公开(公告)号：WO2021021535A1

公开(公告)日：2021-02-04

申请号：PCT/US2020/043168

申请日：2020-07-23

Applicant: MERCK SHARP & DOHME CORP. ,  FENG, Danqing ,  GUIDRY, Erin, N. ,  HUO, Pei ,  KASSICK, Andrew, J. ,  KEKEC, Ahmet ,  LIN, Songnian ,  MOYES, Christopher, R. ,  PISSARNITSKI, Dmitri, A. ,  YAN, Lin ,  ZHU, Yuping

Inventor： FENG, Danqing ,  GUIDRY, Erin, N. ,  HUO, Pei ,  KASSICK, Andrew, J. ,  KEKEC, Ahmet ,  LIN, Songnian ,  MOYES, Christopher, R. ,  PISSARNITSKI, Dmitri, A. ,  YAN, Lin ,  ZHU, Yuping

IPC: A61K38/28 ,  A61P3/10

Abstract: Glucose-responsive insulin conjugates that contain one or more trisaccharides are provided. Such insulin conjugates may display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose, even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule.

公开(公告)号：WO2020205323A1

公开(公告)日：2020-10-08

申请号：PCT/US2020/024372

申请日：2020-03-24

Applicant: MERCK SHARP & DOHME CORP. ,  BRUNELL, Margaret ,  GUIDRY, Erin, N. ,  KAPOOR, Yash ,  KEMP, Eric, A. ,  MINNIHAN, Ellen, C. ,  MITTAL, Sachin ,  PIERSON, Elizabeth ,  REIBARKH, Mikhail ,  SHEN, Tammy, W. ,  WALSH, Erika, R. ,  WALSH, Paul, L.

Inventor： BRUNELL, Margaret ,  GUIDRY, Erin, N. ,  KAPOOR, Yash ,  KEMP, Eric, A. ,  MINNIHAN, Ellen, C. ,  MITTAL, Sachin ,  PIERSON, Elizabeth ,  REIBARKH, Mikhail ,  SHEN, Tammy, W. ,  WALSH, Erika, R. ,  WALSH, Paul, L.

IPC: A61K31/7084 ,  C07H21/00 ,  A61P35/00

Abstract: The invention relates to stable formulations of cyclic dinucleotide STING agonist compounds or pharmaceutically acceptable salts thereof. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intratumoral or subcutaneous administration.

公开(公告)号：WO2022225827A1

公开(公告)日：2022-10-27

申请号：PCT/US2022/025158

申请日：2022-04-18

Applicant: MERCK SHARP & DOHME LLC ,  AXNANDA, Stephanus ,  BRUNSKILL, Andrew Patrick Jude ,  GUIDRY, Erin, N. ,  KEMP, Eric, A. ,  MAGUIRE, Courtney, K. ,  REIBARKH, Mikhail ,  WINSTON, Matthew, S.

Inventor： AXNANDA, Stephanus ,  BRUNSKILL, Andrew Patrick Jude ,  GUIDRY, Erin, N. ,  KEMP, Eric, A. ,  MAGUIRE, Courtney, K. ,  REIBARKH, Mikhail ,  WINSTON, Matthew, S.

IPC: C07D233/64 ,  C07H19/20 ,  C07H19/23 ,  C07H21/02 ,  C07H21/04

Abstract: Novel forms of 2-amino-9-[(2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfidooctahydro-12H-5,8-methanofuro[3,2-l][1,3,6,9,11,2,10]pentaoxadiphospha-cyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one, which include adducts of 2-amino-9-[(2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfidooctahydro-12H-5,8-methanofuro[3,2-l][1,3,6,9,11,2,10]pentaoxadiphospha-cyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one and L-histidine, may be useful as inductors of type I interferon production, specifically as STING active agents.

