Adjuvant formulation comprising a submicron oil droplet emulsion

• US 6,299,884 B1
• Filed: 04/07/1995
• Issued: 10/09/2001
• Est. Priority Date: 05/25/1989
• Status: Expired due to Term

• Current Assignee: Chiron Corporation (Novartis Ag)
• Original Assignee: Chiron Corporation (Novartis Ag)
• Inventors: Van Nest, Gary, Ott, Gary, Barchfeld, Gail
• Primary Examiner(s): Wortman, Donna C.
• Application Number:
  US08/418,870
• Time in Patent Office: 2,377 Days
• Field of Search: 514/8, 514/18, 514/2, 514/21, 514/970, 514/975, 514/78.3, 514/784, 530/351, 530/352, 424/283.1, 424/184.1
• US Class Current: 424/283.1
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• 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: A61P 37/04 Immunostimulants
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 977/802 Virus-based particle
• CPC Class Codes: Y10S 977/918 Immunological

Abstract

An adjuvant composition, comprising a metabolizable oil and an emulsifying agent, wherein the oil and the detergent are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are less than 1 micron in diameter. In preferred embodiments, the emulsifying agent is also an immunostimulating agent, such as a lipophilic muramyl peptide. Alternatively, an immunostimulating agent separate from the emulsifying agent can be used.

Claims

1. A method of stimulating an immune response in a host animal comprising:

administering an antigen to said animal in the presence of an immunostimulating amount of an adjuvant composition consisting essentially of;

(1) a metabolizable oil, wherein the oil is present in an amount of 0.5% to 20% of the total volume and

(2) an emulsifying agent, wherein the emulsifying agent is 0.01% to 2.5% by weight (w/w), and wherein said oil and said emulsifying agent are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are about 100 nm to less than 500 nm in diameter and wherein said composition exists in the absence of any polyoxypropylene-polyoxyethylene block copolymer and in the absence of any muramyl peptide, and further wherein said adjuvant composition is capable of increasing the immune response to said antigen.

2. The method of claim 1, wherein said oil is an animal oil.

3. The method of claim 1, wherein said oil is an unsaturated hydrocarbon.

4. The method of claim 1, wherein said oil is a terpenoid.

5. The method of claim 1, wherein said oil is a vegetable oil.

6. The method of claim 1, wherein said emulsifying agent comprises a non-ionic detergent.

7. The method of claim 1, wherein said emulsifying agent comprises a polyoxyethylene sorbitan mono-, di-, or triester or a sorbitan mono-, di-, or triester.

8. The method of claim 7, wherein said adjuvant composition comprises .02 to 2.5 % by weight of said emulsifying agent.

9. The method of claim 1 wherein the oil is present in an amount of 1% to 12% of the total volume and the emulsifying agent is 0.05% to 1% by weight (w/w).

10. The method of claim 1 wherein the oil is present in an amount of 1% to 4% of the total volume and the emulsifying agent is 0.01% to 0.05% by weight (w/w).

11. The method of claim 1 wherein said emulsifying agent comprises a polyoxyethylene sorbitan mono-, di-, or triester and a sorbitan mono-, di-, or triester.

12. The method of claim 11 wherein said oil comprises squalene.

13. A method of stimulating an immune response in a host animal comprising:

administering an antigen to said animal in the presence of an immunostimulating amount of an adjuvant composition consisting essentially of;

(1) 5% by volume of squalene; and

(2) one or more emulsifying agents selected from the group consisting of polyoxyethylene sorbitan monooleate and sorbitan trioleate, wherein the total amount of emulsifying agent(s) present is 1% by weight (w/w);

wherein said squalene and said emulsifying agent(s) are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are about 100 nm to less than 500 nm in diameter and wherein said composition exists in the absence of any polyoxypropylene-polyoxyethylene block copolymer and in the absence of any muramyl peptide, and further wherein said adjuvant composition is capable of increasing the immune response to said antigen.

14. The method of claim 13, wherein the one or more emulsifying agents are polyoxyethylene sorbitan monooleate and sorbitan trioleate and the total amount of polyoxyethylene sorbitan monooleate and sorbitan trioleate present is 1% by weight (w/w).