A novel TWO-STEP renaturation procedure for efficient production of recombinant BMP-2

Bone morphogenetic proteins (BMPs) stimulate bone formation and thus constitute important protein therapeutics. Here, a novel procedure is presented which allows fast and efficient production of biologically active BMP-2 via a TWO-STEP procedure: the conditions are designed such that the first step favors formation of monomeric species with the correct intramolecular disulfide bridges, the conditions of the second folding reaction stimulate the formation of the intermolecular disulfide bridge. The short processing times and increased yields compared to previously published procedures allow low-cost production of this important protein drug.