公开(公告)号：WO2020123410A1

公开(公告)日：2020-06-18

申请号：PCT/US2019/065294

申请日：2019-12-09

Applicant: AMGEN INC.

Inventor： MURRAY, Justin K. ,  WU, Bin ,  CHENG, Yuan ,  HERBERICH, Bradley J.

IPC: C12N15/11

Abstract: The present invention relates to chemically-modified RNAi constructs for reducing expression of a target gene. In particular, the invention relates to specific patterns of modified nucleotides to be incorporated into RNAi constructs to improve in vivo stability and efficacy. Also described are pharmaceutical compositions comprising the chemically-modified RNAi constructs and methods of inhibiting target gene expression in vivo by administering the chemically-modified RNAi constructs, for example, to treat or ameliorate various disease conditions.

公开(公告)号：WO2010126895A1

公开(公告)日：2010-11-04

申请号：PCT/US2010/032593

申请日：2010-04-27

Applicant: AMGEN INC. ,  ANDREWS, Kristin ,  BO, Yunxin, Y. ,  BOOKER, Shon ,  CEE, Victor, J. ,  D'ANGELO, Noel ,  HERBERICH, Bradley, J. ,  HONG, Fang-Tsao ,  JACKSON, Claire, L., M. ,  LANMAN, Brian, A. ,  LIAO, Hongyu ,  LIU, Longbin ,  NISHIMURA, Nobuko ,  NORMAN, Mark, H. ,  PETTUS, Liping, H. ,  REED, Anthony, B. ,  SMITH, Adrian, L. ,  TADESSE, Seifu ,  TAMAYO, Nuria, A. ,  WU, Bin ,  WURZ, Ryan ,  YANG, Kevin

Inventor： ANDREWS, Kristin ,  BO, Yunxin, Y. ,  BOOKER, Shon ,  CEE, Victor, J. ,  D'ANGELO, Noel ,  HERBERICH, Bradley, J. ,  HONG, Fang-Tsao ,  JACKSON, Claire, L., M. ,  LANMAN, Brian, A. ,  LIAO, Hongyu ,  LIU, Longbin ,  NISHIMURA, Nobuko ,  NORMAN, Mark, H. ,  PETTUS, Liping, H. ,  REED, Anthony, B. ,  SMITH, Adrian, L. ,  TADESSE, Seifu ,  TAMAYO, Nuria, A. ,  WU, Bin ,  WURZ, Ryan ,  YANG, Kevin

IPC: C07D401/14 ,  C07D473/00 ,  A61K31/52 ,  A61P35/00

CPC classification number: C07D473/00 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

Abstract translation: 本发明涉及式I化合物或其药学上可接受的盐; 使用该化合物治疗疾病或病症如癌症的方法; 和含有这些化合物的药物组合物，其中变量如本文所定义。

公开(公告)号：WO2012129338A1

公开(公告)日：2012-09-27

申请号：PCT/US2012/029997

申请日：2012-03-21

Applicant: AMGEN INC. ,  WANG, Hui-Ling ,  CEE, Victor, C. ,  HERBERICH, Bradley, J. ,  JACKSON, Claire, L., M. ,  LANMAN, Brian, Alan ,  NIXEY, Thomas ,  PETTUS, Liping, H. ,  REED, Anthony, B. ,  WU, Bin ,  WURZ, Ryan ,  TASKER, Andrew

Inventor： WANG, Hui-Ling ,  CEE, Victor, C. ,  HERBERICH, Bradley, J. ,  JACKSON, Claire, L., M. ,  LANMAN, Brian, Alan ,  NIXEY, Thomas ,  PETTUS, Liping, H. ,  REED, Anthony, B. ,  WU, Bin ,  WURZ, Ryan ,  TASKER, Andrew

IPC: C07D413/14 ,  C07D417/14 ,  C07D417/04 ,  C07D487/04 ,  A61K31/496 ,  A61K31/4439 ,  A61K31/4745 ,  A61K31/433 ,  A61P35/00

CPC classification number: C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04

Abstract: The invention relates to bicyclic compounds of formulas I and Ia, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

