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31.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：US08129352B2
公开(公告)日：2012-03-06
申请号：US11226995
申请日：2005-09-14
申请人： Patrick L. Iversen , David A. Stein
发明人： Patrick L. Iversen , David A. Stein
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, Picornoviridae, 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黄病毒科，细小病毒科，杯状病毒科，披膜病毒科，动脉病毒科，科罗亚病毒科，蛔虫科和乙肝病毒科的病毒生长中的用途和生产方法。 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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公开(公告)号：US20120053228A1
公开(公告)日：2012-03-01
申请号：US13219409
申请日：2011-08-26
申请人： Patrick L. Iversen , Robert Hudziak
发明人： Patrick L. Iversen , Robert Hudziak
IPC分类号： A61K31/712 , A61P31/12 , A61P31/04 , A61P29/00 , A61P35/00 , A61P9/00 , A61P17/00 , C07H21/02 , A61P31/10
CPC分类号： C12N15/113 , A61K38/00 , C07F9/65583 , C12N15/1132 , C12N15/1135 , C12N15/1136 , C12N15/1138 , C12N2310/11 , C12N2310/314 , C12N2310/3145 , C12N2310/3233 , C12N2320/33
摘要： Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5′ end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.
摘要翻译： 公开了针对编码所选蛋白质的mRNA序列的反义组合物，其在其预处理的mRNA中正常剪接受体下游的1至约25个碱基对的其5'端的区域。 反义化合物是RNase-非活性的，优选为与二亚甲基二酰胺连接的吗啉代寡核苷酸。 这种靶向对于抑制天然的mRNA剪接加工，产生剪接变体mRNAs和抑制蛋白质的正常表达是有效的。
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公开(公告)号：US08067571B2
公开(公告)日：2011-11-29
申请号：US11803107
申请日：2007-05-11
CPC分类号： C07K7/02 , A61K48/00 , C07D295/205 , C07D413/04 , C07D473/34 , C07F9/65583 , C08F112/08 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
摘要翻译： 用于通过含磷亚基间连接连接的由吗啉代亚基组成的反义寡核苷酸的抗菌活性增强至少10倍的方法。 该方法包括以下之一或两者：将富含精氨酸的载体与寡核苷酸的3'或5'末端缀合，并修饰寡核苷酸以含有在生理pH下带正电荷的20％-50％的亚单位连接。 还公开了通过一个或两个修饰具有增强的抗菌活性的反义寡核苷酸。
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公开(公告)号：US20110289608A1
公开(公告)日：2011-11-24
申请号：US13107528
申请日：2011-05-13
IPC分类号： A61P11/06 , A61K31/7125 , C07H21/04 , C07K2/00 , C07K9/00 , A61K49/00 , A61P29/00 , A61P37/02 , A61P19/02 , A61P17/06 , A61P9/10 , A61P35/00 , A61P11/00 , A61P35/02 , C12Q1/06 , C12Q1/70 , C12N5/071
CPC分类号： A61K31/713 , A01K67/027 , A01K2267/03 , C12N15/1136 , C12N15/1138 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/33 , G01N33/5041 , G01N33/56983 , G01N33/6893 , G01N2333/005 , G01N2333/54 , G01N2500/00 , Y02A50/414
摘要： Provided are antisense oligonucleotides and other agents that target and modulate IL-17 and/or IL-23 signaling activity in a cell, compositions that comprise the same, and methods of use thereof. Also provided are animal models for identifying agents that modulate 17 and/or IL-23 signaling activity.
摘要翻译： 提供靶向和调节细胞中IL-17和/或IL-23信号传导活性的反义寡核苷酸和其它试剂，包含其的组合物及其使用方法。 还提供了用于鉴定调节17和/或IL-23信号传导活性的药剂的动物模型。
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公开(公告)号：US20100234280A1
公开(公告)日：2010-09-16
申请号：US12723035
申请日：2010-03-12
CPC分类号： A61K48/00 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： An antibacterial antisense conjugate and method of using the same for treating a bacterial infection in a mammalian host are disclosed. The conjugate includes an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotide contains 10-20 nucleotide bases and has a targeting nucleic acid sequence complementary to a target sequence containing or within 10 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 50° to 60° C. The carrier peptide is an arginine-rich peptide containing between 6 and 12 amino acids.
摘要翻译： 公开了一种抗菌反义结合物及其用于治疗哺乳动物宿主细菌感染的方法。 缀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，并且具有与含有或在其下游方向的10个碱基的靶序列互补的靶向核酸序列，其编码细菌复制物必需的细菌蛋白质的细菌mRNA的翻译起始密码子 其中化合物以Tm在50℃至60℃之间的靶mRNA结合。载体肽是含有6-12个氨基酸的富含精氨酸的肽。
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公开(公告)号：US20090111977A1
公开(公告)日：2009-04-30
申请号：US11941033
申请日：2007-11-15
IPC分类号： C07H21/00
CPC分类号： A61K31/675 , C07K2319/10 , C12N15/1132 , C12N2310/11 , C12N2810/6054
摘要： A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.
