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1. 发明申请

US20060160759A1 Influenza therapeutic 审中-公开
标题翻译：流感治疗
公开(公告)号：US20060160759A1
公开(公告)日：2006-07-20
申请号：US11102097
申请日：2005-04-08
申请人： Jianzhu Chen , Qing Ge , Herman Eisen
发明人： Jianzhu Chen , Qing Ge , Herman Eisen
IPC分类号： A61K48/00 , C12Q1/70 , C07H21/02
CPC分类号： A61K9/5146 , A61K9/5153 , A61K38/00 , C12N15/111 , C12N15/1131 , C12N2310/111 , C12N2310/14 , C12N2310/321 , C12N2310/53 , C12N2320/11 , C12N2320/32 , C12N2799/021 , C12N2310/3521
摘要： The present invention provides compositions comprising an RNAi-inducing entity targeted to an influenza virus transcript and any of a variety of delivery agents. The invention further includes methods of use of the compositions for inhibiting a biological activity of an influenza virus and/or for treatment or prevention of influenza. The invention provides target portion sequences that are favorably conserved for RNAi across a plurality of influenza virus A strains isolated from human hosts and/or avian hosts and RNAi-inducing entities, e.g., siRNAs and shRNAs, targeted to such favorably conserved target portions. The invention provides a variety of nucleic acids comprising sequences identical or complementary to at least a portion of one or more of these favorably conserved target portion sequences. The invention further provides methods and compositions for delivering RNAi-inducing agents to an organ or tissue of a mammalian subject, e.g., to the lung. Methods of diagnosing influenza and determining the susceptibility of an influenza virus to inhibition by an RNAi-inducing agent are also provided. Transgenic animals that express an RNAi-inducing agent targeted to an influenza gene are another aspect of the invention.
摘要翻译：本发明提供了包含针对流感病毒转录物的RNAi诱导实体和各种递送试剂中的任一种的组合物。本发明还包括使用该组合物抑制流感病毒的生物学活性和/或用于治疗或预防流感的方法。本发明提供了针对分离自人宿主和/或禽类宿主和RNAi诱导实体（例如siRNA和shRNA）的多个流感病毒A菌株的RNAi有利地保守的靶标部分序列，靶向这些有利的保守靶部分。本发明提供了多种核酸，其包含与这些有利保守的靶部分序列中的一种或多种的至少一部分相同或互补的序列。本发明进一步提供了将哺乳动物受试者的器官或组织例如向肺部递送RNAi诱导剂的方法和组合物。还提供了诊断流感和确定流感病毒对RNAi诱导剂抑制的易感性的方法。表达靶向流感基因的RNAi诱导剂的转基因动物是本发明的另一方面。

2. 发明申请

US20050008617A1 Compositions and methods for delivery of short interfering RNA and short hairpin RNA 审中-公开
标题翻译：用于递送短干扰RNA和短发夹RNA的组合物和方法
公开(公告)号：US20050008617A1
公开(公告)日：2005-01-13
申请号：US10674087
申请日：2003-09-29
申请人： Jianzhu Chen , Herman Eisen , Qing Ge
发明人： Jianzhu Chen , Herman Eisen , Qing Ge
IPC分类号： A61K38/00 , A61K48/00 , C12N15/11 , C12N15/113
CPC分类号： C12N15/1131 , A61K9/5146 , A61K9/5153 , A61K38/00 , C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/32 , C12N2799/021
摘要： The present invention provides compositions comprising an RNAi-inducing entity any of a variety of different delivery agents. Preferred RNAi-inducing agents include siRNA, shRNA, and RNAi-inducing vectors. Preferred delivery agents include cationic polymers, modified cationic polymers, lipids, and surfactants suitable for introduction into the lung. The invention further provides methods of inhibiting expression of a target transcript in a mammal and methods of treating or preventing a disease or condition in a mammal by administration of the compositions.
摘要翻译：本发明提供包含多种不同递送剂的RNAi诱导实体的组合物。优选的RNAi诱导剂包括siRNA，shRNA和RNAi诱导载体。优选的递送剂包括阳离子聚合物，改性阳离子聚合物，脂质和适用于引入肺的表面活性剂。本发明还提供抑制哺乳动物中靶转录物表达的方法以及通过施用组合物治疗或预防哺乳动物疾病或病症的方法。

