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：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：WO2010042649A2

公开(公告)日：2010-04-15

申请号：PCT/US2009/059888

申请日：2009-10-07

Applicant: AMGEN INC. ,  TASKER, Andrew ,  FALSEY, James Richard ,  RZASA, Robert M. ,  HERBERICH, Bradley J. ,  ZHANG, Dawei

Inventor： TASKER, Andrew ,  FALSEY, James Richard ,  RZASA, Robert M. ,  HERBERICH, Bradley J. ,  ZHANG, Dawei

IPC: C07D237/30 ,  C07D237/32 ,  C07D237/34 ,  A61K31/498 ,  A61P9/00

CPC classification number: C07D401/12 ,  C07D237/30 ,  C07D237/32 ,  C07D237/34 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

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 4 , L, R 1 , R 2 , R 3 , R 5 and m are as 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, ankylosing spondylitis, 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一类新化合物。 该化合物具有通式I，其中A 4，L，R 1，R 2，R 3，R 4，R 4，R 5， R 5和m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，所述化合物和组合物用于治疗p38图谱激酶介导的疾病，包括类风湿性关节炎，牛皮癣，慢性阻塞性肺病，强直性脊柱炎，疼痛和其它炎性病症 以及用于制备式I化合物的中间体和方法。

公开(公告)号：WO2020243702A2

公开(公告)日：2020-12-03

申请号：PCT/US2020/035545

申请日：2020-06-01

Applicant: AMGEN INC.

Inventor： DAS, Amrita ,  HERBERICH, Bradley J. ,  MURRAY, Justin K. ,  HOMANN, Oliver ,  OLLMANN, Michael ,  LIN, Daniel C. H.

IPC: C12N15/113 ,  A61K31/713 ,  A61P3/06

Abstract: The present invention relates to RNAi constructs for reducing expression of the SCAP gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

公开(公告)号：WO2014022752A1

公开(公告)日：2014-02-06

申请号：PCT/US2013/053380

申请日：2013-08-02

Applicant: AMGEN INC.

Inventor： CEE, Victor J. ,  BROWN, James ,  CHAVEZ JR., Frank ,  CHEN, Jian J. ,  HERBERICH, Bradley J. ,  HARRINGTON, Essa Hu ,  LANMAN, Brian Alan ,  LEE, Matthew ,  PETTUS, Liping H. ,  REED, Anthony B. ,  TASKER, Andrew ,  WANG, Hui-Ling ,  WU, Bin ,  WURZ, Ryan

IPC: C07D471/22 ,  C07D498/22 ,  A61K31/4725 ,  A61K31/498 ,  A61P35/00

CPC classification number: C07D471/22 ,  C07D498/22

Abstract: The invention relates to 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：WO2006039718A3

公开(公告)日：2006-04-13

申请号：PCT/US2005/035873

申请日：2005-10-03

Applicant: AMGEN INC

Inventor： PATEL, Vinod F. ,  KIM, Joseph L. ,  GEUNS-MEYER, Stephanie D. ,  CHAFFEE, Stuart C. ,  CEE, Victor J. ,  HODOUS, Brian L. ,  BELLON, Steven ,  HARMANGE, Jean-christophe ,  OLIVIERI, Philip R. ,  THAMAN, Maya C. ,  DIMAURO, Erin F. ,  BUCHANAN, John L. ,  MCGOWAN, David C. ,  ALBRECHT, Brian K. ,  DEAK, Holly L. ,  BEMIS, Jean E. ,  WHITE, Ryan ,  MARTIN, Matthew W. ,  HABGOOD, Gregory J. ,  TEMPEST, Paul A. ,  MASSE, Craig E. ,  BUCKNER, William H. ,  HERBERICH, Bradley J. ,  GRACEFFA, Russell ,  ZHANG, Dawei ,  XU, Shimin ,  SHAM, Kelvin ,  RZASA, Robert M. ,  FALSEY, James Richard ,  CHAKRABARTI, Partha P. ,  CAO, Guo-qiang ,  TOMLINSON, Susan Ann ,  PETTUS, Liping H. ,  SMITH, Adrian Leonard ,  PARAS, Nick A. ,  LIU, Gang ,  DEMORIN, Frenel F. ,  TASKER, Andrew ,  REED, Anthony

