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1.发明授权Antisense oligomers and methods for inducing immune tolerance and immunosuppression 有权反义寡聚体和诱导免疫耐受和免疫抑制的方法公开(公告)号：US08415313B2
公开(公告)日：2013-04-09
申请号：US11433033
申请日：2006-05-11
CPC分类号： A61K31/675 , C12N15/1138 , C12N2310/11 , C12N2310/3233 , C12N2310/3513
摘要： A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound, including partially positively charged, containing 12-40 subunits and a base sequence effective to hybridize to a target region within the sequence identified by SEQ ID NO:9, to form a duplex structure between the compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in the cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.
摘要翻译： 公开了一种用于将人树突状细胞诱导到T细胞的抗原特异性激活能力降低的条件下，并且在成熟树突状细胞中细胞外IL-10的产生增加的方法和组合物。 将一群树突状细胞暴露于包含部分带正电荷的基本上不带电荷的反义化合物，其含有12-40个亚单位和碱基序列，其有效地与SEQ ID NO：9所鉴定的序列内的靶区域杂交以形成双链体 化合物和具有至少45℃的Tm的转录物之间的结构。双链体阻断细胞中全长CD86的表达，这又导致T细胞抗原特异性激活的能力降低，并且在 成熟的树突状细胞，细胞外IL-10的产生增加。
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公开(公告)号：US08314072B2
公开(公告)日：2012-11-20
申请号：US11173847
申请日：2005-07-01
CPC分类号： C12N15/1137 , C07F9/65583 , C07F9/65613 , C12N15/113 , C12N2310/11 , C12N2310/3145 , C12N2310/3233
摘要： A method and antisense compound for inhibiting the growth of pathogenic bacterial cells are disclosed. The compound contains no more than 12 nucleotide bases and has a targeting nucleic acid sequence of no fewer than 10 bases in length that is 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. The compound binds to a target mRNA with a Tm of between 50° to 60° C. The relatively short antisense compounds are substantially more active than conventional antisense compounds having a targeting base sequence of 15 or more bases.
摘要翻译： 公开了一种用于抑制病原菌细胞生长的方法和反义化合物。 该化合物含有不超过12个核苷酸碱基，并且具有长度不小于10个碱基的靶向核酸序列，该靶向核酸序列与在细菌的翻译起始密码子的下游方向上含有或在10个碱基内的靶序列互补 编码细菌复制必需的细菌蛋白质的mRNA。 该化合物以Tm在50℃至60℃之间的靶mRNA结合。相对较短的反义化合物比具有15个或更多碱基的靶向碱基序列的常规反义化合物显着更具活性。
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公开(公告)号：US08299206B2
公开(公告)日：2012-10-30
申请号：US12271036
申请日：2008-11-14
IPC分类号： C07D413/04 , C07D413/14 , C07K9/00
CPC分类号： C08G73/06 , C08G65/329 , C08G65/33317 , C08G65/33337 , C08G65/3348 , C08L2203/02
摘要： Improved methods are described for solid-phase synthesis of morpholino oligomers, in which a protected morpholino ring nitrogen is deprotected between coupling steps using a heterocyclic amine salt in a trifluoroethanol-containing solvent, where the salt is a salt of a heterocyclic amine, having a pKa in the range of 1-4 in its protonated form, with an acid selected from a sulfonic acid, trifluoroacetic acid, and hydrochloric acid. Examples are 3-chloropyridinium methanesulfonate (CPM) and 4-cyanopyridinium trifluoroacetate (CYTFA).
