Selective sulfonation of benzodiazepine derivatives
AssigneeImmunoGen, Inc.
InventorsScott A. Hilderbrand, Benjamin M. Hutchins
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Abstract
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.
Claims20
A method of preparing an antibody-cytotoxic agent conjugate comprising the steps of:
- (a) reacting an imine-containing cytotoxic agent represented by the following formula:
- or a pharmaceutically acceptable salt thereof, with sodium bisulfate salt or sodium metabisulfite salt in a mixture of an organic solvent and water in the absence of a buffer to form a modified cytotoxic agent comprising a modified imine moiety represented by the following formula:
- or a pharmaceutically acceptable salt thereof;
- and
- (b) reacting the modified cytotoxic agent with an antibody to form the antibody-cytotoxic agent conjugate.
Dependencies are inferred from the claim text.