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Last Updated: December 22, 2024

Claims for Patent: 8,703,181


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Summary for Patent: 8,703,181
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)
Application Number:13/654,373
Patent Claims: 1. A method of delivering an antineoplastic agent to a tumor, the method comprising administering by injection a composition of an aqueous medium comprising a liposome having an interior space that: 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 a salt of a cationic antineoplastic agent to a patient having a tumor in an amount sufficient to deliver a therapeutically effective dose of the antineoplastic agent to the tumor.

2. The method 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 method of claim 1 wherein the lipids comprise a neutral PEG-lipid derivative or an anionic PEG-lipid derivative.

4. The method of claim 1 wherein the composition is a fluid pharmaceutical formulation for parenteral administration.

5. The method of claim 1 wherein the agent is a microtubule stabilizing agent.

6. The method of claim 5 wherein the microtubule stabilizing agent is a taxane.

7. The method of claim 6 wherein the amount of taxane is at least 0.05 mole per mole of said lipids.

8. The method 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 method of claim 6 wherein the liposome comprises a targeting moiety that is a protein comprising an antigen binding sequence of an antibody.

10. The method of claim 6 wherein the composition is a fluid pharmaceutical formulation for parenteral administration.

11. A method of delivering irinotecan to a tumor, the method comprising administering by injection a composition comprising a liposome having an interior space that: 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 to a patient having a tumor in an amount sufficient to deliver a therapeutically effective dose of irinotecan to the tumor.

12. The method 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 method of claim 12 wherein the molar ratio is at least 0.1.

14. The method of claim 11 wherein the composition is a fluid pharmaceutical formulation for parenteral administration.

15. The method of claim 14 wherein, when the composition is administered into the bloodstream of a mouse, the irinotecan has a half-release time from the liposome of at least 24 hours.

16. The method of claim 14 wherein, when the composition is administered into the bloodstream of a rat, the irinotecan has a half-release time from the liposome of at least 48 hours.

17. The method of claim 14 wherein at least 90% of the irinotecan remains in the interior space after storage of the composition for 6 months at 4 to 8.degree. C.

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