Lipase variants for pharmaceutical use

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 9/20 (2006.01) A61K 38/46 (2006.01) A61K 38/54 (2006.01)

Patent

CA 2670643

The pharmaceutical use of lipases related to the Thermomyces lanuginosus (Humicola lanuginosa) lipase comprising amino acids 1-269 of SEQ ID NO: 2, optionally in combination with a protease and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II. The lipases of the invention have, e.g., an improved digestion performance in vitro, an improved activity at a pH in the neutral range, an improved stability at low pH, an are stable against protease-degradation, and/or are stable in the presence of pepsin and bile salts. The invention also relates to methods of determining digestion performance in vitro of lipases, as well as to certain novel variants of the lipase of T. lanuginosus.

L'invention concerne l'utilisation pharmaceutique de lipases relatives à la lipase de Thermomyces lanuginosus (Humicola lanuginosa) comprenant les acides aminés 1 à 269 de SEQ ID N° : 2, éventuellement en combinaison avec une protéase et/ou une amylase. Les exemples d'indications médicales sont les suivants : traitement de troubles digestifs, insuffisance pancréatique exocrine (PEI), pancréatite, fibrose cystique, diabète de type I et/ou diabète de type II. Les lipases de l'invention présentent, par exemple, une performance de digestion améliorée in vitro et une activité améliorée à un pH dans la plage neutre, une stabilité améliorée à un pH faible et sont stables vis-à-vis d'une dégradation de protéase et/ou stables en présence de pepsine et de sels biliaires. L'invention concerne également des procédés de détermination de performance de digestion in vitro des lipases ainsi que certaines nouvelles variantes de la lipase de T. lanuginosus.

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