3. 发明申请

US20060058255A1 RNAi-based therapeutics for allergic rhinitis and asthma 审中-公开
标题翻译：基于RNAi的过敏性鼻炎和哮喘治疗
公开(公告)号：US20060058255A1
公开(公告)日：2006-03-16
申请号：US11069611
申请日：2005-03-01
申请人： Jianzhu Chen , Herman Eisen , Qing Ge
发明人： Jianzhu Chen , Herman Eisen , Qing Ge
IPC分类号： A61K48/00 , C07H21/02
CPC分类号： C12N15/113 , C12N15/111 , C12N15/1137 , C12N15/1138 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/32
摘要： The present invention provides compositions comprising one or more RNAi agents (e.g., siRNAs, shRNAs, or RNAi vectors) for the treatment of conditions and diseases mediated by (e.g., featuring IgE-mediated hypersensitivity), as well as systems for identifying RNAi agents effective for this purpose. The compositions are suitable for the treatment of allergic rhinitis and/or asthma. In certain embodiments of the invention the RNAi agent is targeted to a transcript that encodes a protein selected from the group consisisting of the FCεRIα chain, the FCεRIβ chain, c-Kit, Lyn, Syk, ICOS, OX40L, CD40, CD80, CD86, Re1A, Re1B, 4-1BB ligand, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, CD83, SLAM, common γ chain, and COX-2. In addition, the invention provides RNAi agent/delivery agent compositions and methods of use. In certain embodiments of the invention compositions comprising an RNAi agent are delivered by the respiratory route.
摘要翻译：本发明提供包含用于治疗由（例如，特征为IgE介导的超敏反应）介导的病症和疾病的一种或多种RNAi剂（例如siRNA，shRNA或RNAi载体）的组合物，以及用于鉴定有效的RNAi剂的系统以此目的。该组合物适用于治疗过敏性鼻炎和/或哮喘。在本发明的某些实施方案中，RNAi试剂靶向编码选自FCepsilonRIα链，FCepsilonRIbeta链，c-Kit，Lyn，Syk，ICOS，OX40L，CD40，CD80，CD86， Re1A，Re1B，4-1BB配体，TLR1，TLR2，TLR3，TLR4，TLR5，TLR6，TLR7，TLR8，TLR9，CD83，SLAM，通用γ链和COX-2。此外，本发明提供RNAi剂/递送剂组合物和使用方法。在本发明的某些实施方案中，包含RNAi试剂的组合物通过呼吸途径递送。

4. 发明申请

US20110112169A1 RNAi-BASED THERAPEUTICS FOR ALLERGIC RHINITIS AND ASTHMA 审中-公开
标题翻译：用于过敏性RHINITIS和ASTHMA的基于RNAi的治疗方法
公开(公告)号：US20110112169A1
公开(公告)日：2011-05-12
申请号：US12891626
申请日：2010-09-27
申请人： Jianzhu Chen , Herman N. Eisen , Qing Ge
发明人： Jianzhu Chen , Herman N. Eisen , Qing Ge
IPC分类号： A61K31/713 , C07H21/02 , A61K31/7105 , A61P11/00 , A61P11/06 , C12N15/63
CPC分类号： C12N15/113 , C12N15/111 , C12N15/1137 , C12N15/1138 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/32
摘要： The present invention provides compositions comprising one or more RNAi agents (e.g., siRNAs, shRNAs, or RNAi vectors) for the treatment of conditions and diseases mediated by (e.g., featuring IgE-mediated hypersensitivity), as well as systems for identifying RNAi agents effective for this purpose. The compositions are suitable for the treatment of allergic rhinitis and/or asthma. In certain embodiments of the invention the RNAi agent is targeted to a transcript that encodes a protein selected from the group consisting of the FCεRIα chain, the FCεRIβ chain, c-Kit, Lyn, Syk, ICOS, OX40L, CD40, CD80, CD86, Re1A, Re1B, 4-1BB ligand, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, CD83, SLAM, common γ chain, and COX-2. In addition, the invention provides RNAi agent/delivery agent compositions and methods of use. In certain embodiments of the invention compositions comprising an RNAi agent are delivered by the respiratory route.
摘要翻译：本发明提供包含用于治疗由（例如，特征为IgE介导的超敏反应）介导的病症和疾病的一种或多种RNAi剂（例如siRNA，shRNA或RNAi载体）的组合物，以及用于鉴定有效的RNAi剂的系统以此目的。该组合物适用于治疗过敏性鼻炎和/或哮喘。在本发明的某些实施方案中，所述RNAi试剂靶向编码选自下组的蛋白质的转录物：FC＆amp;RIα链，FC＆amp; RI＆bgr; 链，c-Kit，Lyn，Syk，ICOS，OX40L，CD40，CD80，CD86，Re1A，Re1B，4-1BB配体，TLR1，TLR2，TLR3，TLR4，TLR5，TLR6，TLR7，TLR8，TLR9，CD83，SLAM ，普通γ链和COX-2。此外，本发明提供RNAi剂/递送剂组合物和使用方法。在本发明的某些实施方案中，包含RNAi试剂的组合物通过呼吸途径递送。

