Production of recombinant BMP-2
View Patent ↗In order to recombinantly prepare a biologically active protein of the TGF-β superfamily, a protein, whose amino terminus consists of the pro sequence of a protein of the TGF-β superfamily, or parts thereof, to which the mature domain of this protein or of another protein of TGF-β superfamily which exhibits at least 35% homology with mature BMP-2 is attached, is expressed in prokaryotes under conditions in which at least a part of the protein is obtained in the form of inclusion bodies, the inclusion bodies are isolated and solubilized under denaturing conditions, the denatured, monomeric and biologically inactive protein which has been solubilized from the inclusion bodies is renatured, with folding and dimerization to give the soluble, biologically active conformation and, where appropriate, after the renaturation, the mature protein is released proteolytically from its pro form.
1. A method for promoting bone healing or producing bone replacement material or implants comprising administering to a subject in need thereof a therapeutically effective amount of recombinantly generated pro-BMP-2 wherein said pro-BMP-2 consists of an amino acid sequence which is (i) amino acids 22-284 of SEQ ID NO: 7, concatenated to (ii) amino acids 285-398 of SEQ ID NO: 7.
2. A composition for promoting bone growth comprising recombinantly generated pro-BMP-2, wherein said pro-BMP-2 consists of an amino acid sequence which is (i) amino acids 22-284 of SEQ ID NO: 7, concatenated to (ii) amino acids 285-398 of SEQ ID NO: 7, and a pharmaceutically acceptable carrier.
3. A method for promoting bone growth comprising administering to a subject in need thereof a therapeutically effective amount of recombinantly generated pro-BMP-2, wherein said pro-BMP-2 consists of an amino acid sequence which is (i) amino acids 22-284 of SEQ ID NO: 7, concatenated to (ii) amino acids 285-398 of SEQ ID NO:7.
4. The method of claim 3 , wherein said pro-BMP-2 is administered in the form of a preparation comprising a physiologically tolerated support material which is coated or impregnated with the pro-BMP-2.