Merck Sharp + Dohme Corp.

Other

Merck + Co., Inc.

Merck Sharp & Dohme LLC

Songnian Lin

Lin Yan

Emma R Parmee

Pei Huo

Danqing D Feng

Dmitri A Pissarnitski

Ahmet Kekec

Yuping Zhu

Ravi P Nargund

Xibin Liao

Libo Xu

Lihu Yang

Zhicai Wu

Christina B Madsen-Duggan

Zhi-Cai Shi

Jiayi Xu

Changyou Zhou

Shawn P Walsh

Brian T Campbell

Weiguo Liu

John E Stelmach

Fengqi Zhang

Sheryl Davis Debenham

Anandan Palani

Paul E Finke

Feroze Ujjainwalla

Tomi K Sawyer

Ping Liu

Dooseop Kim

Haifeng Tang

Rui Liang

Elisabetta Bianchi

John S Debenham

Yusheng Xiong

Helen Y Chen

Ryan Stafford

Bing Li

Richard Berger

Gang Yin

Timothy A Blizzard

Zhiqiang Zhao

Yingjun Mu

Edward Metzger

Min Ge

Sunita V Dewnani

Roman Kats-Kagan

Gui-Bai Liang

Rui Zhang

Christopher R Moyes

Chris Moyes

Brenda Pipik

Christian P Stevenson

Alice Yam

Nancy J Kevin

Edward P Bowman

Harry R Davis

Timothy Allen Blizzard

Qinghong Fu

Zhiqiang Yang

Xiaofan Li

Zhiyong Hu

Zhiqiang Guo

Bart Harper

Cristina Abrahams

Ming Wang

Jiafang He

Zack Zhiqiang Guo

Jose M Castro-Perez

Candido Gude

Byron Dubois

Craig A Parish

Hong-Ping Guan

David N Hunter

Erin N Guidry

Willy Solis

Eric Dean Cline

Samuel S Engel

Junhao Yang

Aarron Willingham

Sheng-Ping Wang

Liangsu Wang

Thomas P Roddy

Weijuan Tang

Fiona Wai Yu Lau

Sunita Malkani

Joseph L Duffy

Stephen F Previs

Douglas G Johns

Samuel E Engel

Steven F Previs

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.

Glucose-responsive insulin conjugates

Interleukin-2 (IL-2) conjugates comprising at least one or more amino acid substitutions that bias binding to the IL-2 receptor &#x3b2;&#x3b3;dimer over binding the IL-2 receptor &#x3b1;&#x3b2;&#x3b3;trimer and a non-natural amino acid at or near the N-terminus conjugated to a water-soluble polymer are described. The IL-2 conjugates are useful for treatment and prevention of cell proliferation and cancer in a patient.

Human interleukin-2 conjugates biased for the interleukin-2 receptor beta GAMMAc dimer and conjugated to a nonpeptidic, water-soluble polymer

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.

Conjugate based systems for controlled insulin delivery

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).

Tyrosine-specific functionalized insulin and insulin analogs

The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). 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.

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

Methods of treating diabetes by administering a glucagon receptor antagonist in combination with a cholesterol absorption inhibitor

Insulin dimers conjugated to peptides having at least one incretin activity are disclosed.

Insulin dimer-incretin conjugates

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.

Glucose responsive insulin comprising a tri-valent sugar cluster for treatment of diabetes

The present invention provides compositions comprising insulin receptor partial agonists in association with GLP-1 analogues (e.g., liraglutide) as well as methods for using the compositions for example, to treat or prevent diabetes or to decrease body weight.

Insulin receptor partial agonists and GLP-1 analogues

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

Insulin receptor partial agonists

The compounds of Formula I act as MGAT2 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity. 

Isoquinoline derivatives as MGAT2 inhibitors

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.

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Holmdel, NJ, United States of America

Songnian Lin