Bone morphogenetic protein-9 and -10 variants with enhanced therapeutic effect due to reduced side effects of ectopic ossification and pharmaceutical composition comprising same
The present invention relates to a BMP-9 variant and a derivative thereof. The variant stimulates endothelial cell-specific signaling, but does not stimulate ectopic ossification-related signaling, as compared to wild-type BMP-9, and thus has the effects of enhancing therapeutic effects on various diseases, including tumors, cardiovascular disease, fibrotic diseases, inflammatory diseases, metabolic diseases, and autoimmune diseases, and reducing side effects.
1 . A bone morphogenetic protein-9 (BMP-9) variant represented by any one amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 28.
2 . A BMP-9 variant-Fc fusion protein in which an Fc fragment of an immunoglobulin is linked to the BMP-9 variant according to claim 1 .
3 . The BMP-9 variant-Fc fusion protein according to claim 2 , wherein the Fc fragment of the immunoglobulin is represented by the amino acid sequence of SEQ ID NO: 30.
4 . The BMP-9 variant-Fc fusion protein according to claim 2 , wherein the BMP-9 variant and the Fc fragment of the immunoglobulin are linked to each other via a linker.
5 . The BMP-9 variant-Fc fusion protein according to claim 4 , wherein the linker is represented by the amino acid sequence of SEQ ID NO: 31.
6 . A pharmaceutical composition comprising the BMP-9 variant according to claim 1 or the BMP-9 variant-Fc fusion protein according to claim 2 as an active ingredient.
7 . The composition according to claim 6 , comprising a pharmaceutically acceptable carrier.
8 . The composition according to claim 7 , wherein the pharmaceutically acceptable carrier is selected from among saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures of one or more thereof.
9 . The composition according to claim 6 , comprising a pharmaceutically acceptable adjuvant.
10 . The composition according to claim 9 comprising at least one selected from the group consisting of excipients, diluents, dispersants, buffers, antimicrobial preservatives, bacteriostats, surfactants, binders, lubricants, antioxidants, thickeners, and viscosity modifiers.