Methods for stabilizing protein solutions

• US 7,803,914 B2
• Filed: 10/08/2004
• Issued: 09/28/2010
• Est. Priority Date: 10/09/2003
• Status: Expired due to Fees

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Hayasaka, Akira, Igawa, Tomoyuki, Sekimori, Yasuo
• Primary Examiner(s): KAM, CHIH MIN
• Application Number:
  US10/574,827
• Publication Number:
  US 20070249812A1
• Time in Patent Office: 2,181 Days
• Field of Search: 530/387.1, 424/130.1
• US Class Current: 530/387.1
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002

Abstract

The present inventors examined use of citric acid buffers for suppressing cryoprecipitation of IgM at a pH range and salt concentration suitable for storing IgM. As a result, the present inventors discovered that citric acid buffers significantly suppress cryoprecipitation.

Claims

1. A method for suppressing cryoprecipitation of IgM in a solution at a temperature of 1°

C. to 7°

C., wherein the method comprises adding a citric acid buffer to a first solution comprising the IgM to form a second solution comprising the IgM at a concentration of 20 mg/ml or greater, and maintaining the second solution at 1°

C. to 7°

C., thereby suppressing cryoprecipitation of the IgM.

2. The method of claim 1, wherein the pH of the second solution is 5 to 8.

3. The method of claim 2, wherein the pH of the second solution is 5 to 6.

4. The method of claim 1, comprising cooling the second solution to a temperature of 7°

C.

5. The method of claim 1, comprising cooling the second solution to a temperature of 4°

C.

6. The method of claim 1, comprising cooling the second solution to a temperature of 1°

C.

7. The method of claim 1, wherein the concentration of citric acid buffer in the second solution is 1 mM to 500 mM.

8. The method of claim 7, wherein the concentration of citric acid buffer in the second solution is 5 mM to 100 mM.

9. The method of claim 8, wherein the concentration of citric acid buffer in the second solution is 10 mM to 50 mM.

10. The method of claim 1, wherein the IgM is purified.

11. The method of claim 1, comprising cooling the second solution to a temperature between 1°

C. and 7°

C.

12. The method of claim 1, wherein the second solution is maintained at a temperature of 1°

C.

13. The method of claim 1, wherein the second solution is maintained at a temperature of 4°

C.

14. The method of claim 1, wherein the second solution is maintained at a temperature of 7°

C.

15. The method of claim 1, wherein the concentration of the IgM in the second solution is 25 mg/ml or greater.

16. The method of claim 1, wherein cryoprecipitation of IgM is suppressed 30% or more, expressed as a cryoprecipitation increase suppression rate.

17. The method of claim 1, wherein cryoprecipitation of IgM is suppressed 50% or more, expressed as a cryoprecipitation increase suppression rate.

18. The method of claim 1, wherein cryoprecipitation of IgM is suppressed 80% or more, expressed as a cryoprecipitation increase suppression rate.