Drug fusions and conjugates

Abstract

The present invention relates to drug fusions that have improved serum half lives. These fusions and conjugates comprise polypeptides, immunoglobulin (antibody) single variable domains and GLP and/or exendin molecules. The invention further relates to uses, formulations, compositions and devices comprising such drug fusions and conjugates.

1 . A drug fusion or conjugate comprising:
 (a) an insulinotropic agent or an incretin drug selected from: (i) GLP-1, (ii) exendin-4, and (iii) PYY (Peptide YY), present as a fusion or a conjugate; and   (b) a dAb which binds serum albumin selected from: (i) the DOM 7h-14-10 domain antibody (dAb) (SEQ ID NO 26); (ii) the DOM 7h-11-15 dAb (SEQ ID NO 27); or (iii) the DOM 7h-14-10R108C domain antibody (dAb) (SEQ ID NO 42);   wherein the fusion or conjugate has an elimination half life in a human of 12 hours or more.   
     
     
         2 . The drug fusion or conjugate of  claim 1 , wherein said fusion or conjugate has an elimination half life in a human of 12-21 days. 
     
     
         3 . A drug fusion or conjugate according to  claim 1  which is Exendin 4, (G4S) 3 , linker DOM7h-14-10 fusion (DMS7139) 
       
         
           
                 
               
                   (SEQ ID NO 24) 
                 
                   HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGG 
                 
                     
                 
                   SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKA 
                 
                     
                 
                   PKLLIMWRSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGL 
                 
                     
                 
                   RHPKTFGQGTKVEIKR. 
                 
             
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . The drug fusion or conjugate according to  claim 3 , where said fusion or conjugate has an elimination half life in a human of 12-21 days. 
     
     
         5 . A method of treating a metabolic disorder selected from the group consisting of hyperglycemia, impaired glucose tolerance, beta cell deficiency, diabetes (type 1 or type 2 diabetes or gestational diabetes), and obesity, wherein said method comprises administering a drug fusion or conjugate according to  claim 1  to a subject. 
     
     
         6 . The method of  claim 5 , wherein said method further comprises the step of administering an additional therapeutic agent to said subject. 
     
     
         7 . The method of  claim 6 , wherein said additional therapeutic agent is administered to said subject concurrently with said drug fusion or conjugate. 
     
     
         8 . The method of  claim 6 , wherein said additional therapeutic agent is administered to said subject sequentially to said drug fusion or conjugate. 
     
     
         9 . A method of treating a metabolic disorder selected from the group consisting of hyperglycemia, impaired glucose tolerance, beta cell deficiency, diabetes (type 1 or type 2 diabetes or gestational diabetes), and obesity, wherein said method comprises administering a drug fusion or conjugate according to  claim 3  to a subject. 
     
     
         10 . The method of  claim 9 , wherein said method further comprises the step of administering an additional therapeutic agent to said subject. 
     
     
         11 . The method of  claim 10 , wherein said additional therapeutic agent is administered to said subject concurrently with said drug fusion or conjugate. 
     
     
         12 . The method of  claim 10 , wherein said additional therapeutic agent is administered to said subject sequentially to said drug fusion or conjugate. 
     
     
         13 . A method of treating a metabolic disorder selected from the group consisting of hyperglycemia, impaired glucose tolerance, beta cell deficiency, diabetes (type 1 or type 2 diabetes or gestational diabetes), and obesity, wherein said method comprises administering Exendin 4, (G4S)3, linker DOM7h-14-10 fusion (DMS7139) 
       
         
           
                 
               
                   (SEQ ID NO 24) 
                 
                   HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGG 
                 
                     
                 
                   SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKA 
                 
                     
                 
                   PKLLIMWRSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGL 
                 
                     
                 
                   RHPKTFGQGTKVEIKR 
                 
                   to a subject. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         14 . The method of  claim 13 , wherein said method further comprises the step of administering an additional therapeutic agent to said subject. 
     
     
         15 . The method of  claim 13 , wherein said additional therapeutic agent is administered to said subject concurrently with said drug fusion or conjugate. 
     
     
         16 . The method of  claim 13 , wherein said additional therapeutic agent is administered to said subject sequentially to said drug fusion or conjugate.