Therapeutic use of bone morphogenetic proteins

Abstract

The invention relates to a polypeptide selected from bone morphogenetic protein 10 (BMP10), or a bone morphogenetic protein 9 (BMP9) variant lacking osteogenic activity, for use in the treatment of a vascular disease or a respiratory disease. The invention also relates to novel BMP9 variants and to pharmaceutical compositions comprising said polypeptides.

1 . A polypeptide selected from bone morphogenetic protein (BMP10), or a bone morphogenetic protein 9 (BMP9) variant lacking osteogenic activity, for use in the treatment of a vascular disease or a respiratory disease. 
     
     
         2 . The polypeptide of  claim 1 , wherein the vascular disease is selected from: hereditary haemorrhagic telangiectasia; atherosclerosis; and hepatopulmonary syndrome. 
     
     
         3 . (canceled) 
     
     
         4 . The polypeptide of  claim 1 , wherein the respiratory disease is selected from: obstructive lung diseases such as chronic obstructive pulmonary disease (COPD), chronic bronchitis and emphysema; pulmonary vascular diseases such as pulmonary edema and pulmonary hemorrhage; respiratory failure and respiratory distress syndrome, such as acute lung injury and acute respiratory distress syndrome; and interstitial lung diseases, such as idopathic pulmonary fibrosis. 
     
     
         5 . The polypeptide of  claim 1 , wherein the polypeptide is BMP10. 
     
     
         6 . The polypeptide of  claim 5 , wherein the polypeptide is BMP10 comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         7 . The polypeptide of  claim 5 , wherein the polypeptide is BMP10 encoded by the nucleotide sequence of SEQ ID NO: 1. 
     
     
         8 . The polypeptide of  claim 5 , wherein the polypeptide is the prodomain bound form of BMP10 (pro.BMP10). 
     
     
         9 . The polypeptide of  claim 8 , wherein the pro.BMP10 comprises a propeptide sequence comprising the amino acid sequence of residues 22-316 of SEQ ID NO: 2 non-covalently bound to a mature BMP10 sequence comprising the amino acid sequence of residues 317-424 of SEQ ID NO: 2. 
     
     
         10 . The polypeptide of  claim 9 , wherein the pro.BMP10 comprises a tetramer containing two of said propeptide sequences and two of said mature BMP10 sequences. 
     
     
         11 . The polypeptide of  claim 1 , wherein the polypeptide is a BMP9 variant lacking osteogenic activity. 
     
     
         12 . The polypeptide of  claim 11 , wherein the polypeptide is a variant of the prodomain bound form of BMP9 (pro.BMP9). 
     
     
         13 . The polypeptide of  claim 12 , wherein the variant of pro.BMP9 comprises a variant of: the propeptide sequence having the amino acid sequence of residues 23-319 of SEQ ID NO: 4 non-covalently bound to a mature BMP9 sequence having the amino acid sequence of residues 320-429 of SEQ ID NO: 4. 
     
     
         14 . The polypeptide of  claim 13 , wherein the variant of pro.BMP9 comprises a tetramer containing two of said propeptide sequences and two of said mature BMP9 sequences. 
     
     
         15 . The polypeptide of  claim 11 , wherein the BMP9 variant lacking osteogenic activity comprises a substitution, deletion or insertion mutant of the amino acid sequence of SEQ ID NO: 4. 
     
     
         16 . The polypeptide of  claim 15 , wherein the BMP9 variant lacking osteogenic activity comprises a substitution mutant of the amino acid sequence of SEQ ID NO: 4. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . A pharmaceutical composition comprising BMP10, or a BMP9 variant lacking osteogenic activity, for use in the treatment of a vascular disease or a respiratory disease. 
     
     
         21 . A BMP9 variant comprising the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 6. 
     
     
         22 . (canceled) 
     
     
         23 . A pharmaceutical composition comprising the BMP9 variant of  claim 21 . 
     
     
         24 . A vector comprising a nucleotide sequence encoding BMP10 or a BMP9 variant for use in the treatment of a vascular disease or a respiratory disease. 
     
     
         25 . The vector of  claim 24 , wherein the vector comprises the nucleotide sequence of SEQ ID NO: 1. 
     
     
         26 . (canceled)