公开(公告)号：US20150184164A1

公开(公告)日：2015-07-02

申请号：US14561080

申请日：2014-12-04

申请人： ISIS PHARMACEUTICALS, INC.

发明人： Sanjay Bhanot ,  Xing-Xian Yu ,  Michael L. McCaleb

IPC分类号： C12N15/113 ,  A61K31/713

CPC分类号： C12N15/1138 ,  A61K31/711 ,  A61K31/713 ,  A61K45/06 ,  C07H21/04 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/323 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525

摘要： Provided herein are methods, compounds, and compositions for reducing expression of fibroblast growth factor receptor 4 (FGFR4) mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a metabolic disease, or a symptom thereof.

摘要翻译： 本文提供了用于在动物中减少成纤维细胞生长因子受体4（FGFR4）mRNA和蛋白质的表达的方法，化合物和组合物。 这些方法，化合物和组合物可用于治疗，预防，延缓或改善代谢疾病或其症状。

公开(公告)号：US20130281509A1

公开(公告)日：2013-10-24

申请号：US13631437

申请日：2012-09-28

申请人： Isis Pharmaceuticals, Inc.

发明人： Sanjay Bhanot ,  Xing Xian Yu ,  Michael L. McCaleb

IPC分类号： C07H21/04 ,  A61K45/06 ,  A61K31/711

CPC分类号： C12N15/1138 ,  A61K31/711 ,  A61K31/713 ,  A61K45/06 ,  C07H21/04 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/323 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525

摘要： Provided herein are methods, compounds, and compositions for reducing expression of fibroblast growth factor receptor 4 (FGFR4) mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a metabolic disease, or a symptom thereof.

公开(公告)号：US20130165496A1

公开(公告)日：2013-06-27

申请号：US13662263

申请日：2012-10-26

申请人： Isis Pharmaceuticals, Inc.

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.

公开(公告)号：US20130150425A1

公开(公告)日：2013-06-13

申请号：US13660885

申请日：2012-10-25

申请人： Isis Pharmaceuticals, Inc.

发明人： Susan M. Freier ,  Sanjay Bhanot

IPC分类号： C12N15/113 ,  A61K45/06 ,  A61K31/7088

CPC分类号： C12N15/1138 ,  A61K31/7088 ,  A61K31/7115 ,  A61K31/712 ,  A61K31/7125 ,  A61K45/06 ,  C07H21/04 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525 ,  C12N2310/3521

摘要： Provided herein are methods, compounds, and compositions for reducing expression of GCCR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

公开(公告)号：US08969316B2

公开(公告)日：2015-03-03

申请号：US13662263

申请日：2012-10-26

申请人： Isis Pharmaceuticals, Inc.

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： C07H21/02 ,  C07H21/04 ,  A61K31/70 ,  C12N15/113 ,  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：US20140275207A1

公开(公告)日：2014-09-18

申请号：US13804846

申请日：2013-03-14

申请人： ISIS PHARMACEUTICALS, INC.

发明人： Sanjay K. Pandey ,  Robert McKay ,  Sanjay Bhanot ,  Xing-Xian Yu

IPC分类号： C07H21/00

CPC分类号： C12N15/1137 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/533 ,  C12Y301/03048 ,  C12N2310/321 ,  C12N2310/3525

摘要： Disclosed herein are compounds, compositions and methods for modulating the expression of LMW-PTPase in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Also provided are methods for the prevention, amelioration and/or treatment of diabetes, insulin resistance, insulin deficiency, hypercholesterolemia, hyperglycemia, dyslipidemia, hyperlipidemia, hypertriglyceridemia, and hyperfattyacidemia. In some embodiments, the diabetes is type II diabetes by administration of antisense compounds targeted to LMW-PTPase.

摘要翻译： 本文公开了用于调节细胞，组织或动物中LMW-PTPase表达的化合物，组合物和方法。 还提供了目标验证的方法。 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。 还提供了用于预防，改善和/或治疗糖尿病，胰岛素抵抗，胰岛素缺乏，高胆固醇血症，高血糖，血脂异常，高脂血症，高甘油三酯血症和高脂肪酸血症的方法。 在一些实施方案中，通过施用靶向LMW-PTPase的反义化合物，糖尿病是II型糖尿病。

公开(公告)号：US20130143943A1

公开(公告)日：2013-06-06

申请号：US13650801

申请日：2012-10-12

申请人： Isis Pharmaceuticals, Inc.

发明人： Sanjay Bhanot ,  Susan M. Freier ,  Kenneth W. Dobie

IPC分类号： C07H21/04

CPC分类号： C07H21/04 ,  A61K38/00 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  C12N2310/3525

摘要： Compounds, compositions and methods are provided for modulating the expression of glucocorticoid receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucocorticoid receptor. Methods of using these compounds for modulation of glucocorticoid receptor expression and for diagnosis and treatment of diseases and conditions associated with expression of glucocorticoid receptor are provided.

摘要翻译： 提供化合物，组合物和方法用于调节糖皮质激素受体的表达。 组合物包含靶向编码糖皮质激素受体的核酸的寡核苷酸。 提供了使用这些化合物调节糖皮质激素受体表达和诊断和治疗与糖皮质激素受体表达相关的疾病和病症的方法。

公开(公告)号：US20130116301A1

公开(公告)日：2013-05-09

申请号：US13623337

申请日：2012-09-20

申请人： Isis Pharmaceuticals, Inc.

发明人： Susan M. Freier ,  Sanjay Bhanot

IPC分类号： C12N15/113

CPC分类号： C12N15/1138 ,  A61K31/711 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/3525

摘要： Provided herein are methods, compounds, and compositions for reducing expression of GCGR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

公开(公告)号：US20150167005A1

公开(公告)日：2015-06-18

申请号：US14539831

申请日：2014-11-12

申请人： ISIS PHARMACEUTICALS, INC.

发明人： Susan M. Freier ,  Rosanne M. Crooke ,  Mark J. Graham ,  Kristina M. Lemonidis ,  Sanjay Bhanot ,  Diane Tribble ,  Andrew T. Watt

IPC分类号： C12N15/113

CPC分类号： C12N15/1137 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/321 ,  C12N2310/351 ,  C12N2320/30

摘要： Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.

公开(公告)号：US08912160B2

公开(公告)日：2014-12-16

申请号：US14152825

申请日：2014-01-10

申请人： Isis Pharmaceuticals, Inc.

发明人： Susan M. Freier ,  Rosanne M. Crooke ,  Mark J. Graham ,  Kristina M. Lemonidis ,  Sanjay Bhanot ,  Andrew T. Watt ,  Diane Tribble

IPC分类号： C12N15/11 ,  A61K48/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/1137 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/321 ,  C12N2310/351 ,  C12N2320/30

摘要： Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.