Binding molecules

Details Binding molecules Binding molecules

C - Chemistry, Metallurgy

07

K

C07K 16/00 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2663828

The present invention relates to methods for engineering VH domains to improve their solubility and stability. The invention provides for the incorporation of defined amino acid substitutions based on 3-D structural information into the V segments of a heavy chain locus, expressing the locus in a non-human mammal and selecting soluble VH domains. Further stabilising or solubilising mutations maybe introduced as a result affinity maturation during B-cell maturation in vivo.

La présente invention concerne des procédés permettant de mettre au point des domaines VH par ingénierie de manière à améliorer leur solubilité et leur stabilité. Cette invention consiste à introduire des substitutions d'acide aminé définies dans les segments V d'un locus de chaîne lourde sur la base d'informations structurelles en 3D, à exprimer le locus chez un mammifère non humain, puis à sélectionner des domaines VH solubles. Des mutations de stabilisation ou de solubilisation peuvent également être introduites suite à une maturation d'affinité au cours de la maturation in vivo des lymphocytes B.

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