A humanized immunoglobulin, or antigen-binding fragment thereof

Abstract

A humanized immunoglobulin, or antigen-binding fragment thereof, which specifically binds to beta amyloid peptide (Aβ) with a binding affinity of at least 107 M-1, comprising (i) a light chain comprising at least one variable region complementarity determining region (CDR) from the 3D6 immunoglobulin light chain variable region sequence set forth as SEQ ID NO:2, and a variable framework region from a human acceptor immunoglobulin light chain sequence, and (ii) a heavy chain comprising at least one variable region CDR from the 3D6 immunoglobulin heavy chain variable region sequence set forth as SEQ ID NO:4, and a variable framework region from a human acceptor immunoglobulin heavy chain, provided that the humanized immunoglobulin, or antigen binding fragment thereof, comprises: (a) at least one substitution of a canonical framework residue selected from the group consisting of L2, L48, L64, L71, H24, H26, H27, H29, H71, and H94 (Kabat numbering convention), (b) at least one substitution of an interchain packing framework residue selected from the group consisting of L36, L38, L44, L46, L87, L98, H37, H39, H45, H47, H91, H93, and H103 (Kabat numbering convention), and (c) at least one substitution of a vernier zone framework residue selected from the group consisting of L4, L35, L47, L49, L66, L68, L69, H2, H28, H30, H48, H49, H67, H69, and H80 (Kabat numbering convention), or at least one substitution of a rare framework residue selected from the group consisting of L1, L15, L83, L85, H40 and H42 (Kabat numbering convention), wherein the substitution is with the corresponding amino acid residue from the mouse 3D6 light chain variable region sequence or the mouse 3D6 heavy chain variable region sequence.