Engineered antibodies with reduced immunogenicity and...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/46 (2006.01) C07K 2/00 (2006.01) C12N 15/13 (2006.01)

Patent

CA 2742861

Hybrid antibodies and antibody binding fragments thereof having decreased immunogenicity and methods of mak-ing them are provided. The methods involve replacing one or more amino acid residues within at least one donor framework re-gion of a hybrid antibody or antigen binding fragment thereof that has undergone somatic hypermutation with the amino acid residue from the corresponding position of a germline framework sequence. Also provided are hybrid antibodies or antigen bind-ing fragments thereof containing at least two donor framework regions that are derived from the same germline gene family or germline gene family member and wherein at least one amino acid residue within a framework region has been replaced with an amino acid residue from the corresponding position within a germline framework region. The hybrid antibodies or antigen binding fragments thereof may contain human framework regions and nonhuman CDRs.

Cette invention concerne des anticorps hybrides et des fragments hybrides de liaison à lantigène présentant une immunogénicité réduite, et leurs méthodes de fabrication. Les méthodes impliquent de remplacer un ou plusieurs résidus dacides aminés au sein dau moins une région cadre dun anticorps hybride ou dun fragment hybride de liaison à lantigène qui a subi une hypermutation somatique avec le résidu dacide aminé de la position correspondante dune séquence cadre de gènes souches. Linvention concerne également des anticorps hybrides ou des fragments hybrides de liaison à lantigène contenant au moins deux régions cadres dérivées de la même famille de gènes souches ou du même élément de famille de gènes souches, au moins un résidu dacide aminé au sein dune région cadre ayant été remplacé par un résidu dacide aminé de la position correspondante au sein dune région cadre de gènes souches. Les anticorps hybrides ou les fragments hybrides de liaison à lantigène peuvent contenir des régions cadres humaines et des régions non humaines déterminant la complémentarité.

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