Conjugates for the Prevention or Treatment of Nicotine Addiction

Abstract

The present invention relates in part to nicotine-derived hapten-carrier conjugates of the formula (III): wherein m, n, W, -(spacer)-, X* and Y are as defined in the description. In certain embodiments, said nicotine-derived hapten-carrier conjugates can be used to prepare vaccines for the treatment and/or prevention of nicotine addiction.

1 . A hapten of the formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         W is —CH 2 — or —O—; and 
         X is —NH 2  or —SH. 
       
     
     
         2 . The hapten according to  claim 1 , wherein W is in position 2, 5 or 6 of the pyridine ring. 
     
     
         3 . The hapten according to  claim 1  or  claim 2 , wherein W is —O— and W is in position 5 of the pyridine ring. 
     
     
         4 . The hapten according to  claim 1  or  claim 2 , wherein the hapten is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         5 . A hapten-spacer conjugate of the formula (II): 
       
         
           
           
               
               
           
         
         wherein W is —CH 2 — or —O—; 
         -(spacer)- is a C 1 -C 8  alkylene group, a C 3 -C 10  cycloalkylene group or a C 1 -C 12  alkylene group interrupted by 1 to 4 oxygen atoms and optionally interrupted by a —N(H)C(O)—; and 
         X is —NH 2  or —SH. 
       
     
     
         6 . The hapten-spacer conjugate according to  claim 5 , wherein X is —SH. 
     
     
         7 . The hapten-spacer conjugate according to  claim 5 , wherein X is —NH 2 . 
     
     
         8 . The hapten-spacer conjugate according to any one of  claims 5  to  7 , wherein -(spacer)- is a C 1 -C 8  alkylene group. 
     
     
         9 . The hapten-spacer conjugate according to any one of  claims 5  to  8 , wherein W is —O—; and W is in position 5 of the pyridine ring. 
     
     
         10 .- 24 . (canceled) 
     
     
         25 . A composition comprising CpG 24555 and a plurality of hapten-carrier conjugates of the formula (IV): 
       
         
           
           
               
               
           
         
         wherein 
         Y is diphtheria toxoid or CRM 197 ; and 
         n is an integer in the range of 1 to 40 inclusive. 
       
     
     
         26 . A composition comprising CpG 24555, aluminum hydroxide, and a plurality of hapten-carrier conjugates of the formula (IV): 
       
         
           
           
               
               
           
         
         wherein 
         Y is diphtheria toxoid or CRM 197 ; 
         and n is an integer in the range of 1 to 40 inclusive. 
       
     
     
         27 .- 31 . (canceled) 
     
     
         32 . A method for aiding smoking cessation in smokers wishing to quit or preventing relapse in ex-smokers who have successfully quit through vaccination with an anti-nicotine vaccine or through previous treatment with a pharmacotherapy or by self-quit, or preventing nicotine dependence in a person in need of such treatment, the method comprising administering the composition according to  claim 25  or  26 .