Polysaccharide conjugates of biomolecules

• US 6,949,524 B2
• Filed: 07/02/2002
• Issued: 09/27/2005
• Est. Priority Date: 08/08/1997
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Products GmbH (Siemens AG)
• Original Assignee: DADE Behring Beteiligungs GmbH (Siemens AG)
• Inventors: Singh, Rajendra, Mehta, Harshvardhan
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Khare, Devesh
• Application Number:
  US10/188,578
• Publication Number:
  US 20030027788A1
• Time in Patent Office: 1,183 Days
• Field of Search: 536/4.1, 536/18.5, 536/29.1, 536/51, 536/123.1, 536/124, 536/126, 514/8, 514/2, 514 12- 19, 514/154, 514/54
• US Class Current: 514/54
• CPC Class Codes: A01N 43/16 with oxygen as the ring hetero atom
• CPC Class Codes: C08B 37/0021 Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
• CPC Class Codes: C08H 1/00 Macromolecular products derived from proteins food proteins A23; glue, gelatine C09H
• CPC Class Codes: G01N 2333/988 Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9

Abstract

Compounds that are modified polysaccharides having pendant aldehyde functionalities are disclosed. Each of the aldehyde functionalities is attached through a linker to a position corresponding to a hydrogen atom of a different hydroxyl group of unmodified polysaccharide. Also disclosed is a method for introducing an amine-reactive functionality into a dextran. The method comprises (a) reacting the dextran with an alkylating agent having a functionality that reacts with an hydroxyl group of the dextran thereby forming an alkylated dextran wherein the alkylating agent has an olefin group and (b) treating the alkylated dextran to convert the olefin group to an amine-reactive functionality. A polysaccharide can be conjugated to a biomolecule by carrying out the above method and reacting the amine-reactive functionality with an amine functionality on the biomolecule to produce polysaccharide conjugated to the biomolecule.

Claims

1. A compound produced by reaction of a polymer comprising a sequence of repeating monosaccharide units, each of which is independently selected from monosaccharide units of the formula:

wherein one of the A'"'"'s is a bond to the C1 glycosidic carbon of another of said units and the other A'"'"'s are independently selected from the group consisting of H and QL, wherein L is a linking group linking O and Q and Q is C(H)=O with the proviso that at least two of the A'"'"'s in said polymer are QL with a polylpeptide.

2. The compound according to claim 1 wherein the polypeptide is a biomolecule.

3. The compound according to claim 1 wherein the polypeptide is a receptor.

4. The compound according to claim 1 wherein the polypeptide is a binding pair member.

5. The compound according to claim 1 wherein the polypeptide is an antibody.