公开(公告)号：WO2016164288A1

公开(公告)日：2016-10-13

申请号：PCT/US2016/025813

申请日：2016-04-04

Applicant: MERCK SHARP & DOHME CORP. ,  FENG, Danqing ,  GUIDRY, Erin, N. ,  HUO, Pei ,  KAARSHOLM, Niels, C. ,  LIN, Songnian ,  NARGUND, Ravi, P. ,  YAN, Lin

Inventor： FENG, Danqing ,  GUIDRY, Erin, N. ,  HUO, Pei ,  KAARSHOLM, Niels, C. ,  LIN, Songnian ,  NARGUND, Ravi, P. ,  YAN, Lin

IPC: A61K47/48 ,  A61K38/28

CPC classification number: A61K47/549 ,  A61K38/28 ,  A61K47/61 ,  A61P3/10 ,  C07K14/62

Abstract: Insulin conjugates comprising an insulin analog molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract translation: 胰岛素缀合物包含共价连接到具有两个臂的至少一个双齿连接体的胰岛素类似物分子，每个臂独立地连接到包含糖的配体，并且其中所述连接体的至少一个配体的糖是岩藻糖。 胰岛素缀合物显示药代动力学（PK）和/或药效学（PD）谱，其对糖类如葡萄糖或α-甲基甘露糖的全身浓度有反应，即使在不存在外源多价的情况下施用于有需要的受试者时 糖结合分子如Con A.

公开(公告)号：WO2012068187A1

公开(公告)日：2012-05-24

申请号：PCT/US2011/060893

申请日：2011-11-16

Applicant: MERCK SHARP & DOHME CORP. ,  BARRETT, Stephanie, E. ,  BUSUEK, Marina ,  COLLETTI, Steven, L. ,  GARBACCIO, Robert, M. ,  GUIDRY, Erin, N. ,  KOWTONIUK, Robert, A. ,  LIAO, Jing ,  PARISH, Craig, A. ,  PARMAR, Rubina, G. ,  PEI, Tao ,  SCHLOSSER, Kevin, M. ,  TELLERS, David, M. ,  TOBIAS, Sandra, C. ,  TRUONG, Quang, T. ,  WALDMAN, Jacob, H. ,  WANG, Weimin ,  WILLIAMS, J. Michael

Inventor： BARRETT, Stephanie, E. ,  BUSUEK, Marina ,  COLLETTI, Steven, L. ,  GARBACCIO, Robert, M. ,  GUIDRY, Erin, N. ,  KOWTONIUK, Robert, A. ,  LIAO, Jing ,  PARISH, Craig, A. ,  PARMAR, Rubina, G. ,  PEI, Tao ,  SCHLOSSER, Kevin, M. ,  TELLERS, David, M. ,  TOBIAS, Sandra, C. ,  TRUONG, Quang, T. ,  WALDMAN, Jacob, H. ,  WANG, Weimin ,  WILLIAMS, J. Michael

IPC: A61K31/7088

CPC classification number: A61K47/48092 ,  A61K47/549 ,  C08G69/10 ,  C08G73/028 ,  C08L79/02

Abstract: The present invention provides poly(amide) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.

Abstract translation: 本发明提供用于递送用于治疗目的的寡核苷酸的聚（酰胺）聚合物，多偶联物，组合物和方法。

公开(公告)号：WO2015051052A3

公开(公告)日：2015-07-02

申请号：PCT/US2014058714

申请日：2014-10-02

Applicant: MERCK SHARP & DOHME ,  LIN SONGNIAN ,  YAN LIN ,  KEKEC AHMET ,  ZHU YUPING ,  HUNTER DAVID N ,  HUO PEI ,  FENG DANQING ,  NARGUND RAVI P ,  MOYES CHRISTOPHER R ,  ZHAO ZHIQIANG ,  PIPIK BRENDA ,  PISSARNITSKI DMITRI ,  DUFFY JOSEPH L ,  GUIDRY ERIN N

Inventor： LIN SONGNIAN ,  YAN LIN ,  KEKEC AHMET ,  ZHU YUPING ,  HUNTER DAVID N ,  HUO PEI ,  FENG DANQING ,  NARGUND RAVI P ,  MOYES CHRISTOPHER R ,  ZHAO ZHIQIANG ,  PIPIK BRENDA ,  PISSARNITSKI DMITRI ,  DUFFY JOSEPH L ,  GUIDRY ERIN N

