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1. 发明申请

WO2012061810A1 BASE MODIFIED OLIGONUCLEOTIDES 审中-公开
标题翻译：基因修饰寡核苷酸
公开(公告)号：WO2012061810A1
公开(公告)日：2012-05-10
申请号：PCT/US2011/059588
申请日：2011-11-07
申请人： MIRAGEN THERAPEUTICS , VAGLE, Kurt , DALBY, Christina , MARSHALL, William S.
发明人： VAGLE, Kurt , DALBY, Christina , MARSHALL, William S.
IPC分类号： C12N15/11
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/141 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/33 , C12N2310/3521 , C12N2310/3523 , C12N2310/3525 , C12N2310/3527 , C12N2310/3529 , C12N2320/52
摘要： The present invention relates to oligonucleotides with base modified nucleosides for enhancement of binding affinity.
摘要翻译：本发明涉及具有用于增强结合亲和力的碱修饰核苷的寡核苷酸。

2. 发明申请

WO2010129672A1 LIPOPHILIC POLYNUCLEOTIDE CONJUGATES 审中-公开
标题翻译：脂多糖共混物
公开(公告)号：WO2010129672A1
公开(公告)日：2010-11-11
申请号：PCT/US2010/033729
申请日：2010-05-05
申请人： MIRAGEN THERAPEUTICS , MARSHALL, William S. , VAGLE, Kurt
发明人： MARSHALL, William S. , VAGLE, Kurt
IPC分类号： C07H21/00
CPC分类号： C07J41/0055 , A61K48/0033 , C07J43/003 , C07J51/00 , C12N15/111 , C12N15/113 , C12N15/87 , C12N2310/113 , C12N2310/315 , C12N2310/3515
摘要： Disclosed are lipophilic polynucleotide conjugates including polynucleotide-cholesterol conjugates and methods of delivering therapeutic polynucleotides to a mammalian cell or patient in need of treatment using said conjugates. The disclosure further provides methods of synthesizing the lipophilic polynucleotide conjugates.The conjugates are designed to mimic or target cellular miRNAs. The lipophilic moiety, such as cholesterol or cholesterol derivative, is spaced from the polynucleotide by a substantially linear hydrocarbon group. Due to an absence of significantly polar groups and/or exchangeable protons in the vicinity of the lipophilic moiety, the interaction between the lipophilic moiety and cell membranes is enhanced to provide for efficient entry into cells.
摘要翻译：公开了亲脂性多核苷酸缀合物，包括多核苷酸 - 胆固醇缀合物和将治疗性多核苷酸递送至需要使用所述缀合物治疗的哺乳动物细胞或患者的方法。本公开进一步提供了合成亲脂性多核苷酸缀合物的方法。设计缀合物以模拟或靶向细胞miRNA。亲脂性部分，例如胆固醇或胆固醇衍生物，通过基本上线性的烃基与多核苷酸间隔开。由于在亲油部分附近不存在显着的极性基团和/或可交换的质子，增强了亲脂部分和细胞膜之间的相互作用以提供有效进入细胞。

3. 发明申请

WO2012083005A2 MICRORNA INHIBITORS COMPRISING LOCKED NUCLEOTIDES 审中-公开
标题翻译：包含锁定核苷酸的微阵列抑制剂
公开(公告)号：WO2012083005A2
公开(公告)日：2012-06-21
申请号：PCT/US2011/065121
申请日：2011-12-15
申请人： MIRAGEN THERAPEUTICS , DALBY, Christina , MARSHALL, William S. , ROOIJ, Eva Van , MONTGOMERY, Rusty
发明人： DALBY, Christina , MARSHALL, William S. , ROOIJ, Eva Van , MONTGOMERY, Rusty
IPC分类号： C12Q1/68
CPC分类号： C12N15/113 , A61K31/7105 , C12N2310/113 , C12N2310/315 , C12N2310/3231 , C12N2310/346 , C12Q2600/178
摘要： The invention provides chemically modified oligonucleotides capable of inhibiting the expression (e.g., abundance) of miR-208 family miRNAs, including miR-208a, miR-208b, and/or miR-499. The invention provides in some embodiments, oligonucleotides capable of inhibiting, in a specific fashion, the expression or abundance of each of miR-208a, miR-208b, and miR-499. The invention further provides pharmaceutical compositions comprising the oligonucleotides, and methods of treating patients having conditions or disorders relating to or involving a miR-208 family miRNA, such as a cardiovascular condition. In various embodiments, the oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.
摘要翻译：本发明提供能够抑制miR-208家族miRNA（包括miR-208a，miR-208b和/或miR-499）的表达（例如丰度）的化学修饰的寡核苷酸。本发明在一些实施方案中提供能够以特定方式抑制miR-208a，miR-208b和miR-499中每一种的表达或丰度的寡核苷酸。本发明进一步提供了包含寡核苷酸的药物组合物，以及治疗与miR-208家族miRNA相关或涉及miR-208家族miRNA例如心血管病症的病症或病症的患者的方法。在各种实施方案中，寡核苷酸提供效力，递送效率，靶特异性，毒性和/或稳定性中的一种或多种的优点。

