Stable Frozen Virus Formulation

Abstract

A live virus composition that maintains infectivity and provides improved virus stability during one or more freeze/thaw cycles and/or during long term storage in a liquid state at temperatures ranging from just above freezing to ambient temperatures.

1 . A live virus composition comprising a herpes simplex virus, a protein, at least one sugar, sodium chloride and sodium phosphate at pH 7.4, wherein the composition is frozen. 
     
     
         2 . The live virus composition of  claim 1 , wherein the composition may be thawed and stored at 2° C. to at least 25° C. 
     
     
         3 . The live virus of  claim 2 , wherein following thawing, the live virus composition is frozen again and stored at a temperature of at least −30° C. 
     
     
         4 . The live virus composition of  claim 1 , wherein the composition may be thawed and stored at 2° C. to 8° C. 
     
     
         5 . The live virus of  claim 4 , wherein following thawing, the live virus composition is frozen again and stored at a temperature of at least −30° C. 
     
     
         6 . The live virus composition according to  claim 1 , wherein the protein is partially hydrolyzed gelatin or human serum albumin. 
     
     
         7 . The live virus composition according to  claim 1 , wherein the concentration of partially hydrolyzed gelatin is from 0.01% to 1% (w/v). 
     
     
         8 . The live virus composition according to  claim 1 , wherein the concentration of human serum albumin is from 0.25% to 1%. 
     
     
         9 . The live virus composition according to  claim 1 , wherein at least one sugar is sorbitol, myo-inositol or sucrose. 
     
     
         10 . The live virus composition according to  claim 9 , wherein the concentration of sorbitol is 2% (w/v). 
     
     
         11 . The live virus composition according to  claim 9 , wherein the concentration of myo-inositol is 4% (w/v). 
     
     
         12 . The live virus composition according to  claim 9 , wherein the concentration of sucrose is 9% (w/v) to 15% (w/v). 
     
     
         13 . The live virus composition according to  claim 1 , wherein the concentration of sodium chloride is 145 mM. 
     
     
         14 . The live virus composition according to  claim 1 , wherein the concentration of sodium phosphate is 102 mM. 
     
     
         15 . The live virus composition according to  claim 1 , wherein the partially hydrolyzed gelatin is porcine. 
     
     
         16 - 30 . (canceled) 
     
     
         31 . The live virus composition according to  claim 1 , wherein the herpes simplex virus is selected from the group consisting of talimogene laherparepvec, Seprehvir™, G207, OrienX010, NV1020, M032, ImmunoVEX and OncoVEX GALV/CD . 
     
     
         32 . A method for killing tumor cells in a patient comprising administering to a subject in need thereof a live virus composition according to  claim 1  under conditions effective to kill tumor cells in the patient. 
     
     
         33 . The method for killing tumor cells in a patient according to  claim 32 , wherein the live virus composition is administered in combination with a check point inhibitor. 
     
     
         34 . The method for killing tumor cells according to  claim 33 , wherein the live virus composition is administered prior to, simultaneously with or following the checkpoint inhibitor. 
     
     
         35 . The method according to  claim 32 , wherein the tumor cells are selected from the group consisting of astrocytoma, oligodendroglioma, meningioma, neurofibroma, glioblastoma, ependymoma, Schwannoma, neurofibrosarcoma, medulloblastoma, melanoma cells, pancreatic cancer cells, prostate carcinoma cells, breast cancer cells, lung cancer cells, colon cancer cells, hepatoma cells, mesothelioma, bladder cancer cells, and epidermoid carcinoma cells. 
     
     
         36 . The method according to  claim 32 , wherein the patient is a human. 
     
     
         37 . The method according to  claim 32 , wherein the administration is carried out by injection. 
     
     
         38 . The live virus composition according to  claim 1 , wherein infectivity is increased compared to the same live virus composition lacking a protein.