Methods for the humanization of antibodies and humanized antibodies thereby obtained

Abstract

Method for the humanization of the VH and VL variable regions of an animal antibody of known sequence, humanized animal antibody obtainable according to the method, in particular anti-NGF and anti-TrkA humanized animal antibodies.

1 . A method for humanizing the VH and VL variable regions of an anti-NGF antibody of non-human origin, comprising the steps of:
 a) providing the crystallographic structure of the VH and VL regions of the anti-NGF antibody;   b) pre-selecting a series of 0 to n possible frameworks acceptors of human origin or humanized antibodies, whose structure was determined experimentally with a resolution of no less than 3 Å, based on the highest level of homology and identity with the primary sequence of the framework of the anti-NGF antibody;   c) conducting a structural comparison between the VH and VL variable regions of the anti-NGF antibody and the regions VH and VL obtained in b), respectively and calculating for each comparison the RMS, to identify the region VH and the region VL of human origin with the smaller RMS; and   d) inserting in appropriate position the sequences of the regions CDR of the anti-NGF antibody in the human sequences identified in c).   
     
     
         2 - 24 . (canceled)