Enhanced ciruclation effector composition and method

• US 6,180,134 B1
• Filed: 06/07/1995
• Issued: 01/30/2001
• Est. Priority Date: 03/23/1993
• Status: Expired due to Term

• Current Assignee: SEQUUS Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: SEQUUS Pharmaceuticals, Inc. (Johnson & Johnson)
• Inventors: Martin, Francis J., Barenholz, Yechezkel, Woodle, Martin C., Zalipsky, Samuel
• Primary Examiner(s): Huff, Sheela
• Application Number:
  US08/480,332
• Time in Patent Office: 2,064 Days
• Field of Search: 424/450, 424/85.8, 424/85.2, 424/85.4, 424/812, 530/319, 530/391.1, 530/350, 530/331-324
• 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 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, which is a target cell or cell matrix, comprising

liposomes having an outer surface layer of polyethylene glycol chains, each chain having a free distal end, and

covalently attached to a portion of said distal chain ends, a polypeptide or polysaccharide effector molecule which (i) interferes with specific binding between said first and second binding members, and (ii) is rapidly removed by renal clearance from the bloodstream when administered in free form,

wherein binding of the liposomes to one of said first or second binding members is effective to inhibit binding between said first and second binding members.

2. The composition of claim 1, wherein the polyethylene glycol chains have a molecular weight between about 1,000 and 10,000 daltons.

3. The composition of claim 1, wherein the effector is selected from the group consisting of:

(a) a CD4 glycoprotein;

(b) a polysaccharide which binds to endothelial leukocyte adhesion molecule (ELAM), for use in treating inflammation related to neutrophil recruitment and tissue infiltration;

(c) polymyxin B or polymyxin B decapeptide, for treating the subject for septic shock; and

(d) a peptide, for inhibiting a ligand-receptor cell-binding event.

4. The composition of claim 3, for use in treating the subject for septic shock, wherein the effector is polymyxin B.

5. 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 or cell matrix, comprising

liposomes having an outer surface layer of polyethylene glycol chains, each chain having a free distal end, and

covalently attached to a portion of said distal chain ends, a polypeptide or polysaccharide effector molecule selected from the group consisting of:

(a) a CD4 glycoprotein,

(b) a polysaccharide which binds to endothelial leukocyte adhesion molecule (ELAM),

(c) polymyxin B or polymyxin B decapeptide; and

(d) a peptide,

wherein binding of the liposomes to one of said first or second binding members is effective to inhibit binding between said first and second binding members.

6. The composition of claim 5, wherein the polyethylene glycol chains have a molecular weight between about 1,000 and 10,000 daltons.

7. The composition of claim 6, for use in treating the subject for septic shock, wherein the effector is polymyxin B.