METHODS FOR PREPARING ALUMINUM PRECIPITATE COMPOUNDS FOR USE IN THERAPEUTICS AND VACCINES
The invention relates to means and methods for preparing aqueous composition comprising aluminium and a protein said composition comprising less than 700 ppm heavy metal on the basis of weight with respect to the aluminium content. The invention further relates to aqueous compositions comprising a protein and an aluminium-salt, said composition comprising less than 350 ppb heavy metal based on the weight of the aqueous composition.
1 . An aqueous composition comprising an inactivated Japanese Encephalitis Virus (JEV) antigen, a reactive compound, and an aluminum salt, wherein the composition is about 0.5 ml in volume which equals one dose and:
(i) comprises less than 1.25 ppb copper (Cu);
(ii) comprises between 0.1 mg/mL and 2.5 mg/mL aluminum;
(iii) is buffered to a pH between 6.5 and 8.5; and
(iv) wherein the aluminium salt which is aluminium hydroxide (Al(OH)3) or aluminium phosphate (AlPO4).
2 . The composition of claim 1 , wherein the inactivated JEV antigen is present at a concentration of about 0.01 μg/mL to 1 mg/mL.
3 . The composition of claim 1 , wherein the inactivated JEV antigen is present at a concentration of about 10 μg/mL.
4 . The composition of claim 1 , wherein the reactive compound is selected from the group consisting of formaldehyde, ethanol, polysorbate 20, polysorbate 80, sulphite, and a combination of any thereof.
5 . The composition of claim 1 , wherein the reactive compound is sulphite.
6 . The composition of claim 1 , wherein the amount of aluminum salt per dose is about 0.25 mg.
7 . The composition of claim 1 , comprising less than 350 ppb heavy metal based on the weight of the composition, wherein said heavy metal is selected from the group consisting of nickel (Ni), tungsten (W), cobalt (Co), osmium (Os), ruthenium (Ru), cadmium (Cd), silver (Ag), iron (Fe), vanadium (V), chromium (Cr), lead (Pb), rubidium (Rb), and molybdenum (Mo).
8 . A method of preparing an aqueous composition comprising an inactivated Japanese Encephalitis Virus (JEV) antigen, a reactive compound, and an aluminum salt, wherein the composition is about 0.5 ml in volume which equals one dose and:
(i) comprises less than 1.25 ppb copper (Cu);
(ii) comprises between 0.1 mg/mL and 2.5 mg/mL aluminum;
(iii) is buffered to a pH between 6.5 and 8.5; and
(iv) comprises an aluminium salt which is is aluminium hydroxide (Al(OH)3) or aluminium phosphate (AlPO4).
9 . The method of claim 8 , wherein the inactivated JEV antigen is present at a concentration of about 0.01 μg/mL to 1 mg/mL.
10 . The method of claim 8 , wherein the inactivated JEV antigen is present at a concentration of about 10 μg/mL.
11 . The method of claim 8 , wherein the reactive compound is selected from the group consisting of formaldehyde, ethanol, polysorbate 20, polysorbate 80, sulphite, and a combination of any thereof.
12 . The method of claim 8 , wherein the reactive compound is sulphite.
13 . The method of claim 8 , wherein the amount of aluminum salt per dose is about 0.25 mg.
14 . The method of claim 8 , wherein the composition comprises less than 350 ppb heavy metal based on the weight of the composition, wherein said heavy metal is selected from the group consisting of nickel (Ni), tungsten (W), cobalt (Co), osmium (Os), ruthenium (Ru), cadmium (Cd), silver (Ag), iron (Fe), vanadium (V), chromium (Cr), lead (Pb), rubidium (Rb), and molybdenum (Mo).
15 . The method of claim 8 , wherein the composition comprises between 5 ppb and 250 ppb Fe based on the weight of the composition.
16 . The method of claim 8 , wherein the composition comprises less than 40 ppb nickel (Ni) based on the weight of the composition.
17 . The method of claim 8 , wherein the composition is stable for at least one month at a temperature of 2-8° C.
18 . The method of claim 8 , wherein the composition is stable at temperatures higher than 20° C. for at least one month.
19 . A method of inducing an immune response against Japanese Encephalitis Virus (JEV) in a subject, the method comprising administrating to the subject about 0.5 ml of an aqueous composition comprising;
(i) an inactivated Japanese Encephalitis Virus (JEV) antigen; and
(ii) an aluminum salt,
wherein the composition comprises less than about 1.25 ppb copper (Cu), contains between about 0.1 mg/mL and about 2.5 mg/mL aluminum, is buffered to a pH between about 6.5 and about 8.5, and the aluminum salt is selected from the group consisting of aluminum hydroxide (Al(OH) 3 ) and aluminum phosphate (AlPO 4 ).
20 . The method of claim 19 , wherein the composition additionally comprises a sulphite.