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US 9,175,033 B2Granted
Methods for preparing complex multivalent immunogenic conjugates
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorChe-Hung Robert Lee
Life of this patent
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Abstract
Methods for preparing complex multivalent immunogenic conjugates that include simultaneously reacting a plurality or immunogenic-distinct polysaccharides with at least one protein to make the complex multivalent immunogenic conjugates. The simultaneous reaction involves reaction of a hydrazide group on one reactant with an aldehyde or cyanate ester group on the other reactant.
Claims11
A method for making a complex multivalent immunogenic conjugate, comprising:
- reacting a protein with 1-amino-2,3-propanediol (APDO) in the presence of 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride at a pH of from about 5.5 to about 7 resulting in a solution of an APDO-modified protein;
- reacting the APDO-modified protein with an oxidizing agent resulting in a solution of an aldehyde-activated protein;
- contacting a mixture of a plurality of hydrazide-activated immunogenic-distinct polysaccharides with the aldehyde-activated protein at a pH of about 5 to about 8 such that the plurality of hydrazide-activated immunogenic-distinct polysaccharides simultaneously react with at least one aldehyde-activated protein resulting in a complex multivalent conjugate that includes at least one C═N double bond formed between each attached immunogenic-distinct polysaccharide and the protein;
- and
- reducing all of the C═N double bonds of the complex multivalent conjugate to C—N bonds resulting in a complex multivalent immunogenic conjugate product.
2 more elements
A method for preparing a hydrazide-activated protein, comprising:
- reacting a protein with hydrazine, carbohydrazide, hydrazine chloride, a dihydrazide, or a mixture thereof in the presence of (i) a carbodiimide and (ii) at least one other amino acid, wherein the amino acid is selected from at least one of lysine, arginine, histidine, glycine, serine, threonine, glutamic acid or cysteine.
Dependencies are inferred from the claim text.