Zenjiro Sampei, Tomoyuki Igawa, Tetsuhiro Soeda, Yukiko Okuyama-Nishida, Chifumi Moriyama, Tetsuya Wakabayashi, Eriko Tanaka, Atsushi Muto, Tetsuo Kojima, Takehisa Kitazawa, Kazutaka Yoshihashi, Aya Harada, Miho Funaki, Kenta Haraya, Tatsuhiko Tachibana, Sachiyo Suzuki, Keiko Esaki, Yoshiaki Nabuchi, Kunihiro Hattori
In hemophilia A, routine prophylaxis with exogenous factor VIII (FVIII) requires frequent intravenous injections and can lead to the development of anti-FVIII alloantibodies (FVIII inhibitors). To overcome these drawbacks, we screened asymmetric bispecific IgG antibodies to factor IXa (FIXa) and factor X (FX), mimicking the FVIII cofactor function. Since the therapeutic potential of the lead bispecific antibody was marginal, FVIII-mimetic activity was improved by modifying its binding properties to FIXa and FX, and the pharmacokinetics was improved by engineering the charge properties of the variable region...
2013: PloS One