Therapeutic use of bone morphogenetic proteins

Abstract

The invention relates to a bone morphogenetic protein 9 (BMP9) variant lacking osteogenic activity, and its use in the treatment of a vascular disease or a respiratory disease.

1 . An isolated polypeptide which is a BMP9 variant lacking osteogenic activity and comprising the amino acid sequence of SEQ ID NO: 7. 
     
     
         2 . A variant of the polypeptide according to  claim 1 , wherein one or more of the following amino acids of the polypeptide of  claim 1  have been substituted with Alanine: H326, 1)342, S343, W344, I346, K349, F362, K372, I375, L379, H381, L382, K383, K390, S402, L404, K406, V411, T413, L414, Y416 and Y418. 
     
     
         3 . A pharmaceutical composition comprising the polypeptide according to  claim 1 . 
     
     
         4 . An isolated nucleotide sequence encoding the polypeptide according to  claim 1 . 
     
     
         5 . A vector comprising a nucleotide sequence encoding the polypeptide according to  claim 1 . 
     
     
         6 . The vector according to  claim 5 , wherein the vector is a viral vector selected from the group consisting of: retrovirus, adenovirus, lentivirus, herpes simplex, vaccinia and adeno-associated virus. 
     
     
         7 . A method of treating a vascular disease or a respiratory disease, comprising administering to a subject in need thereof a therapeutically effective amount of a polypeptide as defined in  claim 1 . 
     
     
         8 . The method according to  claim 7 , wherein the vascular disease is selected from: pulmonary hypertension, pulmonary arterial hypertension, hereditary haemorrhagic telangiectasia, atherosclerosis and hepatopulmonary syndrome. 
     
     
         9 . The method according to  claim 7 , 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 idiopathic pulmonary fibrosis. 
     
     
         10 . A method of treating a vascular disease or a respiratory disease, comprising administering to a subject in need thereof a therapeutically effective amount of a vector as defined in  claim 5 . 
     
     
         11 . The method according to  claim 10 , wherein the vascular disease is selected from: pulmonary hypertension, pulmonary arterial hypertension, hereditary haemorrhagic telangiectasia, atherosclerosis and hepatopulmonary syndrome. 
     
     
         12 . The method according to  claim 10 , 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 idiopathic pulmonary fibrosis. 
     
     
         13 . A pharmaceutical composition comprising the variant according to  claim 2 . 
     
     
         14 . An isolated nucleotide sequence encoding the variant according to  claim 2 . 
     
     
         15 . A vector comprising a nucleotide sequence encoding the variant according to  claim 2 . 
     
     
         16 . The vector according to  claim 15 , wherein the vector is a viral vector selected from the group consisting of: retrovirus, adenovirus, lentivirus, herpes simplex, vaccinia and adeno-associated virus. 
     
     
         17 . A method of treating a vascular disease or a respiratory disease, comprising administering to a subject in need thereof a therapeutically effective amount of a variant as defined in  claim 2 . 
     
     
         18 . The method according to  claim 17 , wherein the vascular disease is selected from: pulmonary hypertension, pulmonary arterial hypertension, hereditary haemorrhagic telangiectasia, atherosclerosis and hepatopulmonary syndrome. 
     
     
         19 . The method according to  claim 17 , 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 idiopathic pulmonary fibrosis. 
     
     
         20 . A method of treating a vascular disease or a respiratory disease, comprising administering to a subject in need thereof a therapeutically effective amount of a vector as defined in  claim 15 . 
     
     
         21 . The method according to  claim 20 , wherein the vascular disease is selected from: pulmonary hypertension, pulmonary arterial hypertension, hereditary haemorrhagic telangiectasia, atherosclerosis and hepatopulmonary syndrome. 
     
     
         22 . The method according to  claim 20 , 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 idiopathic pulmonary fibrosis.