5. 发明申请

US20090124567A1 Influenza Therapeutic 审中-公开
标题翻译：流感治疗
公开(公告)号：US20090124567A1
公开(公告)日：2009-05-14
申请号：US12167593
申请日：2008-07-03
申请人： Jianzhu Chen , Herman N. Eisen , Qing Ge
发明人： Jianzhu Chen , Herman N. Eisen , Qing Ge
IPC分类号： A61K31/7052 , C07H21/00 , C12N5/00 , A61P31/16 , C12N15/63 , A01K67/033
CPC分类号： C12N15/1131 , A61K38/00 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/32 , C12N2799/021
摘要： The present invention provides methods and compositions for inhibiting influenza infection and/or replication based on the phenomenon of RNA interference (RNAi) well as systems for identifying effective siRNAs and shRNAs for inhibiting influenza virus and systems for studying influenza virus infective mechanisms. The invention also provides methods and compositions for inhibiting infection, pathogenicity and/or replication of other infectious agents, particularly those that infect cells that are directly accessible from outside the body, e.g., skin cells or mucosal cells. In addition, the invention provides compositions comprising an RNAi-inducing entity, e.g., an siRNA, shRNA, or RNAi-inducing vector targeted to an influenza virus transcript and any of a variety of delivery agents. The invention further includes methods of use of the compositions for treatment of influenza.
摘要翻译：本发明提供了用于基于RNA干扰（RNAi）现象抑制流感感染和/或复制的方法和组合物以及用于鉴定用于抑制流感病毒的有效siRNA和shRNA以及用于研究流感病毒感染机制的系统的系统。本发明还提供用于抑制感染，致病性和/或其他感染因子的复制的方法和组合物，特别是感染可以从身体外部直接接近的细胞的感染，例如皮肤细胞或粘膜细胞的方法和组合物。此外，本发明提供了包含RNAi诱导实体的组合物，例如靶向流感病毒转录物的siRNA，shRNA或RNAi诱导载体以及各种递送试剂中的任何一种。本发明还包括使用该组合物治疗流感的方法。

