公开(公告)号：US20160251407A1

公开(公告)日：2016-09-01

申请号：US15025912

申请日：2014-10-02

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

发明人： Songnian Lin ,  Lin Yan ,  Ahmet Kekec ,  Yuping Zhu ,  David N. Hunter ,  Pei Huo ,  Danqing Feng ,  Ravi P. Nargund ,  Christopher R. Moyes ,  Zhiqiang Zhao ,  Brenda Pipik ,  Dmitri Pissarnitski ,  Joseph L. Duffy ,  Erin Guidry

IPC分类号： C07K14/62 ,  A61K38/28 ,  A61K47/48

CPC分类号： A61K47/61 ,  A61K38/28 ,  A61K47/549 ,  A61K47/64 ,  C07K14/62

摘要： 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.

摘要翻译： 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：US20220273770A1

公开(公告)日：2022-09-01

申请号：US17629501

申请日：2020-07-23

申请人： Danqing FENG ,  Erin N. GUIDRY ,  Pei HUO ,  Andrew J. KASSICK ,  Ahmet KEKEC ,  Songnian LIN ,  Christopher R MOYES ,  Dmitri A. PISSARNITSKI ,  Lin YAN ,  Yuping ZHU ,  Merck Sharp & Dohme Corp.

发明人： Danqing Feng ,  Erin N. Guidry ,  Pei Huo ,  Andrew J. Kassick ,  Ahmet Kekec ,  Songnian Lin ,  Christopher R. Moyes ,  Dmitri A. Pissarnitski ,  Lin Yan ,  Yuping Zhu

IPC分类号： A61K38/28 ,  A61K47/54 ,  A61P3/10

摘要： 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：US20180110863A1

公开(公告)日：2018-04-26

申请号：US15564805

申请日：2016-04-04

申请人： Danqing FENG ,  Erin N. GUIDRY ,  Pei HUO ,  Niels C. KAARSHOLM ,  Songnian LIN ,  Ravi P. NARGUND ,  Lin YAN ,  Merck Sharp & Dohme Corp.

发明人： Danqing Feng ,  Erin N. Guidry ,  Pei Huo ,  Niels C. Kaarsholm ,  Songnian Lin ,  Ravi P. Nargund ,  Lin Yan

IPC分类号： A61K47/54 ,  A61K38/28 ,  A61P3/10

摘要： 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.

公开(公告)号：US11820805B2

公开(公告)日：2023-11-21

申请号：US16771818

申请日：2018-12-13

申请人： Merck Sharp & Dohme Corp. ,  Lin Yan ,  Pei Huo ,  Ahmet Kekec ,  Danqing D. Feng ,  Yuping Zhu ,  Dmitri Pissarnitski ,  Chris Moyes ,  Songnian Lin

发明人： Lin Yan ,  Pei Huo ,  Ahmet Kekec ,  Danqing D. Feng ,  Yuping Zhu ,  Dmitri Pissarnitski ,  Chris Moyes ,  Songnian Lin

IPC分类号： C07K14/62 ,  A61K47/61 ,  A61K47/54 ,  A61K38/00

CPC分类号： C07K14/62 ,  A61K47/549 ,  A61K47/61 ,  A61K38/00

摘要： The present disclosure provides conjugates that comprise an insulin molecule conjugated via a conjugate framework to two or more separate ligands that each include a saccharide, wherein the framework, ligand, saccharide and insulin molecule optionally comprise a fatty chain (e.g., a C8-30 fatty chain), wherein when said insulin molecule is conjugated both to a C8-30 fatty chain and one or more separate ligands that each include a saccharide, said C8-30 fatty chain is linked to insulin molecule only, and wherein when the framework or ligand comprises a fatty chain the insulin molecule is conjugated to two or more separate ligands. In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

公开(公告)号：US20210198339A1

公开(公告)日：2021-07-01

申请号：US16771818

申请日：2018-12-13

申请人： Lin YAN ,  Pei HUO ,  Ahmet KEKEC ,  Danqing D. FENG ,  Yuping ZHU ,  Dmitri PISSARNITSKI ,  Chris MOYES ,  Songnian LIN ,  Merck Sharp & Dohme Corp.

发明人： Lin Yan ,  Pei Huo ,  Ahmet Kekec ,  Danqing D. Feng ,  Yuping Zhu ,  Dmitri Pissarnitski ,  Chris Moyes ,  Songnian Lin

IPC分类号： C07K14/62 ,  A61K47/54 ,  A61K47/61

摘要： The present disclosure provides conjugates that comprise an insulin molecule conjugated via a conjugate framework to two or more separate ligands that each include a saccharide, wherein the framework, ligand, saccharide and insulin molecule optionally comprise a fatty chain (e.g., a C8-30 fatty chain), wherein when said insulin molecule is conjugated both to a C8-30 fatty chain and one or more separate ligands that each include a saccharide, said C8-30 fatty chain is linked to insulin molecule only, and wherein when the framework or ligand comprises a fatty chain the insulin molecule is conjugated to two or more separate ligands. In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

公开(公告)号：US20190175744A1

公开(公告)日：2019-06-13

申请号：US16083201

申请日：2017-03-13

申请人： Anandan PALANI ,  Chunhui HUANG ,  Zhiqiang YANG ,  Lin YAN ,  Songnian LIN ,  Pei HUO ,  Qiaolin DENG ,  Elisabetta BIANCHI ,  Federica ORVIETO ,  Merck Sharp & Dohme Corp.

