Phosphazene polyelectrolytes as immunoadjuvants

• US 5,494,673 A
• Filed: 07/11/1994
• Issued: 02/27/1996
• Est. Priority Date: 07/12/1993
• Status: Expired due to Term

• Current Assignee: Virus Research Institute
• Original Assignee: Virus Research Institute
• Inventors: Andrianov, Alexander K., Roberts, Bryan E., Payne, Lendon G., Jenkins, Sharon A.
• Primary Examiner(s): KIM, KAY KWANG AE
• Application Number:
  US08/273,285
• Time in Patent Office: 596 Days
• Field of Search: 424/280.1, 424/208.1, 424/227.1, 424/499, 424/497, 424/193.1, 424/199.1, 424/204.1, 424/234.1, 424/93.1, 424/93.4, 424/93.6, 424/256.1, 424/209. 1
• US Class Current: 424/280.1
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C08G 79/025 Polyphosphazenes
• 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

Abstract

An immunoadjuvant soluble polyphosphazene polyelectrolyte is disclosed. In one embodiment, the polymeric adjuvant is an poly(organophosphazene) with (i) ionized or ionizable pendant groups that contain, for example, carboxylic acid, sulfonic acid, or hydroxyl moieties, and (ii) pendant groups that are susceptible to hydrolysis under the conditions of use, to impart biodegradability to the polymer.

Claims

1. A method for producing an immune response in an animal comprising:

producing an immune response in an animal by administering to the animal an antigen and a polyphosphazene polyelectrolyte adjuvant in an amount effective to elicit an immune response in the animal against said antigen, said polyphosphazene being at least partially soluble in water.

2. The method of claim 1 wherein the antigen and polyphosphazene are first combined and the combination is administered to the animal.

3. The method of claim 1 wherein said administering is a parenteral administration.

4. The method of claim 1 wherein the polyphosphazene contains carboxylatophenoxy pendant groups.

5. The method of claim 1 wherein the polyphosphazene is a copolymer which comprises poly [di(carboxylatophenoxy)phosphazene].

6. The method of claim 1 wherein the polyphosphazene polymer is poly [di(carboxylatophenoxy)phosphazene-co-di(chloro)phosphazene-co-(carboxylatophenoxy)(chloro)phosphazene)].

7. The method of claim 1 wherein the polyphosphazene polyelectrolyte contains hydrolyzable side chains selected from the group consisting of amino acid, amino acid ester, chlorine, imidazole, glycerol, and glucosyl.

8. The method of claim 1 wherein the polyphosphazene polyelectrolyte is cross-linked by a multivalent cation.

9. The method of claim 1 wherein the polyphosphazene polyelectrolyte is physically mixed with the antigen.

10. The method of claim 1 wherein the antigen is selected from the group consisting of proteins, peptides, polysaccharides, glycoproteins, and glycolipids.

11. The method of claim 1 wherein the antigen is selected from the group consisting of influenza proteins, hepatitis B proteins, bacterial proteins and bacterial lipopolysaccharides.

12. The method of claim 3 wherein the polyphosphazene contains carboxylatophenoxy pendant groups.

13. The method of claim 9 wherein said administering is a parenteral administration.

14. The method of claim 1 wherein the polyphosphazene has a molecular weight in excess of 1000.

15. The method of claim 1 wherein the ratio of antigen to polyphosphazene is from 0.5:

1 to 0.0001;

1.

16. The method of claim 15 wherein the polyphosphazene has a molecular weight in excess of 1000.

17. The method of claim 14 wherein the polyphosphazene is a copolymer which comprises poly [di(carboxylathophenoxy)phosphazene].

18. The method of claim 15 wherein the polyphosphazene is a copolymer which comprises poly [di(carboxylathophenoxy)phosphazene].