6. 发明申请

US20060148747A1 Antisense antiviral compound and method for treating influenza viral infection 有权
标题翻译：反义抗病毒化合物及治疗流感病毒感染的方法
公开(公告)号：US20060148747A1
公开(公告)日：2006-07-06
申请号：US11259434
申请日：2005-10-25
申请人： David Stein , Qing Ge , Jianzhu Chen , Patrick Iversen
发明人： David Stein , Qing Ge , Jianzhu Chen , Patrick Iversen
IPC分类号： A61K48/00 , C07F9/6533 , C07H21/02
CPC分类号： C12N15/1131 , C12N2310/3145 , C12N2310/3233 , C12N2310/3513
摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5′ or 3′ terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 25 bases of the 3′ terminus of the positive sense cRNA and; and c) the 50 bases surrounding the AUG start codon of an influenza viral mRNA.
摘要翻译：本发明提供反义抗病毒化合物及其在抑制正粘病毒科的病毒生长和用于病毒感染治疗中的用途和生产方法。该化合物特别可用于治疗哺乳动物的流感病毒感染。反义抗病毒化合物是基本上不带电荷的吗啉代寡核苷酸，其具有1）核酸酶抗性主链，2）12-40个核苷酸碱基，和3）长度为至少12个碱基的靶向序列与选自以下的靶区域杂交：）流感病毒A，流感病毒B和流感病毒C的负义病毒RNA片段的5'或3'末端25个碱基; b）正义cRNA的3'末端的末端25个碱基; 和c）围绕流感病毒mRNA的AUG起始密码子的50个碱基。

7. 发明申请

US20100204297A1 INFLUENZA THERAPEUTIC 审中-公开
标题翻译：流感治疗
公开(公告)号：US20100204297A1
公开(公告)日：2010-08-12
申请号：US11909413
申请日：2006-03-22
申请人： Jianzhu Chen , Qing Ge , Herman N. Eisen
发明人： Jianzhu Chen , Qing Ge , Herman N. Eisen
IPC分类号： A61K31/713 , C07K7/08 , C07K14/00 , A61P31/16 , C12N15/63
CPC分类号： A61K9/5146 , A61K9/5153 , A61K38/00 , C12N15/111 , C12N15/1131 , C12N2310/111 , C12N2310/14 , C12N2310/321 , C12N2310/53 , C12N2320/11 , C12N2320/32 , C12N2799/021 , C12N2310/3521
摘要： The present invention provides compositions comprising an RNAi-inducing entity targeted to an influenza virus transcript and any of a variety of delivery agents. The invention further includes methods of use of the compositions for inhibiting a biological activity of an influenza virus and/or for treatment or prevention of influenza. The invention provides target portion sequences that are favorably conserved for RNAi across a plurality of influenza virus A strains isolated from human hosts and/or avian hosts and RNAi-inducing entities, e.g., siRNAs and shRNAs, targeted to such favorably conserved target portions. The invention provides a variety of nucleic acids comprising sequences identical or complementary to at least a portion of one or more of these favorably conserved target portion sequences. The invention further provides methods and compositions for delivering RNAi-inducing agents to an organ or tissue of a mammalian subject, e.g., to the lung. Methods of diagnosing influenza and determining the susceptibility of an influenza virus to inhibition by an RNAi-inducing agent are also provided. Transgenic animals that express an RNAi-inducing agent targeted to an influenza gene are another aspect of the invention.
摘要翻译：本发明提供了包含针对流感病毒转录物的RNAi诱导实体和各种递送试剂中的任一种的组合物。本发明还包括使用该组合物抑制流感病毒的生物学活性和/或用于治疗或预防流感的方法。本发明提供了针对分离自人宿主和/或禽类宿主和RNAi诱导实体（例如siRNA和shRNA）的多个流感病毒A菌株的RNAi有利地保守的靶标部分序列，靶向这些有利的保守靶部分。本发明提供了多种核酸，其包含与这些有利保守的靶部分序列中的一种或多种的至少一部分相同或互补的序列。本发明进一步提供了将哺乳动物受试者的器官或组织例如向肺部递送RNAi诱导剂的方法和组合物。还提供了诊断流感和确定流感病毒对RNAi诱导剂抑制的易感性的方法。表达靶向流感基因的RNAi诱导剂的转基因动物是本发明的另一方面。

