Thursday, March 21, 2013
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Controlled Fab-arm exchange
(cFAE) approach to develop bispecific antibodies for therapeutic use
In vitro and mouse studies identified a method to develop
bispecific antibodies as therapeutics. The cFAE method involved expressing
matched mutant methyl domains in two IgG1
antibodies and combining the antibodies with a weak reducing agent to
preserve the heavy-chain and light-chain pairings. Bispecific antibodies were
designed including those that target both CD20
as well as those that target HER2 and CD3.
In cancer cells and in mice xenograft models for gastric carcinoma, the HER2-
and CD3-targeting antibody decreased cancer cell survival compared with a
control antibody. Next steps include developing bispecific antibody
Published online March 21, 2013
Patent applications filed;
licensed to Novartis
AG, Janssen Pharmaceuticals N.V., Kyowa
Hakko Kirin Co. Ltd. and an undisclosed company for
specific programs; available for licensing
Labrijn, A.F. et al.
Proc. Natl. Acad. Sci. USA; published online March 11, 2013;
Contact: Paul W.H.I. Parren, Genmab A/S, Brooklyn Park,
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