A4.6.1

Antibody Name: A4.6.1
References: Baca, M., Presta, L.G., O'Connor, S.J. and Wells, J.A. "Antibody humanization using monovalent phage display" J. Biol. Chem. (1997) 272:10678-10684.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1|k
Antigen: Vascular Endothelial Growth Factor (VEGF)
Laboratory: Genentech, CA
Design: Anti-VEGF Fab phagemid library to randomise several FR positions (VL 4, 71 VH 24, 37, 67, 69, 71, 73, 75, 76, 78, 93, 94)
Frameworks: VH SGIII | VL kI consensus sequences.
CDRs: All 6 VH and VL, Kabat Definition except CDR-H1 26-35.
Backmutations: Best version hu2.10 non-mouse(NM)
VH V37I(NM) R71L N73T KN75-76AS L78V(NM) R94K
VL F71Y L46V (increase in association rate)
Binding: By surface plasmon resonance on Pharmacia BIAcore instrument within 6-fold of chimaeric mAb.
Expression: E.coli
Comment: This technique could revolutionise the humanisation cycle (mutate-test-mutate).
Clinical Indication: Potentially useful as an anti-tumour therapeutic since it is a neutralising mAb known to inhibit mitogenic signalling.

explanation of symbols and abbreviations

José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.