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公开(公告)号：US07094765B1
公开(公告)日：2006-08-22
申请号：US09493427
申请日：2000-01-29
CPC分类号： A61K31/07
摘要： The present invention provides an improved method for reducing the risk or severity of restenosis following cardiac angioplasty. The method includes administering to a target vessel region, a morpholino antisense compound having uncharged phosphorus-containing backbone linkages, and spanning the start codon of a human c-myc mRNA. Also disclosed are novel antisense compounds and compositions, and a method for assaying the effectiveness of antisense delivery and uptake to a target vessel region.
摘要翻译： 本发明提供了用于降低心脏血管成形术后再狭窄风险或严重程度的改进方法。 该方法包括向目标血管区域施用具有不带电荷的含磷骨架连接的吗啉代反义化合物，并跨越人c-myc mRNA的起始密码子。 还公开了新的反义化合物和组合物，以及用于测定反义递送和对靶血管区域的摄取的有效性的方法。
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42.发明授权公开(公告)号：US06245747B1
公开(公告)日：2001-06-12
申请号：US09114399
申请日：1998-07-13
IPC分类号： A01N4304
CPC分类号： A61K9/0009 , A61K9/0019 , A61K9/5015 , A61K9/5052 , A61K41/0028 , A61K47/6925 , C12N15/1135 , C12N15/87 , C12N2310/315
摘要： The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in utility for agents such as oligonucleotides which are plagued with problems in reaching targeted sites in necessary therapeutic levels. The delivery system includes gas-filled microbubbles formed in a nitrogen-free environment. Microbubbles formed through sonication in a nitrogen-free environment are smaller and more stable than microbubbles sonicated in the presence of room air.
摘要翻译： 本发明涉及用于递送治疗剂的新的和改进的药物组合物和方法。 本发明的方法和组合物可以与几种治疗剂一起使用，并且可以实现治疗物质的位点特异性递送。 这可以允许较低的剂量和用于改善传统上达到目标部位的药物的功效，并且可以导致药物如寡核苷酸的用途，所述药物如在需要治疗水平达到目标部位时遇到问题的寡核苷酸。递送系统包括形成的充气微泡 在无氮环境中。 在无氮环境中通过超声处理形成的微泡比在室内空气存在下超声处理的微泡更小，更稳定。
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公开(公告)号：US6124271A
公开(公告)日：2000-09-26
申请号：US12198
申请日：1998-01-23
IPC分类号： A61K31/7088 , A61K47/48 , A61P31/04 , A61K31/70 , C07H21/00
CPC分类号： A61K47/48092 , A61K47/48023 , A61K47/48315
摘要： A method and comjugate for treating H. pylori infection in a subject are disclosed. The conjugate is composed of (a) a nuclease-resistant antisense oligomer effective to inhibit H. pylori infection in the subject by base-specific Watson-Crick binding to an H. pylori mRNA transcript, and (b) a transport moiety conjugated to the oligomer. The transport moiety is effective to facilitate uptake of the conjugate from the environment of the stomach into the cytoplasm of H. pylori cells by active transport or by pH-gradient transport across of the cell membrane of H. pylori. The conjugate is administered by oral route, preferably in a swellable polymer bolus designed to release the conjugate in sustained release.
摘要翻译： 公开了用于治疗受试者中幽门螺杆菌感染的方法和共轭物。 缀合物由（a）通过碱基特异性Watson-Crick结合幽门螺杆菌mRNA转录物有效抑制幽门螺杆菌感染的核酸酶抗性反义寡聚体，和（b）与 低聚物。 运输部分有利于通过主动转运或通过幽门螺旋杆菌的细胞膜上的pH梯度转运来促进缀合物从胃的环境吸收到幽门螺杆菌细胞的细胞质中。 缀合物通过口服途径施用，优选在可膨胀聚合物推注中，其设计用于释放持续释放的缀合物。
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公开(公告)号：US10017763B2
公开(公告)日：2018-07-10
申请号：US13819634
申请日：2011-09-02
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/14 , C12N2310/314 , C12N2310/3233 , C12N2310/344 , C12N2310/3513
摘要： Morpholino oligomers containing modified intersubunit linkages and/or terminal groups are provided for use within dsRNA molecules. The oligomers are oligonucleotide analogs containing predetermined sequences of base-pairing moieties. Also provided are such oligomers conjugated to peptide transporter moieties, where the transporters are preferably composed of arginine subunits, or arginine dimers, alternating with neutral amino acid subunits.
