苷和寡聚化合物，其包含这些双改性双环核苷中的至少一种。更具体地，双改性双环核苷在5'-亚甲基和亚甲基桥上具有至少一个取代基，并且可以是手性的。预期这些双改性双环核苷可用于增强寡聚化合物的一种或多种性质，包括例如增强核酸酶抗性。

105. 发明申请

US20100035964A1 ANTISENSE MODULATION OF CONNECTIVE TISSUE GROWTH FACTOR EXPRESSION 失效
标题翻译：连接组织生长因子表达的抗原调节
公开(公告)号：US20100035964A1
公开(公告)日：2010-02-11
申请号：US12011761
申请日：2008-01-28
申请人： William Gaarde , Andrew T. Watt , Brett P. Monia , Mausumee Guha
发明人： William Gaarde , Andrew T. Watt , Brett P. Monia , Mausumee Guha
IPC分类号： A61K31/7088 , C07H21/04
CPC分类号： C12N15/1136 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , Y02P20/582 , C12N2310/3525
摘要： Antisense compounds, compositions and methods are provided for modulating the expression of connective tissue growth factor. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding connective tissue growth factor. Methods of using these compounds for modulation of connective tissue growth factor expression and for treatment of diseases associated with expression of connective tissue growth factor are provided.
摘要翻译：提供反义化合物，组合物和方法用于调节结缔组织生长因子的表达。组合物包含靶向编码结缔组织生长因子的核酸的反义化合物，特别是反义寡核苷酸。提供了使用这些化合物调节结缔组织生长因子表达和治疗与结缔组织生长因子表达相关的疾病的方法。

106. 发明申请

US20090326040A1 ANTISENSE MODULATION OF APOLIPOPROTEIN B EXPRESSION 审中-公开
标题翻译：丙泊酚B表达的抗体调节
公开(公告)号：US20090326040A1
公开(公告)日：2009-12-31
申请号：US11573537
申请日：2005-08-10
申请人： Richard S. Geary , Zhengrong Yu , Rosanne M. Crooke
发明人： Richard S. Geary , Zhengrong Yu , Rosanne M. Crooke
IPC分类号： A61K31/7088
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： Methods for the rapid and long-term lowering of lipid levels in human subjects and for the treatment of conditions associated with elevated LDL-cholesterol and elevated apolipoprotein B are provided.
摘要翻译：提供了快速和长期降低人类受试者脂质水平和治疗与升高的LDL-胆固醇和升高的载脂蛋白B相关的病症的方法。

107. 发明申请

US20090312398A1 COMPOSITIONS AND THEIR USES DIRECTED TO IL-4R ALPHA 失效
标题翻译：组合物及其与IL-4R ALPHA相关的用途
公开(公告)号：US20090312398A1
公开(公告)日：2009-12-17
申请号：US11816705
申请日：2006-02-24
申请人： James G. Karras , Susan Gregory , Jeffrey R. Crosby , Mausumee Guha , David Tung , Susan M. Freier
发明人： James G. Karras , Susan Gregory , Jeffrey R. Crosby , Mausumee Guha , David Tung , Susan M. Freier
IPC分类号： A61K31/7125 , A61K31/712 , A61P11/00 , A61K31/7115 , A61K31/7088
CPC分类号： C12N15/1138 , A61K38/00 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/345 , C12N2310/3525
摘要： Disclosed herein are compounds, compositions and methods for modulating the expression of IL-4R alpha in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders related to expression of IL 4R-α, airway hyperresponsiveness, and/or pulmonary inflammation.
摘要翻译：本文公开了用于调节细胞，组织或动物中IL-4Rα的表达的化合物，组合物和方法。还提供了目标验证的方法。还提供了所公开的化合物和组合物在制备用于治疗与IL 4R-α表达，气道高反应性和/或肺部炎症相关的疾病和病症的药物中的用途。

