Trisaccharide Derivates, and Their Use as Adjuvants

Abstract

The present invention relates to the use of trisaccharide derivates comprising a substituted trisaccharide core, which trisaccharide core is fully substituted with fatty acid ester groups, and optionally one or more anionic groups as adjuvants, to the trisaccharide derivates as such, to a method for preparing such trisaccharides, to trisaccharides obtained with such method, to adjuvant compositions comprising such trisaccharide derivates and to a vaccine or kit comprising such adjuvant compositions.

1 - 10 . (canceled) 
     
     
         11 . A trisaccharide derivate comprising a substituted trisaccharide core, which trisaccharide core is fully substituted with fatty acid ester groups, and optionally one or more anionic groups as an adjuvant. 
     
     
         12 . The trisaccharide derivate according to  claim 11 , wherein the substituted trisaccharide core is derived from raffinose, melezitose, maltotriose, nigerotriose, maltotriulose or kestose. 
     
     
         13 . The trisaccharide derivate according to  claim 11 , wherein the substituted trisaccharide core comprises one or two sulphate ester or phosphate ester groups as anionic groups. 
     
     
         14 . The trisaccharide derivate according to  claim 11 , wherein the anionic group is a sulphate ester. 
     
     
         15 . The trisaccharide derivate according to  claim 11 , wherein the fatty acid ester group is an ester of a straight, branched, saturated or unsaturated fatty acid with a chain length of 4 to 20 carbon atoms. 
     
     
         16 . The trisaccharide derivate according to  claim 11 , wherein the fatty acid ester is the ester of lauric acid, myristic acid, palmitic acid, stearic acid or arachidic acid. 
     
     
         17 . The trisaccharide derivate according to  claim 11 , wherein the fatty acid ester groups of the substituted trisaccharide core are all identical. 
     
     
         18 . The trisaccharide derivate according to  claim 11 , wherein the substituted trisaccharide core is derived from raffinose, melezitose or maltotriose and wherein the trisaccharide derivate is fully substituted with identical fatty acid ester groups per substituted trisaccharide. 
     
     
         19 . The trisaccharide derivate according to  claim 11 , wherein the substituted trisaccharide core is derived from raffinose, melezitose or maltotriose and wherein the trisaccharide core comprises one sulphate ester or phosphate ester group and ten identical fatty acid ester groups per substituted trisaccharide or two sulphate or phosphate ester groups and nine identical fatty acid ester groups per substituted trisaccharide. 
     
     
         20 . The trisaccharide derivate according to  claim 11 , wherein the fatty acid ester groups are the esters of lauric acid. 
     
     
         21 . A method for preparing a trisaccharide derivate comprising the steps of:
 i) providing a trisaccharide and dissolving it in a solvent; and   ii) esterifying all OH-groups of the trisaccharide with a fatty acid, or source thereof.   
     
     
         22 . The method according to  claim 21 , wherein at least one of the OH-groups of the trisaccharide is reacted with an anionic agent. 
     
     
         23 . The method according to  claim 22 , wherein the anionic agent is a sulphating agent such as pyridine.SO 3  or TEA.SO 3  or a phosphating agent. 
     
     
         24 . The method according to  claim 21 , wherein the solvent used is dimethylformamide, pyridine or a mixture thereof. 
     
     
         25 . The method according to  claim 21 , wherein the ratio trisaccharide:anionic agent:fatty acid equivalents is 1:0-3:8-11 respectively. 
     
     
         26 . The method according to  claim 21 , wherein the trisaccharide is raffinose, melezitose, maltotriose, nigerotriose, maltotriulose or kestose. 
     
     
         27 . The method according to  claim 21 , wherein the trisaccharide is raffinose, melezitose or maltotriose. 
     
     
         28 . The method according to  claim 21 , wherein the fatty acid is a straight, branched, saturated or unsaturated fatty acid with a chain length of between 4 to 20 carbon atoms. 
     
     
         29 . The method according to  claim 21 , wherein the fatty acid is lauric acid, myristic acid, palmitic acid, stearic acid or arachidic acid. 
     
     
         30 . The method according to  claim 21 , wherein the trisaccharide is raffinose, melezitose or maltotriose and wherein the trisaccharide is fully esterified with identical fatty acids or with on average one sulphate ester or phosphate ester group and ten identical fatty acid ester groups per trisaccharide or two sulphate or phosphate ester groups and nine identical fatty acid ester groups per trisaccharide. 
     
     
         31 - 33 . (canceled) 
     
     
         34 . An adjuvant composition comprising a trisaccharide derivate according to  claim 11  and a pharmaceutical acceptable recipient and/or diluent. 
     
     
         35 . The adjuvant composition according to  claim 34  formulated as an oil in water emulsion. 
     
     
         36 . The adjuvant composition according to  claim 35  wherein the oil phase of the emulsion comprises squalane and/or polysorbate. 
     
     
         37 - 38 . (canceled)