IPC: C07D239/84 ,  C07D239/95 ,  C07D401/12 ,  C07D409/04 ,  C07D405/12 ,  C07D409/14 ,  C07D405/04 ,  C07D403/10 ,  C07D401/04 ,  C07D471/04 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D409/12 ,  C07D215/12

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I, wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

公开(公告)号：WO2021247885A2

公开(公告)日：2021-12-09

申请号：PCT/US2021/035730

申请日：2021-06-03

Applicant: AMGEN INC.

Inventor： LIN, Daniel C. H. ,  OLLMANN, Michael ,  MURRAY, Justin K. ,  HERBERICH, Bradley J. ,  DAS, Amrita ,  COLLINS, Patrick ,  HOMANN, Oliver

IPC: C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3525 ,  C12N2310/3533 ,  C12Y101/00

Abstract: The present invention relates to RNAi constructs for reducing expression of the HSD17B13 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

公开(公告)号：WO2019028382A1

公开(公告)日：2019-02-07

申请号：PCT/US2018/045212

申请日：2018-08-03

Applicant: AMGEN INC.

Inventor： ACHMATOWICZ, Michal ,  ROMANINI, Dante ,  FALSEY, James R. ,  HERBERICH, Bradley J. ,  THIEL, Oliver R.

IPC: A61K47/68 ,  C07K16/00 ,  C07K14/605

Abstract: The present disclosure relates to a method of capping, reducing, and oxidizing cys-mAbs in order to provide homogenous material for subsequent conjugation reactions. The present method demonstrates robust ways to manufacture conjugates of cysteine-engineered antibodies that offer high yield and consistent product quality.

公开(公告)号：WO2018136440A1

公开(公告)日：2018-07-26

申请号：PCT/US2018/013918

申请日：2018-01-16

Applicant: AMGEN INC.

Inventor： CHENG, Yuan ,  NETIROJJANAKUL, Chawita ,  HOLDER, Jerry Ryan ,  WU, Bin ,  FALSEY, James R. ,  HERBERICH, Bradley J. ,  SHAM, Kelvin ,  MIRANDA, Leslie P. ,  LU, Shu-Chen ,  VENIANT-ELLISON, Murielle M. ,  STANISLAUS, Shanaka ,  YIE, Junming ,  XU, Jing

IPC: A61K39/395 ,  C07K16/28 ,  A61P3/10

Abstract: Methods of treating metabolic diseases and disorders using a composition comprising an antigen binding protein specific for the GIPR polypeptide conjugated to a GLP-1 receptor agonist are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the composition comprises an antibody or functional fragment thereof comprising a cysteine at one or more conjugation site(s) wherein the GLP-1 receptor agonist is conjugated to the antibody or functional fragment thereof through the side-chain of the cysteine residue.

公开(公告)号：WO2014134308A1

公开(公告)日：2014-09-04

申请号：PCT/US2014/019030

申请日：2014-02-27

Applicant: AMGEN INC.

Inventor： WURZ, Ryan ,  TASKER, Andrew ,  TADESSE, Seifu ,  PETTUS, Liping H. ,  NGUYEN, Thomas T. ,  HONG, Fang-Tsao ,  HERBERICH, Bradley J. ,  HARRINGTON, Essa ,  CHEN, Jian J. ,  BROWN, James

IPC: C07D471/04 ,  A61K31/519 ,  A61P35/00

CPC classification number: C07D471/04

Abstract: The invention encompasses compounds represented by the following general structures: formula (I) and formula (II), wherein X; R 1 -R 3 ; R11; R12; and R14 are as defined in the claims and pharmaceutically acceptable salts thereof, pharmaceutical compositions, uses and methods for prophylaxis and treatment of cancer.

Abstract translation: 本发明包括由以下一般结构表示的化合物：式（I）和式（II），其中X; R1-R3; R11; R12; 和R14如权利要求书及其药学上可接受的盐，药物组合物，用途和预防和治疗癌症的方法中所定义。