Humanization of antibodies

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/13 (2006.01) C07K 16/00 (2006.01) C07K 16/46 (2006.01) C12N 15/09 (2006.01) C40B 30/04 (2006.01) C40B 40/02 (2006.01) C40B 40/08 (2006.01) C40B 40/10 (2006.01) C40B 50/06 (2006.01)

Patent

CA 2537055

The present invention provides methods of re-engineering or re-shaping an antibody from a first species, wherein the re-engineered or re-shaped antibody does not elicit undesired immune response in a second species, and the re- engineered or re-shaped antibody retains substantially the same antigen binding-ability of the antibody from the first species. In accordance with the present invention, a combinatorial library comprising the CDRs of the antibody from the first species fused in frame with framework regions derived from a second species can be constructed and screened for the desired modified antibody. In particular, the present invention provides methods utilizing low homology acceptor antibody frameworks for efficiently humanizing an antibody or a fragment thereof. The present invention also provides antibodies produced by the methods of the invention.

La présente invention concerne des procédés de reconstruction ou de refonte d'un anticorps provenant d'une première espèce. En l'occurrence, l'anticorps ainsi reconstruit ou refondu n'élicite pas de réponse immunitaire non désirée dans une deuxième espèce, de même qu'il conserve sensiblement la même aptitude à se lier à un antigène que l'anticorps de la première espèce. Ainsi, la présente invention permet, d'une part de construire une échantillothèque combinatoire comprenant les CDR de l'anticorps de la première espèce fusionné dans un cadre comportant des régions d'infrastructure dérivant d'une seconde espèce, et d'autre part de rechercher systématiquement l'anticorps modifié désiré. En particulier, l'invention offre des procédés utilisant des infrastructures d'anticorps accepteurs faiblement homologues permettant d'humaniser de façon efficace un anticorps ou l'un de ses fragments. L'invention concerne également des anticorps produits avec les procédés de l'invention.

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