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1. 发明申请

WO2007090073A2 OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR THE USE IN MODULATION OF MICRORNAS 审中-公开
标题翻译：用于微波调制的低分子化合物和组合物
公开(公告)号：WO2007090073A2
公开(公告)日：2007-08-09
申请号：PCT/US2007/061186
申请日：2007-01-27
申请人： ISIS PHARMACEUTICALS, INC. , ESAU, Christine , SWAYZE, Eric, E. , BHAT, Balkrishen , KINBERGER, Garth, A.
发明人： ESAU, Christine , SWAYZE, Eric, E. , BHAT, Balkrishen , KINBERGER, Garth, A.
IPC分类号： C12N15/11 , C07H21/00
CPC分类号： C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/346 , C12N2320/51 , C12N2310/3527 , C12N2310/3525
摘要： Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapuetic index. Further provided are methods for selectively modulating miRNA activity in a cell.
摘要翻译：提供化合物，组合物和方法用于调节miRNA的水平表达，加工和功能。组合物包含靶向小的非编码RNA和miRNA的寡聚化合物。寡聚化合物具有有效的miRNA抑制活性，并进一步表现出改善的治疗指数。还提供了选择性调节细胞中的miRNA活性的方法。

2. 发明申请

WO2007027894A3 ANTISENSE COMPOUNDS HAVING ENHANCED ANTI-MICRORNA ACTIVITY 审中-公开
公开(公告)号：WO2007027894A3
公开(公告)日：2007-03-08
申请号：PCT/US2006/034032
申请日：2006-08-29
申请人： ISIS PHARMACEUTICALS, INC. , ESAU, Christine , SWAYZE, Eric, E.
发明人： ESAU, Christine , SWAYZE, Eric, E.
IPC分类号： C12N15/11 , A61K31/711 , C07H19/06 , C07H19/16
摘要： Antisense compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The antisense compounds exhibit enhanced anti- miRNA activity. Further provided are methods for enhancing the inhibitory activity of an antisense compound targeting a miRNA, comprising incorporating stability enhancing sugar modifications into the antisense compounds.

3. 发明申请

WO2005013901A2 OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR USE IN MODULATION OF SMALL NON-CODING RNAS 审中-公开
标题翻译：用于调节小型非编码RNAs的低分子化合物和组合物
公开(公告)号：WO2005013901A2
公开(公告)日：2005-02-17
申请号：PCT/US2004/025300
申请日：2004-07-30
申请人： ISIS PHARMACEUTICALS, INC. , ESAU, Christine , LOLLO, Bridget , BENNETT, C., Frank , FREIER, Susan, M. , GRIFFEY, Richard, H. , BAKER, Brenda, F. , VICKERS, Timothy , MARCUSSON, Eric, G. , KOLLER, Erich , SWAYZE, Eric, E. , JAIN, Ravi , BHAT, Balkrishen , PERALTA, Eigen
发明人： ESAU, Christine , LOLLO, Bridget , BENNETT, C., Frank , FREIER, Susan, M. , GRIFFEY, Richard, H. , BAKER, Brenda, F. , VICKERS, Timothy , MARCUSSON, Eric, G. , KOLLER, Erich , SWAYZE, Eric, E. , JAIN, Ravi , BHAT, Balkrishen , PERALTA, Eigen
IPC分类号： A61K
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/11 , C12N2310/113 , C12N2310/14 , C12N2310/141 , C12N2310/31 , C12N2310/315 , C12N2310/317 , C12N2310/3181 , C12N2310/32 , C12N2310/321 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/351 , C12N2310/3515 , C12N2320/11 , C12N2320/30 , C12N2320/50 , C12N2310/3525
摘要： Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.
摘要翻译：提供化合物，组合物和方法用于调节小非编码RNA的表达和功能。组合物包含靶向小的非编码RNA的寡聚化合物。还提供了使用这些化合物调节小非编码RNA以及这些RNA的下游靶标以及用于诊断和治疗与小非编码RNA相关的疾病的方法。

