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Summary for Patent: 8,329,213
|Title:||Liposomes useful for drug delivery|
|Abstract:||The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provides methods of making the liposome compositions provided by the present invention.|
|Inventor(s):||Hong; Keelung (San Francisco, CA), Drummond; Daryl C. (Pacifica, CA), Kirpotin; Dmitri (San Francisco, CA)|
|Assignee:||Merrimack Pharmaceuticals, Inc. (Cambridge, MA)|
1. A composition of a liposome having an interior space, said composition comprising the liposome in an aqueous medium, wherein the interior space: 1) is aqueous, 2) is
separated from the aqueous medium by a membrane comprised of one or more lipids, and 3) contains sucrose octasulfate polyanion in the form of an acid or a salt of a cationic antineoplastic agent.
2. The composition of claim 1 wherein molar ratio of the agent to the one or more lipids in totality is at least about 0.05, at least about 0.1, at least about 0.2, at least about 0.3, at least about 0.5, at least about 0.7, or at least about 1.0.
3. The composition of claim 1 wherein the lipids comprise a neutral PEG-lipid derivative or an anionic PEG-lipid derivative.
4. The composition of claim 1 wherein the composition is a fluid pharmaceutical formulation for parenteral administration.
5. The composition of claim 1 wherein the agent is a microtubule stabilizing agent.
6. The composition of claim 5 wherein the microtubule stabilizing agent is a taxane.
7. The composition of claim 6 wherein the amount of the encapsulated taxane is at least 0.05 mole per mole of said lipids.
8. The composition of claim 6 wherein the interior space is essentially free of a solubilizing aid selected from a micelle-forming surfactant compound and a cyclodextrin compound and the taxane does not comprise a hydrophilic polymer moiety.
9. The composition of claim 6 wherein the liposome comprises a targeting moiety that is a protein comprising an antigen binding sequence of an antibody.
10. The composition of claim 6 wherein the composition is a fluid pharmaceutical formulation for parenteral administration.
11. A composition comprising a liposome having an interior space, wherein said interior space: 1) is an interior aqueous space containing a sucrose octasulfate salt of irinotecan, and 2) is encapsulated by a membrane comprising one or more lipids.
12. The composition of claim 11 wherein molecules of irinotecan are at a molar ratio to the one or more lipids in their totality of at least about 0.05, about 0.1, about 0.2, or about 0.3.
13. The composition of claim 12 wherein the molar ratio is at least 0.1.
14. The composition of claim 11 wherein the composition is a fluid pharmaceutical formulation for parenteral administration.
15. The composition of claim 14 wherein, when administered into the bloodstream of a mouse, the irinotecan has a half-release time from the liposome of at least 24 hours.
16. The composition of claim 14 wherein, when administered into the bloodstream of a rat, the irinotecan has a half-release time from the liposome of at least 48 hours.
17. The composition of claim 14 wherein at least 90% of the irinotecan remains in the interior space after storage for 6 months at 4 to 8.degree. C.
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