发明人： Anandan Palani ,  Chunhui Huang ,  Zhiqiang Yang ,  Lin Yan ,  Songnian Lin ,  Pei Huo ,  Qiaolin Deng ,  Elisabetta Bianchi ,  Federica Orvieto

IPC分类号： A61K47/64 ,  A61K38/28 ,  A61K38/26

摘要： Insulin-incretin conjugates comprising a peptide having agonist activity at the glucagon-like 1 (GLP-1) receptor, the glucagon (GCG) receptor, and/or the gastric inhibitory protein (GIP) receptor conjugated to an insulin molecule having agonist activity at the insulin receptor and use of the conjugates for treatment of metabolic diseases, for example, Type 2 diabetes, are described.

公开(公告)号：US11530250B2

公开(公告)日：2022-12-20

申请号：US16980579

申请日：2019-03-18

申请人： Merck Sharp & Dohme Corp. ,  Ahmet Kekec ,  Nancy Jo Kevin ,  Bing Li ,  Songnian Lin ,  Craig A. Parish ,  Weijuan Tang

发明人： Ahmet Kekec ,  Nancy Jo Kevin ,  Bing Li ,  Songnian Lin ,  Craig A. Parish ,  Weijuan Tang

IPC分类号： C07K14/62 ,  C07K1/107

摘要： The present invention relates to tyrosine-specific functionalized insulin analogs and processes of making such tyrosine-specific functionalized insulin analogs using R-3H-1,2,4-triazoline-3,5-(4H)diones (PTAD).

公开(公告)号：US20210002345A1

公开(公告)日：2021-01-07

申请号：US16980579

申请日：2019-03-18

申请人： Ahmet KEKEC ,  Nancy Jo KEVIN ,  Bing LI ,  Songnian LIN ,  Craig A. PARISH ,  Weijuan TANG ,  Merck Sharp & Dohme Corp.

发明人： Ahmet Kekec ,  Nancy Jo Kevin ,  Bing Li ,  Songnian Lin ,  Craig A. Parish ,  Weijuan Tang

IPC分类号： C07K14/62 ,  C07K1/107

摘要： The present invention relates to tyrosine-specific functionalized insulin analogs and processes of making such tyrosine-specific functionalized insulin analogs using R-3H-1,2,4-triazoline-3,5-(4H)diones (PTAD).

公开(公告)号：US20150336991A1

公开(公告)日：2015-11-26

申请号：US14652883

申请日：2013-12-12

申请人： Emma R. PARMEE ,  Songnian LIN ,  Brian CAMPBELL ,  Sunita V. DEWNANI ,  Roman KATS-KAGAN ,  Jiayi XU ,  Libo XU ,  Rui ZHANG ,  MERCK SHARP & DOHME CORP.

发明人： Songnian Lin ,  Rui Zhang ,  Brian Campbell ,  Sunita V. Dewnani ,  Jiayi Xu ,  Libo Xu ,  Emma R. Parmee ,  Roman Kats-Kagan

IPC分类号： C07F9/6539 ,  A61K31/4439 ,  C07D401/04 ,  A61K31/444 ,  C07D471/04 ,  A61K31/427 ,  C07F9/58 ,  A61K31/675 ,  C07D403/14 ,  A61K31/497 ,  C07D417/14 ,  C07D401/14 ,  A61K31/437

CPC分类号： C07F9/6539 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/497 ,  A61K31/675 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D417/14 ,  C07D471/04 ,  C07F7/0812 ,  C07F9/58 ,  C07F9/65583

摘要： Novel pyridine-2-carboxamide derivatives of formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are effective as glucokinase activating agents. Pharmaceutical compositions and methods of treatment are also included.

摘要翻译： 公开了式I的新型吡啶-2-甲酰胺衍生物及其药学上可接受的盐可用于治疗或预防2型糖尿病和类似病症。 这些化合物作为葡萄糖激酶活化剂是有效的。 还包括药物组合物和治疗方法。

公开(公告)号：US20150320724A1

公开(公告)日：2015-11-12

申请号：US14649651

申请日：2013-12-08

申请人： Hong-Ping GUAN ,  Jose M. CASTRO-PEREZ ,  Harry R. DAVIS ,  Samuel S. ENGEL ,  Douglas G. JOHNS ,  Songnian LIN ,  Steven F. PREVIS ,  Thomas P. RODDY ,  Liangsu WANG ,  Sheng-Ping WANG ,  Yusheng XIONG ,  MERCK SHARP & DOHME CORP.

发明人： Hong-Ping Guan ,  Jose M. Castro-Perez ,  Harry R. Davis ,  Samuel E. Engel ,  Douglas G. Johns ,  Songnian Lin ,  Stephen F. Previs ,  Thomas P. Roddy ,  Liangsu Wang ,  Sheng-Ping Wang ,  Yusheng Xiong

IPC分类号： A61K31/4184 ,  A61K31/194 ,  A61K31/403 ,  A61K9/24 ,  A61K31/397 ,  A61K31/415

CPC分类号： A61K31/397 ,  A61K9/209 ,  A61K31/194 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/435 ,  A61K31/44 ,  A61K45/06 ,  A61K2300/00

摘要： Use of a glucagon receptor antagonist in combination with a cholesterol absorption inhibitor for the treatment of diabetes and related conditions is disclosed.

摘要翻译： 公开了将胰高血糖素受体拮抗剂与胆固醇吸收抑制剂组合用于治疗糖尿病和相关病症的用途。