Stabilised protein solutions

• US 20150086566A1
• Filed: 03/15/2013
• Published: 03/26/2015
• Est. Priority Date: 05/14/2012
• Status: Active Grant

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Jensen, Ole Elvang
• Granted Patent: US 11,466,051 B2
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 1/34 by filtration, ultrafiltration or reverse osmosis
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The invention relates to a method of stabilizing highly concentrated protein solutions during ultrafiltration by addition of sucrose to the highly concentrated protein solution, in particular, but not exclusively to a method of stabilizing highly concentrated antibody solutions during ultrafiltration by addition of sucrose to the highly concentrated antibody solution.

Claims

1. A method of ultrafiltration of a highly concentrated protein solution, wherein sucrose is added to the solution when the protein concentration of the solution is between 40 and 60 g/L before further concentration by ultrafiltration.

2. The method according to claim 1, wherein the difference between the calculated protein concentration and the measured protein concentration in the highly concentrated ultrafiltration retentate is decreased.

3. The method according to claim 1, wherein the difference between the calculated protein concentration and the measured protein concentration in the highly concentrated ultrafiltration retentate is less than 30%.

4. The method according to claim 1, wherein the addition of sucrose stabilizes the highly concentrated solution to be ultrafiltrated.

5. The method according to claim 1, wherein the level of HMWP aggregates is 1% or below 1% in the highly concentrated ultrafiltration retentate.

6. The method according to claim 1, wherein the recovery of the protein during ultrafiltration is increased.

7. The method according to claim 1, wherein the recovery of the protein during ultrafiltration is 94% or above, of the total amount of protein in the highly concentrated protein solution to be ultrafiltrated.

8. The method according to claim 1, wherein the sucrose is added to the highly concentrated protein solution in the concentration of between 50 mM and 300 mM.

9. The method according to claim 1, wherein the protein is an antibody.

10. The method according to claim 1, wherein the antibody is a monoclonal antibody.

11. The method according to claim 1, wherein the antibody is an anti-IL-20 monoclonal antibody.

14. A pharmaceutical composition comprising a protein or an antibody concentrated from a protein or antibody solution by using the method of claim 1.

15. A method of treating an inflammatory disease which comprises administering to a patient the pharmaceutical composition of claim 14.

12. (canceled)

13. (canceled)