Long-acting oxyntomodulin variants and methods of producing same

Abstract

This invention is directed to a chorionic gonadotrophin carboxy terminal peptide (CTP)-modified dual GLP-1/Glucagon receptor agonist, and methods of producing and using the same.

What is claimed is: 
     
         1 . A polynucleotide encoding a CTP-modified polypeptide comprising a dual GLP-1/glucagon receptor agonist and one to five chorionic gonadotropin carboxy terminal peptides (CTP) attached to the amino terminus or carboxy terminus of said agonist, wherein said CTP is from the beta-subunit of human chorionic gonadotropin and comprises positions one to ten of SEQ ID NO: 3. 
     
     
         2 . The polynucleotide of  claim 1 , wherein said GLP-1/Glucagon receptor agonist is oxyntomodulin. 
     
     
         3 . The polynucleotide of  claim 1 , wherein the amino acid sequence of at least one CTP is selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2. 
     
     
         4 . The polynucleotide of  claim 1 , wherein at least one CTP is glycosylated or truncated. 
     
     
         5 . The polynucleotide of  claim 1 , wherein at least one CTP is attached to said agonist via a linker. 
     
     
         6 . The polynucleotide of  claim 5 , wherein said linker is a peptide bond. 
     
     
         7 . The polynucleotide of  claim 6 , wherein two, three, four or five chorionic gonadotrophin carboxy terminal peptides are attached to the carboxy terminus of said agonist. 
     
     
         8 . The polynucleotide of  claim 1 , wherein three chorionic gonadotrophin carboxy terminal peptides are attached to said agonist, one CTP on the amino terminus and two CTP on the carboxy terminus of said agonist. 
     
     
         9 . The polynucleotide of  claim 1 , wherein two chorionic gonadotrophin carboxy terminal peptides are attached to said agonist, one CTP on the carboxy terminus and one CTP on the amino terminus of said agonist. 
     
     
         10 . The polynucleotide of  claim 1 , wherein two chorionic gonadotrophin carboxy terminal peptides are attached to said agonist on the amino terminus of said agonist. 
     
     
         11 . The polynucleotide of  claim 1 , wherein the nucleic acid sequence encoding said CTP-modified polypeptide is selected from a sequence comprising SEQ ID NO: 8, SEQ ID NO: 14, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, and SEQ ID NO: 28.