Stabilization of herpes virus preparations

• US 6,258,362 B1
• Filed: 04/26/1999
• Issued: 07/10/2001
• Est. Priority Date: 04/24/1998
• Status: Expired due to Fees

• Current Assignee: Cantab Pharmaceuticals Research Limited
• Original Assignee: Cantab Pharmaceuticals Research Limited
• Inventors: Varley, Claire Alison, Loudon, Peter Thomas
• Primary Examiner(s): SALIMI, ALI REZA
• Application Number:
  US09/300,073
• Time in Patent Office: 806 Days
• Field of Search: 424/229.1, 424/230.1, 424/280.1, 435/3, 435/5, 435/14, 34/405, 342/84
• US Class Current: 424/229.1
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/245 Herpetoviridae, e.g. herpes simplex virus
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: C12N 2710/16634 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Stabilized dried pharmaceutical compositions dispersible in aqueous liquid or injection comprise (i) virus e.g. for use as a vaccine or vector, preferably a herpesvirus, e.g. attenuated or genetically disabled infectious herpes simplex virus or varicella zoster virus, (ii) polysaccharide, e.g. dextran, and/or a source of mixed aminoacids of vegetable or bacterial origin, (iii) a buffer, and (iv) a mono- or oligo-saccharide or derivative thereof.

Claims

1. A stabilized dried pharmaceutical composition, which is dispersible in aqueous liquid for injection, and which comprises (i) infectious genetically disabled herpesvirus, (ii) a polysaccharide or polysaccharide derivative having a molecular weight from about 5000, to about 70,000, and/or a source of mixed amino acids of vegetable or bacterial origin, (iii) a buffer, and (iv) a monosaccharide, oligosaccharide, or sugar alcohol, thereby to stabilize said disabled herpesvirus in said preparation.

2. A composition according to claim 1, which contains at least one amino acid or amino acid salt, for example L-glutamate or L-aspartate.

3. A composition according to claim 1 which is free from animal protein.

4. A composition according to claim 3, which is free from non-herpesvirus protein.

5. A composition according to claim 1 which contains a disaccharide.

6. A composition according to claim 5 wherein the disaccharide is lactose, sucrose, or trehalose.

7. A composition according to claim 1 which contains a monosaccharide or a sugar alcohol.

8. A composition according to claim 1 which contains vegetable peptone.

9. A composition according to claim 1 which contains dextran with a molecular weight in the range from about 5000 to about 70,000.

10. The composition according to claim 1, wherein the polysaccharide or polysaccharide derivative has a molecular weight from about 11,000 to about 40,000.

11. An injectable pharmaceutical liquid preparation which has been prepared by dispersing a stabilized dried composition according to claim 1 in sterile liquid for injection.

12. A composition according to claim 1, which comprises (i) infectious genetically disabled herpesvirus, (ii) dextran, (iii) buffer, (iv) sodium glutamate, and (v) sucrose.

13. A composition according to claim 1, wherein the buffer is Tris or Phosphate buffer.

14. A method of administering a composition according to claim 1 to a subject to immunize said subject, wherein said method comprises dispersing said composition in a sterile liquid, followed by administering said liquid to said subject by injection.

15. A method of preparing a pharmaceutical composition, which comprises lyophilizing an aqueous liquid comprising (i) infectious genetically disabled herpesvirus, (ii) a polysaccharide or polysaccharide derivative having a molecular weight from about 5000 to about 70,000, and/or a source of mixed amino acids of vegetable or bacterial origin, (iii) a buffer, and (iv) a monosaccharide, oligosaccharide, or sugar alcohol.

16. The method of claim 15, wherein the polysaccharide or polysaccharide derivative has a molecular weight from about 11,000 to about 40,000.

17. A method according to claim 15, wherein said aqueous liquid comprises a disaccharide at a concentration from 2 to 12% w/v.

18. A method according to claim 15, wherein said aqueous liquid comprises vegetable peptone at a concentration in the range from about 1 to about 4% w/v.

19. A method according to claim 15, wherein said aqueous liquid comprises dextran at a concentration from 1 to 5% w/v.