Abstract translation: 本发明涉及式I和Ia的双环化合物及其盐。 在一些实施方案中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。 在另外的实施方案中，本发明涉及包含本文公开的化合物的药物组合物及其在预防和治疗Pim激酶相关病症和疾病，优选癌症中的用途。

公开(公告)号：WO2010025201A1

公开(公告)日：2010-03-04

申请号：PCT/US2009/055093

申请日：2009-08-26

Applicant: AMGEN INC. ,  PETTUS, Liping H. ,  TASKER, Andrew ,  WANG, Hui-Ling ,  WU, Bin ,  WURZ, Ryan

Inventor： PETTUS, Liping H. ,  TASKER, Andrew ,  WANG, Hui-Ling ,  WU, Bin ,  WURZ, Ryan

IPC: C07D471/04 ,  A61K31/5025 ,  A61P29/00 ,  A61P31/00 ,  A61P17/00

CPC classification number: C07D471/04

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and n are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of p38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula (I).

Abstract translation: 本发明包括一类新的可用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关病症的化合物。 化合物具有通式I，其中A，R 1，R 2，R 3，R 4，R 5，R 6，X和n如本文所定义。 本发明还包括药物组合物，其包含一种或多种式I化合物，这些化合物和组合物用于治疗p38地图激酶介导的疾病包括类风湿性关节炎，银屑病，慢性阻塞性肺病，疼痛和其它炎性疾病以及中间体 和可用于制备式（I）化合物的方法。

公开(公告)号：WO2018039647A1

公开(公告)日：2018-03-01

申请号：PCT/US2017/048757

申请日：2017-08-25

Applicant: AMGEN INC.

Inventor： OLLMANN, Michael ,  LI, Yang ,  ZHANG, Jun ,  BISWAS, Kaustav ,  HOMANN, Oliver ,  MIRANDA, Leslie P. ,  MURRAY, Justin K. ,  WU, Bin ,  YOON, Oh Kyu ,  ALLEN, John Gordon ,  NETIROJJANAKUL, Chawita ,  CHENG, Yuan

IPC: C12N15/113

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

Abstract translation: 本发明涉及用于减少ASGR1基因表达的RNAi构建体。 还描述了使用这种RNAi构建体来治疗或预防心血管疾病（例如冠状动脉疾病和心肌梗塞）并降低血清非HDL胆固醇水平的方法。

公开(公告)号：WO2014165277A2

公开(公告)日：2014-10-09

申请号：PCT/US2014/025062

申请日：2014-03-12

Applicant: AMGEN INC.

Inventor： MURRAY, Justin K. ,  HOLDER, Jerry Ryan ,  WANSKA, Malgorzata ,  TEGLEY, Christopher M. ,  FALSEY, James R. ,  DOHERTY, Elizabeth M. ,  MIRANDA, Leslie P. ,  BISWAS, Kaustav ,  WU, Bin ,  SHAM, Kelvin ,  LONG, Jason C.

IPC: C07K14/435

CPC classification number: C07K14/43518 ,  A61K38/00 ,  A61K38/1767 ,  A61K47/48284 ,  A61K47/48438 ,  A61K47/643 ,  A61K47/6817

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract translation: 公开了包含分离的多肽的物质组合物，其是外周限制的Nav1.7抑制剂。 在一些公开的实施方案中，分离的多肽是Nav1.7的抑制剂。 其它实施方案是本发明组合物和包含本发明组合物的药物组合物的共轭实施方案。 公开了编码本发明多肽和表达载体的一些实施方案的分离的核酸，以及含有它们的重组宿主细胞。 还公开了治疗或预防疼痛的方法。

公开(公告)号：WO2012148775A1

公开(公告)日：2012-11-01

申请号：PCT/US2012/034272

申请日：2012-04-19

Applicant: AMGEN INC. ,  D'AMICO, Derin C. ,  HERBERICH, Bradley J. ,  JACKSON, Claire L.M. ,  PETTUS, Liping H. ,  TASKER, Andrew ,  WANG, Hui-Ling ,  WU, Bin ,  WURZ, Ryan

