Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides
AssigneeBoard of Regents, The University of Texas System
InventorsGabriel Lopez-Berestein, Ana Maria Tari
Life of this patent
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Abstract
An improved delivery system for antisense oligonucleotides involves a liposomal composition, comprising a liposome which consists essentially of neutral phospholipids and an antisense oligonucleotide that is entrapped in the liposome and is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides.
Claims19
A liposomal composition of antisense oligonucleotides, including (a) a liposome which consists essentially of neutral phospholipids, and (b) an antisense oligonucleotide that is entrapped in the liposome and is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides;
- where if the antisense oligonucleotide is a phosphodiester oligonucleotide, the molar ratio of phospholipid to oligo is between about 100:1 and about 3,000:1;
- if the antisense oligonucleotide is a phosphorothioate oligonucleotide, the molar ratio of phospholipid to oligo is between about 10:1 and about 50:1:
- and if the antisense oligonucleotide is a p-ethoxy oligonucleotide, the molar ratio of phospholipid to oligo is between about 5:1 and about 100:1.
A method of preparing a liposomal composition of antisense oligonucleotides, including the steps of:
- (a) hydrating a lyophilized composition that consists essentially of neutral phospholipids and an antisense oligonucleotide that is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides;
- where if the antisense oligonucleotide is a phosphodiester oligonucleotide, the molar ratio of phospholipid to oligo is between about 100:1 and about 3,000:1;
- if the antisense oligonucleotide is a phosphorothioate oligonucleotide, the molar ratio of phospholipid to oligo is between about 10:1 and about 50:1;
- and if the antisense oligonucleotide is a p-ethoxy oligonucleotide, the molar ratio of phospholipid to oligo is between about 5:1 and about 100:1;
- thereby forming an aqueous suspension which includes free oligonucleotide and liposomes entrapping oligonucleotide;
- and
- (b) separating the free oligonucleotide from the liposomes by dialysis.
Dependencies are inferred from the claim text.