摘要翻译： 公开了用于选择性杀死抗原活化的T细胞的方法和缀合物。 缀合物由靶向人cFLIP蛋白的基本上不带电的反义化合物和与反义化合物共价偶联的反向TAT（rTAT）多肽组成。 相对于缀合物对非活化T细胞的摄取，rTAT多肽有效产生缀合物选择性吸收抗原激活的T细胞。 cFLIP反义化合物引起活化的淋巴细胞活化诱导的细胞死亡（AICD）。 该方法可用于治疗移植排斥反应和自身免疫病症。
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公开(公告)号：US07468418B2
公开(公告)日：2008-12-23
申请号：US10836804
申请日：2004-04-29
CPC分类号： A61K49/0056 , A61K47/64 , A61K49/0043 , A61K49/0054 , C12N15/113 , C12N15/87 , C12N2310/11 , C12N2310/314 , C12N2310/3233 , C12N2310/3513 , C12N2320/32
摘要： Compositions and methods for enhancing delivery of molecules, e.g. biological agents, into cells are described. The composition is a conjugate of the biological agent, preferably a nucleic acid analog having a substantially uncharged backbone, covalently linked to a peptide transporter moiety as described. Conjugation of the peptide transporter to a substantially uncharged nucleic acid analog, such as a morpholino oligomer, is also shown to enhance binding of the oligomer to its target sequence and enhance antisense activity.
摘要翻译： 用于增强分子递送的组合物和方法，例如 描述了生物制剂进入细胞。 组合物是生物制剂的缀合物，优选具有基本上不带电的主链的核酸类似物，其与所述的肽转运蛋白部分共价连接。 还显示肽转运蛋白与基本上不带电的核酸类似物如吗啉代低聚物的缀合增强寡聚物与其靶序列的结合并增强反义活性。
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38.发明申请公开(公告)号：US20080311556A1
公开(公告)日：2008-12-18
申请号：US10567470
申请日：2004-08-06
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
CPC分类号： C12N15/1131 , C12N2310/11 , C12N2310/3145 , C12N2310/3233
摘要： The invention provides sense antiviral compounds and methods of their use in inhibition of growth of viruses of the Flaviviridae, Picornoviridae, Caliciviridae, Togaviridae, Coronaviridae families and hepatitis E virus in the treatment of a viral infection. The sense 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 3′-terminal end (40) bases of the negative-sense RNA strand of the virus.
摘要翻译： 本发明提供了有用的抗病毒化合物及其用于抑制黄病毒科，细小病毒科，杯状病毒科，披膜病毒科，Coronaviridae家族和戊型肝炎病毒病毒生长的病毒治疗病毒感染的方法。 正义抗病毒化合物是具有（12-40）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3'-末端内的茎环二级结构相关的区域互补的靶向序列 病毒的负义RNA链的末端（40）碱基。
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公开(公告)号：US07402574B2
公开(公告)日：2008-07-22
申请号：US11077871
申请日：2005-03-10
CPC分类号： A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0331 , C12N15/113 , C12N15/8509 , C12N2310/11 , C12N2310/3145 , C12N2310/3233
摘要： A method and composition for treating colorectal cancer is disclosed. The method involves administering to a subject, a therapeutically effective amount of a morpholino antisense compound (i) having a nuclease-resistant backbone, (ii) capable of uptake by target cancer cells in the subject, (iii) containing between 10-40 nucleotide bases, and (iv) having a base sequence effective to hybridize to a region of processed or preprocessed human SNAIL RNA transcript.
摘要翻译： 公开了一种治疗结肠直肠癌的方法和组合物。 该方法涉及向受试者施用治疗有效量的具有核酸酶抗性主链的吗啉代反义化合物（i），（ii）能够被受试者中靶细胞摄取的能力，（iii）含有10-40个核苷酸 碱基，和（iv）具有有效地与经处理或预处理的人SNAIL RNA转录物区域杂交的碱基序列。
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公开(公告)号：US07238675B2
公开(公告)日：2007-07-03
申请号：US10719633
申请日：2003-11-21
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/311 , C12N2310/312 , C12N2310/314 , C12N2310/315 , C12N2310/318 , C12N2310/3233 , Y02A50/471 , Y02A50/475 , Y02A50/481
摘要： The invention relates to compositions comprising oligomers antisense to bacterial 16S or 23S rRNA and capable of selectively modulating the biological activity thereof, and methods for their use. More particularly, the invention relates to antisense oligomers directed to 16S or 23S rRNA found in one or more particular bacteria, or generally conserved among bacteria in general, and to pharmaceutical compositions and methods of treatment comprising the same.
摘要翻译： 本发明涉及包含与细菌16S或23S rRNA反义并能够选择性调节其生物活性的寡聚物的组合物及其使用方法。 更具体地，本发明涉及在一种或多种特定细菌中发现的或通常在细菌中通常保守的16S或23S rRNA的反义寡聚体以及包含其的药物组合物和治疗方法。
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