4. 发明申请

WO2009058907A2 TARGETING MICRORNAS FOR THE TREATMENT OF LIVER CANCER 审中-公开
标题翻译：靶向治疗肝癌的微阵列
公开(公告)号：WO2009058907A2
公开(公告)日：2009-05-07
申请号：PCT/US2008/081645
申请日：2008-10-29
申请人： ISIS PHARMACEUTICALS, INC. , ROSETTA GENOMICS LTD. , BENNETT, C., Frank , CHAJUT, Ayelet , ESAU, Christine , MARCUSSON, Eric, G. , YERUSHALMI, Noga
发明人： BENNETT, C., Frank , CHAJUT, Ayelet , ESAU, Christine , MARCUSSON, Eric, G. , YERUSHALMI, Noga
IPC分类号： A61K31/7105 , A61P35/00 , C12N15/11
CPC分类号： C12N15/113 , A61K31/407 , A61K31/44 , A61K31/4745 , A61K31/513 , A61K31/555 , A61K31/704 , A61K31/7048 , A61K31/7068 , A61K31/7088 , A61K31/7105 , A61K45/06 , C12N2310/113 , C12N2310/141 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/346 , C12N2310/3525
摘要： Provided herein are methods for the treatment of liver cancer. These methods encompass the administration of a compound comprising a modified oligonucleotide, wherein the modified oligonucleotide is targeted to a miRNA. Also provided herein are compositions for the treatment of liver cancer. Such compositions include compounds comprising a modified oligonucleotide, wherein the modified oligonucleotide is targeted to a miRNA. Certain miRNAs have been identified as overexpressed in liver cancer, such as, for example, hepatocellular carcinoma, and are thus selected for targeting by modified oligonucleotides. Further, certain miRNAs have been identified as overexpressed in hepatocellular carcinoma cells exposed to dioxin, and are thus selected for targeting by modified oligonucleotides. Antisense inhibition of certain of these miRNAs has been found to inhibit cell proliferation and induce apoptosis.
摘要翻译：本文提供了用于治疗肝癌的方法。这些方法包括施用包含修饰的寡核苷酸的化合物，其中修饰的寡核苷酸靶向于miRNA。本文还提供了用于治疗肝癌的组合物。这样的组合物包括包含修饰的寡核苷酸的化合物，其中修饰的寡核苷酸靶向于miRNA。某些miRNA已被鉴定为在肝癌中过度表达，例如肝细胞癌，因此被选择用修饰的寡核苷酸靶向。此外，某些miRNA已被鉴定为在暴露于二恶英的肝细胞癌细胞中过表达，因此被选择用修饰的寡核苷酸靶向。已经发现某些这些miRNA的反义抑制抑制细胞增殖并诱导细胞凋亡。

5. 发明申请

WO2007027775A2 METHODS FOR USE IN MODULATING MIR-122A 审中-公开
标题翻译：用于调节MIR-122A的方法
公开(公告)号：WO2007027775A2
公开(公告)日：2007-03-08
申请号：PCT/US2006/033866
申请日：2006-08-29
申请人： ISIS PHARMACEUTICALS, INC. , ESAU, Christine , BHANOT, Sanjay
发明人： ESAU, Christine , BHANOT, Sanjay
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/11 , C12N2310/113 , C12N2310/315 , C12N2310/321 , C12N2310/3231 , C12N2310/3341 , C12N2310/341 , C12N2310/345 , C12N2310/346 , C12N2310/3525
摘要： Methods are provided for the treatment of cardiovascular or metabolic diseases characterized by elevated serum total cholesterol, elevated serum LDL-cholesterol, or elevated serum triglycerides, through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Further provided are methods for reducing hepatic steatosis or liver tissue triglyceride accumulation through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Such methods employ oligomeric compounds which hybridize with or sterically interfere with nucleic acid molecules comprising or encoding miR-122a. Such oligomeric compounds may include one or more modifications thereon, which may improve the activity, stability, or nuclease resistance of the oligomeric compound. These modified oligomeric compounds are used as single compounds or in compositions, including pharmaceutical compositions, to modulate or mimic the targeted nucleic acid comprising or encoding miR-122a.
摘要翻译：本发明提供了治疗以血清总胆固醇升高，血清LDL-胆固醇升高或血清甘油三酯升高为特征的心血管或代谢疾病的方法，通过施用调节血清或活性水平或活性的寡聚化合物的miR-122a。进一步提供了通过施用调节miR-122a的水平或活性的寡聚化合物来减少肝脂肪变性或肝组织甘油三酯积聚的方法。此类方法使用与包含或编码miR-122a的核酸分子杂交或空间干涉的寡聚化合物。这样的寡聚化合物可以在其上包含一个或多个修饰，其可以改进寡聚化合物的活性，稳定性或核酸酶抗性。这些修饰的寡聚化合物用作单一化合物或用于包括药物组合物的组合物中，以调节或模拟包含或编码miR-122a的靶向核酸。

6. 发明申请

WO2021113820A1 CONJUGATES AND METHODS FOR TREATING LIVER FIBROSIS 审中-公开
公开(公告)号：WO2021113820A1
公开(公告)日：2021-06-10
申请号：PCT/US2020/063617
申请日：2020-12-07
申请人： GENEVANT SCIENCES GMBH , HEYES, James , HOLLAND, Richard J. , WOOD, Mark , MARTIN, Alan D. , ESAU, Christine , SCHWARZ, Margrit , YE, Xin , LI, Alice , PASETKA, Chris Justin , CROWE, David , TYLER, Steven
发明人： HEYES, James , HOLLAND, Richard J. , WOOD, Mark , MARTIN, Alan D. , ESAU, Christine , SCHWARZ, Margrit , YE, Xin , LI, Alice , PASETKA, Chris Justin , CROWE, David , TYLER, Steven
IPC分类号： A61K38/19 , C07K16/28 , A61K38/17
摘要： Provided herein are certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to treat certain diseases, such as liver fibrosis, e.g., in the setting of NASH or ASH.

