Covalently-modified polyanionic bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins with bigeneric spacers, and methods of preparing such polysaccharides and conjugates and of confirming covalency
AssigneeMerck & Co., Inc.
InventorsStephen Marburg, Richard L. Tolman, Peter J. Kniskern
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Abstract
Covalently modified bacterial polysaccharides and proteins; covalent conjugates of such polysaccharides linked by a bigeneric spacer, which permits proof of covalency and facilitates purification of conjugated materials, with immunogenic bacterial membrane or other proteins, which conjugates are useful components of bacterial vaccines; and methods of preparing such polysaccharides, proteins and conjugates and of confirming the covalency of the linkage between polysaccharides and proteins.
Claims20
Stable, covalently-coupled polysaccharide-protein conjugates comprising polyanionic bacterial polysaccharides having acid groups and immunogenic proteins coupled through bigeneric spacers, containing thioether bonds, which may be represented by the formula A-E-S-B, wherein E is ##STR35## where R is H or CH.sub.3 ;
- A is ##STR36## where m is 0 to 4, n is 0 to 3, W is O or NH, and Y is CH.sub.2, O, S, NR', or CHCO.sub.2 H, where R' is H or C.sub.1 - or C.sub.2 -alkyl, such that when Y is CH.sub.2, then both m and n are not equal to zero, and when Y is O or S, then m is 2, 3 or 4 and n is 2 or 3 and B is ##STR37## where p is 1 to 3, q is 0 to 2, Z is NH.sub.2, ##STR38## CO.sub.2 H or H, and D is ##STR39## where R' is as defined above.
A stable, covalently-coupled polysaccharide-protein conjugate consisting of an Haemophilus influenzae type b polysaccharide coupled through a spacer of the formula:
- ##STR41## to a meningococcal B serotype outer membrane protein.
A method of treating mammalian species against the bacteremia of the cognate organisms, which comprises administering to said species an immunologically-effective amount of a composition comprising one or more types of polysaccharide-protein conjugates comprising bacterial capsular polysaccharides having acid groups coupled through bigeneric spacers, containing thioether bonds, to immunogenic proteins, and a member of the group consisting of a pharmaceutically-acceptable carrier, an adjuvant, and a pharmaceutically-acceptable carrier and adjuvant.
Dependencies are inferred from the claim text.