Receptor antagonist-lipid conjugates and delivery vehicles containing same

• US 20040013720A1
• Filed: 04/25/2003
• Published: 01/22/2004
• Est. Priority Date: 11/02/2000
• Status: Abandoned Application

• Current Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Original Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Inventors: Ellens, Harma M., Monck, Myrna A., Yeh, Ping-Yang
• Application Number:
  US10/415,160
• Publication Number:
  US 20040013720A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/127 Liposomes
• 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: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

Disclosed are vesicular drug delivery vehicles, such as liposomes, comprising a targeting ligand which comprises a non-biological, biomitric antagonist to a receptor that is upregulated at a disease site.

Claims

14-1. (Amended) A liposome according to claim 1, further comprising a vesicle-forming lipid selected from the group consisting of phosphatidylcholines, sphingomyelin, and combinations thereof.

16-2. (Amended) A liposome according to claim 14, further comprising cholesterol.

17-3. (Amended) A liposome according to claim 14, further comprising a PEGylated lipid.

19-4. (Amended) A liposome according to claim 1, wherein the conjugate is inserted into the liposomal bilayer during formation of the bilayer.

20-5. (Amended) A liposome according to claim 1 wherein the liposome comprises a therapeutic active or a contrast agent suitable for diagnostic imaging entrapped in the liposome.

21. A conjugate useful for preparing a targeted liposome, comprising:

(a) a vesicle-forming lipid having a polar head group and a hydrophobic tail, and

(b) a non-biological, biomimetic antagonist to a receptor upregulated at a disease site, directly or indirectly chemically linked to the polar head group of the vesicle-forming lipid.

22. A conjugate according to claim 21 substantially as hereinbefore defined with reference to Example 2.

23-6. (Amended) A method of treating or diagnosing a disease characterized by upregulation of a receptor, comprising administering to a patient in need thereof a safe and effective amount of a liposome according to claim 1, wherein the antagonist has binding affinity to the upregulated receptor.

29-7. (Amended) A pharmaceutical composition comprising the liposome according to claim 1 and a pharmaceutically acceptable carrier or diluent.