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公开(公告)号：US07888012B2
公开(公告)日：2011-02-15
申请号：US11433724
申请日：2006-05-11
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键，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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公开(公告)号：US20100292189A1
公开(公告)日：2010-11-18
申请号：US12848873
申请日：2010-08-02
申请人： Patrick L. Iversen , David A. Stein
发明人： Patrick L. Iversen , David A. Stein
IPC分类号： A61K31/675 , C07D413/14 , A61P31/14
CPC分类号： C12N15/1131 , C12N2310/11 , C12N2310/314 , C12N2310/3145 , C12N2310/3233
摘要： A method of inhibiting replication of a flavivirus in animal cells, and an oligonucleotide compound for use in the method are disclosed. The oligonucleotide analog (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the cells, (iii) contains between 8-40 nucleotide bases, and (iv) has a sequence of at least 8 bases complementary to a region of the virus' positive strand RNA genome that includes at least a portion of SEQ ID NOS:1-4. Exposure of cells infected with a flavivirus to the analog is effective to form within the cells, a heteroduplex structure composed of the virus ssRNA and the oligonucleotide, characterized by a Tm of dissociation of at least 45° C., and having disrupted base pairing between the virus' 5′ and 3′ cyclization sequences.
摘要翻译： 公开了抑制黄病毒在动物细胞中的复制的方法和用于该方法的寡核苷酸化合物。 寡核苷酸类似物（i）具有核酸酶抗性主链，（ii）能够被细胞吸收，（iii）含有8-40个核苷酸碱基，和（iv）具有至少8个碱基互补的序列 包含SEQ ID NO：1-4的至少一部分的病毒“正链RNA”基因组的区域。 用黄病毒感染的细胞暴露于类似物是有效的在细胞内形成，由病毒ssRNA和寡核苷酸组成的异源双链结构，其特征在于解离的Tm至少为45℃，并且具有中间的碱基配对 病毒'5'和3'环化序列。
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公开(公告)号：US07807801B2
公开(公告)日：2010-10-05
申请号：US10913996
申请日：2004-08-05
申请人： Patrick L. Iversen , David A. Stein
发明人： Patrick L. Iversen , David A. Stein
CPC分类号： C12N15/1131 , C12N2310/11 , C12N2310/314 , C12N2310/3145 , C12N2310/3233
摘要： A method of inhibiting replication of a flavivirus in animal cells, and an oligonucleotide compound for use in the method are disclosed. The oligonucleotide analog (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the cells, (iii) contains between 8-40 nucleotide bases, and (iv) has a sequence of at least 8 bases complementary to a region of the virus' positive strand RNA genome that includes at least a portion of SEQ ID NOS:1-4. Exposure of cells infected with a flavivirus to the analog is effective to form within the cells, a heteroduplex structure composed of the virus ssRNA and the oligonucleotide, characterized by a Tm of dissociation of at least 45° C., and having disrupted base pairing between the virus' 5′ and 3′ cyclization sequences.
摘要翻译： 公开了抑制黄病毒在动物细胞中的复制的方法和用于该方法的寡核苷酸化合物。 寡核苷酸类似物（i）具有核酸酶抗性主链，（ii）能够被细胞吸收，（iii）含有8-40个核苷酸碱基，和（iv）具有至少8个碱基互补的序列 包含SEQ ID NO：1-4的至少一部分的病毒“正链RNA”基因组的区域。 用黄病毒感染的细胞暴露于类似物是有效的在细胞内形成，由病毒ssRNA和寡核苷酸组成的异源双链结构，其特征在于解离的Tm至少为45℃，并且具有中间的碱基配对 病毒'5'和3'环化序列。
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公开(公告)号：US20100137408A1
公开(公告)日：2010-06-03
申请号：US12613428
申请日：2009-11-05
IPC分类号： A61K31/7088 , C07H21/02 , A61P31/04
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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85.发明申请Cancer treatment by combined inhibition of proteasome and telomerase activities 有权癌症治疗联合抑制蛋白酶体和端粒酶活性公开(公告)号：US20100010064A1
公开(公告)日：2010-01-14
申请号：US11918581
申请日：2006-04-14
IPC分类号： A61K31/711 , C12N5/08 , A61K31/69 , A61P35/00 , A61K48/00
CPC分类号： C12N15/1137 , A61K31/454 , A61K45/06 , C12N2310/11 , C12N2310/3145 , C12N2310/3515 , C12Y207/07049 , A61K2300/00
摘要： A method and kit for inhibiting the proliferation of cancer cells are disclosed, based on a combination of a proteasome inhibitor and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with the proteasome inhibitor alone or the telomerase inhibitor alone. Preferably, efficacy is supraadditive or synergistic in nature relative to the combined effects of the individual agents, with minimal exacerbation of side effects.
