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Monovalent, transferrin receptor-binding antibody with improved blood brain barrier (BBB) penetration

A monovalent, transferrin receptor-binding Fab fragment could be used to improve the delivery of antibodies through the BBB. An antibody was constructed that consisted of a single transferrin receptor-binding Fab fragment fused to the C-terminal end of the heavy chain of a b-amyloid (Ab)-specific mAb. In a mouse model of amyloid precursor protein (APP)-driven amyloidosis, the engineered antibody improved parenchymal exposure and increased Ab binding in the brain by 50-fold compared with an unmodified Ab mAb. In a mouse model of Alzheimer's disease (AD), the engineered antibody decreased Ab plaque burden more efficiently than the unmodified Ab mAb. Next steps include generating modular, monovalent, transferrin receptor-binding antibodies specific to primate and human receptors (see BBB-conquering antibodies, page 1).

SciBX 7(4); doi:10.1038/scibx.2014.129
Published online Jan. 30, 2014

Patent and licensing status undisclosed

Niewoehner, J. et al. Neuron; published online Jan. 8, 2014;
doi:10.1016/j.neuron.2013.10.061
Contact: Per-Ola Freskgård, Roche, Basel, Switzerland
e-mail:

per-ola.freskgard@roche.com
Contact: Anirvan Ghosh, same affiliation as above
e-mail:

anirvan.ghosh@roche.com