Potentiation of immune responses with liposomal adjuvants

• US 6,090,406 A
• Filed: 02/26/1990
• Issued: 07/18/2000
• Est. Priority Date: 04/12/1984
• Status: Expired due to Fees

• Current Assignee: Transave Inc. (Insmed Incorporated)
• Original Assignee: The Liposome Co., Inc. (Perrigo Company PLC)
• Inventors: Estis, Leonard, Keyes, Lynn D., Recine, Marie S., Weiner, Alan L., Alving, Carl R., Janoff, Andrew S., Popescu, Mircea C.
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Hartley, Michael G.
• Application Number:
  US07/485,388
• Time in Patent Office: 3,795 Days
• Field of Search: 424/196.11, 424/206.1, 424/204.1, 424/234.1, 424/265.1, 424/812, 424/88, 424/89, 424/92, 424/405, 264/4.1
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• 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: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: Y10S 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector

Abstract

A high integrity liposome comprising at least one stabile lipid and at least one peptide-like therapeutic agent associated with said liposome, adapted for parenteral administration to an animal, including a human, and method according to manufacture and use. Immunizing dosage forms comprising a liposome and an immunogen, wherein said liposome and immunogen are present in an immunization dose. Additionally, a dosage form, including such form particularly adapted to producing an immune response, comprising a salt according to an organic acid derivative of a sterol and an immunogen wherein said organic acid derivative of a sterol and immunogen are present in an immunization dose, and method according to use is disclosed. Further, a dosage form, including such form particularly adapted to producing an immune response, comprising dimyristoylphosphatidylcholine (DMPC)/cholesterol liposomes, optionally in an aluminum hydroxide gel, and an immunogen wherein said DMPC/cholesterol and immunogen are present in an immunization dose, and method according to use.

Claims

1. A method of potentiating an immune response in an animal which comprises administering to the animal a dosage form comprising:

(a) a liposome which comprises;

(i) a lipid consisting essentially of an organic acid derivative of a sterol; and

,

(ii) an antigenic peptide; and

,

(b) a pharmaceutically acceptable carrier,

wherein said organic acid is selected from the group consisting of a carboxylic, dicarboxylic, polycarboxylic, hydroxy, amino and polyamino acid attached to said sterol at a hydroxyl group by an ether or ester linkage, and wherein the liposome is present in the dosage form in an immunization dose.

2. The method of claim 1, wherein the animal is a human.

3. The method of claim 1, wherein the liposome is a multilamellar liposome.

4. The method of claim 1, wherein the liposome has a size of about 1 micron.

5. The method of claim 1, wherein the sterol is cholesterol.

6. The method of claim 1, wherein the organic acid is a dicarboxylic acid having up to seven carbon atoms.

7. The method of claim 6, wherein the acid is succinic acid.

8. The method of claim 1, wherein the organic acid is citric acid.

9. The dosage form of claim 1, wherein the sterol comprises a salt form of the organic acid.

10. The dosage form of claim 9, wherein the salt form is a tris(hydroxymethyl)aminomethane salt.

11. The method of claim 1, wherein the antigenic peptide is a viral peptide.

12. The method of claim 1, further comprising administering an immunomodulator to the animal.

13. The method of claim 12, wherein the immunomodulator is a cytokine.

14. The method of claim 1, wherein the sterol is cholesterol hemisuccinate.

15. The method of claim 14, wherein the salt form is the tris salt of cholesterol hemisuccinate.

16. The method of claim 14, wherein the immunogen is a viral peptide.