摘要翻译： 基于蛋白酶体抑制剂和端粒酶抑制剂的组合，公开了抑制癌细胞增殖的方法和试剂盒。 当用于癌症治疗时，两种化合物组合增强了单独使用蛋白酶体抑制剂或单独使用端粒酶抑制剂获得的抗癌治疗功效。 优选地，相对于各个试剂的组合效应，效力是相对于辅助的或协同的，并且副作用的加剧最小化。
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86.发明授权公开(公告)号：US07582615B2
公开(公告)日：2009-09-01
申请号：US11715572
申请日：2007-03-07
CPC分类号： C12N15/1131 , C12N2310/11 , C12N2310/3145 , C12N2310/3233 , C12N2310/3513 , C12N2760/10011
摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Arenaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Arenavirus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 19 nucleotide region of the 5′-terminal regions of the viral RNA, viral complementary RNA and/or mRNA identified by SEQ ID NO:1.
摘要翻译： 本发明提供了反义抗病毒化合物及其在抑制竞争链球菌科家族病毒生长和用于病毒感染治疗中的用途和生产方法。 这些化合物特别可用于治疗哺乳动物中的雷亚病毒感染。 反义抗病毒化合物是基本上不带电荷的吗啉代寡核苷酸具有12-40个亚基的序列，包括至少12个亚基，其具有与5'末端区域的19个核苷酸区域内的病毒RNA序列相关的区域互补的靶向序列 的病毒RNA，由SEQ ID NO：1鉴定的病毒互补RNA和/或mRNA。
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公开(公告)号：US20090088562A1
公开(公告)日：2009-04-02
申请号：US11801885
申请日：2007-05-10
申请人： Dwight D. Weller , Jed N. Hassinger
发明人： Dwight D. Weller , Jed N. Hassinger
IPC分类号： C07H21/00
CPC分类号： C07H21/00 , C12N15/111 , C12N15/1131 , C12N15/1132 , C12N15/1135 , C12N15/1137 , C12N15/1138 , C12N2310/3145 , C12N2310/3233 , C12N2310/351 , C12N2310/3513 , C12N2320/51 , C12N2330/30
摘要： Morpholino oligomers containing both uncharged and cationic intersubunit linkages are provided. The oligomers are oligonucleotide analogs containing predetermined sequences of base-pairing moieties. The presence of the cationic intersubunit linkages in the oligomers, typically at a level of about 10-50% of total linkages, provides enhanced antisense activity, in various antisense applications, relative to the corresponding uncharged oligomers. 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： 提供了含有不带电荷和阳离子亚单元连接的吗啉代低聚物。 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。 低聚物中阳离子亚单位键的存在通常为总键的约10-50％，在各种反应应用中相对于相应的不带电荷的低聚物提供增强的反义活性。 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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88.发明申请Antisense antiviral compound and method for treating influenza viral infection 审中-公开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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公开(公告)号：US20050182005A1
公开(公告)日：2005-08-18
申请号：US10845057
申请日：2004-05-13
IPC分类号： A61K48/00 , C07H21/02 , C12N15/113
CPC分类号： C12N15/113 , C07H21/02 , C12N2310/11 , C12N2310/113 , C12N2310/14 , C12N2310/3145 , C12N2310/315 , C12N2310/321 , C12N2310/533 , C12N2310/3521
摘要： The invention relates to isolated anti-microRNA molecules. In another embodiment, the invention relates to an isolated microRNA molecule. In yet another embodiment, the invention provides a method for inhibiting microRNP activity in a cell.
摘要翻译： 本发明涉及分离的抗微小RNA分子。 在另一个实施方案中，本发明涉及分离的微小RNA分子。 在另一个实施方案中，本发明提供了抑制细胞中的microRNP活性的方法。
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公开(公告)号：US06784291B2
公开(公告)日：2004-08-31
申请号：US09848868
申请日：2001-05-04
申请人： Patrick L. Iversen , Robert Hudziak
发明人： Patrick L. Iversen , Robert Hudziak
IPC分类号： C07H2104
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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