The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

Keith W Miller

Joseph F Cotten

Stuart A Forman

Douglas Raines

Syed Shaukat Husain

Gregory D Cuny

Youssef Jounaidi

Joseph F Cotton

Douglas E Raines

Fusion proteins comprising IL2 and IL2Rβ (e.g., CIRB), IL2, IL2Rβ and IL21R (e.g., CIRB21), and/or comprising IL2, IL2Rβ, and CD28 (e.g., CIRB28); natural killer (NK) cells that express the fusion proteins and methods of use thereof, e.g., to treat subjects with cancer; and regulatory T cells (T-regs) that express a fusion protein comprising IL2, IL2Rβ, and CD28 and methods of use thereof, e.g., to treat subjects with autoimmune disease or GVHD.

Tethered interleukin-2 to its receptor IL-2RBETA, a platform to enhance natural killer and regulatory T cell activity

The invention is directed to compounds according to formula (I): where Ris LC(O)OT or LC(O)OLC(O)OT; Ris a substituted or unsubstituted C-Calkyl, C-Calkenyl, or C-Calkynyl, or R; n is an integer from 0 to 5; each Ris independently halogen or R; Rand Rare independently H, halogen, CN or CF; Land Lare each independently a bond, a substituted or unsubstituted C-Calkylene, C-Calkenylene, or C-Calkynylene; and T is H, a substituted or unsubstituted C-Calkyl, C-Calkenyl, or C-Calkynyl, nitrophenol, or cyclopropyl. The invention is also directed to a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and to methods for providing anesthesia in mammals by administering such a pharmaceutical composition.

Etomidate analogues that do not inhibit adrenocortical steroid synthesis

The invention is directed to compounds according to formula (I): where Ris LC(O)OT or LC(O)OLC(O)OT; Ris a substituted or unsubstituted C-Calkyl, C-Calkenyl, or C-Calkynyl, or R; n is an integer from 0 to 5; each Ris independently halogen or R; Land Lare each independently a bond, a substituted or unsubstituted C-Calkylene, C-Calkenylene, or C-Calkynylene; and T is H, a substituted or unsubstituted C-Calkyl, C-Calkenyl, or C-Calkynyl, nitrophenol, or cyclopropyl. The invention is also directed to a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and to methods for providing anesthesia in mammals by administering such a pharmaceutical composition.

Etomidate analogues with improved pharmacokinetic and pharmacodynamic properties

The invention is directed to compounds according to formula (I): where Ris LC(O)OT or LC(O)OLC(O)OT; Ris a substituted or unsubstituted C-Calkyl, C-Calkenyl, or C-Calkynyl, or R; n is an integer from 0 to 5; each Ris independently halogen or R; Land Lare each independently a bond, a substituted or unsubstituted C-Calkylene, C-Calkenylene, or C-Calkynylene; and T is H, a substituted or unsubstituted C-Calkyl, C-Calkenyl, or C-Calkynyl, nitrophenol, or cyclopropyl. The invention is also directed to a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and to methods for providing anesthesia in mammals by administering such a pharmaceutical composition. 

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Lincoln, MA, United States of America

Keith W Miller