公开(公告)号：US08372967B2

公开(公告)日：2013-02-12

申请号：US12299583

申请日：2007-05-07

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

发明人： Sanjay Bhanot ,  Richard 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 ,  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：US20090306357A1

公开(公告)日：2009-12-10

申请号：US12299583

申请日：2007-05-07

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

发明人： Sanjay Bhanot ,  Richard 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：US20090326042A1

公开(公告)日：2009-12-31

申请号：US12299768

申请日：2007-05-07

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

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

IPC分类号： A61K31/7052 ,  C07H21/00 ,  C12N5/00 ,  A61P9/00

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：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

IPC分类号： A61K48/00 ,  A61P43/00 ,  C07H21/04 ,  C12N15/87

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：US20060089325A1

公开(公告)日：2006-04-27

申请号：US11251610

申请日：2005-10-13

申请人： Sanjay Bhanot ,  Brett Monia ,  Richard Geary ,  Lise Kjems

发明人： Sanjay Bhanot ,  Brett Monia ,  Richard Geary ,  Lise Kjems

IPC分类号： A61K48/00 ,  A61K38/22 ,  A61K38/28 ,  A61K31/426 ,  A61K31/155 ,  A61K31/175

CPC分类号： A61K31/175 ,  A61K31/155 ,  A61K31/425 ,  A61K31/426 ,  A61K31/64 ,  A61K31/70 ,  A61K31/7105 ,  A61K31/7125 ,  A61K38/22 ,  A61K38/2278 ,  A61K38/28 ,  A61K45/06 ,  A61K2300/00

摘要： Compositions and methods are provided for decreasing blood glucose levels in an animal or for preventing or delaying the onset of a rise in blood glucose levels in an animal, comprising administering to said animal an antisense inhibitor of PTP1B expression in combination with at least one glucose-lowering drug. The present invention is also directed to compositions and methods for improving insulin sensitivity in an animal or for preventing or delaying the onset of insulin resistance in an animal. Also provided are compositions and methods for treating or preventing a metabolic condition in an animal. The metabolic condition may be, e.g., diabetes or obesity.

摘要翻译： 提供了用于降低动物体内血糖水平或用于预防或延迟动物血糖水平升高的组合物和方法，包括向所述动物施用反义抑制剂PTP1B表达与至少一种葡萄糖 - 降低药物。 本发明还涉及用于改善动物体内胰岛素敏感性或预防或延迟动物体内胰岛素抵抗发作的组合物和方法。 还提供了用于治疗或预防动物代谢状况的组合物和方法。 代谢病症可以是例如糖尿病或肥胖症。

公开(公告)号：US20070299028A1

公开(公告)日：2007-12-27

申请号：US11679159

申请日：2007-02-26

申请人： Andrew Siwkowski ,  Edward Wancewicz ,  Thomas Leedom ,  Lynnetta Watts ,  Mausumee Guha ,  Brett Monia ,  Richard Griffey ,  Richard Geary ,  Scott Henry ,  Arthur Levin

发明人： Andrew Siwkowski ,  Edward Wancewicz ,  Thomas Leedom ,  Lynnetta Watts ,  Mausumee Guha ,  Brett Monia ,  Richard Griffey ,  Richard Geary ,  Scott Henry ,  Arthur Levin

IPC分类号： A61K31/7088 ,  A61P3/00 ,  A61P3/10 ,  C07H21/00

CPC分类号： C07H21/02 ,  A61K31/70 ,  C07H21/04 ,  C12N15/111 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2320/32 ,  C12N2500/40 ,  C12N2310/3525 ,  C12N2310/3527

摘要： The present invention provides antisense compounds and methods for modulating the expression of target genes expressed in the kidney. In particular, this invention provides antisense oligonucleotide compounds optimized for targeting nucleic acid molecules expressed in the kidney. Such compounds are shown herein to efficiently modulate the expression of target genes PTEN, SGLT2 and connective tissue growth factor (CTGF) in the kidney.

