Cation exchange chromatographic support and method for using same

1. A cation-exchange chromatographic support, comprising a membrane matrix and a copolymer immobilized on the surface of the membrane matrix, wherein the copolymer comprises a (meth)acrylamide-based compound and/or a (meth)acrylate-based compound as monomer units, and the support has one or more species of cation-exchange groups including at least a weak cation-exchange group at a density higher than 30 mmol/L per volume of the support.

2. The cation-exchange chromatographic support according to claim 1 , wherein monomer units other than monomer units having the cation-exchange groups in the copolymer are neutral monomers having no charge, and the neutral monomers are a hydrophobic monomer unit and/or a hydrophilic monomer unit.

3. The cation-exchange chromatographic support according to claim 1 , wherein the copolymer comprises at least one species of hydrophobic monomer unit as a monomer unit.

4. The cation-exchange chromatographic support according to claim 1 , wherein the weak cation-exchange group is derived from any of an acrylic acid monomer, a methacrylic acid monomer, an acrylic acid compound monomer, and a methacrylic acid compound monomer.

5. The cation-exchange chromatographic support according to claim 1 , wherein the weak cation-exchange group is derived from a methacrylic acid monomer.

6. The cation-exchange chromatographic support according to claim 2 , wherein the mass percentage of the hydrophobic monomer unit and/or the hydrophilic monomer unit in the copolymer is higher than that of the cation-exchange group-containing monomer units.

7. The cation-exchange chromatographic support according to claim 1 , wherein the one or more species of cation-exchange groups consist only of weak cation exchange groups.

8. The cation-exchange chromatographic support according to claim 1 , wherein the one or more species of cation-exchange groups are a mixture of a weak cation-exchange group and a strong cation-exchange group.

9. The cation-exchange chromatographic support according to claim 1 , wherein the copolymer is immobilized on the surface of the membrane matrix through covalent bond.

10. The cation-exchange chromatographic support according to claim 1 , wherein the copolymer comprises the (meth)acrylamide-based compound as a hydrophilic monomer unit.

11. The cation-exchange chromatographic support according to claim 1 , wherein the copolymer comprises the (meth)acrylate-based compound as a hydrophilic monomer unit.

12. The cation-exchange chromatographic support according to claim 1 , wherein the copolymer comprises 2-hydroxyethyl methacrylate as a hydrophilic monomer unit.

13. The cation-exchange chromatographic support according to claim 1 , wherein the membrane matrix comprises polyethylene.

14. The cation-exchange chromatographic support according to claim 13 , wherein the graft ratio of the copolymer graft-polymerized onto the membrane matrix is 20 to 200%.

15. The cation-exchange chromatographic support according to claim 1 , wherein the copolymer substantially has no cross-linked structure.

16. The cation-exchange chromatographic support according to claim 1 , wherein the cation-exchange chromatographic support reduces the percentage of aggregates by 50% or more when 100 mg of antibodies including monomers and the aggregates is flow-through purified with respect to 1 mL of the support.

17. A purification method for purifying a physiologically active substance from a mixed solution containing impurities and the physiologically active substance, the purification method comprising contacting the mixed solution with a cation-exchange chromatographic support to obtain the physiologically active substance with improved purity, the cation-exchange chromatographic support comprising a membrane matrix and a copolymer immobilized on the surface of the membrane matrix, wherein the copolymer comprises a (meth)acrylamide-based compound and/or a (meth)acrylate-based compound as monomer units, and the support has one or more species of cation-exchange groups including at least a weak cation-exchange group at a density higher than 30 mmol/L per volume of the support.

18. The purification method according to claim 17 , wherein the purification method is based on a flow-through technique.

19. The purification method according to claim 17 , wherein the physiologically active substance is a monomer of an antibody protein.

20. The purification method according to claim 17 , wherein purification using an anion-exchange chromatographic support is performed before or after the purification step with the cation-exchange chromatographic support.

21. The purification method according to claim 20 , wherein buffer replacement is not performed between the purification step with the cation-exchange chromatographic support and the purification step with the anion-exchange chromatographic support.

22. The purification method according to claim 20 , wherein the hydrogen ion exponent of the buffer is changed by the addition of an acid or a base between the purification step with the cation-exchange chromatographic support and the purification step with the anion-exchange chromatographic support.

23. The purification method according to claim 17 , further comprising a purification step by affinity chromatography before the purification step with the cation-exchange chromatographic support.

24. The purification method according to claim 23 , wherein buffer replacement is not performed after elution of the physiologically active substance in the affinity chromatography step.

25. The purification method according to claim 23 , wherein the elution buffer for use in the elution of the physiologically active substance in the affinity chromatography step is composed mainly of a monovalent acid.

26. The cation-exchange chromatographic support according to claim 1 , wherein the density is higher than 59 mmol/L.

27. The purification method for purifying a physiologically active substance from a mixed solution containing impurities and the physiologically active substance according to claim 17 , wherein the physiologically active substance is a biomolecule.

28. The purification method for purifying a physiologically active substance from a mixed solution containing impurities and the physiologically active substance according to claim 27 , wherein the biomolecule is an antibody.

29. The cation-exchange chromatographic support according to claim 1 , wherein the density is higher than 40 mmol/L.

30. The cation-exchange chromatographic support according to claim 1 , wherein the density is higher than 49 mmol/L.