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91.发明授权Antisense antiviral compound and method for treating influenza viral infection 有权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。
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92.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：US20130011420A1
公开(公告)日：2013-01-10
申请号：US13469892
申请日：2012-05-11
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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93.发明申请ANTISENSE ANTIVIRAL COMPOUND AND METHOD FOR TREATING INFLUENZA VIRAL INFECTION 有权抗真菌化合物和治疗流感病毒感染的方法公开(公告)号：US20110118334A1
公开(公告)日：2011-05-19
申请号：US12945081
申请日：2010-11-12
申请人： Patrick L. Iversen
发明人： Patrick L. Iversen
IPC分类号： A61K31/7052 , C07H21/00 , C12N7/06 , A61P31/12
CPC分类号： C07F9/65616 , A61K31/165 , A61K31/43 , A61K31/5377 , A61K31/545 , A61K31/7056 , A61K38/08 , A61K38/10 , C07K7/06 , C07K7/08 , C12N15/113 , C12N15/1131 , C12N2310/11 , C12N2310/315 , C12N2310/3181 , C12N2310/321 , C12N2310/3231 , C12N2310/3233 , C12N2310/3513 , C12N2310/3521
摘要： The present invention relates to 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. Exemplary antisense antiviral compounds are substantially uncharged, or 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 30 bases of the 5′ or 3′ terminus of the positive sense vcRNA; c) the 45 bases surrounding the AUG start codon of an influenza viral mRNA and; d) 50 bases surrounding the splice donor or acceptor sites of influenza mRNAs subject to alternative splicing.
摘要翻译： 本发明涉及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。 示例性的反义抗病毒化合物是基本上不带电荷或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）阳性vcRNA的5'或3'末端的末端30个碱基; c）流感病毒mRNA的AUG起始密码子周围的45个碱基; d）围绕可变剪接的流感mRNA的剪接供体或受体位点周围的50个碱基。
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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：US07754238B2
公开(公告)日：2010-07-13
申请号：US10190419
申请日：2002-07-02
CPC分类号： A61K9/167 , A61K31/00 , A61K31/337 , A61K31/4353 , A61K31/436 , A61K31/7088 , A61K47/6925
摘要： Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, an angioplasty procedure and/or stent implantation. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, an antisense oligonucleotide, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury.
摘要翻译： 给予包含与微粒载体缀合的抗再狭窄化合物的制剂有效地抑制血管中的狭窄形成。 这种狭窄通常在没有治疗的情况下导致对血管的创伤，例如切口，过度压力，血管成形术程序和/或支架植入。 抗再狭窄化合物通常是抗增殖，免疫抑制或抗炎药物，例如雷帕霉素，他克莫司，紫杉醇，地塞米松或活性类似物或衍生物，反义寡核苷酸或其组合。 微粒载体包含气体填充的微泡或生物相容的聚合物微粒的悬浮液，在药学上可接受的液体载体中，并且有效地将缀合的治疗剂递送到血管损伤部位。
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98.发明申请公开(公告)号：US20100074927A1
公开(公告)日：2010-03-25
申请号：US12561991
申请日：2009-09-17
IPC分类号： A61K9/00 , A61K33/24 , A61K31/7048 , A61K31/704 , A61K31/7068 , A61K31/675 , A61K31/519 , A61K31/505 , A61K31/436 , A61K31/4375 , A61K31/4745 , A61K31/337 , A61K31/282 , A61K31/166 , A61K31/138 , A61P35/00
CPC分类号： A61K9/0019 , A61K9/167 , A61K31/337 , A61K31/436 , A61K31/7088 , A61K47/6925
摘要： Microparticle carriers, particularly protein-encapsulated microbubbles, are used to deliver antiproliferative drugs to target sites in a subject. In particular, antirestenotic drugs are delivered to areas of vascular injury for treatment or prevention of hyperproliferative disease, e.g. stenosis, in blood vessels; and antineoplastic drugs are targeted to tumor sites.
摘要翻译： 微粒载体，特别是蛋白质包封的微泡，用于将抗增生药物递送至受试者的靶位点。 特别地，抗再狭窄药物被递送到血管损伤的区域以用于治疗或预防过度增殖性疾病，例如， 血管狭窄; 抗肿瘤药物靶向肿瘤部位。
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99.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：US20090186848A1
公开(公告)日：2009-07-23
申请号：US12402461
申请日：2009-03-11
IPC分类号： A61K31/7088
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.
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