C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 16/00 (2006.01) A61K 39/395 (2006.01) C12N 15/09 (2006.01) C12N 15/13 (2006.01)
Patent
CA 2689941
The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of immunobinders, and in particular of single chain antibodies (scFvs), including such properties as stability, solubility, and/or antigen binding affinity. The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions at amino acid positions identified by analysis of a database of selected, stable scFv sequences, wherein preferred amino acid residues for substitution have been identified. The invention also provides immunobinders prepared according to the engineering methods of the invention. The invention also provides preferred scFv framework scaffolds, into which CDR sequences can be inserted, as well as scFv antibodies made using these preferred framework scaffolds. The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of immunobinders, and in particular of single chain antibodies (scFvs), including such properties as stability, solubility, and/or antigen binding affinity. The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions at amino acid positions identified by analysis of a database of selected, stable scFv sequences, wherein preferred amino acid residues for substitution have been identified. The invention also provides immunobinders prepared according to the engineering methods of the invention. The invention also provides preferred scFv framework scaffolds, into which CDR sequences can be inserted, as well as scFv antibodies made using these preferred framework scaffolds.
L'invention concerne des méthodes consistant à utiliser une analyse basée sur les séquences et des stratégies rationnelles pour modifier et améliorer les propriétés structurales et biophysiques d'agents de liaison immunologique, et notamment d'anticorps monocaténaires (scFv), telles que la stabilité, la solubilité et/ou l'affinité de liaison aux antigènes. L'invention concerne des méthodes de production par génie biochimique d'agents d'immunoliaison, et notamment de scFv, par réalisation d'une ou plusieurs substitutions au niveau de positions d'acides aminés identifiées par analyse d'une base de données de séquences scFv stables sélectionnées, après identification de résidus d'acides aminés préférés pour la substitution. L'invention concerne également des agents d'immunoliaison produits selon les méthodes de génie biochimique susmentionnées. Elle se rapporte en outre à des échafaudages charpentes de scFv préférés, dans lesquels des séquences CDR peuvent être insérées, ainsi que des anticorps scFv fabriqués au moyen de ces échafaudages charpentes préférés.
Borras Leonardo
Urech David
Esbatech An Alcon Biomedical Research Unit Llc
Esbatech Ag
Smart & Biggar
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