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1. (WO2016062734) VH-VL-INTERDOMAIN ANGLE BASED ANTIBODY HUMANIZATION

Pub. No.:    WO/2016/062734    International Application No.:    PCT/EP2015/074294
Publication Date: Fri Apr 29 01:59:59 CEST 2016 International Filing Date: Thu Oct 22 01:59:59 CEST 2015
IPC: C07K 16/00
Applicants: F. HOFFMANN-LA ROCHE AG
HOFFMANN-LA ROCHE INC.
Inventors: BUJOTZEK, Alexander
GEORGES, Guy
LIPSMEIER, Florian
Title: VH-VL-INTERDOMAIN ANGLE BASED ANTIBODY HUMANIZATION
Abstract:
Herein is reported a method for selecting one or more variant antibody Fv fragments derived from a parent antibody Fv fragment comprising the steps of i) generating a multitude of variant antibody Fv fragments by grafting/transferring one or more specificity determining residues from the parent antibody Fv fragment on an acceptor antibody Fv fragment, whereby each variant antibody Fv fragment of the multitude of variant antibody Fv fragments differs from the other variant antibody Fv fragments by at least one amino acid residue, ii) determining the VH- VL-orientation for the parent Fv fragment and for each of the variant antibody Fv fragments of the multitude of variant antibody Fv fragments based on a sequence fingerprint of the antibody Fv fragment, and iii) selecting those variant antibody Fv fragments that have the smallest difference in the VH-VL-orientation compared to the parent antibody's VH-VL-orientation and thereby selecting one or more variant antibody Fv fragments derived from a parent antibody Fv fragment, whereby the one or more variant antibody Fv fragments bind to the same antigen as the parent antibody Fv fragment.