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：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.