IPC: A61K47/48 ,  A61P3/10

CPC classification number: A61K47/4823 ,  A61K38/28 ,  A61K47/48092 ,  A61K47/549 ,  A61K47/61 ,  C07K14/62

Abstract: Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract translation: 胰岛素缀合物包含共价连接到具有两个臂的至少一个双齿连接体的胰岛素分子，每个臂独立地连接到包含糖的配体，并且其中至少一个连接体的配体是岩藻糖。 胰岛素缀合物显示药代动力学（PK）和/或药效学（PD）谱，其对糖类如葡萄糖或α-甲基甘露糖的全身浓度有反应，即使在不存在外源多价的情况下施用于有需要的受试者时 糖结合分子如Con A.

公开(公告)号：WO2015051052A2

公开(公告)日：2015-04-09

申请号：PCT/US2014/058714

申请日：2014-10-02

Applicant: MERCK SHARP & DOHME CORP. ,  LIN, Songnian ,  YAN, Lin ,  KEKEC, Ahmet ,  ZHU, Yuping ,  HUNTER, David, N. ,  HUO, Pei ,  FENG, Danqing ,  NARGUND, Ravi, P. ,  MOYES, Christopher, R. ,  ZHAO, Zhiqiang ,  PIPIK, Brenda ,  PISSARNITSKI, Dmitri ,  DUFFY, Joseph, L. ,  GUIDRY, Erin, N.

Inventor： LIN, Songnian ,  YAN, Lin ,  KEKEC, Ahmet ,  ZHU, Yuping ,  HUNTER, David, N. ,  HUO, Pei ,  FENG, Danqing ,  NARGUND, Ravi, P. ,  MOYES, Christopher, R. ,  ZHAO, Zhiqiang ,  PIPIK, Brenda ,  PISSARNITSKI, Dmitri ,  DUFFY, Joseph, L. ,  GUIDRY, Erin, N.

IPC: A61K47/48 ,  A61K38/28

CPC classification number: A61K47/61 ,  A61K38/28 ,  A61K47/549 ,  A61K47/64 ,  C07K14/62

Abstract: Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract translation: 胰岛素缀合物包含共价连接至具有两个臂的至少一个双齿连接体的胰岛素分子，每个臂独立地连接至包含糖的配体，并且其中连接体的至少一个配体是岩藻糖是 披露。 即使当给予有需要的受试者时，胰岛素缀合物显示响应于糖的系统浓度（例如葡萄糖或α-甲基甘露糖）的药代动力学（PK）和/或药效学（PD）曲线，所述受试者不存在外源性多价 糖结合分子如Con A。

公开(公告)号：WO2014130607A1

公开(公告)日：2014-08-28

申请号：PCT/US2014/017260

申请日：2014-02-20

Applicant: SIRNA THERAPEUTICS, INC. ,  CHANG, Wonsuk ,  GUIDRY, Erin, N. ,  STANTON, Matthew, G. ,  ZEWGE, Daniel

Inventor： CHANG, Wonsuk ,  GUIDRY, Erin, N. ,  STANTON, Matthew, G. ,  ZEWGE, Daniel

IPC: C12N15/11 ,  C07H21/04 ,  C07H21/02 ,  C07H21/00

CPC classification number: C12N15/113 ,  C07H19/10 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/319

Abstract: The present invention relates to RNAi molecules, and compositions thereof, comprising a 2' internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5' end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5' modified nucleotides that comprise, among other potential modifications, a 2' internucleoside linkage. The invention further relates to 5' modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

Abstract translation: 本发明涉及RNAi分子及其组合物，其包含连接位置1的核苷酸和反义链的5'末端的位置2的核苷酸的2'核苷间键。 具体地，本发明涉及能够介导包含5'修饰的核苷酸的RNA干扰的单链和双链短干扰核酸（siNA）分子，其包括2'核苷间键的其它潜在修饰。 本发明还涉及用作产生本发明的RNAi分子的试剂的5'修饰的核苷酸和使用所公开的RNAi分子的方法。