Improved anti-ige antibodies and method of improving...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/13 (2006.01) A61K 39/395 (2006.01) C07K 16/00 (2006.01) C07K 16/42 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2295540

The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of substituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

L'invention concerne un procédé pour adapter l'affinité d'un polypeptide vis-à-vis d'une molécule cible, selon les étapes suivantes: (1) identification des résidus aspartyle sujets à l'isomérisation; (2) substitution par des résidus-variantes et criblage des mutants résultants pour rechercher l'affinité vis-à-vis de la molécule cible. Selon un mode de réalisation préféré, le procédé de substitution des résidus consiste en une maturation de l'affinité avec révélation des phages. Selon un deuxième mode de réalisation préféré, le polypeptide est un anticorps et la molécule cible est un antigène. Selon un troisième mode de réalisation préféré, l'anticorps a une activité anti-IgE et la molécule cible est l'IgE. Selon un autre mode de réalisation, on décrit un anticorps anti-IgE ayant une affinité améliorée vis-à-vis de l'IgE.

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