Viral vectors

• US 20060188480A1
• Filed: 01/25/2006
• Published: 08/24/2006
• Est. Priority Date: 07/25/2003
• Status: Active Grant

• Current Assignee: BioVex Ltd. (Amgen Inc.)
• Original Assignee: BioVex Ltd. (Amgen Inc.)
• Inventors: Simpson, Guy Richard, Coffin, Robert Stuart
• Granted Patent: US 7,981,669 B2
• Time in Patent Office: Days
• US Class Current: 424/93.200
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/763 Herpes virus
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/191 Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/50 acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/16643 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2800/108 episomal vectors
• CPC Class Codes: C12N 2840/20 translation of more than one cistron

Abstract

The present invention provides a herpes virus which lacks a functional ICP34.5 encoding gene and which comprises two or more of—(i) a gene encoding a prodrug converting enzyme; (ii) a gene encoding a protein capable of causing cell to cell fusion; and (iii) a gene encoding an immunomodulatory protein.

Claims

1. A herpes virus which lacks a functional ICP34.5 encoding gene and which comprises two or more of:

(i) a heterologous gene encoding a prodrug converting enzyme;

(ii) a heterologous gene encoding a protein capable of causing cell to cell fusion; and

(iii) a heterologous gene encoding an immunomodulatory protein.

2. A herpes virus according to claim 1, which comprises:

(i) a heterologous gene encoding a prodrug converting enzyme; and

(ii) a heterologous gene encoding a protein capable of causing cell to cell fusion.

3. A virus according to claim 1 wherein said prodrug converting enzyme is a cytosine deaminase.

4. A virus according to claim 1 wherein said protein capable of causing cell to cell fusion is a gibbon ape leukaemia fusogenic glycoprotein.

5. A herpes virus according to claim 1, which comprises:

(i) a heterologous gene encoding a encoding an immunomodulatory protein; and

(ii) a heterologous gene encoding a protein capable of causing cell to cell fusion.

6. A herpes virus according to claim 1, which comprises:

(i) a heterologous gene encoding a prodrug converting enzyme; and

(ii) a heterologous gene encoding an immunomodulatory protein.

7. A virus according to claim 1 wherein the immunomodulatory protein is GM-CSF, TNFα

or CD40L.

8. A virus according to an) one of the preceding claims claim 1 which comprises one or more further heterologous genes capable of enhancing the anti-tumour therapeutic effect of the virus.

9. A virus according to claim 1 which further lacks a functional gene encoding ICP47.

10. A virus according to claim 1 which further lacks a functional gene encoding ICP6, glycoprotein H and/or thymidine kinase.

11. A virus according to claim 1 which further lacks a gene encoding a functional protein capable of inhibiting dendritic cell function.

12. A virus according to claim 11 in which said gene encoding a functional protein capable of inhibiting dendritic cell function is UL43 or vhs.

13. A virus according to claim 1 which is a strain of herpes simplex virus 1 or 2.

14. A virus according to an) one of the preceding claims claim 1 which is a non-laboratory virus strain.

15. A virus according to claim 14 which is derived from HSV1 JS1 as deposited at the European collection of cell cultures (ECAAC) under provisional accession number 01010209.

19. A pharmaceutical composition comprising as active ingredient a virus according to claim 1 and a pharmaceutically acceptable carrier or diluent.

20. A method of treating a tumour in an individual in need thereof by administering to said individual an effective amount of a virus according to claim 1.

21. A method according to claim 20 wherein said virus is administered by direct intra-tumoral inoculation.

16. (canceled)

17. (canceled)

18. (canceled)