Patent ID: 8293888

Claim:
A process for forming a derivative of a starting sialic acid compound comprising, reacting an intermediate formed from said starting sialic acid compound, wherein said intermediate is formed by a step comprising introducing a primary amine group, a secondary amine group or a hydrazine on a terminal sialic acid unit of said starting sialic acid compound, with a bifunctional reagent of formula I wherein (a) R is H or sulfo; R 1 is a linker group selected from alkanediyl, arylene, alkarylene, heteroarylene and alkylheteroarylene, any of which are optionally interrupted by carbonyl, ester, sulfide, ether, amide and/or amine linkages; and X is a functional group selected from vinylsulphone, N-maleimido, N-iodoacetamido, orthopyridyl disulfide, protected hydroxyl, protected amino, and azido groups; or (b) R is H or sulfo; R 1 is a linker group; X is a functional group; and said bifunctional reagent of formula I is a member selected from the group consisting of: bis[2-(succinimidyloxycarbonyl-oxy)ethyl]sulfone (BSOCOES) or its sulfo analog, disuccinimidyl tartrate (DST) or its sulfo analog, succinimidyl 3-(bromoacetamido)propionate (SBAP), N-succinimidyliodoacetate (SIA), N-5-Azido-2-nitrobenzoyloxysuccinimide (ANB-NOS), N-Hydroxysuccinimidyl-4-azidosalicylic acid (NHS-ASA), Sulfosuccinimidyl 2-(7-azido-4-methyl-coumarin-3-acetamido) ethyl-1,3′-dithiopropionate (SAED), Sulfosuccinimidyl 2-(m-azido-o-nitro-benzamido)ethyl-1,3′-dithiopropionate (SAND), N-Succinimidyl 6-(4′-azido-2′-nitro-phenylamino)hexanoate (SANPAH), Sulfosuccinimidyl 2-(p-azido-o-salicylamido)ethyl-1,3′-dithiopropionate (SASD), and Sulfosuccinimidyl-(perfluoroazidobenzamido) ethyl-1,3′-dithiopropionate (SFAD); whereby the amine or hydrazine group of said intermediate is acylated by —CO—R 1 —X to form said derivative, wherein said derivative has a formula selected from wherein R 3 is the same as R 2 , or is the product of the reaction of R 2 in the steps of oxidizing, reductive amination and reaction with reagent I, or is the product of the reaction of R 2 in the steps of oxidation, reaction with hydrazine, reduction and reaction with reagent I; wherein R 2 is selected from a mono-, di-, oligo- or poly-saccharide group, a protein, a peptide, a lipid, a drug and a drug delivery system; R 4 is H or alkyl; and R 6 is the same as R 5 , or is the product of the reaction of R 5 in the steps of reduction, oxidation, amination and reaction with reagent I, or is the product of the reaction of R 5 in the steps of reduction, oxidation, reaction with hydrazine, reduction and reaction with reagent I; wherein R 5 is selected from a mono-, di-, oligo- or poly-saccharide group, an alkyl group, an acyl group, a lipid and a drug delivery system.