7. 发明申请

WO2012145374A1 TARGETING miR-378 FAMILY MEMBERS FOR THE TREATMENT OF METABOLIC DISORDERS 审中-公开
标题翻译：目标miR-378家族成员治疗代谢障碍
公开(公告)号：WO2012145374A1
公开(公告)日：2012-10-26
申请号：PCT/US2012/034039
申请日：2012-04-18
申请人： REGULUS THERAPEUTICS INC. , ESAU, Christine
发明人： ESAU, Christine
IPC分类号： A61P3/00 , A61P3/06 , A61P3/10 , C12N15/113 , A61K31/7115 , A61K31/712 , A61K31/7125
CPC分类号： C12N15/113 , A61K31/7115 , A61K31/712 , A61K31/7125 , A61K31/713 , A61K45/06 , C12N2310/113 , C12N2310/322 , C12N2310/3341 , C12N2310/343 , C12N2310/345 , C12N2310/346 , A61K2300/00 , C12N2310/3525 , C12N2310/3533
摘要： Provided herein are methods and compositions for the treatment of metabolic disorders. Also provided herein are methods and compositions for improving insulin resistance, reducing blood glucose levels, and/or reducing blood insulin levels in a subject in need thereof. In certain embodiments, the methods comprise inhibiting the activity of one or more miR-378 family members. In certain embodiments, such methods comprise administering a compound comprising a modified oligonucleotide targeted to one or more miR-378 family members.
摘要翻译：本文提供了用于治疗代谢紊乱的方法和组合物。本文还提供了用于在有需要的受试者中改善胰岛素抵抗，降低血糖水平和/或降低血液胰岛素水平的方法和组合物。在某些实施方案中，所述方法包括抑制一种或多种miR-378家族成员的活性。在某些实施方案中，这些方法包括施用包含靶向一种或多种miR-378家族成员的修饰寡核苷酸的化合物。

8. 发明申请

WO2021081420A2 CONJUGATES AND METHODS FOR TREATING ACROMEGALY 审中-公开
公开(公告)号：WO2021081420A2
公开(公告)日：2021-04-29
申请号：PCT/US2020/057185
申请日：2020-10-23
申请人： GENEVANT SCIENCES GMBH , KONDRATOWICZ, Drew , HEYES, James , HOLLAND, Richard J. , ESAU, Christine , MCCLINTOCK, Kevin , PASETKA, Chris Justin , WOOD, Mark , MARTIN, Alan D. , SCHWARZ, Margrit , CROWE, David , TYLER, Steven
发明人： KONDRATOWICZ, Drew , HEYES, James , HOLLAND, Richard J. , ESAU, Christine , MCCLINTOCK, Kevin , PASETKA, Chris Justin , WOOD, Mark , MARTIN, Alan D. , SCHWARZ, Margrit , CROWE, David , TYLER, Steven
IPC分类号： C12N15/87 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7088 , A61K31/7115 , A61K31/712 , A61K31/713 , A61P5/00 , C07K9/001
摘要： Provided herein are certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. He conjugates are useful to treat certain diseases, such as acromegaly.

9. 发明公开

EP1931780A2 ANTISENSE COMPOUNDS HAVING ENHANCED ANTI-MICRORNA ACTIVITY 无效
标题翻译：具有改进的抗微小RNA活性反义CONNECTIONS
公开(公告)号：EP1931780A2
公开(公告)日：2008-06-18
申请号：EP06802706.9
申请日：2006-08-29
申请人： Isis Pharmaceuticals, Inc.
发明人： ESAU, Christine , SWAYZE, Eric, E.
IPC分类号： C12N15/11
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/3231 , C12N2310/3341 , C12N2320/51 , C12N2310/3525 , C12N2310/3521 , C12N2310/3527
摘要： Antisense compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The antisense compounds exhibit enhanced anti- miRNA activity. Further provided are methods for enhancing the inhibitory activity of an antisense compound targeting a miRNA, comprising incorporating stability enhancing sugar modifications into the antisense compounds.

10. 发明公开

EP1984499A2 OLIGOMERIC COMPOUNDS AND COMPOSITIONS FOR THE USE IN MODULATION OF MICRORNAS 有权转让
标题翻译：低聚物化合物和组合物中的微RNA的调制
公开(公告)号：EP1984499A2
公开(公告)日：2008-10-29
申请号：EP07710352.1
申请日：2007-01-27
申请人： Isis Pharmaceuticals, Inc.
发明人： ESAU, Christine , SWAYZE, Eric, E. , BHAT, Balkrishen , KINBERGER, Garth, A.
IPC分类号： C12N15/11 , C07H21/00
CPC分类号： C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/346 , C12N2320/51 , C12N2310/3527 , C12N2310/3525
摘要： Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapuetic index. Further provided are methods for selectively modulating miRNA activity in a cell.

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