HIGHLY CONCENTRATED STABILIZED IGM SOLUTION

• US 20090285802A1
• Filed: 07/24/2009
• Published: 11/19/2009
• Est. Priority Date: 10/09/2003
• Status: Active Grant

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Igawa, Tomoyuki, Sekimori, Yasuo
• Granted Patent: US 8,920,797 B2
• Time in Patent Office: Days
• US Class Current: 424/130.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 16/3084 against tumour-associated gangliosides
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype

Abstract

The present inventors discovered that stable and highly concentrated IgM solutions can be prepared by using, as an additive, a compound comprising a polyvalent cationic ion, such as magnesium chloride or arginine hydrochloride, to suppress IgM aggregation in solutions.

Claims

1. A solution wherein a high concentration of immunoglobulin is stabilized, and wherein the immunoglobulin is IgM.

2. The solution of claim 1, comprising IgM at a concentration higher than 1 mg/mL.

3. The solution of claim 1, which is an aqueous solution.

4. The solution of claim 1, which is a pharmaceutical formulation.

5. The solution of claim 1, comprising a polyvalent cationic ion.

6. The solution of claim 5, comprising the polyvalent cationic ion at a concentration of 1 mM to 1,000 mM.

7. The solution of claim 5, wherein the polyvalent cationic ion is a magnesium ion or an arginine ion.

8. The solution of claim 5, further comprising sugars.

9. The solution of claim 1, which is pH 5 to pH 8.

10. The solution of claim 1, wherein the solution does not intrinsically comprise human-derived proteins other than IgM.

11. The solution of claim 1, wherein the solution does not intrinsically comprise proteins other than IgM.

12. A pharmaceutical formulation obtained by freezing or lyophilizing the solution of claim 1.

13. A method for stabilizing a solution comprising a high concentration of immunoglobulin, wherein the immunoglobulin is IgM and wherein the method comprises adding a polyvalent cationic ion to the solution.

14. The method of claim 13, wherein the solution comprises IgM at a concentration higher than 1 mg/mL.

15. The method of claim 13, wherein the solution is an aqueous solution.

16. The method of claim 13, wherein the solution is a pharmaceutical formulation.

17. The method of claim 13, which comprises adding a polyvalent cationic ion to the solution such that the solution comprises the polyvalent cationic ion at a concentration of 1 mM to 1,000 MM.

18. The method of claim 13, wherein the polyvalent cationic ion is a magnesium ion or an arginine ion.

19. The method of claim 13, further comprising addition of sugars.

20. The method of claim 13, wherein the pH of the solution is 5 to 8.

21. The method of claim 13, wherein the solution does not intrinsically comprise human-derived proteins other than IgM.

22. The method of claim 13, wherein the solution does not intrinsically comprise proteins other than IgM.

23. A method for stabilizing a pharmaceutical formulation, which comprises the steps of:

(a) performing the method of claim 13; and

(b) freezing or lyophilizing the solution stabilized in step (a).

24. A method for producing a solution comprising a high concentration of stabilized immunoglobulin, wherein the immunoglobulin is IgM and wherein the method comprises the step of adding a polyvalent cationic ion to the solution.

25. The method of claim 24, wherein the solution comprises IgM at a concentration higher than 1 mg/mL.

26. The method of claim 24, wherein the solution is an aqueous solution.

27. The method of claim 24, wherein the solution is a pharmaceutical formulation.

28. The method of claim 24, which comprises the step of adding a polyvalent cationic ion to the solution such that the solution comprises the polyvalent cationic ion at a concentration of 1 mM to 1000 mM.

29. The method of claim 24, wherein the polyvalent cationic ion is a magnesium ion or an arginine ion.

30. The method of claim 24, which further comprises the step of adding sugars.

31. The method of claim 24, wherein the pH of the solution is 5 to 8.

32. The method of claim 24, wherein the solution essentially does not comprise human-derived proteins other than IgM.

33. The method of claim 24, wherein the solution essentially does not comprise proteins other than IgM.

34. A solution which is produced by the method of claim 24.

35. A method for producing a pharmaceutical formulation, wherein the method comprises the steps of:

(a) performing the method of claim 24; and

(b) freezing or lyophilizing the solution produced in step (a).