Merck Sharp + Dohme Corp.

Chris Moyes

Scott D Edmondson

Gregori J Morriello

Cheng Zhu

Bing Li

Ihor E Kopka

Richard Berger

Liping Wang

Stephen D Goble

Lehua Chang

Nam Fung Kar

Dong-Ming Shen

Sookhee Nicole Ha

Songnian Lin

Harvey Wendt

Danqing D Feng

Lin Yan

Dmitri A Pissarnitski

Ahmet Kekec

Pei Huo

Yuping Zhu

Bart Harper

Ding-Ming Shen

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 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.

The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of &#x3b2;3-adrenoceptor. 

Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists

The present invention provides compounds of Formula I, pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of &#x3b2;3-adrenoceptor. 

Hydroxymethyl pyrrolidines as &#x3b2;3 adrenergic receptor agonists

Growing community of inventors

Westfield, NJ, United States of America

Chris Moyes