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公开(公告)号：US08143230B2
公开(公告)日：2012-03-27
申请号：US12299572
申请日：2007-05-07
申请人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric Swayze , Edward Wancewicz
发明人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric Swayze , Edward Wancewicz
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/3515 , C12Y203/0102 , C12N2310/3521
摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。
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公开(公告)号：US20090306005A1
公开(公告)日：2009-12-10
申请号：US12299572
申请日：2007-05-07
申请人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric Swayze , Edward Wancewicz
发明人： Sanjay Bhanot , Richard S. Geary , Robert McKay , Brett P. Monia , Punit P. Seth , Andrew M. Siwkowski , Eric Swayze , Edward Wancewicz
IPC分类号： A61K31/7088 , C07H21/00 , C12N5/02
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/3515 , C12Y203/0102 , C12N2310/3521
摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。
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公开(公告)号：US20080015162A1
公开(公告)日：2008-01-17
申请号：US11745429
申请日：2007-05-07
申请人： Sanjay Bhanot , Richard Geary , Robert McKay , Brett Monia , Punit Seth , Andrew Siwkowski , Eric Swayze , Edward Wancewicz
发明人： Sanjay Bhanot , Richard Geary , Robert McKay , Brett Monia , Punit Seth , Andrew Siwkowski , Eric Swayze , Edward Wancewicz
CPC分类号： C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/31 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/3515 , C12Y203/0102 , C12N2310/3521
摘要： The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
摘要翻译： 本公开描述了短反义化合物，包括长度为化学修饰的高亲和力单体8-16单体的这类化合物。 某些这样的短反义化合物可用于在增加的效力和改善的治疗指数的细胞，组织和动物中还原靶核酸和/或蛋白质。 因此，本文提供了包含用于在体内降低靶RNA的高亲和力核苷酸修饰的短反义化合物。 这样的短反义化合物在比以前描述的反义化合物低的剂量下是有效的，允许降低毒性和治疗成本。 此外，所述短反义化合物具有更大的口服给药潜力。
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公开(公告)号：US20060084094A1
公开(公告)日：2006-04-20
申请号：US11221001
申请日：2005-09-07
申请人： C. Bennett , Robert McKay , Brett Monia , Brenda Baker , Namir Sioufi , Richard Griffey , Balkrishen Bhat , Eric Swayze
发明人： C. Bennett , Robert McKay , Brett Monia , Brenda Baker , Namir Sioufi , Richard Griffey , Balkrishen Bhat , Eric Swayze
CPC分类号： C12N15/111 , C12N15/1137 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/323 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3515 , C12N2320/11 , C12N2320/32 , C12Y301/03048 , C12N2310/3521 , C12N2310/3525
摘要： The present invention provides methods of identifying oligomeric compounds, such as siRNA and double-stranded RNA compounds, having bioactivity in vivo, and kits.
摘要翻译： 本发明提供了鉴定体内具有生物活性的寡聚化合物如siRNA和双链RNA化合物的方法以及试剂盒。
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公开(公告)号：US20070249049A1
公开(公告)日：2007-10-25
申请号：US11627964
申请日：2007-01-27
申请人： Eric Swayze , Punit Seth
发明人： Eric Swayze , Punit Seth
摘要： The present invention provides 6-modified bicyclic nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 6-position. These bicyclicnucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.
