Merck Sharp + Dohme Corp.

Other

Yuping Zhu

Danqing D Feng

Lin Yan

Songnian Lin

Dmitri A Pissarnitski

Ahmet Kekec

Ravi P Nargund

Zhicai Wu

Christina B Madsen-Duggan

Lihu Yang

Alexander Pasternak

Haifeng Tang

Zhi-Cai Shi

Shawn P Walsh

Scott D Edmondson

Ping Liu

Liping Wang

Andrew William Stamford

Anandan Palani

Barbara A Pio

James M Balkovec

Harold B Wood

Gregori J Morriello

Bowei Wang

Cheng Zhu

Michael W Miller

Dooseop Kim

Elisabetta Bianchi

Duane E DeMong

Milana M Maletic

Wanying Sun

Rajan Anand

Qiaolin Deng

William Bert Geiss

Zhiqiang Zhao

Pei Huo

Aurash Shahripour

Yingjun Mu

Zhiyong Hu

Zhiqiang Guo

Jason W Szewczyk

Brenda Pipik

Nardos H Teumelsan

Kevin Michael Belyk

Lehua Chang

Joel M Harris

Vincent Colandrea

Federica Orvieto

Nam Fung Kar

Kake Zhao

Chunhui Huang

Christopher R Moyes

Chris Moyes

Reynalda Keh Dejesus

Yong Huang

David N Hunter

Erin N Guidry

Megan Macala

William B Geiss

Kevin Belyk

Steven H Olson

Joseph L Duffy

Vincent J Colandrea

Reynalda K Dejesus

Duane E Demong

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

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

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

Long-acting co-agonists of the glucagon and GLP-1 receptors

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

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

Insulin receptor partial agonists

This invention relates to compounds having structural Formula (I); and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir 1.1). The compounds of Formula I are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure. 

Inhibitors of the renal outer medullary potassium channel

This invention relates to compounds having structural Formula I: and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir1.1). The compounds of Formula I are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure.

Substituted cyclopropyl compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included. 

Substituted cyclopropyl compounds useful as GPR119 agonists

Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included. 

Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment

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Basking Ridge, NJ, United States of America

Yuping Zhu