Viral vectors

• US 7,981,669 B2
• Filed: 01/25/2006
• Issued: 07/19/2011
• Est. Priority Date: 07/25/2003
• Status: Active Grant

• Current Assignee: BioVex Ltd. (Amgen Inc.)
• Original Assignee: BioVex Ltd. (Amgen Inc.)
• Inventors: Coffin, Robert S., Simpson, Guy Richard
• Primary Examiner(s): LI, BAO Q
• Application Number:
  US11/339,804
• Publication Number:
  US 20060188480A1
• Time in Patent Office: 2,001 Days
• Field of Search: None
• US Class Current: 435/320.1
• 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 simplex virus which is modified such that it lacks a functional ICP34.5 encoding gene, which is derived from HSV1 JS1 as deposited at the European collection of cell cultures (ECAAC) under accession number 01010209 and 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.

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

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

4. A virus according to claim 1, which further comprises a heterologous gene encoding an a protein capable of enhancing an anti-tumor therapeutic effect of the virus.

5. A virus according to claim 4, wherein the protein is an immunomodulatory protein selected from group consisting of GM-CSF, TNFα

and CD40L.

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

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

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

9. A virus according to claim 8, in which said gene encoding a functional protein capable of inhibiting dendritic cell function is UL43 or vhs.

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

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

12. A method according to claim 11 wherein said virus is administered by direct intra-tumoral inoculation.