Details for Patent: 6,265,389
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Title: | Microencapsulation and sustained release of oligonucleotides |
Abstract: | This invention relates to a composition, and method of forming and using said composition, for the sustained release of oligonucleotides, in particular antisense ODNs. The sustained release composition of this invention comprises a polymer matrix of a biocompatible polymer and stabilized oligonucleotide, wherein the stabilized oligonucleotide is dispersed within the biocompatible polymer. The method of the invention, for forming a composition for the sustained release of oligonucleotide, in particular an antisense ODN, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing stabilized oligonucleotide in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the stabilized oligonucleotide. The method of using the sustained release composition of the present invention comprises providing a therapeutically effective blood level of oligonucleotide in a subject for a sustained period by administering to the subject a dose of the sustained release composition described herein. |
Inventor(s): | Burke; Paul A. (Oxnard, CA) |
Assignee: | Alkermes Controlled Therapeutics, Inc. (Cambridge, MA) |
Filing Date: | Jun 25, 1998 |
Application Number: | 09/104,549 |
Claims: | 1. A composition for the sustained release of an antisense oligonucleotide from a polymer matrix, comprising: a) a biocompatible polymer; and b) a therapeutically effective amount of antisense oligonucleotide which is complexed with a metal cation, wherein said antisense oligonucleotide is dispersed within the biocompatible polymer. 2. The sustained release composition of claim 1 wherein the metal cation-complexed antisense oligonuclcotide is in the form of particles. 3. The sustained release composition of claim 1 wherein the biocompatible polymer is selected from the group consisting of poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s, polycaprolactone, polycarbonates, polyesteramides, polyanhydrides, poly(amino acids), polyorthoesters, polycyanoacrylates, poly(p-dioxanone), poly(alkylene oxalate)s, biodegradable polyurethanes, blends and copolymers thereof. 4. The sustained release composition of claim 3 wherein said polymer comprises poly(lactide-co-glycolide). 5. The sustained release composition of claim 1 wherein the metal cation of the metal cation-complexed antisense oligonucleotide is multivalent. 6. The sustained release composition of claim 5 wherein the multivalent metal cation comprises a cation selected from the group consisting of: Zn.sup.+2, Ca.sup.+2, Cu.sup.+2, Mg.sup.+2 and any combination thereof. 7. The sustained release composition of claim 6 wherein the metal cation is Zn.sup.+2. 8. The sustained release composition of claim 1 wherein the antisense oligonucleotide which is complexed to the metal cation has SEQ ID NO. 1. 9. The sustained release composition of claim 1 wherein the antisense oligonucleotide which is complexed to the metal cation has SEQ ID NO. 2. 10. The sustained release composition of claim 1 wherein the antisense oligonucleotide which is complexed to the metal cation is present from about 0.01% (w/w) to about 50% (w/w) based on the dry weight of the composition and the weight of the antisense oligonucleotide prior to stabilization. 11. A method for providing a therapeutically effective amount of an antisense oligonucleotide in a subject for a sustained period comprising administering to the subject a dose of the sustained release composition of claim 1. 12. A method for forming a composition for the sustained release of an antisense oligonucleotide, comprising the steps of: a) dissolving a biocompatible polymer in a polymer solvent to form a polymer solution; b) adding a therapeutically effective amount of antisense oligonucleotide which is complexed with a metal cation, to the polymer solution; and c) solidifying the polymer to form a polymer matrix containing a dispersion of said antisense oligonucleotide. 13. The method of claim 12 wherein the biocompatible polymer is selected from the group consisting of poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s, polycaprolactone, polycarbonates, polyesteramides, polyanhydrides, poly(amino acids), polyorthoesters, polycyanoacrylates, poly(p-dioxanone), poly(alkylene oxalate)s, biodegradable polyurethanes, blends, and copolymers thereof. 14. The method of claim 13 wherein said polymer comprises poly(lactide-co-glycolide). 15. The method of claim 12 wherein the metal cation which is complexed to the antisense oligonucleotide is a multivalent metal cation. 16. The method of claim 15 wherein the multivalent metal cation is selected from the group consisting of: Zn.sup.+2, Ca.sup.+2, Cu.sup.+2, Mg.sup.+2, and any combination thereof. 17. The method of claim 16 wherein the metal cation is Zn.sup.+2. |