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：US20070037763A1

公开(公告)日：2007-02-15

申请号：US11432155

申请日：2006-05-10

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

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

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07F9/6512

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：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：US20060269911A1

公开(公告)日：2006-11-30

申请号：US11432031

申请日：2006-05-10

申请人： Patrick Iversen ,  David Stein ,  Dwight Weller

发明人： Patrick Iversen ,  David Stein ,  Dwight Weller

IPC分类号： C12Q1/70 ,  C12Q1/68

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, Picomoviridae, 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 1240 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病毒感染的治疗中抑制黄病毒科，Picomoviridae，Caliciviridae，Togaviridae，Arteriviridae，Coronaviridae，Astroviridae和Hepeviridae家族病毒生长的方法。 反义抗病毒化合物是具有1240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，其具有与阳性的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RNA链。

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。

公开(公告)号：US20060293268A1

公开(公告)日：2006-12-28

申请号：US11418904

申请日：2006-05-04

申请人： Aida Rieder ,  David Stein ,  Ariel Vagnozzi ,  Dwight Weller ,  Patrick Iversen

发明人： Aida Rieder ,  David Stein ,  Ariel Vagnozzi ,  Dwight Weller ,  Patrick Iversen

IPC分类号： A61K48/00 ,  C07F9/6533

CPC分类号： C12N15/1131 ,  C12N2310/11 ,  C12N2310/3233 ,  C12N2310/3513

摘要： An antiviral antisense composition and method for treating foot-and-mouth disease virus (FMDV) in veterinary animals is disclosed. The composition contains an antisense compound that has a sequence effective to target at least 12 contiguous bases of an FMDV RNA sequence within a region of the positive-strand genomic RNA defined by SEQ ID NO: 25, and preferably, one of the viral sequences within SEQ ID NO:25 identified by SEQ ID NOS: 26-28. The composition is administered in a therapeutically effective amount in treating FMDV.

摘要翻译： 公开了用于在兽医中治疗口蹄疫病毒（FMDV）的抗病毒反义组合物和方法。 该组合物含有反义化合物，该反义化合物具有有效靶向SEQ ID NO：25所定义的正链基因组RNA区域内的FMDV RNA序列的至少12个连续碱基的序列，优选其中一个病毒序列 由SEQ ID NO：26-28鉴定的SEQ ID NO：25。 组合物以治疗有效量施用于治疗FMDV。

公开(公告)号：US20060287268A1

公开(公告)日：2006-12-21

申请号：US11433214

申请日：2006-05-11

申请人： Patrick Iversen ,  Robert Hudziak ,  Dwight Weller

发明人： Patrick Iversen ,  Robert Hudziak ,  Dwight Weller

IPC分类号： A61K48/00 ,  A61K31/675 ,  C07F9/6533

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 a phosphorodiamidate-linked morpholino oligonucleotide containing uncharged phosphorodiamidate linkages interspersed with cationic phosphorodiamidate linkages. 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，是含有分散有阳离子磷酰二胺键的不带电荷的磷酰二胺键的磷酰二亚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。