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45.发明授权公开(公告)号：US08759307B2
公开(公告)日：2014-06-24
申请号：US12109856
申请日：2008-04-25
申请人： David A. Stein , Richard K. Bestwick , Patrick L. Iversen , Benjamin Neuman , Michael Buchmeier , Dwight D. Weller
发明人： David A. Stein , Richard K. Bestwick , Patrick L. Iversen , Benjamin Neuman , Michael Buchmeier , Dwight D. Weller
CPC分类号： C07H21/02 , C07K14/005 , C12N15/1131 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2770/20022
摘要： A method and oligonucleotide compound for inhibiting replication of a nidovirus in virus-infected animal cells are disclosed. The compound (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the infected cells, (iii) contains between 8-25 nucleotide bases, and (iv) has a sequence capable of disrupting base pairing between the transcriptional regulatory sequences in the 5′ leader region of the positive-strand viral genome and negative-strand 3′ subgenomic region. In practicing the method, infected cells are exposed to the compound in an amount effective to inhibit viral replication.
摘要翻译： 公开了用于抑制病毒感染的动物细胞中的Nidovirus复制的方法和寡核苷酸化合物。 化合物（i）具有核酸酶抗性主链，（ii）能够被感染细胞摄取，（iii）含有8-25个核苷酸碱基之间，和（iv）具有能够破坏转录之间碱基配对的序列 正链病毒基因组和负链3'亚基因组区域的5'前导区域中的调节序列。 在实施该方法中，感染的细胞以有效抑制病毒复制的量暴露于化合物。
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46.发明申请dsRNA MOLECULES COMPRISING OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS 有权包含具有修饰的互联网连接和/或终端组的寡核苷酸模拟物的dsRNA分子公开(公告)号：US20130288369A1
公开(公告)日：2013-10-31
申请号：US13819634
申请日：2011-09-02
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/14 , C12N2310/314 , C12N2310/3233 , C12N2310/344 , C12N2310/3513
摘要： Morpholino oligomers containing modified intersubunit linkages and/or terminal groups are provided for use within dsRNA molecules. The oligomers are oligonucleotide analogs containing predetermined sequences of base-pairing moieties. Also provided are such oligomers conjugated to peptide transporter moieties, where the transporters are preferably composed of arginine subunits, or arginine dimers, alternating with neutral amino acid subunits.
摘要翻译： 提供含有修饰的亚单位间键和/或末端基团的吗啉代低聚物用于dsRNA分子内。 寡聚体是含有预定序列的碱基配对部分的寡核苷酸类似物。 还提供了与肽转运蛋白部分缀合的这种寡聚体，其中转运蛋白优选由精氨酸亚基或精氨酸二聚体组成，与中性氨基酸亚基交替。
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47.发明授权公开(公告)号：US08198429B2
公开(公告)日：2012-06-12
申请号：US12853180
申请日：2010-08-09
CPC分类号： C12N15/113 , A61K31/675 , A61K31/713 , C12N15/1131 , C12N2310/11 , C12N2310/3233
摘要： The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.
摘要翻译： 本发明提供反义抗病毒化合物，组合物及其使用和生产方法，主要用于抑制丝状病毒科病毒的复制，包括埃博拉病毒和马尔堡病毒。 化合物，组合物和方法还涉及治疗包括埃博拉和马尔堡病毒在内的哺乳动物中的病毒感染。 反义抗病毒化合物包括具有核酸酶抗性主链的磷酸二亚胺吗啉代寡核苷酸（PMOplus），约15-40个核苷酸碱基，至少两个但通常不超过一半的含哌嗪的亚单位间连接，以及针对AUG起始靶向序列 埃博拉病毒VP35的位点区域，埃博拉病毒VP24，马尔堡病毒VP24或马尔堡病毒NP，包括其组合和混合物。
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公开(公告)号：US20120122769A1
公开(公告)日：2012-05-17
申请号：US13294000
申请日：2011-11-10
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
IPC分类号： A61K38/14 , C07H21/04 , C07K17/10 , A61K31/7088 , A01P1/00 , A61K31/7048 , A61P31/06 , A01N57/16 , C12N5/02 , C07H21/00 , A61K31/7036
CPC分类号： C12N15/113 , C12N2310/314 , C12N2310/3233 , C12N2310/3513
摘要： Antibacterial antisense compounds and methods of their use in treating a Mycobacterium tuberculosis infection in a mammalian host are disclosed. The compounds include an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotides contain 10-20 nucleotide bases and have a targeting nucleic acid sequence complementary to a target sequence containing or within 20 bases, in a downstream direction, of the translational start codon of a bacterial mRNA that encodes a bacterial protein essential for bacterial replication, where the compound binds to a target mRNA with a Tm of between 45° to 60° C. The carrier peptide is an arginine-rich peptide containing between 6 and 14 amino acids. Antisense compounds that target host factor genes that facilitate Mycobacterium tuberculosis infection are also provided, as are methods of using these compounds to treat Mycobacterium tuberculosis infections, alone or in combination with other therapies.
