Liposomal antisense methyl phosphonate oligonucleotides and...

A - Human Necessities – 61 – K

Patent

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A61K 31/70 (2006.01) A61K 9/127 (2006.01) A61K 9/133 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2168243

A liposomal methyl phosphonate oligonucleotide composition useful in treatment of chronic myeloid leukemia comprises (a) a liposome which comprises at least one phospholipid, and (b) an antisense methyl phosphonate oligonucleotide which is entrapped in the liposome. The molar ratio of phospholipid in the liposome to the methyl phosphonate entrapped in the liposome is between about 100:1 and about 10,000:1. A process for making the composition includes the steps of (a) mixing an antisense methyl phosphonate oligonucleotide in a first organic solvent with at least one phospholipid in a second organic solvent, where the molar ratio of phospholipid to methyl phosphonate is between about 100:1 and about 10,000:1, (b) lyophilizing the mixture formed in step (a), producing a lyophilized powder. (c) hydrating the lyophilized powder. and (d) sonicating the hydrated material

Composition d'oligonucléotides de phosphonate de méthyle de liposomes efficace dans le traitement de la leucémie médullaire chronique et comprenant (a) un liposome comprenant au moins un phospholipide et (b) un oligonucléotide antisens de phosphonate de méthyle inclus dans le liposome. Le rapport molaire de phospholipide dans le liposome et du phosphonate de méthyle inclus dans le liposome se situe entre 100:1 et 10.000:1 environ. Un procédé de préparation de la composition comprend les étapes (a) de mélange d'un oligonucléotide antisens de phosphonate de méthyle dans un premier solvant organique avec au moins un phospholipide dans un deuxième solvant organique, où le rapport molaire phospholipide et phosphonate de méthyle se situe entre 100:1 et 10.000:1 environ, (b) de lyophilisation du mélange constitué à l'étape (a), produisant une poudre lyophilisée, (c) d'hydratation de la poudre lyophilisée et (d) de soumission du matériau hydraté à des ultrasons.

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