公开(公告)号：US08258289B2

公开(公告)日：2012-09-04

申请号：US12748281

申请日：2010-03-26

申请人： Sanjay Bhanot ,  Kenneth W. Dobie ,  Xing-Xian Yu ,  Brett P. Monia

发明人： Sanjay Bhanot ,  Kenneth W. Dobie ,  Xing-Xian Yu ,  Brett P. Monia

IPC分类号： C07H21/04

CPC分类号： C12N15/1137 ,  C07H21/02 ,  C12N2310/11 ,  C12N2310/14

摘要： Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 2. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 2. Methods of using these compounds for modulation of diacylglycerol acyltransferase 2 expression and for diagnosis and treatment of diseases and conditions associated with expression of diacylglycerol acyltransferase 2 are provided.

摘要翻译： 提供化合物，组合物和方法用于调节二酰基甘油酰基转移酶2的表达。该组合物包含靶向编码二酰基甘油酰基转移酶的核酸的寡核苷酸2.使用这些化合物调节二酰基甘油酰基转移酶2表达并用于诊断和治疗疾病的方法 提供了与二酰基甘油酰基转移酶2的表达相关的病症。

公开(公告)号：US20120149755A1

公开(公告)日：2012-06-14

申请号：US13185406

申请日：2011-07-18

申请人： Brett P. Monia

发明人： Brett P. Monia

IPC分类号： A61K31/7088 ,  A61P35/04

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C07H21/00 ,  C12N15/1135 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3517 ,  C12N2310/3525 ,  C12N2310/3527 ,  C12N2310/3521

摘要： Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating or preventing conditions, including hyperproliferative conditions, associated with raf expression.

摘要翻译： 提供寡核苷酸，其靶向编码人raf的核酸并能够抑制raf表达。 寡核苷酸可以在一个或多个位置具有化学修饰，并且可以是嵌合寡核苷酸。 还提供了使用本发明的寡核苷酸抑制人raf表达的方法。 本发明还包括抑制细胞过度增殖的方法以及治疗或预防与raf表达相关的病症（包括过度增殖病症）的方法。

公开(公告)号：US20110207797A1

公开(公告)日：2011-08-25

申请号：US13008704

申请日：2011-01-18

申请人： Brett P. Monia ,  Andrew M. Siwkowski ,  Sanjay Bhanot

发明人： Brett P. Monia ,  Andrew M. Siwkowski ,  Sanjay Bhanot

IPC分类号： A61K31/7088 ,  A61P9/00 ,  A61P3/00 ,  A61P3/10 ,  A61P3/04 ,  A61P3/06 ,  A61P1/16 ,  A61P9/10 ,  A61P9/12 ,  A61P7/02

CPC分类号： C12N15/111 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/50 ,  C12N2310/3525

摘要： Described herein are gap-widened antisense oligonucleotides having improved therapeutic index as compared to 5-10-5 MOE gapmer antisense oligonucleotides of the same sequence. Also described are methods of reducing a target RNA in an animal using the gap-widened antisense oligonucleotides of the present invention. Further, are methods for selecting a gap-widened antisense oligonucleotides.

摘要翻译： 与相同序列的5-10-5个MOE gapmer反义寡核苷酸相比，本文描述了具有改善的治疗指数的间隙扩大的反义寡核苷酸。 还描述了使用本发明的间隙加宽的反义寡核苷酸还原动物中的靶RNA的方法。 此外，是选择间隙扩大的反义寡核苷酸的方法。

公开(公告)号：US07981868B2

公开(公告)日：2011-07-19

申请号：US10568488

申请日：2004-08-12

申请人： Brett P. Monia ,  Kenneth W. Dobie ,  Susan M. Freier ,  Ian Popoff ,  James G. Karras

发明人： Brett P. Monia ,  Kenneth W. Dobie ,  Susan M. Freier ,  Ian Popoff ,  James G. Karras

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

CPC分类号： C12N15/1137 ,  A61K31/7052 ,  A61K38/00 ,  C12N2310/11 ,  C12N2310/14 ,  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 decreasing airway hyperresponsiveness or airway inflammation in an animal 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。 还提供了降低动物气道高反应性或气道炎症的方法。

公开(公告)号：US20110059895A1

公开(公告)日：2011-03-10

申请号：US12742076

申请日：2008-11-05

申请人： Susan M. Freier ,  Brett P. Monia ,  Hong Zhang ,  Chenguang Zhao

发明人： Susan M. Freier ,  Brett P. Monia ,  Hong Zhang ,  Chenguang Zhao

IPC分类号： A61K38/16 ,  C07H21/00 ,  C07H21/04 ,  A61K31/7088 ,  A61P7/02 ,  A61P9/10 ,  A61P9/00

CPC分类号： C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525

摘要： Disclosed herein are antisense compounds and methods for decreasing Factor 9 and increasing clotting time in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 9 include thrombosis, embolism, thromoboembolism such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke.

