HERPES VIRUS STRAINS FOR GENE THERAPY

• US 20070264282A1
• Filed: 04/23/2007
• Published: 11/15/2007
• Est. Priority Date: 01/21/2000
• Status: Active Grant

• Current Assignee: BioVex Ltd. (Amgen Inc.)
• Original Assignee: BioVex Ltd. (Amgen Inc.)
• Inventors: Coffin, Robert
• Granted Patent: US 8,277,818 B2
• Time in Patent Office: Days
• US Class Current: 424/199.100
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 35/763 Herpes virus
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 15/869 Herpesviral vectors
• CPC Class Codes: C12N 2710/16021 Viruses as such, e.g. new isolates, mutants or their genomic sequences
• CPC Class Codes: C12N 2710/16033 Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
• CPC Class Codes: C12N 2710/16632 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/16643 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention provides a herpes virus with improved oncolytic properties which comprises a gene encoding an immunomodulatory cytokine and which lacks a functional ICP34.5 gene and a functional ICP47 encoding gene

Claims

1-21. -21. (canceled)

22. A method of treating cancer in an individual in need thereof by administering to a tumor in said individual a therapeutically effective amount of a herpes simplex virus which:

(i) comprises an immunostimulatory protein;

(ii) lacks a functional ICP34.5 encoding gene and a functional ICP47 encoding gene; and

(iii) is replication competent in infected tumor cells.

23. The method of claim 22 wherein said virus kills infected tumor cells by oncolysis and stimulates an anti-tumor immune response.

24. The method of claim 22 wherein tumor cells infected with said virus and non-infected tumor cells are killed.

25. The method of claim 24 wherein said virus is administered to a primary tumor and tumor cells in the primary tumor and tumor cells elsewhere that have spread from the primary tumor site are killed.

26. The method of claim 22 wherein said cancer is selected from the group consisting of prostate, breast, liver, endometrial, bladder, colon or cervical carcinoma, melanoma, lymphoma, glioma and sarcoma.

27. The method of claim 25 wherein said cancer is selected from the group consisting of prostate, breast, lung, liver, endometrial, bladder, colon or cervical carcinoma, adenocarcinoma, melanoma, lymphoma, glioma and sarcoma.

28. The method of claim 22 wherein said virus is administered by direct intratumoral inoculation.

29. The method of claim 22 wherein said virus is administered to a blood vessel supplying the tumor.

30. The method of claim 22 wherein said immunostimulatory protein is GM-CSF.

31. The method of claim 22 wherein said immunostimulatory protein is a cytokine, chemokine or protein capable of regulating T cell proliferation.

32. The method of claim 22 wherein said virus further lacks a functional gene encoding ICP6, glycoprotein H or thymidine kinase.

33. The method of claim 22 wherein said virus is a strain of herpes simplex virus 1 or 2.

34. The method of claim 22 wherein said virus is a clinical isolate.

35. The method of claim 34 wherein said clinical isolate is derived from HSV1 JS1 as deposited at the European collection of cell cultures (ECAAC) under accession number 01010209.

36. A herpes simplex virus which:

(i) comprises a gene encoding an immunostimulatory protein selected from GM-CSF and a chemokine;

(ii) lacks a functional ICP34.5 encoding gene and a functional ICP47 encoding gene; and

(iii) is replication competent in infected tumor cells.

37. The virus of claim 36 wherein said immunostimulatory protein is GM-CSF.

38. The virus of claim 36 which comprises a functional UL43 gene and/or a functional gene encoding vhs.

39. The virus of claim 36 which further lacks a functional gene encoding ICP6, glycoprotein H or thymidine kinase.

40. The virus of claim 36 which is a strain of herpes simplex virus 1 or 2.

41. The virus of claim 36 which is a clinical isolate.

42. A pharmaceutical composition comprising as active ingredient a virus according to claim 36 and a pharmaceutically acceptable carrier or diluent.

43. A pharmaceutical composition comprising as active ingredient a virus according to claim 37 and a pharmaceutically acceptable carrier or diluent.

44. A pharmaceutical composition according to claim 43, wherein the virus is derived from HSV1 JS1 as deposited at the European collection of cell cultures (ECAAC) under accession number 01010209.