公开(公告)号：US09382540B2

公开(公告)日：2016-07-05

申请号：US14701999

申请日：2015-05-01

申请人： Isis Pharmaceuticals, Inc.

发明人： Thazha P. Prakash ,  Punit P. Seth ,  Eric E. Swayze ,  Susan M. Freier ,  Mark J. Graham ,  Rosanne M. Crooke

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12N15/113

CPC分类号： C07H19/20 ,  C07H15/04 ,  C07H21/02 ,  C07H21/04 ,  C12N15/1136 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/32 ,  C12N2310/3525 ,  C12N2310/3231

摘要： Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.

摘要翻译： 本文提供了用于减少动物中ANGPTL3 mRNA和蛋白质表达的方法，化合物和组合物。 本文还提供了用于还原动物体内脂质和/或葡萄糖的方法，化合物和组合物。 这样的方法，化合物和组合物可用于治疗，预防，延迟或改善有需要的个体的任何一种或多种心血管疾病和/或代谢疾病或其症状。

公开(公告)号：US20160090595A1

公开(公告)日：2016-03-31

申请号：US14839521

申请日：2015-08-28

申请人： ISIS PHARMACEUTICALS, INC.

发明人： Thazha P. Prakash ,  Punit P. Seth ,  Eric E. Swayze ,  Mark J. Graham

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  A61K31/7088 ,  A61K31/713 ,  A61K47/549 ,  C07H21/04 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/17 ,  C12N2310/31 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3511 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2310/353 ,  C12N2320/32 ,  C12N2310/3525

摘要： Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

摘要翻译： 本文提供了具有靶向apoplipoprotein C-III（ApoCIII）的缀合物的寡聚化合物。 在某些实施方案中，ApoCIII靶向寡聚化合物与N-乙酰半乳糖胺缀合。本文还公开了靶向ApoCIII的共轭寡聚化合物，用于降低ApoCIII以治疗，预防或改善与ApoCIII相关的疾病，病症或病症。 与ApoCIII有关的某些疾病，病症或病症包括炎性，心血管和/或代谢疾病，病症或病症。 本文公开的共轭低聚化合物可用于治疗有需要的个体中的这些疾病，病症或病症。

公开(公告)号：US20160068846A1

公开(公告)日：2016-03-10

申请号：US14854281

申请日：2015-09-15

申请人： ISIS Pharmaceuticals Inc.

发明人： Robert A. Macleod ,  Youngsoo Kim ,  Tianyuan Zhou ,  Susan M. Freier ,  Punit Seth ,  Eric Swayze ,  Brett Monia

IPC分类号： C12N15/113

CPC分类号： C12N15/1138 ,  A61K31/4166 ,  A61K31/7088 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/30 ,  C12N2310/3525

摘要： Certain embodiments are directed to compounds and compositions targeted to human androgen receptor (AR) for inhibiting androgen receptor levels in a cell, which can be useful for methods of treating cancer and inhibiting cancer cell growth or proliferation.

摘要翻译： 某些实施方案涉及靶向人雄激素受体（AR）的化合物和组合物，用于抑制细胞中的雄激素受体水平，其可用于治疗癌症和抑制癌细胞生长或增殖的方法。

公开(公告)号：US20160060626A1

公开(公告)日：2016-03-03

申请号：US14821982

申请日：2015-08-10

申请人： ISIS PHARMACEUTICALS, INC.

发明人： Rosanne M. Crooke ,  Mark J. Graham ,  Richard Lee ,  Kenneth W. Dobie

IPC分类号： C12N15/113 ,  C12Q1/68

CPC分类号： C12N15/113 ,  C12N15/1136 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2320/30 ,  C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5023 ,  C12N2310/3521

摘要： Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof.

公开(公告)号：US20160060625A1

公开(公告)日：2016-03-03

申请号：US14821641

申请日：2015-08-07

申请人： ISIS PHARMACEUTICALS, INC.

发明人： Adam Mullick ,  Rosanne M. Crooke ,  Mark J. Graham ,  Kenneth W. Dobie ,  Thomas A. Bell, III ,  Richard Lee

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  A61K31/7088 ,  A61K31/713 ,  A61K45/06 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  A61K2300/00

摘要： Provided herein are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for increasing HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disorder, or a symptom thereof.

摘要翻译： 本文提供了用于在动物中降低ApoCIII mRNA和蛋白质表达的方法，化合物和组合物。 本文还提供了用于增加HDL水平和/或改善动物体内TG与HDL的比例以及降低血浆脂质和血浆葡萄糖的方法，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，延迟或改善心血管疾病或代谢紊乱或其症状中的任何一种或多种。

公开(公告)号：US09243291B1

公开(公告)日：2016-01-26

申请号：US13692968

申请日：2012-12-03

申请人： Isis Pharmaceuticals, Inc.