Inventor： D'AMICO, Derin C. ,  HERBERICH, Bradley J. ,  JACKSON, Claire L.M. ,  PETTUS, Liping H. ,  TASKER, Andrew ,  WANG, Hui-Ling ,  WU, Bin ,  WURZ, Ryan

IPC: C07D487/04 ,  A61K31/495 ,  A61P35/00

CPC classification number: C07D487/04

Abstract: The invention relates to bicyclic compounds of formulas I and I', and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

Abstract translation: 本发明涉及式I和I'的双环化合物及其盐。 在一些实施方案中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。 在进一步的实施方案中，本发明涉及包含本文公开的化合物的药物组合物及其在预防和治疗Pim激酶相关病症和疾病，优选癌症中的用途。

公开(公告)号：WO2012078777A1

公开(公告)日：2012-06-14

申请号：PCT/US2011/063776

申请日：2011-12-07

Applicant: AMGEN INC. ,  WANG, Hui-Ling ,  BISWAS, Kaustav ,  CEE, Victor J. ,  CHAVEZ JR., Frank ,  HERBERICH, Bradley ,  JACKSON, Claire L.M. ,  LEE, Matthew ,  NIXEY, Thomas ,  PETTUS, Liping H. ,  REED, Anthony B. ,  RZASA, Robert M. ,  RUMFELT, Shannon ,  TASKER, Andrew ,  WU, Bin ,  WURZ, Ryan

Inventor： WANG, Hui-Ling ,  BISWAS, Kaustav ,  CEE, Victor J. ,  CHAVEZ JR., Frank ,  HERBERICH, Bradley ,  JACKSON, Claire L.M. ,  LEE, Matthew ,  NIXEY, Thomas ,  PETTUS, Liping H. ,  REED, Anthony B. ,  RZASA, Robert M. ,  RUMFELT, Shannon ,  TASKER, Andrew ,  WU, Bin ,  WURZ, Ryan

IPC: C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D491/107 ,  A61K31/497 ,  A61K31/437 ,  A61K31/506 ,  A61K31/444 ,  A61K31/4709

CPC classification number: C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: The invention relates to bicyclic compounds of formula (1'), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

Abstract translation: 本发明涉及式（1'）的双环化合物及其盐。 在一些实施方案中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。 在另外的实施方案中，本发明涉及包含本文公开的化合物的药物组合物及其在预防和治疗Pim激酶相关病症和疾病，优选癌症中的用途。

公开(公告)号：WO2010025202A1

公开(公告)日：2010-03-04

申请号：PCT/US2009/055095

申请日：2009-08-26

Applicant: AMGEN INC. ,  PETTUS, Liping, H. ,  TASKER, Andrew ,  WU, Bin

Inventor： PETTUS, Liping, H. ,  TASKER, Andrew ,  WU, Bin

IPC: C07D471/04 ,  A61K31/444 ,  A61P29/00

CPC classification number: C07D471/04

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , W and X are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula (I), uses of such compounds and compositions for treatment of p38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

Abstract translation: 本发明包括一类新的可用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关病症的化合物。 该化合物具有通式（I），其中R 1，R 2，R 3，R 4，R 5，W和X如本文所定义。 本发明还包括包含一种或多种式（I）化合物的药物组合物，用于治疗p38地图激酶介导的疾病（包括类风湿性关节炎，牛皮癣，慢性阻塞性肺病，疼痛和其它炎症性疾病）的这些化合物和组合物的用途 作为可用于制备式I化合物的中间体和方法。

公开(公告)号：WO2022140344A1

公开(公告)日：2022-06-30

申请号：PCT/US2021/064546

申请日：2021-12-21

Applicant: AMGEN INC.

Inventor： TAN, Glenn, Christopher ,  ZASADZINSKA, Ewelina ,  HOFFMANN, Patrick ,  WU, Bin

IPC: C12N5/00 ,  B01L3/00 ,  C12M1/00 ,  G01N21/64 ,  B01L2200/0668 ,  B01L2300/0896 ,  C12N5/0075

Abstract: The present disclosure provides materials and methods identifying, selecting, and characterizing cells that express and secrete non-Fc containing biomolecules.