摘要翻译： 本发明提供了用于调节在肾中表达的靶基因的表达的反义化合物和方法。 特别地，本发明提供针对在肾中表达的靶向核酸分子而优化的反义寡核苷酸化合物。 本文显示了这样的化合物以有效调节肾脏中靶基因PTEN，SGLT2和结缔组织生长因子（CTGF）的表达。

公开(公告)号：US20050196443A1

公开(公告)日：2005-09-08

申请号：US11000814

申请日：2004-12-01

申请人： Susan Weinbach ,  Lloyd Tillman ,  Richard Geary ,  Gregory Hardee

发明人： Susan Weinbach ,  Lloyd Tillman ,  Richard Geary ,  Gregory Hardee

IPC分类号： A61K47/12 ,  A61K9/20 ,  A61K9/22 ,  A61K9/24 ,  A61K9/26 ,  A61K9/28 ,  A61K9/42 ,  A61K9/48 ,  A61K9/52 ,  A61K9/54 ,  A61K9/66 ,  A61K31/7088 ,  A61K38/00 ,  A61K39/00 ,  A61K39/395 ,  A61K47/04 ,  A61K47/08 ,  A61K47/14 ,  A61K47/16 ,  A61K47/18 ,  A61K47/22 ,  A61K47/26 ,  A61K47/28 ,  A61K47/32 ,  A61K47/34 ,  A61K47/36 ,  A61K47/38 ,  A61K47/42 ,  A61K48/00 ,  A61P1/04 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00

CPC分类号： A61K9/4808 ,  A61K9/4891

摘要： Delayed release oral pharmaceutical formulations and methods for enhanced intestinal drug absorption. The formulation comprises a first population of carrier particles comprising a drug and a penetration enhancer which are released at a first location in the intestine, and a second population of carrier particles comprising a penetration enhancer and a delayed release coating or matrix. This penetration enhancer is released at a second location in the intestine downstream from the first location and enhances absorption of the drug when it reaches the second location.

摘要翻译： 延迟口服药物制剂和增强肠吸收药物的方法。 所述制剂包含第一载体颗粒群，其包含在肠中的第一位置释放的药物和渗透增强剂，以及包含渗透促进剂和延迟释放包衣或基质的第二种载体颗粒。 该渗透促进剂在第一位置下游的肠道的第二位置释放，并且当药物到达第二位置时增强药物的吸收。

公开(公告)号：US20060035858A1

公开(公告)日：2006-02-16

申请号：US11200710

申请日：2005-08-10

申请人： Richard Geary ,  Zhengrong Yu ,  Rosanne Crooke

发明人： Richard Geary ,  Zhengrong Yu ,  Rosanne Crooke

IPC分类号： A61K48/00

CPC分类号： C12N15/113 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/3525

摘要： Methods for the rapid and long-term lowering of lipid levels in human subjects and for the treatment of conditions associated with elevated LDL-cholesterol and elevated apolipoprotein B are provided.

摘要翻译： 提供了快速和长期降低人类受试者脂质水平和治疗与升高的LDL-胆固醇和升高的载脂蛋白B相关的病症的方法。

公开(公告)号：US5167947A

公开(公告)日：1992-12-01

申请号：US428150

申请日：1989-10-26

申请人： Richard Geary

发明人： Richard Geary

IPC分类号： A61K9/00 ,  A61K31/66 ,  A61K47/18

CPC分类号： A61K9/0053 ,  A61K31/66 ,  A61K47/183 ,  A61K9/0031

摘要： The present invention provides a pharmaceutical composition for enhancing gastrointestinal tract absorption of a radioprotective drug comprising a therapeutically effective dosage amount of a bioactive polar radioprotective agent, such as ethiofos, its active metabolites, and pharmaceutically acceptable salts thereof and a chelating agent selected from the group consisting of EDTA, EGTA, citrate and therapeutically acceptable salts thereof.A method for enhancing the rate of gastrointestinal absorption of radioprotective agents is also provided.

摘要翻译： 本发明提供了一种用于增强放射防护药物的胃肠道吸收的药物组合物，其包含治疗有效剂量的生物活性极性放射防护剂，例如乙醚，其活性代谢物及其药学上可接受的盐和选自下组的螯合剂 由EDTA，EGTA，柠檬酸盐及其治疗上可接受的盐组成。 还提供了一种提高放射防护剂胃肠道吸收率的方法。