Antibacterial products

Abstract

The invention provides a combination of an antibacterial agent and a delivery agent, in which the delivery agent is bonded, or capable of binding, to the antibacterial agent, and in which the delivery agent is capable of binding to one or more structures on a bacterial cell membrane. The invention further provides the use of such combinations in treating or preventing bacterial infections.

1 . A combination of an antibacterial agent and a delivery agent, wherein; the delivery agent is a polypeptide or a polypeptide derivative, or a pharmaceutically-acceptable salt thereof, that bears a positive charge of at least 2 units and is capable of binding to one or more structures on a bacterial cell membrane. 
     
     
         2 . The combination according to  claim 1 , wherein the antibacterial agent is a molecule or fragment that modulates the activity of a penicillin binding protein. 
     
     
         3 . The combination according to  claim 1 , wherein the antibacterial agent is an inhibitor of a glycosyltransferase enzyme. 
     
     
         4 . The combination according to  claim 1 , wherein the antibacterial agent is a molecule or fragment that inhibits the synthesis or repair of bacterial cell walls. 
     
     
         5 . The combination according to  claim 1 , wherein the delivery agent is capable of binding to one or more structures on a bacterial cell membrane via the formation of one or more covalent bonds with said structures, or via the formation of one or more hydrogen bonds with said structures or through electrostatic interactions between oppositely charged regions on the delivery agent and the bacterial cell membrane. 
     
     
         6 . The combination according to  claim 1 , wherein the delivery agent comprises one or more functional groups independently selected from the list consisting of, primary amines, amidines, amides, and salts thereof. 
     
     
         7 . The combination according to  claim 6 , wherein the each of the one or more functional groups is independently selected from the list consisting of primary amines, amidines, guanidines, amides, ureas, thioamides, thioureas and acid addition salts thereof. 
     
     
         8 . The combination according to  claim 6 , wherein the delivery agent comprises at least four of said functional groups. 
     
     
         9 . The combination according to  claim 1 , wherein the delivery agent comprises at least two amino acid residues selected from the group consisting of arginine and lysine. 
     
     
         10 . (canceled) 
     
     
         11 . The combination according to  claim 1 , wherein the delivery agent is a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       . 
     
     
         12 . The combination according  claim 1 , wherein the delivery agent is covalently bonded to the antibacterial agent. 
     
     
         13 . The combination according to  claim 1 , wherein the antibacterial agent is a glycopeptide or a phosphoglycolipid molecule or fragment. 
     
     
         14 . The combination according to  claim 1 , wherein the antibacterial agent is selected from the group consisting of moenomycin, moenomycin derivatives, vancomycin, vancomycin derivatives, β-lactam antibiotics and derivatives thereof. 
     
     
         15 . The combination according to  claim 14 , wherein the antibacterial agent is a moenomycin A derivative which is covalently bound to the delivery agent: 
 (i) such that the delivery agent and any associated linker replaces part or all of the 2-amido-cyclopentane-1,3-dione portion of the moenomycin;   (ii) via the moenocinol portion of the moenomycin;   (iii) such that the delivery agent and any associated linker replaces part or all of the moenocinol portion of the moenomycin; or   (iv) via the 2-amino-cyclopentane-1,3-dione portion of the moenomycin.   
     
     
         16 . The combination according to  claim 14 , wherein the delivery agent portion of the combination contains a structure selected from the list consisting of: 
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       . 
     
     
         17 . A pharmaceutical formulation comprising the combination of  claim 1  in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. 
     
     
         18 - 28 . (canceled) 
     
     
         29 . A delivery agent as defined in  claim 16 , or a pharmaceutically acceptable salt thereof. 
     
     
         30 - 40 . (canceled)