Virus strains

• US 7,063,835 B2
• Filed: 01/22/2001
• Issued: 06/20/2006
• Est. Priority Date: 01/21/2000
• Status: Expired due to Term

• Current Assignee: BioVex Ltd. (Amgen Inc.)
• Original Assignee: BioVex Ltd. (Amgen Inc.)
• Inventors: Coffin, Robert S.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Lucas, Zachariah
• Application Number:
  US10/181,692
• Publication Number:
  US 20030113348A1
• Time in Patent Office: 1,975 Days
• Field of Search: 424/199.1, 424/204.1, 424/205.1, 424/229.1, 424/231.1, 424/93.1, 424/93.2, 424/93.6, 435/235.1, 435/236, 435/239, 435/320.1, 514/44, 536/23.7, 536/23.72
• US Class Current: 424/93.2
• 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 relates to non-laboratory virus strains, for example of herpes viruses such as HSV, with improved oncolytic and/or gene delivery capabilities as compared to laboratory virus strains.

Claims

1. A method of treating a tumor in an individual in need thereof, comprising the step of administering to said individual an effective amount of an oncolytic herpes simplex virus 1 strain (HSV1), wherein said oncolytic (HSV1) strain is a clinical isolate from a recurrent cold sore modified such that it lacks a function ICP34.5-encoding gene, wherein said modified clinical isolate has a greater ability than a reference laboratory HSV strain modified in the same manner as the clinical isolate to replicate in or kill tumor cells, and wherein said reference laboratory strain is selected from the group consisting of HSV1 strain 17+, HSV1 strain F and HSV1 strain KOS.

2. The method of claim 1, wherein said clinical isolate has undergone 100 or less cycles of serial passage since isolation from its host.

3. The method of claim 1, wherein said HSV1 strain is further modified such that it lacks one or more of, a functional ICP6-encoding gene or a functional thymidine kinase-encoding gene.

4. The method of claim 1, wherein the HSV1 further lacks a functional ICP47 gene.

5. A method according to claim 1 wherein said HSV1 further comprises a heterologous gene.

6. A method according to claim 5 wherein said heterologous gene is a gene capable of modifying immune responses.

7. A method according to claim 6 wherein said heterologous gene capable of modifying immune responses encodes an immune stimulatory polypeptide or another gene product capable of modifying immune responses, a prodrug activator, a tumour suppressor or a pro-apoptotic gene product.

8. A method according to claim 7 wherein said immune stimulatory polypeptide is granulocyte macrophage colony-stimulating factor (GMCSF), another cytokine or chemokine, RANTES, B7.1 or B7.2 or IL12, or wherein the prodrug activator is nitroeductase or cytochrome p450, or wherein the tumour suppressor is p53.

9. The method of claim 2, wherein said clinical isolate HSV1 has undergone 50 or less cycles of serial passage since isolation from its host.

10. The method of claim 9, wherein said clinical isolate HSV1 has undergone 20 or less cycles of serial passage since isolation from its host.

11. The method of claim 10, wherein said clinical isolate HSV1 has undergone 10 or less cycles of serial passage since isolation from its host.

12. The method of claim 1, wherein said clinical isolate HSV1 has undergone one year or less in culture since isolation from its host.

13. The method of claim 12, wherein said clinical isolate HSV1 has undergone six months or less in culture since isolation from its host.

14. The method of claim 13, wherein said clinical isolate HSV1 has undergone one month or less in culture since isolation from its host.

15. The method of claim 1, wherein said clinical isolate is a HSV1 JS1 strain, HSV1 JS1 being deposited at the European Collection of Cell Cultures (ECACC) under accession number 01010209.

16. The method of claim 1, wherein said individual is human.