In vitro estimation of in vivo half-life binding proteins

Details In vitro estimation of in vivo half-life binding proteins In vitro estimation of in vivo half-life binding proteins

C - Chemistry, Metallurgy

12

Q

C12Q 1/34 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2721740

The present invention discloses methods used to estimate the in vivo half-life of a binding protein of interest. The disclosed methods involve (a) determining for a binding protein of interest and for each of at least two different reference binding proteins an in vitro half-life using an in vitro protease reaction assay, wherein said reference binding proteins have known different in vivo half-lives, (b) determining the correlation between the known in vivo half-lives and the in vitro proteolytic half-lives of each of the reference binding proteins, and (c) estimating from said correlation between the known in vivo half-lives and the in vitro proteolytic half-lives of the reference binding proteins the in vivo half-life of the binding protein of interest that correlates with the in vitro proteolytic half-life of the binding protein of interest.

La présente invention concerne des procédés utilisés pour estimer la demi-vie in vivo d'une protéine de liaison intéressante. Les procédés décrits comprennent les étapes consistant à (a) déterminer la demi-vie in vitro d'une protéine de liaison intéressante et de chacune dau moins deux protéines de liaison de référence différentes en utilisant un dosage in vitro de réaction de protéase, lesdites protéines de liaison de référence ayant des demi-vies in vivo différentes connues, (b) déterminer la corrélation entre les demi-vies in vivo connues et les demi-vies protéolytiques in vitro de chacune des protéines de liaison de référence, et (c) estimer à partir de ladite corrélation entre les demi-vies in vivo connues et les demi-vies protéolytiques in vitro des protéines de liaison de référence, la demi-vie in vivo de la protéine de liaison intéressante qui est corrélée avec la demi-vie protéolytique in vitro de la protéine de liaison intéressante.

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