8. 发明申请

US20090106852A1 Influenza Therapeutic 审中-公开
公开(公告)号：US20090106852A1
公开(公告)日：2009-04-23
申请号：US11952056
申请日：2007-12-06
申请人： Jianzhu Chen , Herman N. Eisen , Qing Ge
发明人： Jianzhu Chen , Herman N. Eisen , Qing Ge
IPC分类号： A01K67/027 , C07H21/02 , A61K31/7105 , A61K9/12 , A61P31/16 , C12N15/63 , C12N5/10
CPC分类号： C12N15/1131 , A61K38/00 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/32 , C12N2799/021
摘要： The present invention provides methods and compositions for inhibiting influenza infection and/or replication based on the phenomenon of RNA interference (RNAi) well as systems for identifying effective siRNAs and shRNAs for inhibiting influenza virus and systems for studying influenza virus infective mechanisms. The invention also provides methods and compositions for inhibiting infection, pathogenicity and/or replication of other infectious agents, particularly those that infect cells that are directly accessible from outside the body, e.g., skin cells or mucosal cells. In addition, the invention provides compositions comprising an RNAi-inducing entity, e.g., an siRNA, shRNA, or RNAi-inducing vector targeted to an influenza virus transcript and any of a variety of delivery agents. The invention further includes methods of use of the compositions for treatment of influenza.

9. 发明授权

US08357664B2 Antisense antiviral compound and method for treating influenza viral infection 有权
标题翻译：反义抗病毒化合物及治疗流感病毒感染的方法
公开(公告)号：US08357664B2
公开(公告)日：2013-01-22
申请号：US11259434
申请日：2005-10-25
申请人： David A. Stein , Qing Ge , Jianzhu Chen , Patrick L. Iversen , Hong M. Moulton
发明人： David A. Stein , Qing Ge , Jianzhu Chen , Patrick L. Iversen , Hong M. Moulton
IPC分类号： A61K48/00
CPC分类号： C12N15/1131 , C12N2310/3145 , C12N2310/3233 , C12N2310/3513
摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5′ or 3′ terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 25 bases of the 3′ terminus of the positive sense cRNA and; and c) the 50 bases surrounding the AUG start codon of an influenza viral mRNA.
摘要翻译：本发明提供反义抗病毒化合物及其在抑制正粘病毒科的病毒生长和用于病毒感染治疗中的用途和生产方法。该化合物特别可用于治疗哺乳动物的流感病毒感染。反义抗病毒化合物是具有1）核酸酶抗性主链，2）12-40个核苷酸碱基的基本上不带电荷的吗啉代寡核苷酸，和3）长度为至少12个碱基的靶向序列与选自以下的靶区域杂交：）流感病毒A，流感病毒B和流感病毒C的负义病毒RNA片段的5'或3'末端25个碱基; b）正义cRNA的3'末端的末端25个碱基; 和c）围绕流感病毒mRNA的AUG起始密码子的50个碱基。

10. 发明申请

US20070004661A1 Antisense antiviral compound and method for treating influenza viral infection 审中-公开
标题翻译：反义抗病毒化合物及治疗流感病毒感染的方法
公开(公告)号：US20070004661A1
公开(公告)日：2007-01-04
申请号：US11433213
申请日：2006-05-11
申请人： David Stein , Qing Ge , Jianzhu Chen , Patrick Iversen , Dwight Weller
发明人： David Stein , Qing Ge , Jianzhu Chen , Patrick Iversen , Dwight Weller
IPC分类号： A61K48/00 , C07H21/02 , C07F9/6533
CPC分类号： C12N15/1131 , C12N2310/3145 , C12N2310/3233 , C12N2310/3513
摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. The antisense antiviral compounds are substantially uncharged, including partially positively charged, morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5′ or 3′ terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 25 bases of the 3′ terminus of the positive sense cRNA and; and c) the 50 bases surrounding the AUG start codon of an influenza viral mRNA.
摘要翻译：本发明提供反义抗病毒化合物及其在抑制正粘病毒科的病毒生长和用于病毒感染治疗中的用途和生产方法。该化合物特别可用于治疗哺乳动物的流感病毒感染。反义抗病毒化合物基本上不带电，包括部分带正电荷的吗啉代寡核苷酸，其具有1）核酸酶抗性主链，2）12-40个核苷酸碱基，和3）与目标区域杂交的至少12个碱基长度的靶向序列选自以下：a）流感病毒A，流感病毒B和流感病毒C的阴性病毒RNA片段的5'或3'末端25个碱基; b）正义cRNA的3'末端的末端25个碱基; 和c）围绕流感病毒mRNA的AUG起始密码子的50个碱基。

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