公开(公告)号：US11041009B2

公开(公告)日：2021-06-22

申请号：US16495703

申请日：2018-03-19

Applicant: Merck Sharp & Dohme Corp.

Inventor： Danqing Feng ,  Pei Huo ,  Ahmet Kekec ,  Songnian Lin ,  Christopher R. Moyes ,  Ravi Nargund ,  Brenda Pipik ,  Dmitri A. Pissarnitski ,  Lin Yan ,  Yuping Zhu

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

Abstract: An insulin conjugate comprising or consisting of a tri-valent sugar cluster is described. In particular aspects, the insulin conjugate displays 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：US20190092833A1

公开(公告)日：2019-03-28

申请号：US16199774

申请日：2018-11-26

Applicant: Merck Sharp & Dohme Corp.

Inventor： Songnian Lin ,  Lin Yan ,  Pei Huo ,  Dmitri Pissarnitski ,  Danqing Feng ,  Ravi Nargund ,  Yuping Zhu ,  Ahmet Kekec ,  Christina B. Madsen-Duggan ,  Zhi-Cai Shi ,  Zhicai Wu ,  Yingjun Mu

IPC: C07K14/62 ,  A61K47/60 ,  A61K38/28 ,  A61K47/55 ,  A61K38/00

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

公开(公告)号：US09427475B2

公开(公告)日：2016-08-30

申请号：US14504476

申请日：2014-10-02

Applicant: Merck Sharp & Dohme Corp.

Inventor： Songnian Lin ,  Lin Yan ,  Pei Huo

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

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 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：US11820805B2

公开(公告)日：2023-11-21

申请号：US16771818

申请日：2018-12-13

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

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

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

CPC classification number: C07K14/62 ,  A61K47/549 ,  A61K47/61 ,  A61K38/00

Abstract: 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：US20220233647A1

公开(公告)日：2022-07-28

申请号：US17614680

申请日：2020-06-01

Applicant: Merck Sharp & Dohme Corp.

Inventor： Danqing Feng ,  Songnian Lin ,  Dmitri A. Pissarnitski ,  Brenda Pipik ,  Lin Yan ,  Yuping Zhu

IPC: A61K38/28 ,  A61K47/54 ,  A61K47/65 ,  A61P3/10

Abstract: Glucose-responsive insulin conjugates that contain one or more linear oligomer sugar cluster are provided. Such insulin conjugates that 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：US20210163568A1

公开(公告)日：2021-06-03

申请号：US17045197

申请日：2019-04-08

Applicant: Merck Sharp & Dohme Corp.

Inventor： Sobhana Babu Boga ,  Ahmet Kekec ,  Songnian Lin ,  Craig A. Parish ,  Weijuan Tang ,  Lin Yan

IPC: C07K14/62 ,  C07K1/00

Abstract: The present invention relates to insulin analogues and processes of making such insulin analogues by direct conversion of a free amine to an azide via diazo-transfer with an azotransfer agent.

公开(公告)号：US20190177393A1

公开(公告)日：2019-06-13

申请号：US16301010

申请日：2017-05-23

Applicant: Merck Sharp & Dohme Corp.

Inventor： Songnian Lin ,  Lin Yan ,  Pei Huo ,  Dmitri Pissarnitski ,  Danqing Feng ,  Ravi Nargund ,  Christina Madsen-Duggan ,  Yuping Zhu ,  Ahmet Kekec ,  Zhicai Wu

IPC: C07K14/62 ,  A61P3/10

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

公开(公告)号：US10017556B2

公开(公告)日：2018-07-10

申请号：US14945461

申请日：2015-11-19

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Songnian Lin ,  Lin Yan ,  Pei Huo ,  Dmitri Pissarnitski ,  Danqing Feng ,  Ravi Nargund ,  Yuping Zhu ,  Ahmet Kekec ,  Christina B. Madsen-Duggan ,  Zhi-Cai Shi ,  Zhicai Wu ,  Yingjun Mu

IPC: C07K14/62 ,  A61K38/28 ,  A61K47/60 ,  A61K47/55 ,  A61K38/00

CPC classification number: C07K14/62 ,  A61K38/00 ,  A61K38/28 ,  A61K47/55 ,  A61K47/60 ,  C07K2319/00

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

公开(公告)号：US09889205B2

公开(公告)日：2018-02-13

申请号：US15191584

申请日：2016-06-24

Applicant: Merck Sharp & Dohme Corp.

Inventor： Songnian Lin ,  Lin Yan ,  Pei Huo

IPC: A61K38/00 ,  A61K47/48 ,  A61K38/28 ,  C07K14/62

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 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：US20170216250A1

公开(公告)日：2017-08-03

申请号：US15484508

申请日：2017-04-11

Applicant: Merck Sharp & Dohme Corp.

Inventor： 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: A61K31/397 ,  A61K31/404 ,  A61K31/415 ,  A61K9/24

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

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