Designer osteogenic proteins
View Patent ↗The invention relates to novel designer osteogenic proteins having altered affinity for a cognate receptor, nucleic acids encoding the same, and methods of use therefor. More preferably, the novel designer osteogenic proteins are designer BMPs and have altered affinity for a cognate BMP receptor. The designer BMPs demonstrate altered biological characteristics and provide potential useful novel therapeutics.
1. A designer bone morphogenetic protein (BMP) comprising the amino acid sequence of SEQ ID NO: 8.
2. The designer BMP of claim 1 , having a binding profile which differs from the binding profile of corresponding wild-type BMP2.
3. The designer BMP of claim 2 , wherein the binding profile of the designer BMP includes at least one of the following: binding to the Activin receptor-Like Kinase 2 (ALK2) receptor with a K D not greater than about 2 nM; binding to the Activin receptor-Like Kinase 3 (ALK3) receptor with a K D not greater than about 2 nM; binding to the Activin receptor-Like Kinase 6 (ALK6) receptor with a K D not greater than about 1 nM; binding to the Activin type IIA Receptor (ActRIIA) with a K D not greater than about 2 nM; binding to the Activin type IIB Receptor (ActRIIB) with a K D not greater than about 0.5 nM; and binding to the Bone Morphogenetic Protein type IIA Receptor (BMPRIIA) with a K D not greater than about 3.5 nM.
4. A nucleic acid encoding the designer BMP of claim 1 .
5. A method of producing a designer BMP comprising the step of introducing an expression vector comprising the nucleic acid of claim 4 into a cell.
6. A designer BMP comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO:14 and SEQ ID NO: 15.
7. The designer BMP of claim 6 , comprising the amino acid sequence of SEQ ID NO: 9.
8. The designer BMP of claim 6 , wherein the binding profile of the designer BMP includes at least one of the following: binding to the Activin receptor-Like Kinase 2 (ALK2) receptor with a K D not greater than about 2 nM; binding to the Activin receptor-Like Kinase 3 (ALK3) receptor with a K D not greater than about 2 nM; binding to the Activin receptor-Like Kinase 6 (ALK6) receptor with a K D not greater than about 1 nM; binding to the Activin type IIA Receptor (ActRIIA) with a K D not greater than about 2 nM; binding to the Activin type IIB Receptor (ActRIIB) with a K D not greater than about 0.5 nM; and binding to the Bone Morphogenetic Protein type IIA Receptor (BMPRIIA) with a K D not greater than about 3.5 nM.
9. A nucleic acid encoding the designer BMP of claim 6 .
10. A method of producing a designer BMP comprising the step of introducing an expression vector comprising the nucleic acid of claim 9 into a cell.