C - Chemistry – Metallurgy – 12 – P
Patent
C - Chemistry, Metallurgy
12
P
C12P 21/08 (2006.01) A61K 39/395 (2006.01) A61P 31/00 (2006.01) A61P 35/00 (2006.01) C07K 16/28 (2006.01) C12N 15/13 (2006.01)
Patent
CA 2633080
The present invention relates to a method for preparing an antibody selective for activating antibody Fc region receptors (FcRs) comprising an ITAM motif or motifs (immunoreceptor tyrosine- based activation motif), comprising the steps of obtaining monoclonal antibodies from a hybridoma, from a heterohybridoma or from any animal, plant or human cell line, replacing each of the His 310 and His 435 residues (Cabat numbering) of the Fc region of said antibody with a residue chosen from lysine, alanine, glycine, valine, leucine, isoleucine, proline, methionine, tryptophan, phenylalanine, serine or threonine, and then selecting the antibodies for which the binding to inhibitory FcRs comprising ITIM motifs (immunoreceptor tyrosine-based inhibition motif) is decreased by at least 30%, preferably by at least 50%, 70%, 80% or else by at least 90% relative to the same antibody having a natural Fc region. The present invention also relates to the use of an antibody derived from the method of the invention in the production of a medicament for use in particular in the treatment of cancer and of infectious pathologies.
La présente invention se rapporte à un procédé de préparation d'un anticorps sélectif envers les récepteurs de la région Fc des anticorps (FcR) activateurs à motif (s) ITAM ( immunoreceptor tyrosine- based activât ion motif) , comprenant les étapes d'obtention d'anticorps monoclonaux à partir d'hybridome, d'hétérohybridome, ou de toute lignée cellulaire animale, végétale ou humaine, de remplacement de chacun des résidus His 310 et His 435 (numérotation de Kabat) de la région Fc dudit anticorps par un résidu choisi parmi la lysine, l'alanine, la glycine, la valine, la leucine, l ' isoleucine, la proline, la méthionine, le tryptophane, la phénylalanine, la serine ou la thréonine, puis de sélection des anticorps dont la fixation aux FcR inhibiteurs à motifs ITIM (immunoreceptor tyrosine-based inhibition motif) est diminuée d'au moins 30%, de préférence d'au moins 50%, 70%, 80% ou encore d'au moins 90% par rapport au même anticorps possédant une région Fc native. La présente invention se rapporte également à l'utilisation d'un anticorps issu du procédé de l'invention dans l'obtention d'un médicament destiné notamment au traitement du cancer et de pathologies infectieuses .
Ducancel Frederic
Jorieux Sylvie
Menez Renee
Siberil Sophie
Stura Enrico
Lfb Biotechnologies
Robic
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