# US 2013/0156797 A1 · Method for Preserving Alum Adjuvants and Alum-Adjuvanted Vaccines > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0156797 A1 - Document ID: US20130156797A1 - Status: Published application - Kind: A1 - Application number: 13/637,828 - Filed: 2011-03-31 - Published: 2013-06-20 - Earliest claimed: 2010-03-31 - Assignees: Stabilitech Ltd. - Inventors: Jeffrey Drew; David Woodward; Amanda Corteyn - Web page: https://patentgrep.com/patent/US20130156797A1 ## CPC - A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 31/10: Sulfides; Sulfoxides; Sulfones - A61K 31/14: Quaternary ammonium compounds, e.g. edrophonium, choline (betaines A61K31/205) - A61K 33/08: Oxides; Hydroxides - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids - A61K 2039/55505: {Inorganic adjuvants} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract A method for preserving an aluminium-salt adjuvant during freezing or drying comprising freezing or drying an aqueous suspension or solution comprising: (a) an aluminium salt adjuvant; (b) a compound of formula (I) or a physiologically acceptable salt or ester thereof or a compound of formula (II) or a physiologically acceptable salt or ester thereof; and (c) optionally, one or more sugars. ## Claims ### Claim 1 A method for preserving an aluminium-salt adjuvant during freezing or drying comprising freezing or drying an aqueous suspension or solution comprising: (a) an aluminium salt adjuvant; (b) a compound of formula (I) or a physiologically acceptable salt or ester thereof wherein: R1 represents hydrogen or C1-6 alkyl; and R4 represents hydrogen; or R1 and R4 together with the atoms to which they are attached form a pyrrolidine ring; R2 represents hydrogen, C1-6 alkyl or —(CH2)2-5NHC(O)(CH2)5-15CH3; and R3 represents C1-6 alkyl; or a compound of formula (II) or a physiologically acceptable salt or ester thereof wherein: X represents —S(O)2— or —S+(Rc)— Ra and Rb independently represent C1-6 alkyl; and Rc represents C1-6 alkyl substituted with a carboxylate anion and with an amine (—NH2) moiety; and (c) one or more sugars. ### Claim 2 (depends on 1) The method according to claim 1 wherein the aqueous suspension or solution is frozen or freeze-dried. ### Claim 3 (depends on 1) The method according to claim 1 in which the aqueous suspension or solution further comprises at least one antigen. ### Claim 4 (depends on 1) The method according to claim 1 in which: the compound of formula (I) is a compound of formula (IA) or a physiologically acceptable salt or ester thereof wherein R5 and R6 independently represent C1-4 alkyl and R7 represents C1-4 alkyl or —(CH2)2-5NHC(O)(CH2)5-15CH3; the compound of formula (I) is a compound of formula (IB) or a physiologically acceptable salt or ester thereof: wherein R8 and R9 independently represent C1-4 alkyl; the compound of formula (II) is a compound of formula (IIA) or a physiologically acceptable salt or ester thereof: wherein Rc and Rd independently represent C1-4 alkyl; or the compound of formula (II) is a compound of formula (IIB) or a physiologically acceptable salt or ester thereof: wherein Re and Rf independently represent C1-4; and Rg represents C1-4 alkyl substituted with a carboxylate anion and with an amine moiety. ### Claim 5 (depends on 1) The method according to claim 1 in which the compound of formula (I) is a N,N-di(C1-6 alkyl)-, N,N,N-tri(C1-6alkyl)-, or N—C1-6 alkyl-glycine or a physiologically acceptable salt or ester thereof. ### Claim 6 (depends on 5) The method according to claim 5 in which the compound of formula (I) is N,N-dimethylglycine, N,N,N-trimethylglycine, or N-methylglycine or a physiologically acceptable salt or ester thereof. ### Claim 7 (depends on 6) The method according to claim 6 in which the compound of formula (I) is N,N-dimethylglycine or a physiologically acceptable salt or ester thereof. ### Claim 8 (depends on 1) The method according to claim 1 in which the compound of formula (I) or (II) is dimethylsulfone, trimethylglycine, cocamidopropyl betaine, proline betaine or S-methyl-L-methionine or a physiologically acceptable salt or ester thereof. ### Claim 9 (depends on 1) The method according to claim 1 wherein the aluminium salt adjuvant is aluminium phosphate or aluminium hydroxide. ### Claim 10 (depends on 3) The method according to claim 3 wherein the or each antigen is provided absorbed on the adjuvant. ### Claim 11 (depends on 1) The method according to claim 1 wherein the concentration of the compound of formula (I) or (II) or physiologically acceptable salt or ester thereof is at least 0.1M. ### Claim 12 (depends on 1) The method according to claim 1 wherein one sugar is used. ### Claim 13 (depends on 1) The method according to claim 1 wherein (a) the sugar is sucrose, the concentration of sucrose is from 0.01 to 0.5M or from 0.01 to 0.2M and the concentration of the compound of formula (I) or (II) or physiologically acceptable salt or ester thereof is from 0.2 to 5M, or (b) the sugar is sucrose, the concentration of sucrose is from 0.01 to 0.5M or from 0.01 to 0.2M and the concentration of the compound of formula (I) or (II) or physiologically acceptable salt or ester thereof is from 0.2 to 2M, or (c) the sugar is mannitol, the concentration of mannitol is from 0.2 to 0.8M and the concentration of the compound of formula (I) or (II) or physiologically acceptable salt or ester thereof is from 0.5 to 1 M, or (d) the sugar is sucrose and the concentration of sucrose is from 0.01 to 0.7M or 0.01. to 0.6M or 0.01 to 0.5M. ### Claim 14 (depends on 1) The method according to claim 1 wherein two or more sugars are used. ### Claim 15 (depends on 14) The method according to claim 14 wherein (a) sucrose is present with another sugar and the other sugar is raffinose, stachyose or a sugar alcohol, or (b) sucrose is present with another sugar and the other sugar is raffinose. ### Claim 16 (canceled) ### Claim 17 (depends on 1) The method according to claim 1 wherein (a) the suspension or solution is freeze-dried, or (b) the suspension or solution is freeze-dried to form an amorphous solid matrix. ### Claim 18 (canceled) ### Claim 19 (depends on 17) The method according to claim 17 wherein a dried amorphous solid matrix is formed and the solid matrix is provided in the form of a powder in a sealed vial, ampoule or syringe. ### Claim 20 (depends on 17) The method according to claim 17 wherein (a) the resulting cake is milled to form a powder and the powder is provided in a sealed vial, ampoule or syringe, or (b) the solid matrix forms part of tablet or capsule. ### Claim 21 (canceled) ### Claim 22 (depends on 1) A vaccine composition comprising: an aluminium-salt adjuvant as defined in claim 1; one or more antigens; a compound of formula (I) or (II) as defined in claim 1 or a physiologically acceptable salt or ester thereof; and one or more sugars. ### Claim 23 (depends on 3) A vaccine composition obtainable by a method as defined in claims 3. ### Claim at position 24 24-25. (canceled)