Immunogen, Inc.

Benjamin M Hutchins

Scott A Hilderbrand

Richard A Silva

Michael Reardon

Michael S Fleming

Nicholas C Yoder

Robert W Herbst

Daniel F Milano

Chen Bai

Amit Gangar

Scott Alan Hilderbrand

The invention relates to novel methods of preparing cell-binding agent-cytotoxic agent conjugates, wherein the cytotoxic agent is an imine-containing cytotoxic agent bearing a maleimide group. In some embodiments, the cell-binding agent (CBA) is covalently linked to the cytotoxic agent through an engineered Cys, such as an engineered Cys in the heavy chain CH3 domain, at a position corresponds to the EU/OU numbering position 442 (or C442) on an antibody CBA. The invention also provides conjugates prepared by the methods of the present invention, compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.

Selective sulfonation of benzodiazepine derivatives

Methods of producing, purifying, and formulating antibody drug conjugates (ADCs) are provided herein. The methods use continuous conjugation processes, single-pass tangential flow filtration, countercurrent diafiltration, and/or in-line process automation technologies. The methods decrease process times and costs and improve product consistency.

Methods for antibody drug conjugation, purification, and formulation

The present invention provides a novel process for preparing a cell-binding agent cytotoxic agent conjugate. The process comprises the steps of: (a) reacting a cytotoxic agent with a bifunctional crosslinking reagent represented by the structural formula (I) or a salt thereof, in a buffer solution comprising a buffering agent to provide a first mixture comprising a cytotoxic agent-linker compound, wherein the buffer solution has high buffer capacity; and (b) reacting the first mixture comprising the cytotoxic agent-linker compound from step (a) with a cell-binding agent in a solution having a pH of 4 to 9 to provide a second mixture comprising the cell-binding agent cytotoxic agent conjugate. The cell-binding agent cytotoxic agent conjugates prepared according to the processes described herein are also included in the present invention. 

Process for preparing cell-binding agent-cytotoxic agent conjugates

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Boxborough, MA, United States of America

Benjamin M Hutchins