Muteins of human neutrophil gelatinase-associated lipocalin...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/12 (2006.01) A61K 38/17 (2006.01) C07K 14/47 (2006.01) C12N 15/62 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2461571

Disclosed is a method for generating a mutein of a protein selected from the group consisting of human neutrophil gelatinase-associated lipocalin (hNGAL), rat .alpha.2- microglobulin-related protein (A2m) and mouse 24p3/uterocalin (24p3), said mutein having detectable affinity to a given target. The method comprises the step of subjecting the protein to mutagenesis at one or more of the sequence positions which correspond to the sequence positions 33 to 54, 66 to 83, 94 to 106, and 123 to 136 of hNGAL, resulting in one or more mutein(s) of the protein. Also disclosed are muteins obtainable by this method.

L'invention concerne un procédé de production d'une mutéine à partir d'une protéine sélectionnée dans le groupe comprenant la lipocaline humaine associée à la gélatinase des polynucléaires neutrophiles (hNGAL), la protéine liée à l'.alpha.¿2?-microglobuline du rat (A2m), et la 24p3/utérocaline murine (24p3), ladite mutéine présentant une affinité détectable avec une cible donnée. Ce procédé comprend l'étape consistant à soumettre la protéine à une mutagénèse en une ou plusieurs positions de sa séquence, qui correspondent aux positions séquentielles 33 à 54, 66 à 83, 94 à 106 et 123 à 136 de hNGAL, étape à l'issue de laquelle l'on obtient une ou plusieurs mutéines de ladite protéine. L'invention se rapporte en outre aux mutéines productibles au moyen dudit procédé.

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