Stable frozen virus formulation
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 liquid composition comprising:
a herpes simplex-1 virus;
partially hydrolyzed gelatin at a concentration of about 0.5% (w/v);
sorbitol at a concentration of about 2% (w/v);
sodium chloride at a concentration of about 50 mM to about 250 mM; and
sodium phosphate at a concentration of about 80 mM to about 120 mM;
wherein the composition is at pH 7-8.
2 . The live virus liquid composition according to claim 1 , wherein the composition further comprises sucrose at a concentration of about 9% (w/v) to about 15% (w/v).
3 . The live virus liquid composition according to claim 1 , wherein the composition further comprises myo-inositol at a concentration of about 4% (w/v).
4 . The live virus liquid composition according to claim 1 , wherein the composition comprises sodium phosphate at a concentration of about 102 mM.
5 . The live virus liquid composition according to claim 1 or 3 , wherein the herpes simplex-1 virus is selected from the group consisting of talimogene la herparepvec, G207, OrienX010, NV1020, and M032.
6 . The live virus liquid composition according to claim 5 , wherein the herpes simplex-1 virus is talimogene laherparepvec.
7 . The live virus liquid composition according to claim 1 , wherein the composition is a frozen composition.
8 . The live virus liquid composition according to claim 1 or 3 , wherein the composition is at about pH 7.4.
9 . The live virus liquid composition according to claim 1 , wherein said composition comprises sodium chloride at a concentration of about 145 mM.
10 . A method for killing tumor cells in a patient comprising administering to a subject in need thereof a live virus liquid composition under conditions effective to kill tumor cells in the patient, wherein said live virus composition comprises:
a herpes simplex virus;
partially hydrolyzed gelatin at a concentration of about 0.5% (w/v);
sorbitol at a concentration of about 2% (w/v);
sodium chloride; and
sodium phosphate,
wherein the composition is at pH 7-8.
11 . The method for killing tumor cells according to claim 10 , wherein the live virus liquid composition is administered prior to, simultaneously with or following the administration of a checkpoint inhibitor.
12 . The method according to claim 10 , wherein said live virus liquid composition comprises:
a herpes simplex-1 virus;
partially hydrolyzed gelatin at a concentration of 0.5% (w/v);
sorbitol at a concentration of 2% (w/v);
myo-inositol at a concentration of 4% (w/v);
sodium chloride at a concentration of 50 mM to 250 mM; and
sodium phosphate at a concentration of 80 mM to 120 mM,
wherein the composition is at pH 7-8.
13 . The method according to claim 12 , wherein said live virus liquid composition is at pH 7.4.
14 . The method according to claim 12 , wherein said herpes simplex-1 virus is talimogene laherparepvec.
15 . The method according to claim 13 , wherein said herpes simplex-1 virus is talimogene laherparepvec.
16 . A live virus liquid composition comprising: a herpes simplex-1 virus;
partially hydrolyzed gelatin at a concentration of 0.5% (w/v);
sorbitol at a concentration of 2% (w/v);
myo-inositol at a concentration of 4% (w/v);
sodium chloride at a concentration of 145 mM;
and sodium phosphate at a concentration of 80 mM to 120 mM,
wherein the composition is at pH 7.4.
17 . The live virus liquid composition according to claim 16 , wherein the herpes simplex-1 virus is talimogene laherparepvec.
18 . The method according to claim 10 or 12 , 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.
19 . The method according to claim 18 , wherein the tumor cells are melanoma cells.
20 . The live virus liquid composition according to claim 17 , wherein the composition comprises sodium phosphate at a concentration of 102 mM.