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：US08039484B2

公开(公告)日：2011-10-18

申请号：US12441733

申请日：2007-10-26

申请人： Min Ge ,  Songnian Lin ,  Shawn P. Walsh ,  Lihu Yang ,  Changyou Zhou

发明人： Min Ge ,  Songnian Lin ,  Shawn P. Walsh ,  Lihu Yang ,  Changyou Zhou

IPC分类号： A61K31/47 ,  A61K31/192 ,  A61K31/277 ,  C07D487/02 ,  C07D217/24 ,  C07D213/36 ,  C07D209/34 ,  C07D311/34 ,  C07D333/56

CPC分类号： C07D333/60 ,  C07C59/72 ,  C07C59/90 ,  C07C235/46 ,  C07C255/54 ,  C07C2602/08 ,  C07C2602/10 ,  C07D207/34 ,  C07D209/34 ,  C07D209/46 ,  C07D213/61 ,  C07D215/233 ,  C07D217/24 ,  C07D307/80 ,  C07D311/58 ,  C07D333/48 ,  C07D405/12 ,  C07D487/04

摘要： Diaryl ethers in which one of the aryl groups is a phenyl fused to a cycloalkyl or heterocyclic ring, to which is attached an acetic acid group, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes mellitus, and of conditions that often accompany this disease, including insulin resistance, obesity and lipid disorders.

摘要翻译： 其中一个芳基是与环烷基或杂环稠合的苯基，其中连接有乙酸基的二芳基醚是G-蛋白偶联受体40（GPR40）的激动剂，并且可用作治疗化合物，特别是在 治疗2型糖尿病以及经常伴随该疾病的病症，包括胰岛素抵抗，肥胖和脂质疾病。

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：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：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：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。

公开(公告)号：US20100105725A1

公开(公告)日：2010-04-29

申请号：US12441733

申请日：2007-10-26

申请人： Min Ge ,  Songnian Lin ,  Shawn P. Walsh ,  Lihu Yang ,  Changyou Zhou

发明人： Min Ge ,  Songnian Lin ,  Shawn P. Walsh ,  Lihu Yang ,  Changyou Zhou

IPC分类号： A61K31/47 ,  A61K31/192 ,  A61K31/277 ,  C07D487/02 ,  C07C255/52 ,  C07C59/84 ,  C07D217/24 ,  C07D213/36 ,  C07D209/34 ,  C07D311/34 ,  C07D333/56

CPC分类号： C07D333/60 ,  C07C59/72 ,  C07C59/90 ,  C07C235/46 ,  C07C255/54 ,  C07C2602/08 ,  C07C2602/10 ,  C07D207/34 ,  C07D209/34 ,  C07D209/46 ,  C07D213/61 ,  C07D215/233 ,  C07D217/24 ,  C07D307/80 ,  C07D311/58 ,  C07D333/48 ,  C07D405/12 ,  C07D487/04

摘要： Diaryl ethers in which one of the aryl groups is a phenyl fused to a cycloalkyl or heterocyclic ring, to which is attached an acetic acid group, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes mellitus, and of conditions that often accompany this disease, including insulin resistance, obesity and lipid disorders.

摘要翻译： 其中一个芳基是与环烷基或杂环稠合的苯基，其中连接有乙酸基的二芳基醚是G-蛋白偶联受体40（GPR40）的激动剂，并且可用作治疗化合物，特别是在 治疗2型糖尿病以及经常伴随该疾病的病症，包括胰岛素抵抗，肥胖和脂质疾病。

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：US20100234409A1

公开(公告)日：2010-09-16

申请号：US11596937

申请日：2005-05-20

申请人： Lihu Yang ,  Songnian Lin ,  Gregori Morriello ,  Liangqin Guo ,  Changyou Zhou

发明人： Lihu Yang ,  Songnian Lin ,  Gregori Morriello ,  Liangqin Guo ,  Changyou Zhou

IPC分类号： A61K31/438 ,  C07D401/10 ,  C07D211/32 ,  C07D235/04 ,  C07D215/04 ,  A61K31/445 ,  A61K31/454 ,  A61K31/4184 ,  A61P37/02 ,  A61P19/02

CPC分类号： C07D211/14 ,  C07D211/18 ,  C07D211/52 ,  C07D211/64 ,  C07D221/20 ,  C07D295/155 ,  C07D309/14 ,  C07D401/10 ,  C07D405/12 ,  C07D471/04

摘要： Compounds of the formulae (I) and (II): (wherein Q, X, E, G1, G2, R2, R3, R4, R5, R6 and Z are as defined herein) which are modulators of chemokine receptor activity and are useful in the prevention or treatment of certain inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which chemokine receptors are involved.

摘要翻译： 式（I）和（II）的化合物（其中Q，X，E，G1，G2，R2，R3，R4，R5，R6和Z如本文所定义），其是趋化因子受体活性的调节剂，并且是有用的 预防或治疗某些炎性和免疫调节性疾病和疾病，过敏性疾病，特应性疾病，包括过敏性鼻炎，皮炎，结膜炎和哮喘，以及自身免疫性疾病如类风湿性关节炎和动脉粥样硬化。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及趋化因子受体的疾病中的用途。

公开(公告)号：US20090312303A1

公开(公告)日：2009-12-17

申请号：US11794705

申请日：2006-01-30

申请人： Min Ge ,  Lihu Yang ,  Changyou Zhou ,  Songnian Lin ,  Haifeng Tang ,  Eric Dean Cline ,  Sunita Malkani

发明人： Min Ge ,  Lihu Yang ,  Changyou Zhou ,  Songnian Lin ,  Haifeng Tang ,  Eric Dean Cline ,  Sunita Malkani

IPC分类号： A61K31/427 ,  C07D277/04 ,  C07D417/12 ,  C07D263/04 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/422 ,  A61K31/397 ,  A61P3/10

CPC分类号： C07D263/44 ,  C07D233/74 ,  C07D271/07 ,  C07D277/34 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12

摘要： Bicyclic compounds containing a phenyl or pyridyl ring fused to a cycloalkyl or heterocyclic ring, to which is attached a 5-membered heterocyclic ring, including pharmaceutically acceptable salts and prodrugs thereof, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

摘要翻译： 包含与环烷基或杂环稠合的苯基或吡啶环的双环化合物，其连接有5元杂环，包括其药学上可接受的盐和前药，是G蛋白偶联受体40（GPR40）的激动剂，并且是有用的 作为治疗性化合物，特别是治疗2型糖尿病，以及通常与该疾病相关的病症，包括肥胖症和脂质疾病，例如混合或糖尿病性血脂异常，高脂血症，高胆固醇血症和高甘油三酯血症。