摘要翻译： 描述了用于固相合成吗啉代低聚物的改进方法，其中在含三氟乙醇的溶剂中使用杂环胺盐的偶联步骤之间脱保护被保护的吗啉代环氮，其中盐是杂环胺的盐，其具有 pKa在其质子化形式的1-4范围内，与酸选自磺酸，三氟乙酸和盐酸。 实例是甲磺酸3-氯吡啶鎓（CPM）和三氟乙酸4-氰基吡啶鎓（CYTFA）。
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公开(公告)号：US20120058946A1
公开(公告)日：2012-03-08
申请号：US13219401
申请日：2011-08-26
申请人： Hong M. Moulton , Ryszard Kole
发明人： Hong M. Moulton , Ryszard Kole
CPC分类号： A61K47/48246 , A61K31/7088 , A61K47/64 , C07K2319/33 , C12N15/113 , C12N15/87 , C12N2310/11 , C12N2810/40
摘要： An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3′UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B/X)R)2XB, where R is arginine; B is β-alanine; and each X is —C(O)—(CH2)n—NH—, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and/or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.
摘要翻译： 公开了用于治疗强直性营养不良DM1或DM2的反义化合物，增强对心脏和四头肌的反义靶向的方法，以及哺乳动物受试者中治疗DM1或DM2的方法。 寡核苷酸具有8-30个碱基，其中至少8个连续碱基分别与DM1或DM2中的肌营养不良肌群蛋白激酶（DMPK）mRNA的3'UTR区域中的polyCUG或polyCCUG重复序列互补。 与寡核苷酸共轭是具有序列（RXRR（B / X）R）2XB的细胞穿透肽，其中R是精氨酸; B是丙氨酸; 并且每个X是-C（O） - （CH 2）n -NH-，其中n是4-6。 反义化合物有效地选择性地阻断强直肌营养不良动物模型中心肌和四头肌中肌肉样蛋白样蛋白（MBNL1）和/或CUGBP的螯合。
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公开(公告)号：US20120027791A1
公开(公告)日：2012-02-02
申请号：US13187338
申请日：2011-07-20
IPC分类号： A61K38/14 , A61P37/06 , C12N5/0784 , C07K9/00 , C12N5/0783 , C12N5/0781
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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6.发明授权公开(公告)号：US08030291B2
公开(公告)日：2011-10-04
申请号：US12402455
申请日：2009-03-11
CPC分类号： C12N15/1131 , C12N2310/11 , C12N2310/31 , C12N2310/32 , 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 Filoviridae family, and in the treatment of a viral infection. The compounds and methods relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds are morpholino oligonucleotides having: a) a nuclease resistant backbone, b) 15-40 nucleotide bases, and c) a targeting sequence of at least 15 bases in length that hybridizes to a target region selected from the following: i) the Ebola virus AUG start site region of VP24; ii) the Ebola virus AUG start site region of VP35; iii) the Marburg virus AUG start site region of VP24; or iv) the Marburg virus AUG start site region of NP.
摘要翻译： 本发明提供了反义抗病毒化合物及其在抑制丝状病毒科病毒生长和用于病毒感染治疗中的用途和生产方法。 该化合物和方法涉及哺乳动物中的病毒感染的治疗，包括埃博拉和马尔堡病毒的灵长类动物。 反义抗病毒化合物是吗啉代寡核苷酸，其具有：a）核酸酶抗性主链，b）15-40个核苷酸碱基，和c）长度为至少15个碱基的靶向序列与选自以下的靶区域杂交：i） 埃博拉病毒AUG起始站点区域VP24; ii）VP35的埃博拉病毒AUG起始区域; iii）马尔堡病毒AUG VP24的起始区域; 或iv）Marburg病毒AUG起始地点的NP。
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公开(公告)号：US20110224283A1
公开(公告)日：2011-09-15
申请号：US13046356
申请日：2011-03-11
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
IPC分类号： A61K31/713 , C07H21/02 , C07K2/00 , C07K7/00 , A61P29/00 , A61P19/02 , A61P25/28 , A61P11/06 , A61P1/00 , A61P3/00 , C12N5/071
CPC分类号： C12N15/1138 , C12N2310/11 , C12N2310/314 , C12N2310/3233 , C12N2310/3513
摘要： Provided are antisense oligonucleotides and other agents that target and modulate nuclear hormone receptors (NHRs) such as the glucocorticoid receptor (GR), compositions that comprise the same, and methods of use thereof.
