Ace2 polypeptide

Abstract

The present invention relates to recombinant ACE2 polypeptide, where the ACE2 polypeptide is present as a dimer. The dimer is formed specifically from glycosylated monomers and is used for producing pharmaceutical products with an extended half-life

What is claimed is: 
     
         1 . A method of treating a heart, kidney or lung disease in a human patient comprising the steps of:
 a) identifying a human patient with heart, kidney or lung disease; and   b) administering to said patient an effective amount of a composition comprising a recombinant, human angiotensin converting enzyme 2 polypeptide dimer having angiotensin II converting activity, wherein the angiotensin converting enzyme 2 polypeptide dimer comprises two monomers of the angiotensin converting enzyme 2 polypeptide, and at least 70% of the total number of angiotensin converting enzyme 2 polypeptides in the composition are in the form of an angiotensin converting enzyme 2 polypeptide dimer;   
       whereby the heart, kidney or lung disease is treated. 
     
     
         2 . The method of  claim 1 , wherein at least 90% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition are in the form of an angiotensin converting enzyme 2 polypeptide dimer. 
     
     
         3 . The method of  claim 1 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated. 
     
     
         4 . The method of  claim 1 , wherein the angiotensin converting enzyme 2 polypeptide dimers contain two Zn ions. 
     
     
         5 . The method of  claim 1 , wherein each monomer of the angiotensin converting enzyme 2 polypeptide dimer comprises amino acids 18-740 of SEQ ID NO:1. 
     
     
         6 . The method of  claim 1 , wherein each monomer of the angiotensin converting enzyme 2 polypeptide dimer consists of amino acids 18-740 of SEQ ID NO:1. 
     
     
         7 . The method of  claim 1 , wherein the disease is a heart or kidney disease selected from high blood pressure, heart insufficiency, myocardial infarction, artherosclerosis, kidney failure, kidney insufficiency, polycystic kidney disease. 
     
     
         8 . The method of  claim 2 , wherein the disease is a lung disease selected from chronic obstructive lung disease, pneumonia, asthma, chronic bronchitis, emphysema, cystic fibrosis, interstitial lung disease, pulmonary hypertonia, lung embolism, sarcoidosis of the lung, tuberculosis, oedema of the lung, Acute Lung Injury, Adult Respiratory Distress Syndrome or lung cancer. 
     
     
         9 . A method of treating Acute Lung Injury (ALI) or Adult Respiratory Distress Syndrome (ARDS) in a human patient comprising the steps of:
 a) identifying a human patient with ALI or ARDS; and   b) administering to said patient an effective amount of a composition comprising a recombinant, human, water-soluble, glycosylated angiotensin converting enzyme 2 polypeptide dimer having angiotensin II converting activity, wherein the angiotensin converting enzyme 2 polypeptide dimer comprises two monomers of the angiotensin converting enzyme 2 polypeptide, and at least 90% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition are in the form of a non-covalently bound angiotensin converting enzyme 2 polypeptide dimer containing two zinc ions and each monomer of the dimer comprises amino acids 18-740 of SEQ ID No: 1;   
       whereby the ALI or ARDS is treated. 
     
     
         10 . The method of  claim 1 , wherein at least 95% of total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition are in the form of an angiotensin converting enzyme 2 polypeptide dimer. 
     
     
         11 . The method of  claim 9 , wherein at least 95% of total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition are in the form of an angiotensin converting enzyme 2 polypeptide dimer. 
     
     
         12 . The method of  claim 1 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated such that the proportion of sugar is greater than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         13 . The method of  claim 9 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated such that the proportion of sugar is greater than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         14 . The method of  claim 1 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated such that the proportion of sugar is greater than 15% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         15 . The method of  claim 9 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated such that the proportion of sugar is greater than 15% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         16 . The method of  claim 1 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated such that the proportion of sugar is greater than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         17 . The method of  claim 9 , wherein the angiotensin converting enzyme 2 polypeptide dimers are glycosylated such that the proportion of sugar is greater than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         18 . The method of  claim 1 , wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         19 . The method of  claim 9 , wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         20 . The method of  claim 1 , wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         21 . The method of  claim 9 , wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         22 . The method of  claim 1 , wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 5% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         23 . The method of  claim 9 , wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 5% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         24 . The method of  claim 1 , wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         25 . The method of  claim 9 , wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         26 . The method of  claim 1 , wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         27 . The method of  claim 9 , wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         28 . The method of  claim 1 , wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 5% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         29 . The method of  claim 9 , wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 5% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         30 . The method of  claim 1 , wherein one or more glycosylation sites corresponding to Asn53, Asn90, Asn103, Asn322, Asn432, Asn546, and Asn690 of SEQ ID NO: 1 are N-glycosylated in more than 60% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         31 . The method of  claim 9 , wherein one or more glycosylation sites corresponding to Asn53, Asn90, Asn103, Asn322, Asn432, Asn546, and Asn690 of SEQ ID NO: 1 are N-glycosylated in more than 60% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         32 . The method of  claim 1 , wherein the one or more glycosylation sites are N-glycosylated in more than 99% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         33 . The method of  claim 9 , wherein the one or more glycosylation sites are N-glycosylated in more than 99% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         34 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         35 . The method of  claim 9 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         36 . A method of treating Acute Lung Injury (ALI) or Adult Respiratory Distress Syndrome (ARDS) in a human patient comprising the steps of:
 a) identifying a human patient with ALI or ARDS; and   b) administering to said patient an effective amount of a composition comprising a recombinant, human, water-soluble, glycosylated angiotensin converting enzyme 2 polypeptide dimer having angiotensin II converting activity, wherein the angiotensin converting enzyme 2 polypeptide dimer comprises two monomers of the angiotensin converting enzyme 2 polypeptide, and at least 90% of the total number of recombinant angiotensin converting enzyme 2 polypeptides in the composition are in the form of a non-covalently bound angiotensin converting enzyme 2 polypeptide dimer containing two zinc ions and each monomer of the dimer comprises amino acids 18-740 of SEQ ID No: 1, and wherein the glycosylation is such that the proportion of sugar is greater than 10% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition, and wherein the fraction of angiotensin converting enzyme 2 multimers in the composition is less than 5% by weight of the angiotensin converting enzyme 2 polypeptides in the composition, and wherein the fraction of angiotensin converting enzyme 2 monomers in the composition is less than 5% by weight of the angiotensin converting enzyme 2 polypeptides in the composition, and wherein the composition further comprises a pharmaceutically acceptable carrier;   
       whereby the ALI or ARDS is treated. 
     
     
         37 . The method of  claim 36 , wherein the glycosylation is such that the proportion of sugar is greater than 15% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition. 
     
     
         38 . The method of  claim 36 , wherein the glycosylation is such that the proportion of sugar is greater than 20% by weight of the total angiotensin converting enzyme 2 polypeptides in the composition.