Enhanced circulation effector composition and method

• US 20040247663A1
• Filed: 04/26/2004
• Published: 12/09/2004
• Est. Priority Date: 03/23/1993
• Status: Active Grant

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Martin, Francis J., Barenholz, Yechezkel, Woodle, Martin C., Bercovier, Herve, Zalipsky, Samuel
• Granted Patent: US 7,150,882 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: Y10S 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector

Abstract

A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Claims

1. A liposome composition, comprising

liposomes, each having an outer layer of hydrophilic chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to a binding member of said effector molecule due to polyvalent presentation of said effector molecule.

2. The composition of claim 1, wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

3. The composition of claim 2 wherein the polysaccharide is sialyl Lewis^x.

4. The composition of claim 2 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

5. The composition of claim 4 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

6. The composition of claim 4 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

7. A liposome composition for use in treating a condition mediated by binding of one binding member to a second binding member, comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to a binding member of said effector molecule due to polyvalent presentation of said effector molecule.

8. The composition of claim 7 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

9. The composition of claim 8 wherein the polysaccharide is sialyl Lewis^x.

10. The composition of claim 8 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

11. The composition of claim 10 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

12. The composition of claim 10 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

13. A liposome composition for use in treating a condition mediated by binding of one binding member, which is present in the bloodstream, to a second binding member, comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to a binding member of said effector molecule due to polyvalent presentation of said effector molecule.

14. The composition of claim 13 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

15. The composition of claim 14 wherein the polysaccharide is sialyl Lewis^x.

16. The composition of claim 14 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

17. The composition of claim 16 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

18. The composition of claim 16 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

19. A liposome composition for use in treating a condition mediated by binding of one binding member, which is a pathogen or cell in the bloodstream, to a second binding member comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to a binding member of said effector molecule due to polyvalent presentation of said effector molecule.

20. The composition of claim 19 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

21. The composition of claim 20 wherein the polysaccharide is sialyl Lewis^x.

22. The composition of claim 20 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

23. The composition of claim 22 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

24. The composition of claim 22 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

25. A liposome composition for use in treating a condition mediated by binding of one binding member to a second binding member, which is a target cell, comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to one of said binding members due to polyvalent presentation of said effector molecule.

26. The composition of claim 25 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

27. The composition of claim 26 wherein the polysaccharide is sialyl Lewis^x.

28. The composition of claim 26 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

29. The composition of claim 28 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

30. The composition of claim 28 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

31. A liposome composition for use in treating a condition mediated by binding of one binding member, which is a pathogen, to a second binding member, which is a target cell, comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to one of said binding members due to polyvalent presentation of said effector molecule.

32. The composition of claim 31 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

33. The composition of claim 32 wherein the polysaccharide is sialyl Lewis^x.

34. The composition of claim 32 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

35. The composition of claim 34 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

36. The composition of claim 34 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

37. A liposome composition for use in treating a condition mediated by binding of one binding member, which is a cell in the bloodstream, to a second binding member, which is a target cell, comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to one of said binding members due to polyvalent presentation of said effector molecule.

38. The composition of claim 37 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

39. The composition of claim 38 wherein the polysaccharide is sialyl Lewis^x.

40. The composition of claim 38 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

41. The composition of claim 40 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

42. The composition of claim 40 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.

43. A liposome composition for use in treating a condition mediated by binding of one binding member, which is a pathogen or a cell in the bloodstream, to a second binding member, which is a target cell, comprising

liposomes, each having an outer layer of hydrophilic polymer chains, and

an effector molecule attached to the distal ends of at least a portion of said chains,

wherein said liposomes have increased binding to a binding member of said effector molecule due to polyvalent presentation of said effector molecule.

44. The composition of claim 43 wherein the effector molecule is selected from the group consisting of F_ab antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).

45. The composition of claim 43 wherein the polysaccharide is sialyl Lewis^x.

46. The composition of claim 43 wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β

, lymphotoxin, GM-CSF, and G-CSF.

47. The composition of claim 46 wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.

48. The composition of claim 46 wherein the interleukin is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.