Ev576 for use in the treatment of viral infections of the respiratory tract

Abstract

The present invention relates to methods of treating and preventing the inflammatory effects of viral infection of the upper and lower respiratory tracts, including infection by SARS coronovirus (SARS), pandemic Influenza A H5N1 (avian influenza) and pandemic influenza A H1N1 (swine 'flu).

1 - 15 . (canceled) 
     
     
         16 . A method of treating viral infection comprising administering to a subject in need thereof a therapeutically effective amount of an agent that inhibits
 i) the classical complement pathway, the alternative complement pathway and the lectin complement pathway; and/or   ii) eicosanoid activity;   
       wherein said agent is:
 (a) a protein comprising the amino acid sequence of SEQ ID NO: 2; 
 (b) a protein comprising amino acids 19 to 168 of SEQ ID NO: 2; 
 (c) a protein comprising an amino acid sequence having at least 90% sequence identity to amino acids 19 to 168 of SEQ ID NO: 2; or 
 (d) a fragment of SEQ ID NO: 2, wherein said fragment comprises six cysteine residues that are spaced relative to each other at a distance of 32 amino acids apart, 62 amino acids apart, 28 amino acids apart, 1 amino acid apart, and 21 amino acids apart, respectively, as arranged from the amino terminus to the carboxyl terminus of SEQ ID NO: 2. 
 
     
     
         17 . The method of  claim 16 , wherein said agent is a protein comprising amino acids 19 to 168 of SEQ ID NO: 2 or a protein comprising an amino acid sequence having at least 90% sequence identity to amino acids 19 to 168 of SEQ ID NO: 2. 
     
     
         18 . The method of  claim 17 , wherein the subject is suffering from viral infection in the respiratory tract. 
     
     
         19 . The method of  claim 17 , wherein the viral infection is caused by an influenza virus or a coronavirus. 
     
     
         20 . The method of  claim 19 , wherein the influenza virus is an influenza A virus. 
     
     
         21 . The method of  claim 20 , wherein the influenza A virus is subtype H1N1 or H5N1. 
     
     
         22 . The method of  claim 19 , wherein the coronavirus is a SARS coronavirus. 
     
     
         23 . The method of  claim 17 , wherein administration of the agent treats respiratory failure caused by the viral infection. 
     
     
         24 . The method of  claim 23 , wherein respiratory failure caused by the viral infection includes acute lung injury or acute respiratory distress syndrome. 
     
     
         25 . The method of  claim 17 , wherein administration of the agent treats sequelae of respiratory failure caused by the viral infection. 
     
     
         26 . The method of  claim 17 , further comprising measuring a viral titer in the subject. 
     
     
         27 . The method of  claim 26 , wherein administration of the agent results in reduction of the viral titer in the subject as compared to that in the untreated subject. 
     
     
         28 . The method of  claim 27 , wherein the viral titer is lung bulk virus titer. 
     
     
         29 . The method of  claim 17 , further comprising determining global virus distribution in lungs of the subject. 
     
     
         30 . The method of  claim 17 , further comprising measuring a neutrophil density within the lungs of the subject. 
     
     
         31 . The method of  claim 30 , wherein administration of the agent results in reduction of the neutrophil density within the lungs of the subject as compared to that in an untreated subject. 
     
     
         32 . The method of  claim 17 , further comprising measuring a total necrotized cell count within the lungs of the subject. 
     
     
         33 . The method of  claim 32 , wherein administration of the agent results in reduction of the total necrotized cell count in the subject as compared to that in an untreated subject. 
     
     
         34 . The method of  claim 17 , further comprising measuring a total protein level within the lungs of the subject. 
     
     
         35 . The method of  claim 34 , wherein administration of the agent results in reduction of the total protein level within the lungs of the subject as compared to that within the lungs of an untreated subject. 
     
     
         36 . The method of  claim 17 , wherein the agent comprises amino acids 19 to 168 of SEQ ID NO:2. 
     
     
         37 . The method of  claim 16 , wherein the agent comprises amino acids 1 to 168 of SEQ ID NO:2. 
     
     
         38 . The method of  claim 17 , wherein the subject is a mammal. 
     
     
         39 . The method of  claim 38 , wherein the mammal is a human. 
     
     
         40 . The method of  claim 17 , wherein the therapeutically effective amount of the agent administered to the subject is from 0.0001 mg/kg to 20 mg/kg. 
     
     
         41 . The method of  claim 17 , wherein the therapeutically effective amount of the agent administered to the subject is from 0.001 mg/kg to 10 mg/kg. 
     
     
         42 . The method of  claim 17 , wherein the therapeutically effective amount of the agent administered to the subject is from 0.2 mg/kg to 2 mg/kg. 
     
     
         43 . The method of  claim 16 , wherein said agent is a protein comprising an amino acid sequence having at least 95% sequence identity to amino acids 19 to 168 of SEQ ID NO: 2. 
     
     
         44 . The method of  claim 16 , wherein said agent is a protein comprising an amino acid sequence having at least 98% sequence identity to amino acids 19 to 168 of SEQ ID NO: 2.