Millennium Pharmaceuticals Limited

The General Hospital Corporation

Massachusetts General Hospital Corporation

Eric S Lightcap

Julian Adams

Peter G Smith

Ross L Stein

Vito J Palombella

Jeffrey E Settleman

Stephen J Brand

George J Mulligan

Peter J Elliott

Stephen J Blakemore

Matthew C Schu

Allison Berger

Cyril H Benes

Jonathan L Blank

Lawrence R Dick

Gopalakrishna R Vaddi

Dan R Burns

Teresa A McCormack

Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Biomarkers of response to NAE inhibitors

Disclosed are methods for the treatment of various solid tumors in patients in need of such treatment. The methods comprise administering to such a patient an NEDD8-activating enzyme (NAE) inhibitor such as ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate (MLN4924) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of various solid tumors.

Administration of NEDD8-activating enzyme inhibitor and chemotherapeutic agents

The invention relates to methods for measuring proteasome activity in biological samples. More particularly, then invention relates to methods for monitoring drug action following in vivo administration of a proteasome inhibitor. The invention provides methods and kits for monitoring pharmacodynamic drug action and for determining dose regimen for a proteasome inhibitor. The invention also provides methods for determining baseline proteasome activity in a mammal.

Method for monitoring proteasome inhibitor drug action

Growing community of inventors

Natick, MA, United States of America

Eric S Lightcap