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Drug delivery

Improved safety for blood brain barrier (BBB)-penetrating antibodies

Mouse studies suggest bispecific antibodies that cross the BBB can be made safer by modifying the effector portion of the antibody. Previous studies identified a BBB-penetrant, bispecific mAb against the Alzheimer's disease (AD) target b-site APP-cleaving enzyme 1 (BACE1) and transferrin receptor protein 1 (TFRC; TFR; CD71). In mice, a variant of the mAb that was unable to bind the Fc g-receptor (FCGR) showed BBB penetration levels comparable to those of the original mAb. In mice, the mAb variant showed a better toxicity profile than the original mAb. Next steps include humanizing the FCGR binding-compromised mAb and conducting further preclinical development.

SciBX 6(20); doi:10.1038/scibx.2013.501
Published online May 23, 2013

Patent pending; licensing status undisclosed

Couch, J.A. et al. Sci. Transl. Med.; published online May 1, 2013;
Contact: Ryan J. Watts, Genentech Inc., South San Francisco, Calif.
Contact: Mark S. Dennis, same affiliation as above