4. 发明申请

WO2010144485A1 CHEMICAL MODIFICATION MOTIFS FOR miRNA INHIBITORS AND MIMETICS 审中-公开
标题翻译：用于miRNA抑制剂和模拟物质的化学修饰
公开(公告)号：WO2010144485A1
公开(公告)日：2010-12-16
申请号：PCT/US2010/037821
申请日：2010-06-08
申请人： MIRAGEN THERAPEUTICS , YAMADA, Christina , MARSHALL, William S.
发明人： YAMADA, Christina , MARSHALL, William S.
IPC分类号： C07H21/04 , C12N15/11
CPC分类号： C12N15/113 , C12N2310/113 , C12N2310/141 , C12N2310/315 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/344
摘要： The present invention provides polynucleotides having chemistry patterns that provide for improved stability, potency, and/or toxicity relative to their use as miRNA inhibitors or miRNA mimetics. The invention further provides pharmaceutical compositions and formulations comprising the polynucleotides, and methods for treating patients having a condition associated with miRNA or mRNA expression.
摘要翻译：本发明提供具有相对于其作为miRNA抑制剂或miRNA模拟物的用途提供改善的稳定性，效力和/或毒性的化学模式的多核苷酸。本发明还提供了包含多核苷酸的药物组合物和制剂，以及用于治疗患有与miRNA或mRNA表达相关的病症的患者的方法。

5. 发明公开

EP3481404A1 METHODS FOR TREATING CUTANEOUS T-CELL LYMPHOMA (CTCL) WITH MIR-155 INHIBITORS 审中-公开
公开(公告)号：EP3481404A1
公开(公告)日：2019-05-15
申请号：EP17825019.7
申请日：2017-07-07
申请人： Miragen Therapeutics, Inc.
发明人： JACKSON, Aimee L. , MARSHALL, William S.
IPC分类号： A61K31/7088 , A61K48/00 , C07H21/02 , C07H21/04 , C12N15/11 , C12N15/113

6. 发明授权

EP2427472B1 LIPOPHILIC POLYNUCLEOTIDE CONJUGATES 有权
标题翻译：亲脂性多核苷酸缀合物
公开(公告)号：EP2427472B1
公开(公告)日：2016-06-22
申请号：EP10772765.3
申请日：2010-05-05
申请人： Miragen Therapeutics
发明人： MARSHALL, William S. , VAGLE, Kurt
IPC分类号： C07J41/00 , C07J43/00 , C07J51/00 , A61K48/00 , A61K31/58
CPC分类号： C07J41/0055 , A61K48/0033 , C07J43/003 , C07J51/00 , C12N15/111 , C12N15/113 , C12N15/87 , C12N2310/113 , C12N2310/315 , C12N2310/3515

7. 发明公开

EP2635681A1 BASE MODIFIED OLIGONUCLEOTIDES 有权
标题翻译：与修饰碱基的寡核苷酸
公开(公告)号：EP2635681A1
公开(公告)日：2013-09-11
申请号：EP11838938.6
申请日：2011-11-07
申请人： Miragen Therapeutics
发明人： VAGLE, Kurt , DALBY, Christina , MARSHALL, William S.
IPC分类号： C12N15/11
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/141 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/33 , C12N2310/3521 , C12N2310/3523 , C12N2310/3525 , C12N2310/3527 , C12N2310/3529 , C12N2320/52
摘要： The present invention relates to oligonucleotides with base modified nucleosides for enhancement of binding affinity.

