Whitehead Institute for Biomedical Research

Immunogen, Inc.

Macrogenics, Inc.

Nicholas C Yoder

Michael Louis Miller

Ezio Bonvini

Hidde L Ploegh

Michael S Fleming

Benjamin M Hutchins

Gundo Diedrich

Bhaswati Barat

Juniper A Scribner

Martin D Witte

Chen Bai

Stuart William Hicks

Amit Gangar

Scott Alan Hilderbrand

Methods and reagents for the installation of click chemistry handles on target proteins are provided, as well as modified proteins comprising click chemistry handles. Further, chimeric proteins, for example, bi-specific antibodies, that comprise two proteins conjugated via click chemistry, as well as methods for their generation and use are disclosed herein.

Using sortases to install click chemistry handles for protein ligation

The invention relates to novel cell-binding agent-cytotoxic agent conjugates, wherein 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 methods of preparing the conjugates of the present invention. The invention further provides composition and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.

Conjugates of cysteine engineered antibodies

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Brookline, MA, United States of America

Nicholas C Yoder