108. 发明授权

US07622455B2 Methods for slowing familial ALS disease progression 有权
标题翻译：减慢家族性ALS疾病进展的方法
公开(公告)号：US07622455B2
公开(公告)日：2009-11-24
申请号：US11526134
申请日：2006-09-21
申请人： C. Frank Bennett , Susan M. Freier , Thomas P. Condon
发明人： C. Frank Bennett , Susan M. Freier , Thomas P. Condon
IPC分类号： A61K48/00
CPC分类号： C12N15/1137 , A61K38/00 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12Y115/01001 , Y02P20/582 , C12N2310/3525
摘要： Methods for slowing disease progression in an individual suffering from familial ALS are provided. Also provided are methods of increasing the survival time of an individual suffering from familial ALS. These methods employ antisense oligonucleotides targeted to SOD1, for use in inhibiting the expression of SOD1 in the central nervous system of an individual suffering from familial ALS.
摘要翻译：提供了减轻患有家族性ALS的个体疾病进展的方法。还提供了增加患有家族性ALS的个体的存活时间的方法。这些方法使用靶向SOD1的反义寡核苷酸，用于抑制患有家族性ALS的个体的中枢神经系统中SOD1的表达。

109. 发明申请

US20090275631A1 THERAPEUTIC ANTISENSE OLIGONUCLEOTIDE COMPOSITION FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE 审中-公开
标题翻译：用于治疗炎症性皮肤疾病的治疗性抗生素寡核苷酸组合物
公开(公告)号：US20090275631A1
公开(公告)日：2009-11-05
申请号：US11720745
申请日：2005-12-02
申请人： Mark K. Wedel
发明人： Mark K. Wedel
IPC分类号： A61K31/711
CPC分类号： A61K31/7125 , A61K9/0031 , A61K31/7088 , A61K31/7105 , A61K31/711 , A61K47/38 , C12N15/1138 , C12N2310/11 , C12N2310/315
摘要： Disclosed herein is a method for the sustained amelioration and/or treatment of ulcerative colitis comprising rectal administration of a compound comprising an antisense oligonucleotide having the sequence 5′-GCCCAAGCTGGCATCCGTCA-3′, ISIS 2302. The method results in a decrease in the indications of ulcerative colitis for an extended period (greater than 90 days) after the conclusion of the administration of the composition. The composition is well tolerated and systemic exposure is minimal.
摘要翻译：本文公开了一种持续改善和/或治疗溃疡性结肠炎的方法，包括直肠给药包含具有序列5'-GCCCAAGCTGGCATCCGTCA-3'，ISIS 2302的反义寡核苷酸的化合物。该方法导致了溃疡性结肠炎在施用组合物后长时间（大于90天）。组合物耐受性良好，全身暴露最小。

110. 发明申请

US20090270491A1 MODULATION OF TUDOR-SN EXPRESSION 审中-公开
标题翻译： TUDOR-SN表达的调节
公开(公告)号：US20090270491A1
公开(公告)日：2009-10-29
申请号：US12488394
申请日：2009-06-19
申请人： Nicholas M. Dean , Ming-Yi Chiang , Kenneth W. Dobie
发明人： Nicholas M. Dean , Ming-Yi Chiang , Kenneth W. Dobie
IPC分类号： A61K31/7088 , C07H21/04 , C07H21/02 , C12N5/00 , A61P29/00 , A61P35/00
CPC分类号： C12N15/1137 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： Compounds, compositions and methods are provided for modulating the expression of Tudor-SN. The compositions comprise oligonucleotides, targeted to nucleic acid encoding Tudor-SN. Methods of using these compounds for modulation of Tudor-SN expression and for diagnosis and treatment of diseases and conditions associated with expression of Tudor-SN are provided.
摘要翻译：提供化合物，组合物和方法用于调节Tudor-SN的表达。组合物包含靶向编码Tudor-SN的核酸的寡核苷酸。提供了使用这些化合物调节Tudor-SN表达和诊断和治疗与Tudor-SN表达相关的疾病和病症的方法。

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