公开(公告)号：US20060281701A1

公开(公告)日：2006-12-14

申请号：US11433840

申请日：2006-05-11

申请人： David Stein ,  Patrick Iversen ,  Sina Bavari ,  Dwight Weller

发明人： David Stein ,  Patrick Iversen ,  Sina Bavari ,  Dwight Weller

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07F9/6533

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.

公开(公告)号：US20060205693A1

公开(公告)日：2006-09-14

申请号：US11264444

申请日：2005-10-31

申请人： David Stein ,  Patrick Iversen ,  Sina Bavari

发明人： David Stein ,  Patrick Iversen ,  Sina Bavari

IPC分类号： A61K48/00

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 substantially uncharged 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 antisense compounds SEQ ID NO:21-26, ii) the AUG start site region of VP24, as exemplified by antisense compound SEQ ID NO:34, iii) the region 85 to 65 base pairs upstream of the AUG start site of VP24, as exemplified by SEQ ID NO:39, iv) the AUG start site region of polymerase L, as exemplified by antisense compound SEQ ID NO: 17, and v) combinations of (i), (ii), (iii), and/or (iv).

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基本上不带电荷的吗啉代寡核苷酸，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，如反义化合物SEQ ID NO：21-26所示，ii）VP24的AUG起始位点区域，如反义化合物SEQ ID NO：34所示，iii）区域85至 VP24的AUG起始位点上游65个碱基对，如SEQ ID NO：39所示，iv）聚合酶L的AUG起始位点区域，如反义化合物SEQ ID NO：17所示，v）（i ），（ii），（iii）和/或（iv）。

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。

公开(公告)号：US20060148747A1

公开(公告)日：2006-07-06

申请号：US11259434

申请日：2005-10-25

申请人： David Stein ,  Qing Ge ,  Jianzhu Chen ,  Patrick Iversen

发明人： David Stein ,  Qing Ge ,  Jianzhu Chen ,  Patrick Iversen

IPC分类号： A61K48/00 ,  C07F9/6533 ,  C07H21/02

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基本上不带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）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。

公开(公告)号：US20060063150A1

公开(公告)日：2006-03-23

申请号：US11226995

申请日：2005-09-14

申请人： Patrick Iversen ,  David Stein

发明人： Patrick Iversen ,  David Stein

IPC分类号： C12Q1/70 ,  G06F19/00 ,  C12P19/34 ,  A61K48/00

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。

公开(公告)号：US20070274957A1

公开(公告)日：2007-11-29

申请号：US11715572

申请日：2007-03-07

申请人： Benjamin Neuman ,  David Stein ,  Michael Buchmeier ,  Patrick Iversen

发明人： Benjamin Neuman ,  David Stein ,  Michael Buchmeier ,  Patrick Iversen

IPC分类号： A61K48/00

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。

公开(公告)号：US20050171044A1

公开(公告)日：2005-08-04

申请号：US11022358

申请日：2004-12-22

申请人： David Stein ,  Richard Bestwick ,  Patrick Iversen ,  Benjamin Neuman ,  Michael Buchmeier

发明人： David Stein ,  Richard Bestwick ,  Patrick Iversen ,  Benjamin Neuman ,  Michael Buchmeier

IPC分类号： A61K48/00 ,  C07F9/6533 ,  C07H21/02 ,  C07K14/165 ,  C12N15/113

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。

公开(公告)号：US20070265214A1

公开(公告)日：2007-11-15

申请号：US11431968

申请日：2006-05-10

申请人： David Stein ,  Douglas Skilling ,  Patrick Iversen ,  Alvin Smith ,  Dwight Weller

发明人： David Stein ,  Douglas Skilling ,  Patrick Iversen ,  Alvin Smith ,  Dwight Weller

IPC分类号： A61K31/675

CPC分类号： A61K31/675

摘要： The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds have morpholino subunits linked by uncharged phosphorodiamidate linkages interspersed with cationic phosphorodiamidate linkages.

摘要翻译： 本发明提供反义抗病毒化合物及其用于抑制微小核糖核酸病毒，杯状病毒，披膜病毒和黄病毒家族病毒生长的方法，如治疗病毒感染。 反义抗病毒化合物具有通过分散有阳离子磷酰二胺键的不带电的磷酰二胺键连接的吗啉亚基。

公开(公告)号：US20070129323A1

公开(公告)日：2007-06-07

申请号：US11518058

申请日：2006-09-08

申请人： David Stein ,  Cornelis Rijnbrand ,  Patrick Iversen ,  Dwight Weller

发明人： David Stein ,  Cornelis Rijnbrand ,  Patrick Iversen ,  Dwight Weller

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07F9/6533

CPC分类号： C12N15/1131 ,  C12N2310/11 ,  C12N2310/3145 ,  C12N2310/3233 ,  C12N2310/3513 ,  C12N2770/32311 ,  C12N2770/32711

摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Picornaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Enterovirus and/or Rhinovirus infection in a mammal. The antisense antiviral compounds are substantially uncharged, including partially positively charged, 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 32 nucleotide region of the viral 5′ untranslated region identified by SEQ ID NO:4.

摘要翻译： 本发明提供反义抗病毒化合物及其在抑制小核糖核酸病毒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。 所述化合物特别可用于治疗哺乳动物中的肠病毒和/或鼻病毒感染。 反义抗病毒化合物是基本上不带电的，包括部分带正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，其具有与与32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 由SEQ ID NO：4鉴定的病毒5'非翻译区。

公开(公告)号：US20070066556A1

公开(公告)日：2007-03-22

申请号：US11517757

申请日：2006-09-08

申请人： David Stein ,  Richard Bestwick ,  Patrick Iversen ,  Dwight Weller

发明人： David Stein ,  Richard Bestwick ,  Patrick Iversen ,  Dwight Weller

IPC分类号： A61K48/00 ,  C07F9/6533

CPC分类号： A61K38/00 ,  C12N15/1131 ,  C12N2310/11 ,  C12N2310/314 ,  C12N2310/3233 ,  C12N2770/32311 ,  C12N2770/32711

摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Picornaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Enterovirus and/or Rhinovirus 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 32 nucleotide region of the viral 5′ untranslated region identified by SEQ ID NO:7.

摘要翻译： 本发明提供反义抗病毒化合物及其在抑制小核糖核酸病毒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。 所述化合物特别可用于治疗哺乳动物中的肠病毒和/或鼻病毒感染。 反义抗病毒化合物基本上不带电，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，其具有与病毒5'非翻译的32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 由SEQ ID NO：7鉴定的区域。