公开(公告)号：US09045754B2

公开(公告)日：2015-06-02

申请号：US11745429

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 E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： C12N15/113

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。

公开(公告)号：US20090306179A1

公开(公告)日：2009-12-10

申请号：US12299609

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 E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： A61K31/7052 ,  C07H21/00 ,  C12N5/00 ,  A61P3/00

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。

公开(公告)号：US20090292006A1

公开(公告)日：2009-11-26

申请号：US12299605

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 E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： A61K48/00 ,  C07H21/04 ,  C12N5/06

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。

公开(公告)号：US06221850B1

公开(公告)日：2001-04-24

申请号：US09130616

申请日：1998-08-07

申请人： Robert McKay ,  Nicholas Dean ,  Brett P. Monia ,  Pamela Scott Nero ,  William A. Gaarde

发明人： Robert McKay ,  Nicholas Dean ,  Brett P. Monia ,  Pamela Scott Nero ,  William A. Gaarde

IPC分类号： A61K4800

CPC分类号： C12N15/1137 ,  C07H21/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/334 ,  C12N2310/3515 ,  C12Q1/6886 ,  C12Q2600/158

摘要： Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. The invention is thus directed to compositions for modulating, diagnostic methods for detecting, and therapeutic methods for inhibiting, the hyperproliferation of cells and formation, development and maintenance of tumors.

摘要翻译： 提供了通过调节编码JunN末端激酶（JNK蛋白）的基因的表达进行治疗的疾病或病症的治疗和诊断的组合物和方法。 本文提供了与编码JNK1，JNK2和JNK3的核酸以及其它JNK蛋白及其特异性同种型特异性杂交的寡核苷酸。 还提供了通过用这种寡核苷酸调节一种或多种JNK蛋白质的表达来治疗患有治疗性干预的疾病或障碍的动物的方法。 还提供了用于治疗和诊断与一种或多种JNK蛋白异常表达相关的疾病或病症的方法。 因此，本发明涉及用于调节，用于检测和用于抑制细胞过度增殖以及形成，发育和维持肿瘤的方法的治疗方法的组合物。

公开(公告)号：US08853178B2

公开(公告)日：2014-10-07

申请号：US13177462

申请日：2011-07-06

申请人： Sanjay Bhanot ,  Lex M. Cowsert ,  Jacqueline R. Wyatt ,  Brett P. Monia ,  Madelline M. Butler ,  Robert McKay ,  Susan M. Freier ,  Kenneth W. Dobie

发明人： Sanjay Bhanot ,  Lex M. Cowsert ,  Jacqueline R. Wyatt ,  Brett P. Monia ,  Madelline M. Butler ,  Robert McKay ,  Susan M. Freier ,  Kenneth W. Dobie

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/345 ,  C12N2310/346 ,  C12Y301/03048 ,  Y02P20/582 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the expression of PTP1B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTP1B. Methods of using these compounds for modulation of PTP1B expression and for treatment of diseases associated with expression of PTP1B are provided.

摘要翻译： 提供化合物，组合物和方法用于调节PTP1B的表达。 组合物包含靶向编码PTP1B的核酸的反义化合物，特别是反义寡核苷酸。 提供了使用这些化合物调节PTP1B表达和治疗与PTP1B表达相关的疾病的方法。

公开(公告)号：US08673871B2

公开(公告)日：2014-03-18

申请号：US12299764

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 E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： A61K31/70 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/68

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。

公开(公告)号：US08586554B2

公开(公告)日：2013-11-19

申请号：US12299607

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 E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： C12N15/11

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。

公开(公告)号：US08362232B2

公开(公告)日：2013-01-29

申请号：US12883049

申请日：2010-09-15

申请人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

发明人： Sanjay Bhanot ,  Richard S. Geary ,  Robert McKay ,  Brett P. Monia ,  Punit P. Seth ,  Andrew M. Siwkowski ,  Eric E. Swayze ,  Edward Wancewicz

IPC分类号： C07H21/04

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。

公开(公告)号：US08299041B2

公开(公告)日：2012-10-30

申请号：US11910606

申请日：2006-04-10

申请人： Sanjay Bhanot ,  Brett P. Monia ,  John G. Geisler ,  Robert McKay ,  Kenneth W. Dobie

发明人： Sanjay Bhanot ,  Brett P. Monia ,  John G. Geisler ,  Robert McKay ,  Kenneth W. Dobie

IPC分类号： A61K48/00

CPC分类号： C12N15/1137 ,  A61K31/202 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3521

摘要： Disclosed herein are compounds, compositions and methods for modulating the expression of ACC1 or ACC2 or both in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

摘要翻译： 本文公开了用于在细胞，组织或动物中调节ACC1或ACC2或两者的表达的化合物，组合物和方法。 还提供了所公开的化合物和组合物在制备用于治疗疾病和病症的药物中的用途。

公开(公告)号：US06448079B1

公开(公告)日：2002-09-10

申请号：US09640101

申请日：2000-08-15

申请人： Brett P. Monia ,  William A. Gaarde ,  Pamela Nero ,  Robert McKay

发明人： Brett P. Monia ,  William A. Gaarde ,  Pamela Nero ,  Robert McKay

IPC分类号： C07H2104

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Y207/11024 ,  Y02P20/582 ,  C12N2310/3525

摘要： Compositions and methods for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of expression of a gene encoding a p38 mitogen-activated protein kinase (p38 MAPK) are provided. Methods for the treatment and diagnosis of diseases or conditions associated with aberrant expression of one or more p38 MAPKs are also provided.

摘要翻译： 提供了用于治疗和诊断适于通过调节编码p38丝裂原活化蛋白激酶（p38MAPK）的基因的表达进行治疗的疾病或病症的组合物和方法。 还提供了用于治疗和诊断与一种或多种p38 MAPK的异常表达相关的疾病或病症的方法。