Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Other

Merck Shapr & Dohme Corp.

Danqing D Feng

Tesfaye Biftu

XiaoXia Qian

Ahmet Kekec

Ann E Weber

Zhicai Wu

Ping Chen

Robert R Wilkening

Lan Wei

Iyassu Sebhat

Lin Yan

Songnian Lin

Dmitri A Pissarnitski

Bing Li

Jacqueline D Hicks

Ravi P Nargund

Jason M Cox

Christina B Madsen-Duggan

Matthew J Wyvratt

Michael H Fisher

Ashok Arasappan

Mitree M Ponpipom

Zhi-Cai Shi

Suresh B Singh

Jinlong Jiang

Charles G Caldwell

Ying-Duo Gao

Lin Chu

Rajan Anand

James Francis Dropinski

Robert L Bugianesi

Zhiqiang Zhao

James M Apgar

Yuping Zhu

Kenneth J Leavitt

Pei Huo

Gui-Bai Liang

Yingjun Mu

Brenda Pipik

Erin Guidry

Tesfaye Bitfu

Jinyou Xu

Guizhen Dong

Vincent Colandrea

Elizabeth M Naylor

Narindar N Girotra

Troy McCracken

Anthony Mastracchio

Christopher R Moyes

Alexander J Kim

Chan-Hwa Kuo

Hong Dong Chu

Chris Moyes

David N Hunter

Erin N Guidry

Xiaoxia Qian

Gui Bai Liang

Michael H Fischer

Vincent J Colandrea

Troy Mccracken

Joseph L Duffy

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

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

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 

Azabenzimidazole tetrahydrofuran derivatives

The novel benzimidazole hexahydrofuro[3,2-B]furan derivatives of the present invention are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 

Benzimidazole hexahydrofuro[3,2-b]furan derivatives

Benzimidazole tetrahydrofuran derivatives

Novel compounds described herein are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPKactivated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 

Benzimidazole tetrahydropyran derivatives

Novel compounds of the structural formula (I) are activators of AMP-protein kinase and may be useful in the treatment, prevention and suppression of diseases mediated by the AMPK activated protein kinase. The compounds of the present invention may be useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 

Azabenzimidazole tetrahydropyran derivatives

Azabenzimidazole hexahydrofuro[3,2-b]furan derivatives

The present invention is directed to novel substituted aminotetrahydrothiopyrans and derivatives thereof of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved. 

Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes

Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension. 

Cyclic azabenzimidazole derivatives useful as anti-diabetic agents

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Branchburg Township, NJ, United States of America

Danqing D Feng