8. 发明申请

WO2018009855A1 METHODS FOR TREATING CUTANEOUS T-CELL LYMPHOMA (CTCL) WITH MIR-155 INHIBITORS 审中-公开
标题翻译：用MIR-155抑制剂治疗皮肤T细胞淋巴瘤（CTCL）的方法
公开(公告)号：WO2018009855A1
公开(公告)日：2018-01-11
申请号：PCT/US2017/041180
申请日：2017-07-07
申请人： MIRAGEN THERAPEUTICS, INC.
发明人： JACKSON, Aimee L. , MARSHALL, William S.
IPC分类号： A61K31/7088 , A61K48/00 , C07H21/02 , C07H21/04 , C12N15/11 , C12N15/113
摘要： The present invention provides compositions and methods for treating cutaneous T-cell lymphoma (CTCL) with intralesional administration of one or more miR-155 inhibitors. In certain embodiments, the intralesional administration of one or more oligonucleotide inhibitors of miR-155 reduces the redness, thickness, height, scaling, and/or surface area of one or more untreated lesions on the skin of said subject.
摘要翻译：本发明提供了用病灶内施用一种或多种miR-155抑制剂治疗皮肤T细胞淋巴瘤（CTCL）的组合物和方法。在某些实施方案中，一种或多种miR-155的寡核苷酸抑制剂的病灶内施用减少所述受试者皮肤上的一个或多个未治疗损伤的发红，厚度，高度，鳞屑和/或表面积。

9. 发明授权

EP2635681B1 BASE MODIFIED OLIGONUCLEOTIDES 有权
公开(公告)号：EP2635681B1
公开(公告)日：2017-08-23
申请号：EP11838938.6
申请日：2011-11-07
申请人： Miragen Therapeutics
发明人： VAGLE, Kurt , DALBY, Christina , MARSHALL, William S.
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/141 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/33 , C12N2310/3521 , C12N2310/3523 , C12N2310/3525 , C12N2310/3527 , C12N2310/3529 , C12N2320/52

10. 发明公开

EP2427472A1 LIPOPHILIC POLYNUCLEOTIDE CONJUGATES 有权
标题翻译：亲脂性多核苷酸缀合物
公开(公告)号：EP2427472A1
公开(公告)日：2012-03-14
申请号：EP10772765.3
申请日：2010-05-05
申请人： Miragen Therapeutics
发明人： MARSHALL, William S. , VAGLE, Kurt
IPC分类号： C07H21/00
CPC分类号： C07J41/0055 , A61K48/0033 , C07J43/003 , C07J51/00 , C12N15/111 , C12N15/113 , C12N15/87 , C12N2310/113 , C12N2310/315 , C12N2310/3515
摘要： Disclosed are lipophilic polynucleotide conjugates including polynucleotide-cholesterol conjugates and methods of delivering therapeutic polynucleotides to a mammalian cell or patient in need of treatment using said conjugates. The disclosure further provides methods of synthesizing the lipophilic polynucleotide conjugates.The conjugates are designed to mimic or target cellular miRNAs. The lipophilic moiety, such as cholesterol or cholesterol derivative, is spaced from the polynucleotide by a substantially linear hydrocarbon group. Due to an absence of significantly polar groups and/or exchangeable protons in the vicinity of the lipophilic moiety, the interaction between the lipophilic moiety and cell membranes is enhanced to provide for efficient entry into cells.
摘要翻译：公开了包含多核苷酸 - 胆固醇缀合物的亲脂性多核苷酸缀合物和将治疗性多核苷酸递送至需要使用所述缀合物治疗的哺乳动物细胞或患者的方法。本公开进一步提供了合成亲脂性多核苷酸缀合物的方法。缀合物被设计为模拟或靶向细胞miRNA。亲脂性部分，例如胆固醇或胆固醇衍生物，与多核苷酸间隔基本线性的烃基。由于在亲脂性部分附近缺乏显着的极性基团和/或可交换的质子，亲脂性部分和细胞膜之间的相互作用得到增强以提供有效进入细胞。

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