STABILIZED THERAPEUTIC AND IMAGING AGENTS

• US 20100111840A1
• Filed: 06/04/2009
• Published: 05/06/2010
• Est. Priority Date: 03/08/2001
• Status: Abandoned Application

• Current Assignee: Nanovalent Pharmaceuticals, Inc.
• Original Assignee: Nanovalent Pharmaceuticals, Inc.
• Inventors: Wartchow, Charles Aaron, Brunke, Karen J., Pease, John S., BEDNARSKI, Mark David, DeChene, Neal Edward
• Application Number:
  US12/478,248
• Publication Number:
  US 20100111840A1
• Time in Patent Office: Days
• US Class Current: 424/1.210
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 47/6913 the liposome being modified on its surface by an antibody
• CPC Class Codes: A61K 51/1234 Liposomes
• CPC Class Codes: A61K 51/1237 Polymersomes, i.e. liposomes with polymerisable or polymerized bilayer-forming substances
• CPC Class Codes: A61K 9/1273 Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances polymers grafted or coated on phosphatidyl liposomes A61K9/1271, on non-phosphatidyl liposomes A61K9/1272
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Stabilized lipid construct comprising a liposome or polymerized vesicle, a targeting entity, a therapeutic entity, and a stabilizing entity are provided, as well as methods for their preparation and use.

Claims

1. A stabilized lipid construct comprising a coated liposome or polymerized vesicle, a targeting entity, therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle.

2. The stabilized lipid construct of claim 1, wherein the polymerized vesicle comprises 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine.

3. The stabilized lipid construct of claim 1, wherein the liposome or polymerized vesicle comprises DTPA lipid derivative N,N-Bis[[[[(13′

15′

-pentacosadiynamido-3,6-dioxaoctyl)carbamoyl]methyl](carboxymethyl)amino]ethyl]-glycine.

4. The stabilized lipid construct of claim 1, wherein the liposome or polymerized vesicle comprises a mixture of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine and DTPA lipid derivative N,N-Bis[[[[(13′

15′

pentacosadiynamido-3,6-dioxaoctyl)carbamoyl]methyl](carboxymethyl)amino]ethyl]-glycine.

5. The stabilized lipid construct of claim 1, wherein the stabilizing entity is selected from the group consisting of a natural polymer, a semi-synthetic polymer, and a synthetic polymer.

6. The stabilized lipid construct of claim 5, wherein the stabilizing entity is selected from the group consisting of dextran, modified dextran, and poly (ethylene imine).

7. The stabilized lipid construct of claim 1, wherein the stabilizing entity provides physical stability or colloidal stability.

8. The stabilized lipid construct of claim 1, wherein the stabilizing entity provides the capacity for multivalency.

9. The stabilized lipid construct of claim 1, wherein the therapeutic entity is selected from the group consisting of Y-90, Bi-213, At-211, Cu-67, Sc-47, Ga-67, Rh-105, Pr-142, Nd-147, Pm-151, Sm-153, Ho-166, Gd-159, Tb-161, Eu-152, Er-171, Re-186, and Re-188.

10. The stabilized lipid construct of claim 9, wherein said therapeutic entity is ⁹⁰Y.

11. The stabilized lipid construct of claim 1, wherein said targeting entity targets the stabilized lipid construct to a cell surface.

12. The stabilized lipid construct of claim 1, wherein the targeting entity is associated with the stabilized lipid construct by covalent means.

13. The stabilized lipid construct of claim 1, wherein the targeting entity is associated with the stabilized lipid construct by non-covalent means.

14. The stabilized lipid construct of claim 1, wherein said targeting entity is an antibody.

15. The stabilized lipid construct of claim 14, wherein said antibody has a target selected from the group consisting of P-selectin, E-selectin, pleiotropin, G-protein coupled receptors, endosialin, endoglin, VEGF receptors, PDGF receptor, EGF receptor, FGF receptors, the matrix metalloproteases including MMP2 and MMP9, and prostate specific membrane antigen (PSMA).