摘要翻译： 公开了抗细菌反义化合物及其用于治疗哺乳动物宿主中结核分枝杆菌感染的方法。 所述化合物包括与载体肽缀合的反义寡核苷酸，其显着增强寡核苷酸的抗菌活性。 反义寡核苷酸含有10-20个核苷酸碱基，并且具有与包含编码细菌复制必需的细菌蛋白质的细菌mRNA的翻译起始密码子在下游方向的20个碱基内的靶序列互补的靶向核酸序列 其中化合物以45℃至60℃的Tm结合靶mRNA。载体肽是含有6至14个氨基酸的富含精氨酸的肽。 还提供靶向促进结核分枝杆菌感染的宿主因子基因的反义化合物，以及使用这些化合物单独或与其它疗法组合治疗结核分枝杆菌感染的方法。
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49.发明申请ANTISENSE ANTIVIRAL COMPOUNDS AND METHODS FOR TREATING A FILOVIRUS INFECTION 有权抗真菌化合物和治疗FILOVIRUS感染的方法公开(公告)号：US20120035136A1
公开(公告)日：2012-02-09
申请号：US12853180
申请日：2010-08-09
IPC分类号： A61K31/675 , A61P31/14
CPC分类号： C12N15/113 , A61K31/675 , A61K31/713 , C12N15/1131 , C12N2310/11 , C12N2310/3233
摘要： The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.
摘要翻译： 本发明提供反义抗病毒化合物，组合物及其使用和生产方法，主要用于抑制丝状病毒科病毒的复制，包括埃博拉病毒和马尔堡病毒。 化合物，组合物和方法还涉及治疗包括埃博拉和马尔堡病毒在内的哺乳动物中的病毒感染。 反义抗病毒化合物包括具有核酸酶抗性主链的磷酸二亚胺吗啉代寡核苷酸（PMOplus），约15-40个核苷酸碱基，至少两个但通常不超过一半的含哌嗪的亚单位间连接，以及针对AUG起始靶向序列 埃博拉病毒VP35的位点区，埃博拉病毒VP24，马尔堡病毒VP24或马尔堡病毒NP，包括其组合和混合物。
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50.发明授权Antisense antiviral compound and method for treating ssRNA viral infection 有权反义抗病毒化合物和治疗ssRNA病毒感染的方法公开(公告)号：US08084433B2
公开(公告)日：2011-12-27
申请号：US11432031
申请日：2006-05-10
CPC分类号： C12N15/1131 , C07K19/00 , C12N15/111 , C12N2310/11 , C12N2310/314 , C12N2310/3233 , C12N2310/3513 , C12N2310/531 , C12N2320/11 , C12N2770/00011 , C12N2770/10011 , C12N2770/12011 , C12N2770/16011 , C12N2770/20011 , C12N2770/24011 , C12N2770/28011 , C12N2770/32011 , C12N2770/36011
摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picomoviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.
摘要翻译： 本发明提供反义抗病毒化合物及其在抑制病毒感染的治疗中抑制黄病毒科，Picomoviridae，Caliciviridae，Togaviridae，Arteriviridae，Coronaviridae，Astroviridae和Hepeviridae家族病毒生长的方法。 反义抗病毒化合物是具有12-40个亚基序列的基本上不带电荷的吗啉代寡核苷酸，包括至少12个亚基，其具有与在5'-末端40个碱基内的茎环二级结构相关的区域互补的靶向序列 病毒的正义RNA链。
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