Method for the Production of Proteins

A method for purification of a gamma-carboxy-glutamic (GLA)-residue containing serine protease in solution, wherein the GLA-residue containing serine proteases comprises a Factor IX polypeptide, the method comprising:

• subjecting the solution to one or more purification steps selected from the group consisting of anion exchange chromatography, hydrophobic interaction chromatography, immunoaffinity purification, size exclusion chromatography, diafiltration, and ultrafiltration,
• adjusting calcium in the solution to obtain a molar ratio of free calcium ions and Factor IX polypeptide (Ca2+:FIX polypeptide) lower than 0.5;
• and
• adjusting the pH of the solution to a value between 4.5 and 6.9 or to a value between 8.6 and 10,