16. The stabilized lipid construct of claim 1, wherein said targeting entity has a vascular target.

17. The stabilized lipid construct of claim 16, wherein said targeting entity is Vitaxin or LM609.

18. The stabilized lipid construct of claim 16, wherein said targeting entity is selected from the group consisting of an anti-VCAM-1 antibody, an anti-ICAM-1 antibody, an anti-VEGFR antibody, and an anti-integrin antibody.

33. The stabilized lipid construct of claim 1, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

40. The stabilized lipid construct of claim 1, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.

19. A stabilized lipid construct comprising a coated liposome or polymerized vesicle and a therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle.

20. The stabilized lipid construct of claim 19, wherein the polymerized vesicle comprises 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine.

21. The stabilized lipid construct of claim 19, wherein the liposome or polymerized vesicle comprises DTPA lipid derivative N,N-Bis[[[[(13′

15′

-pentacosadiynamido-3,6-dioxaoctyl)carbamoyl]methyl](carboxymethyl)amino]ethyl]glycine.

22. The stabilized lipid construct of claim 19, wherein the liposome or polymerized vesicle comprises a mixture of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine and DTPA lipid derivative N,N-Bis[[[[(13′

15′

-pentacosadiynamido-3,6-dioxaoctyl)carbamoyl]methyl](carboxymethyl)amino]ethyl]-glycine.

23. The stabilized lipid construct of claim 19, wherein the stabilizing entity is selected from the group consisting of a natural polymer, a semi-synthetic polymer, and a synthetic polymer.

24. The stabilized lipid construct of claim 23, wherein the stabilizing entity is selected from the group consisting of dextran, modified dextran, and poly (ethylene imine).

25. The stabilized lipid construct of claim 19, wherein the stabilizing entity provides physical stability or colloidal stability.

26. The stabilized lipid construct of claim 19, wherein the stabilizing entity provides the capacity for multivalency.

27. The stabilized lipid construct of claim 19, wherein the stabilizing entity is selected from the group consisting of dextran, aminodextran and poly (ethylene imine).

34. The stabilized lipid construct of claim 19, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

41. The stabilized lipid construct of claim 19, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.

28. A stabilized lipid construct for controlled release of a therapeutic agent, comprising a coated liposome or polymerized vesicle and a therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle.

35. The stabilized lipid construct of claim 28, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

42. The stabilized lipid construct of claim 28, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.

29. A method of treating a patient comprising administering a therapeutic agent to a patient in need thereof in a sufficient amount, said therapeutic agent comprising a stabilized lipid construct, said stabilized lipid construct comprising a coated liposome or polymerized vesicle, a targeting entity, and a therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle.

36. The method of claim 29, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

43. The method of claim 29, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.

30. A stabilized lipid construct comprising a coated liposome or polymerized vesicle, a targeting entity, and a therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle, and the stabilizing entity is selected from the group consisting of dextran and modified dextran.

37. The stabilized lipid construct of claim 30, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

44. The stabilized lipid construct of claim 30, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.

31. A stabilized lipid construct comprising a coated liposome or polymerized vesicle and a therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle, and the stabilizing entity is selected from the group consisting of dextran and modified dextran.

38. The stabilized lipid construct of claim 31, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

45. The stabilized lipid construct of claim 31, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.

32. A stabilized lipid construct for controlled release of a therapeutic agent, comprising a coated liposome or polymerized vesicle, a targeting entity, and a therapeutic entity, wherein the coating comprises a stabilizing entity which is associated with the liposome or polymerized vesicle by covalent means and is only on the surface of the liposome or polymerized vesicle, and the stabilizing entity is selected from the group consisting of dextran and modified dextran.

39. The stabilized lipid construct of claim 32, wherein the liposome or polymerized vesicle has a size of less than about 0.2 μ

m.

46. The stabilized lipid construct of claim 32, wherein the liposome or polymerized vesicle comprises phospholipid containing at least one phosphatidylcholine moiety, phosphatidylethanolamine moiety, or cholesterol.