Virus strains

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.

1 . Use of a modified, oncolytic, non-laboratory virus strain in the manufacture of a medicament for the oncolytic treatment of cancer. 
     
     
         2 . Use according to  claim 1  wherein said non-laboratory strain: (a) has undergone one year or less in culture since isolation of its unmodified precursor strain from its host, or (b) has undergone 100 or less cycles of serial passage since isolation of its 10 unmodified precursor strain from its host, or (c) has a greater ability than a reference laboratory strain with equivalent modifications to infect or replicate in a tumour cell, to kill tumour cells, or to spread between cells in tissue, or (d) has substantially the ability of its unmodified precursor strain in respect of 15 one or more of the properties defined in (c). 
     
     
         3 . Use according to  claim 2  wherein, in (c), said greater ability is a statistically significantly greater ability; or wherein, in (d), substantially the ability is the same ability or an ability not statistically significantly different. 
     
     
         4 . Use according to  claim 1  wherein said non-laboratory virus strain is a strain of a herpes virus, adenovirus, picornavirus, retrovirus or alphavirus. 
     
     
         5 . Use according to  claim 4  wherein said non-laboratory virus strain is a strain of a herpes virus. 
     
     
         6 . Use according to  claim 5  wherein said non-laboratory virus strain is a strain of a herpes simplex virus (HSV). 
     
     
         7 . Use according to  claim 6  wherein said HSV strain is a strain of HSV 1 or HSV2. 
     
     
         8 . Use according to  claim 7  wherein said HSV strain is modified such that it lacks one or more of a functional ICP34.5-encoding gene, a functional ICP6-encoding gene, a functional glycoprotein H-encoding gene, or a functional thyrnidine kinase-encoding gene. 
     
     
         9 . Use according to  claim 6  wherein the non-laboratory virus strain is an HSV strain and the virus lacks a functional ICP34.5-encoding gene. 
     
     
         10 . Use according to  claim 9  wherein the non-laboratory virus strain further lacks a functional ICP47 gene. 
     
     
         11 . Use according to  claim 1  wherein said non-laboratory virus strain further comprises a heterologous gene. 
     
     
         12 . Use according to  claim 11  wherein said heterologous gene is a gene capable of modifying immune responses. 
     
     
         13 . Use according to  claim 12  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. 
     
     
         14 . Use according to  claim 13  wherein said immune stimulatory polypeptide is granulocyte macrophage colony-stimulating factor (GMCSF), another cytokine or chemokine, RANTES, 137.1 or 137.2 or ILI 2, or wherein the prodrug activator is nitroreductase or cytochrome p450, or wherein the tumour suppressor is p53. 
     
     
         15 . Use according to  claim 1  wherein the non-laboratory strain is an HSV strain and the reference strain is HSVI strain 17+, HSVI strain F or HSV1 strain KOS with equivalent modifications to the non-laboratory strain. 
     
     
         16 . Use of a modified, replication incompetent, non-laboratory virus strain comprising a heterologous gene in the manufacture of a medicament for the delivery of said gene to a subject. 
     
     
         17 . Use according to  claim 16  wherein said non-laboratory virus strain: (a) has undergone one year or less in culture since isolation of its unmodified precursor strain from its host, or (b) has undergone 100 or less cycles of serial passage since isolation of its unmodified precursor strain from its host, or (c) has a greater ability than a reference laboratory strain with equivalent modifications to infect a target cell, or (d) has a greater ability than a reference laboratory strain with equivalent modifications, to infect a neuron, to spread between cells in nervous tissue, to be transported within an axon, to infect a dendritic cell or to induce an immune response, or (e) has substantially the ability of its unmodified precursor strain in respect of one or more of the properties defined in (c) or (d). 
     
     
         18 . Use according to  claim 17  wherein, in (c), a greater ability is a statistically significantly greater ability; or, in (d), substantially the ability is the same ability or an ability not statistically significantly different. 
     
     
         19 . Use according to  claim 16  wherein the non-laboratory virus strain is selected from the group consisting of a herpes virus, adenovirus, picornavirus, retrovirus or alphavirus. 
     
     
         20 . Use according to  claim 19  wherein in an HSV strain, the virus is modified such that it lacks one, two, three or all of a functional ICP27-encoding gene, a functional ICP4-encoding gene, a functional ICPO-encoding gene, or a functional ICP22-encoding gene; or, in an non-HSV strain, the virus lacks a functional gene equivalent to one of said HSV genes; and/or, in an HSV strain, the virus lacks a functional vmw65 gene due to a mutation in said gene which abolishes its transcriptional-activation activity; or in a non-HSV strain, the virus lacks a functional gene equivalent to vmw65 due to a mutation in said gene which abolishes its transcriptional-activation activity. 
     
     
         21 - 40 . (canceled) 
     
     
         41 . A method of producing a modified non-laboratory virus strain comprising:
 (i) providing a non-laboratory strain of a virus; (ii) modifying it to render it replication incompetent and, (iii) inserting a heterologous gene.   
     
     
         42 . (canceled) 
     
     
         43 . A modified, oncolytic, non-laboratory virus strain wherein the virus strain is selected from the group consisting a herpes virus, adenovirus, picornavirus, retrovirus or alphavirus. 
     
     
         44 . A modified non-laboratory virus strain comprising a heterologous gene. 
     
     
         45 - 55 . (canceled) 
     
     
         56 . A pharmaceutical composition comprising a virus of  claim 43 . 
     
     
         57 . A virus according to  claim 43  for use in the treatment of the human or animal body. 
     
     
         58 . (canceled) 
     
     
         59 . A method of delivering a gene to an individual in need thereof by administering to said individual an effective amount of a virus as defined in  claim 16 . 
     
     
         60 . A method of treating or preventing a peripheral nervous system disorder by administering to a peripheral nerve of an individual in need thereof an effective amount of a virus as defined in  claim 2 . 
     
     
         61 . A method of treating or preventing a central nervous system disorder comprising administering to an individual in need thereof a virus as defined in claim  23 .