摘要翻译： 提供靶向和调节核激素受体（NHR）的反义寡核苷酸和其他试剂，例如糖皮质激素受体（GR），包含其的组合物及其使用方法。
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公开(公告)号：US20110172418A1
公开(公告)日：2011-07-14
申请号：US12854648
申请日：2010-08-11
IPC分类号： C07F9/6561
CPC分类号： C12N15/1135 , C12N15/111 , C12N2310/11 , C12N2310/314 , C12N2310/3233 , C12N2310/351 , C12N2320/30
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 a 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。 该方法包括向靶血管区域施用具有含磷骨架键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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公开(公告)号：US20110166082A1
公开(公告)日：2011-07-07
申请号：US12983798
申请日：2011-01-03
IPC分类号： A61K31/675 , A61K38/00 , A61K38/10 , C07D413/14 , C07K9/00 , G01N33/48 , A61P21/00
CPC分类号： C12N15/1136 , A61K31/675 , A61K47/645 , C07H21/00 , C07K7/08 , C12N2310/11 , C12N2310/31 , C12N2310/3145 , C12N2310/3233 , C12N2310/3513 , C12N2320/30 , C12Q1/6876 , C12Q2600/158 , Y10T436/143333
摘要： A method and compound for treating skeletal muscle mass deficiency in a human subject are disclosed. The composition is an oligomer of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, contains between 10-40 nucleotide bases, has a base sequence effective to hybridize to an expression-sensitive region of processed or preprocessed human myostatin RNA transcript, identified, in its processed form, by SEQ ID NO:6, and is capable of uptake by target muscle cells in the subject. In practicing the method, the compound is administered in an amount and at a dosage schedule to produce an overall reduction in the level of serum myostatin measured in the patient, and preferably to bring the myostatin level within the a range determined for normal, healthy individuals.
摘要翻译： 公开了一种用于治疗人类受试者骨骼肌质量不足的方法和化合物。 该组合物是吗啉代亚基的低聚物和将一个亚基的吗啉代氮连接到相邻亚单位的5'环外碳的含磷亚基间连接，含有10-40个核苷酸碱基之间，具有有效地与表达杂交的碱基序列 经处理或预处理的人肌生成抑制素RNA转录物的敏感区域，以其加工形式由SEQ ID NO：6鉴定，并且能够被摄体中的靶肌细胞摄取。 在实施该方法中，化合物以量和剂量方案施用以产生在患者体内测量的血清肌生成抑制素水平的总体降低，优选使肌生成抑制素水平在正常健康个体确定的范围内 。
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10.发明授权公开(公告)号：US07507196B2
公开(公告)日：2009-03-24
申请号：US11433840
申请日：2006-05-11
CPC分类号： C12N15/1131 , C12N2310/11 , C12N2310/31 , C12N2310/32 , 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 Filoviridae family, and in the treatment of a viral infection. The compounds and methods relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds are morpholino oligonucleotides having: a) a nuclease resistant backbone, b) 15-40 nucleotide bases, and c) a targeting sequence of at least 15 bases in length that hybridizes to a target region selected from the following: i) the AUG start site region of VP35, as exemplified by SEQ ID NOS:67-71 or ii) the AUG start site region of VP24, as exemplified by SEQ ID NOS:72-76.
摘要翻译： 本发明提供了反义抗病毒化合物及其在抑制丝状病毒科病毒生长和用于病毒感染治疗中的用途和生产方法。 该化合物和方法涉及哺乳动物中的病毒感染的治疗，包括埃博拉和马尔堡病毒的灵长类动物。 反义抗病毒化合物是吗啉代寡核苷酸，其具有：a）核酸酶抗性主链，b）15-40个核苷酸碱基，和c）长度为至少15个碱基的靶向序列与选自以下的靶区域杂交：i） VP35的AUG起始位点区域，如SEQ ID NO：67-71所示，或ii）VP24的AUG起始位点区域，如SEQ ID NO：72-76所例示。
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