摘要翻译： 本发明提供了包含这些核苷类似物的6-修饰的双环核苷类似物和寡聚化合物。 在优选的实施方案中，核苷类似物在6-位具有（R）或（S） - 双键。 这些双环核苷类似物可用于增强包括核酸酶抗性的寡聚化合物的性质。
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6.发明申请公开(公告)号：US20070167392A1
公开(公告)日：2007-07-19
申请号：US11565858
申请日：2006-12-01
申请人： Balkrishen Bhat , Thazha Prakash , Prasad Dande , Charles Allerson , Richard Griffey , Eric Swayze
发明人： Balkrishen Bhat , Thazha Prakash , Prasad Dande , Charles Allerson , Richard Griffey , Eric Swayze
IPC分类号： A61K48/00 , C07H21/02 , C07F9/6512
CPC分类号： C12N15/113 , C07H21/02 , C12N15/111 , C12N2310/14 , C12N2310/315 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/3231 , C12N2310/341 , C12N2310/346 , C12N2320/30 , C12N2320/51 , C12N2310/3521
摘要： The present invention provides double stranded compositions wherein each strand is modified to have a motif defined by positioning of β-D-ribonucleosides and sugar modified nucleosides. More particularly, the present compositions comprise one strand having a gapped motif and another strand having a gapped motif, a hemimer motif, a blockmer motif, a fully modified motif, a positionally modified motif or an alternating motif. At least one of the strands has complementarity to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In some embodiments, the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
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公开(公告)号：US20060030603A1
公开(公告)日：2006-02-09
申请号：US10913683
申请日：2004-08-05
申请人： Punit Seth , Dale Robinson , Elizabeth Jefferson , Eric Swayze
发明人： Punit Seth , Dale Robinson , Elizabeth Jefferson , Eric Swayze
IPC分类号： A61K31/44 , A61K31/17 , C07D213/54 , C07C335/12
CPC分类号： C07C275/34 , C07C275/30 , C07C335/16 , C07D207/34 , C07D213/38 , C07D213/61 , C07D307/56
摘要： Antibacterial compounds are described herein having either formula (I) or formula (II): wherein R1A, R1B, R1C, R1D, X, Z, Q, R2A, R2B, R2C and R2D are as defined herein. Compositions comprising compounds of formulas (I) and (II) are also provided.
摘要翻译： 本文描述了具有式（I）或式（II）的抗菌化合物：其中R 1A，R 1B，R 1C，R“ X，Z，Q，R 2A，R 2B，R 2C和R 2D， / SUB>如本文所定义。 还提供了包含式（I）和（II）化合物的组合物。
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8.发明申请公开(公告)号：US20050118605A9
公开(公告)日：2005-06-02
申请号：US10700884
申请日：2003-11-04
申请人： Brenda Baker , Anne Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric Swayze , Stanley Crooke , Thazha Prakash , Kallanthottathil Rajeev
发明人： Brenda Baker , Anne Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric Swayze , Stanley Crooke , Thazha Prakash , Kallanthottathil Rajeev
CPC分类号： C12N15/111 , C12N15/113 , C12N2310/14 , C12N2310/333 , C12N2310/336 , C12N2320/50
摘要： Oligomer compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capble of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers has a modified base for binding to an adenine or guanine base in the opposite strand. Oligonucleotide/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein the oligomer has a modified base for binding to an adenine or guanine base in the opposite strand.
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公开(公告)号：US20050053976A1
公开(公告)日：2005-03-10
申请号：US10859825
申请日：2004-06-03
申请人： Brenda Baker , Anne Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric Swayze , Stanley Crooke
发明人： Brenda Baker , Anne Eldrup , Muthiah Manoharan , Balkrishen Bhat , Richard Griffey , Eric Swayze , Stanley Crooke
CPC分类号： A61K31/713
摘要： Oligomer compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capble of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes at least one nucleotide comprising a chimeric organic composition. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide comprising a chimeric organic composition.
摘要翻译： 提供包含第一和第二寡聚物的低聚物组合物，其中至少一部分第一寡聚体能够与至少一部分第二寡聚物杂交，至少一部分第一寡聚体与所选择的寡核苷酸杂交互补和杂交 靶核酸，并且所述第一或第二寡聚体中的至少一个包含至少一个包含嵌合有机组合物的核苷酸。 还提供寡聚物/蛋白质组合物，其包含与选定的靶核酸互补并且能够与选定的靶核酸杂交的寡聚体和至少一种包含至少一部分RNA诱导的沉默复合物（RISC）的蛋白质，其中至少一个核苷酸包含 嵌合有机组合物。
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公开(公告)号：US06253168B1
公开(公告)日：2001-06-26
申请号：US09076405
申请日：1998-05-12
申请人： Richard Griffey , Eric Swayze
发明人： Richard Griffey , Eric Swayze
IPC分类号： G06G748
CPC分类号： G06F19/709 , C40B50/02
摘要： The present invention provides methods for the generation of virtual libraries of compounds. These compounds are generated in silico. The present invention encompasses methods for tracking the addition of fragments, use of reagents, and transformations performed. Further, methods for interfacing the information necessary to generate libraries of compounds with instrumentation that conducts the actual synthesis of the compounds are provided. Also provided are methods for the in silico docking of the library compounds to identified target molecules of interest.
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