公开(公告)号：US20210284694A1

公开(公告)日：2021-09-16

申请号：US17253864

申请日：2019-06-20

申请人： Merck Sharp & Dohme corp. ,  Ra Pharmaceuticals, Inc.

发明人： Alonso Ricardo ,  Thomas Joseph Tucker ,  Nicolas Cedric Boyer ,  Joseph R. Stringer ,  Derek M. LaPlaca ,  Angela Dawn Kerekes ,  Chengwei Wu ,  Sookhee Nicole Ha ,  Hyewon Youm ,  Mark W. Embrey ,  Elisabetta Bianchi ,  Danila Branca ,  Raffaele Ingenito ,  Willy Costantini ,  Alessia Santoprete ,  Roberto Costante ,  Immacolata Conte ,  Stefania Colarusso ,  Eric J. Gilbert ,  Aurash Shahripour ,  Yusheng Xiong

IPC分类号： C07K7/64

摘要： Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

公开(公告)号：US20210214395A1

公开(公告)日：2021-07-15

申请号：US17253815

申请日：2019-06-20

申请人： Merck Sharp & Dohme Corp.

发明人： Yusheng Xiong ,  Thomas Joseph Tucker ,  Chengwei Wu ,  Elisabetta Bianchi ,  Danila Branca ,  Angela Dawn Kerekes ,  Abbas M. Walji ,  Hubert B. Josien ,  Fa-Xiang Ding ,  Hyewon Youm ,  Alessia Santoprete ,  Raffaele Ingenito

IPC分类号： C07K7/56

摘要： Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R4, and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions

公开(公告)号：US11306125B2

公开(公告)日：2022-04-19

申请号：US17253815

申请日：2019-06-20

申请人： Merck Sharp & Dohme Corp.

发明人： Yusheng Xiong ,  Thomas Joseph Tucker ,  Chengwei Wu ,  Elisabetta Bianchi ,  Danila Branca ,  Angela Dawn Kerekes ,  Abbas M. Walji ,  Hubert B. Josien ,  Fa-Xiang Ding ,  Hyewon Youm ,  Alessia Santoprete ,  Raffaele Ingenito

IPC分类号： C07K7/56 ,  A61K38/00

摘要： Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R4, and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions

公开(公告)号：US20210163538A1

公开(公告)日：2021-06-03

申请号：US17253783

申请日：2019-06-20

申请人： Merck Sharp & Dohme corp. ,  Ra Pharmaceuticals, Inc.

发明人： Alonso Ricardo ,  Thomas Joseph Tucker ,  Nicolas Cedric Boyer ,  Ketki Ashok Dhamnaskar ,  Zhong Ma ,  Angela Dawn Kerekes ,  Chengwei Wu ,  Sookhee Nicole Ha ,  Hyewon Youm ,  Elisabetta Bianchi ,  Danila Branca ,  Raffaele Ingenito ,  Willy Costantini ,  Aurash Shahripour ,  Yusheng Xiong

IPC分类号： C07K7/64

摘要： Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

公开(公告)号：US20190389909A1

公开(公告)日：2019-12-26

申请号：US16446940

申请日：2019-06-20

申请人： Merck Sharp & Dohme Corp.

发明人： Harold B. Wood ,  Hubert B. Josien ,  Thomas Joseph Tucker ,  Angela Dawn Kerekes ,  Ling Tong ,  Abbas M. Walji ,  Anilkumar G. Nair ,  Fa-Xiang Ding ,  Elisabetta Bianchi ,  Danila Branca ,  Chengwei Wu ,  Yusheng Xiong ,  Sookhee Nicole HA ,  Jian Liu ,  Sobhana Babu Boga

IPC分类号： C07K7/64 ,  A61P3/06

摘要： Disclosed are compounds of Formula I, or a salt thereof: where A, B, D, X, R1, R2 and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

公开(公告)号：US10413593B2

公开(公告)日：2019-09-17

申请号：US15519565

申请日：2015-10-22

申请人： MERCK SHARP & DOHME CORP.

发明人： Elisabetta Bianchi ,  Paul E. Carrington ,  Qiaolin Deng ,  Ravi Nargund ,  Federica Orvieto ,  Anandan Palani ,  Antonello Pessi ,  Thomas Joseph Tucker ,  Chengwei Wu

IPC分类号： C07K14/605 ,  A61K38/26 ,  A61K38/28

摘要： Described are peptide analogs of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have relatively balanced agonist activity at the glucagon-like peptide 1 (GLP-1) receptor and the glucagon (GCG) receptor, and the use of such GLP-1 receptor/GCG receptor co-agonists for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

公开(公告)号：US20170360893A1

公开(公告)日：2017-12-21

申请号：US15519565

申请日：2015-10-22

申请人： MERCK SHARP & DOHME CORP.

发明人： Elisabetta Bianchi ,  Paul E. Carrington ,  Qiaolin Deng ,  Ravi Nargund ,  Federica Orvieto ,  Anandan Palani ,  Antonello Pessi ,  Thomas Joseph Tucker ,  Chengwei Wu

IPC分类号： A61K38/28 ,  C07K14/605 ,  A61K38/26

CPC分类号： A61K38/28 ,  A61K38/26 ,  C07K14/605 ,  A61K2300/00

摘要： Described are peptide analogs of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have relatively balanced agonist activity at the glucagon-like peptide 1 (GLP-1) receptor and the glucagon (GCG) receptor, and the use of such GLP-1 receptor/GCG receptor co-agonists for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity

公开(公告)号：US20160114000A1

公开(公告)日：2016-04-28

申请号：US14920012

申请日：2015-10-22

申请人： MERCK SHARP & DOHME CORP.

发明人： Elisabetta Bianchi ,  Paul E. Carrington ,  Qiaolin Deng ,  Ravi Nargund ,  Federica Orvieto ,  Anandan Palani ,  Antonello Pessi ,  Thomas Joseph Tucker ,  Chengwei Wu

IPC分类号： A61K38/26 ,  A61K38/28 ,  C07K14/605

CPC分类号： A61K38/28 ,  A61K38/26 ,  C07K14/605 ,  A61K2300/00

摘要： Described are peptide analogs of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have relatively balanced agonist activity at the glucagon-like peptide 1 (GLP-1) receptor and the glucagon (GCG) receptor, and the use of such GLP-1 receptor/GCG receptor co-agonists for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

摘要翻译： 描述了胰高血糖素的肽类似物，其已被修饰为对二肽基肽酶IV（DPP-IV）的切割和失活具有抗性，并增加肽类似物的体内半衰期，同时使肽类似物具有相对平衡的激动剂活性 胰高血糖素样肽1（GLP-1）受体和胰高血糖素（GCG）受体，以及使用这样的GLP-1受体/ GCG受体辅助激动剂来治疗代谢紊乱如糖尿病，非酒精性脂肪肝 疾病（NAFLD），非酒精性脂肪性肝炎（NASH）和肥胖症。