Enhanced circulation effector composition and method

• US 20070087047A1
• Filed: 12/01/2006
• Published: 04/19/2007
• Est. Priority Date: 03/23/1993
• Status: Abandoned Application

• Current Assignee: Shell Oil Company (Shell Plc)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Barenholz, Yechezkel, Bercovier, Herve, Zalipsky, Samuel, Woodle, Martin, Martin, Francis
• Application Number:
  US11/633,129
• Publication Number:
  US 20070087047A1
• 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 a hydrophilic, and

an effector molecule attached to the distal ends of said chains, said effector molecule having binding affinity to a cell receptor,

wherein said liposome-bound effector molecule binds to the cell receptor and sterically hinders the cell receptor.

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 a hydrophilic polymer,

an effector molecule attached to the distal ends of said chains, said effector molecule having binding affinity to a cell receptor,

wherein said liposome-bound effector molecule binds to the cell receptor and sterically hinders the cell receptor.

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.