摘要翻译： 本文公开了用于减少因子9并增加有需要的个体中的凝血时间的反义化合物和方法。 通过施用靶向因子9的反义化合物可以改善的疾病状况的实例包括血栓形成，栓塞，血栓栓塞如深静脉血栓形成，肺栓塞，心肌梗死和中风。

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：US20090105177A1

公开(公告)日：2009-04-23

申请号：US12173744

申请日：2008-07-15

申请人： Brett P. Monia ,  Mark J. Graham

发明人： Brett P. Monia ,  Mark J. Graham

IPC分类号： A61K31/7088 ,  C07H21/04 ,  C12N5/02 ,  C12Q1/48 ,  C12Q1/68

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Y203/0102

摘要： Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 1. Methods of using these compounds for modulation of diacylglycerol acyltransferase 1 expression and for diagnosis and treatment of disease associated with expression of diacylglycerol acyltransferase 1, such as obesity and obesity-related conditions, are provided.

摘要翻译： 提供化合物，组合物和方法用于调节二酰基甘油酰基转移酶1的表达。该组合物包含靶向编码二酰基甘油酰基转移酶的核酸的寡核苷酸1.使用这些化合物调节二酰基甘油酰基转移酶1表达并用于诊断和治疗疾病相关的方法 提供了二酰基甘油酰基转移酶1的表达，如肥胖和肥胖相关条件。

公开(公告)号：US07414033B2

公开(公告)日：2008-08-19

申请号：US10803482

申请日：2004-03-18

申请人： Brett P. Monia ,  Mark J. Graham

发明人： Brett P. Monia ,  Mark J. Graham

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

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Y203/0102

摘要： Compounds, compositions and methods are provided for modulating the expression of diacylglycerol acyltransferase 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding diacylglycerol acyltransferase 1. Methods of using these compounds for modulation of diacylglycerol acyltransferase 1 expression and for diagnosis and treatment of disease associated with expression of diacylglycerol acyltransferase 1, such as obesity and obesity-related conditions, are provided.

摘要翻译： 提供化合物，组合物和方法用于调节二酰基甘油酰基转移酶1的表达。该组合物包含靶向编码二酰基甘油酰基转移酶的核酸的寡核苷酸1.使用这些化合物调节二酰基甘油酰基转移酶1表达并用于诊断和治疗疾病相关的方法 提供了二酰基甘油酰基转移酶1的表达，如肥胖和肥胖相关条件。

公开(公告)号：US06900187B2

公开(公告)日：2005-05-31

申请号：US10080794

申请日：2002-02-22

申请人： Martin Gleave ,  Paul S. Rennie ,  Hideaki Miyake ,  Colleen Nelson ,  Brett P. Monia

发明人： Martin Gleave ,  Paul S. Rennie ,  Hideaki Miyake ,  Colleen Nelson ,  Brett P. Monia

IPC分类号： C12N15/09 ,  A61K31/00 ,  A61K31/136 ,  A61K31/337 ,  A61K31/66 ,  A61K31/704 ,  A61K31/7125 ,  A61K38/00 ,  A61K41/00 ,  A61K45/00 ,  A61K45/06 ,  A61K48/00 ,  A61P43/00 ,  C07H21/00 ,  C07K14/775 ,  C12N15/113 ,  A61K31/70

CPC分类号： C12N15/113 ,  A61K31/00 ,  A61K31/337 ,  A61K31/66 ,  A61K31/704 ,  A61K41/0038 ,  A61K45/06 ,  A61K48/00 ,  C07H21/00 ,  C07K14/775 ,  C12N15/1135 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525 ,  A61K2300/00

摘要： A compound consisting of an oligonucleotide of sequence CAGCAGCAGAGTCTTCATCAT, where the oligonucleotide has a phosphorothioate backbone throughout, the sugar moieties of nucleotides 1-4 and 18-21 bear 2′-O-methoxyethyl modifications, and the remaining nucleotides (nucleotides 5-17) are 2′-deoxynucleotides, and where the cytosines of nucleotides 1, 4 and 19 are 5-methylcytosines. The compound has increased stability in vivo and improved in vitro and in vivo antitumor activity.

摘要翻译： 由序列CAGCAGCAGAGTCTTCATCAT的寡核苷酸组成的化合物，其寡核苷酸全部具有硫代磷酸酯主链，核苷酸1-4和18-21的糖部分具有2'-O-甲氧基乙基修饰，剩余的核苷酸（核苷酸5-17） 是2'-脱氧核苷酸，其中核苷酸1,4和19的胞嘧啶是5-甲基胞嘧啶。 该化合物具有增加的体内稳定性和改善的体外和体内抗肿瘤活性。