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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：US07625873B2
公开(公告)日：2009-12-01
申请号：US11432216
申请日：2006-05-10
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：US20130289091A1
公开(公告)日：2013-10-31
申请号：US13680790
申请日：2012-11-19
IPC分类号： C12N15/113
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：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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公开(公告)号：US08067571B2
公开(公告)日：2011-11-29
申请号：US11803107
申请日：2007-05-11
CPC分类号： C07K7/02 , A61K48/00 , C07D295/205 , C07D413/04 , C07D473/34 , C07F9/65583 , C08F112/08 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
摘要翻译： 用于通过含磷亚基间连接连接的由吗啉代亚基组成的反义寡核苷酸的抗菌活性增强至少10倍的方法。 该方法包括以下之一或两者：将富含精氨酸的载体与寡核苷酸的3'或5'末端缀合，并修饰寡核苷酸以含有在生理pH下带正电荷的20％-50％的亚单位连接。 还公开了通过一个或两个修饰具有增强的抗菌活性的反义寡核苷酸。
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公开(公告)号：US20100234280A1
公开(公告)日：2010-09-16
申请号：US12723035
申请日：2010-03-12
CPC分类号： A61K48/00 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： An antibacterial antisense conjugate and method of using the same for treating a bacterial infection in a mammalian host are disclosed. The conjugate includes an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotide contains 10-20 nucleotide bases and has a targeting nucleic acid sequence 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, where the compound binds to a target mRNA with a Tm of between 50° to 60° C. The carrier peptide is an arginine-rich peptide containing between 6 and 12 amino acids.
摘要翻译： 公开了一种抗菌反义结合物及其用于治疗哺乳动物宿主细菌感染的方法。 缀合物包括与载体肽缀合的反义寡核苷酸，其显着增强寡核苷酸的抗菌活性。 反义寡核苷酸含有10-20个核苷酸碱基，并且具有与含有或在其下游方向的10个碱基的靶序列互补的靶向核酸序列，其编码细菌复制物必需的细菌蛋白质的细菌mRNA的翻译起始密码子 其中化合物以Tm在50℃至60℃之间的靶mRNA结合。载体肽是含有6-12个氨基酸的富含精氨酸的肽。
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公开(公告)号：US08536147B2
公开(公告)日：2013-09-17
申请号：US12723413
申请日：2010-03-12
CPC分类号： C07K7/02 , A61K48/00 , C07D295/205 , C07D413/04 , C07D473/34 , C07F9/65583 , C08F112/08 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
摘要翻译： 用于通过含磷亚基间连接连接的由吗啉代亚基组成的反义寡核苷酸的抗菌活性增强至少10倍的方法。 该方法包括以下之一或两者：将富含精氨酸的载体与寡核苷酸的3'或5'末端缀合，并修饰寡核苷酸以含有在生理pH下带正电荷的20％-50％的亚单位连接。 还公开了通过一个或两个修饰具有增强的抗菌活性的反义寡核苷酸。
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公开(公告)号：US20100234281A1
公开(公告)日：2010-09-16
申请号：US12723413
申请日：2010-03-12
CPC分类号： C07K7/02 , A61K48/00 , C07D295/205 , C07D413/04 , C07D473/34 , C07F9/65583 , C08F112/08 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
摘要翻译： 用于通过含磷亚基间连接连接的由吗啉代亚基组成的反义寡核苷酸的抗菌活性增强至少10倍的方法。 该方法包括以下之一或两者：将富含精氨酸的载体与寡核苷酸的3'或5'末端缀合，并修饰寡核苷酸以含有在生理pH下带正电荷的20％-50％的亚单位连接。 还公开了通过一个或两个修饰具有增强的抗菌活性的反义寡核苷酸。
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公开(公告)号：US20080194463A1
公开(公告)日：2008-08-14
申请号：US11803107
申请日：2007-05-11
CPC分类号： C07K7/02 , A61K48/00 , C07D295/205 , C07D413/04 , C07D473/34 , C07F9/65583 , C08F112/08 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
摘要翻译： 用于通过含磷亚基间连接连接的由吗啉代亚基组成的反义寡核苷酸的抗菌活性增强至少10倍的方法。 该方法包括以下之一或两者：将富含精氨酸的载体与寡核苷酸的3'或5'末端缀合，并修饰寡核苷酸以含有在生理pH下带正电荷的20％-50％的亚单位连接。 还公开了通过一个或两个修饰具有增强的抗菌活性的反义寡核苷酸。
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公开(公告)号：US07790694B2
公开(公告)日：2010-09-07
申请号：US11487009
申请日：2006-07-13
CPC分类号： A61K48/00 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2320/50
摘要： An antibacterial antisense conjugate and method of using the same for treating a bacterial infection in a mammalian host are disclosed. The conjugate includes an antisense oligonucleotide conjugated to a carrier peptide that significantly enhances the antibacterial activity of the oligonucleotide. The antisense oligonucleotide contains 10-20 nucleotide bases and has a targeting nucleic acid sequence 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, where the compound binds to a target mRNA with a Tm of between 50° to 60° C. The carrier peptide is an arginine-rich peptide containing between 6 and 12 amino acids.
摘要翻译： 公开了一种抗菌反义结合物及其用于治疗哺乳动物宿主细菌感染的方法。 缀合物包括与载体肽缀合的反义寡核苷酸，其显着增强寡核苷酸的抗菌活性。 反义寡核苷酸含有10-20个核苷酸碱基，并且具有与含有或在其下游方向的10个碱基的靶序列互补的靶向核酸序列，其编码细菌复制物必需的细菌蛋白质的细菌mRNA的翻译起始密码子 其中化合物以Tm在50℃至60℃之间的靶mRNA结合。载体肽是含有6-12个氨基酸的富含精氨酸的肽。
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