发明人： Sebastien Burel

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6876 ,  C12Q2600/136 ,  C12Q2600/142 ,  C12Q2600/158 ,  C12Q2600/16

摘要： Described herein are compounds useful for the treatment and investigation of diseases, methods for the prediction of in vivo toxicity of compounds useful for the treatment and investigation of diseases, and methods of discovering and identifying compounds useful for the treatment and investigation of diseases that have reduced in vivo toxicity.

摘要翻译： 本文描述了可用于疾病治疗和调查的化合物，用于预测用于治疗和调查疾病的化合物的体内毒性的方法，以及发现和鉴定可用于治疗和调查已经减少的疾病的化合物的方法 体内毒性。

公开(公告)号：US20150376623A1

公开(公告)日：2015-12-31

申请号：US14753860

申请日：2015-06-29

申请人： EXCALIARD PHARMACEUTICALS, INC. ,  ISIS PHARMACEUTICALS, INC.

发明人： Nicholas M. Dean ,  J. Gordon Foulkes ,  Niall O'Donnell ,  C. Frank Bennett ,  Susan M. Freier

IPC分类号： C12N15/113

CPC分类号： C12N15/1136 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/30 ,  C12N2310/3521

摘要： This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds.

摘要翻译： 本发明提供了包含能够抑制表达结缔组织因子的修饰寡核苷酸和含有其的组合物的化合物，以及治疗过度放射性疾病和纤维化疾病的方法，以及使用这些化合物减少伤口愈合引起的瘢痕形成。

公开(公告)号：US09221864B2

公开(公告)日：2015-12-29

申请号：US14391264

申请日：2013-03-20

申请人： Isis Pharmaceuticals, Inc.

发明人： Punit P. Seth ,  Eric E. Swayze ,  Stephen Hanessian ,  Benjamin R. Schroeder ,  Robert D. Giacometti ,  Bradley L. Merner

IPC分类号： C07H21/00 ,  C07H19/04 ,  C07H19/06

CPC分类号： C07H19/06 ,  C07H19/04 ,  C07H21/00

摘要： The present disclosure provides tricyclic nucleosides and oligomeric compounds prepared therefrom. The tricyclic nucleosides each have a tricyclic ribosyl sugar moiety wherein a bridge between the 2′ and 4′ ribosyl ring carbon atoms further comprises a fused carbocyclic or heterocyclic ring. The tricyclic nucleosides are expected to be useful for enhancing properties of oligomeric compounds including for example binding affinity and nuclease resistance.

摘要翻译： 本公开提供由其制备的三环核苷和寡聚化合物。 三环核苷各自具有三环核糖糖部分，其中2'和4'核糖基环碳原子之间的桥连还包含稠合的碳环或杂环。 预期三环核苷可用于增强低聚化合物的性质，包括结合亲和力和核酸酶抗性。

公开(公告)号：US20150353929A1

公开(公告)日：2015-12-10

申请号：US14584112

申请日：2014-12-29

申请人： Isis Pharmaceuticals, Inc. ,  Cold Spring Harbor Laboratory

发明人： Brenda F. Baker ,  Adrian R. Krainer ,  Yimin Hua

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2320/33 ,  C12N2310/3525

摘要： Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA 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, including spinal muscular atrophy.

摘要翻译： 本文公开了用于调节细胞，组织或动物中SMN2mRNA的剪接的化合物，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（包括脊髓性肌肉萎缩）的药物中的用途。

公开(公告)号：US09187749B2

公开(公告)日：2015-11-17

申请号：US14124621

申请日：2012-06-08

申请人： Gourab Bhattacharjee ,  Alexey Revenko ,  Robert A. MacLeod

发明人： Gourab Bhattacharjee ,  Alexey Revenko ,  Robert A. MacLeod

IPC分类号： C12N15/11 ,  C12N15/113 ,  A61K48/00 ,  A61K31/7088 ,  A61K45/06

CPC分类号： C12N15/1137 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/005 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/321 ,  C12N2310/3525

摘要： Disclosed herein are methods for decreasing Factor 12 and treating or preventing inflammatory conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 12 include hereditary angioedema (HAE). Methods for inhibiting Factor 12 can also be used as a prophylactic treatment to prevent individuals at risk for developing an inflammatory condition, such as, hereditary angioedema.

摘要翻译： 本文公开了减少因子12并治疗或预防有此需要的个体的炎性病症的方法。 通过施用靶向因子12的反义化合物可以改善的疾病状况的实例包括遗传性血管性水肿（HAE）。 抑制因子12的方法也可以用作预防性治疗，以防止处于发展为诸如遗传性血管性水肿的炎性疾病的风险的个体。