Composition Comprising a Peptide and an Inhibitor of Viral Neuraminidase

Abstract

Described is a composition comprising a peptide which consists of 7-17 adjacent amino acids and comprises the hexamer TX1EX2X3E, where X1, X2, and X3 can be any natural or non-natural amino acid, and the peptide is cyclized and does not exhibit TNF receptor binding activity, and an inhibitor of viral neuraminidase.

1 .- 16 . (canceled) 
     
     
         17 . A composition, comprising:
 a peptide, selected from the group consisting of CGQRETPEGAEAKPWYC (SEQ ID NO: 1), QRETPEGAEAKPWY (SEQ ID NO: 5), PKDTPEGAEALKPWY (SEQ ID NO: 6) and CGPKDTPEGAELKPWYC (SEQ ID NO: 7), wherein the peptide has no TNF receptor binding activity and is cyclized, and   an inhibitor of viral neuraminidase, wherein the inhibitor of viral neuraminidase is a sialic acid analog.   
     
     
         18 . The composition of  claim 17 , wherein the peptide comprises the amino acid sequence CGQRETPEGAEAKPWYC (SEQ ID NO: 1) and is cyclized via the C-residues. 
     
     
         19 . The composition of  claim 18 , wherein the peptide is cyclized via a disulfide bridge between said C-residues. 
     
     
         20 . The composition of  claim 17 , further comprising a pharmaceutically acceptable carrier. 
     
     
         21 . The composition of  claim 20 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of water, sodium chloride, sodium phosphate, sodium acetate, sodium carbonate, citrate, glycine, glycylglycine, histidine, lysine, arginine, TRIS, sodium citrate, Ringer's solution, dextrose, mannite, trehalose, saccharose, sorbite, fructose, maltose, lactose or dextrane, Hank's solution, fixed oils, ethyl oleate, stabilizing agents, pharmaceutically acceptable proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids and amino acid copolymers. 
     
     
         22 . The composition of  claim 17 , wherein the composition comprises, independently of each other,
 the peptide in an amount of 1 μg to 10 g, and   the inhibitor of viral neuraminidase in an amount of 1 μg to 10 g.   
     
     
         23 . The composition of  claim 17 , wherein the composition is in a liquid form and comprises, independently of each other,
 the peptide in an amount of 1 μg to 10 g, and   the inhibitor of viral neuraminidase in an amount of 1 μg to 10 g,   and is provided in a volume of 0.5 to 10 ml.   
     
     
         24 . The composition of  claim 17 , wherein the composition is further defined as a nebulizable powder formulation or as a nebulizable liquid formulation. 
     
     
         25 . A set, comprising:
 a first container comprising a peptide, selected from the group consisting of   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   CGQRETPEGAEAKPWYC, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   QRETPEGAEAKPWY, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   PKDTPEGAEALKPWY 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   CGPKDTPEGAELKPWYC, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       wherein the peptide has no TNF receptor binding activity and is cyclized, and
 a second container comprising an inhibitor of viral neuraminidase, wherein the inhibitor of viral neuraminidase is a sialic acid analog. 
 
     
     
         26 . The set of  claim 25 , wherein the peptide comprises the amino acid sequence CGQRETPEGAEAKPWYC (SEQ ID NO: 1) and is cyclized via the C-residues. 
     
     
         27 . A method of treating one or more symptoms of influenza comprising the steps of:
 obtaining a peptide, selected from the group consisting of CGQRETPEGAEAKPWYC (SEQ ID NO: 1), QRETPEGAEAKPWY (SEQ ID NO: 5), PKDTPEGAEALKPWY (SEQ ID NO: 6) and CGPKDTPEGAELKPWYC (SEQ ID NO: 7), wherein the peptide has no TNF receptor binding activity and is cyclized, and an inhibitor of viral neuraminidase; and   treating one or more symptoms of influenza, wherein the inhibitor of viral neuraminidase treats one or more symptoms of influenza and the peptide treats pulmonary inflammation associated with influenza;   wherein the inhibitor of viral neuraminidase is a sialic acid analog.   
     
     
         28 . The composition of  claim 17 , wherein the inhibitor of viral neuraminidase is selected from the group consisting of Laninamivir, its prodrug CS-8958, Zanamivir, Peramivir, Oseltamivir phosphate, Oseltamivir carboxylate, Oseltamivir, including racemic, optically pure, salt-free, salt, enantiomeric and diastereomeric forms thereof. 
     
     
         29 . The set of  claim 25 , wherein the inhibitor of viral neuraminidase is selected from the group consisting of Laninamivir, its prodrug CS-8958, Zanamivir, Peramivir, Oseltamivir phosphate, Oseltamivir carboxylate, Oseltamivir, including racemic, optically pure, salt-free, salt, enantiomeric and diastereomeric forms thereof. 
     
     
         30 . The set of  claim 26 , wherein the inhibitor of viral neuraminidase is selected from the group consisting of Laninamivir, its prodrug CS-8958, Zanamivir, Peramivir, Oseltamivir phosphate, Oseltamivir carboxylate, Oseltamivir, including racemic, optically pure, salt-free, salt, enantiomeric and diastereomeric forms thereof. 
     
     
         31 . The method of  claim 27 , wherein the inhibitor of viral neuraminidase is selected from the group consisting of Laninamivir, its prodrug CS-8958, Zanamivir, Peramivir, Oseltamivir phosphate, Oseltamivir carboxylate, Oseltamivir, including racemic, optically pure, salt-free, salt, enantiomeric and diastereomeric forms thereof.