US2013345129A1PendingUtilityA1

Sugar chain added glp-1 peptide

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Assignee: GLYTECH INCPriority: Jun 19, 2007Filed: Jun 7, 2013Published: Dec 26, 2013
Est. expiryJun 19, 2027(~0.9 yrs left)· nominal 20-yr term from priority
Inventors:Yasuhiro KajiharaTakashi TsujiIzumi SakamotoYuri NambuKazuhiro FukaeKatsunari TezukaHiroaki Asai
A61P 9/10A61P 3/10A61P 3/04C07K 14/605A61P 1/12A61K 38/00A61P 1/14
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Claims

Abstract

The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.

Claims

exact text as granted — not AI-modified
1 . An oligosaccharide chain added glucagon-like peptide-1 (GLP-1) peptide having GLP-1 activity, wherein one amino acid is substituted with an oligosaccharide chain added amino acid, wherein said oligosaccharide chain is not an O-linked oligosaccharide chain, in
 (a) GLP-1;   (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or   (c) a GLP-1 analog.   
     
     
         2 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein the oligosaccharide chain added GLP-1 peptide is:
 (a1) an oligosaccharide chain added GLP-1 peptide having one amino acid further added to the C terminal (position 37) of GLP-1, wherein said added amino acid is substituted with an oligosaccharide chain added amino acid;   (a2) an oligosaccharide chain added GLP-1 peptide having one amino acid further added to the N terminal (position 7) of   
       GLP-1, wherein said added amino acid is substituted with an oligosaccharide chain added amino acid; or
 (a3) an oligosaccharide chain added GLP-1 peptide wherein an amino acid at one site selected from positions 18, 20, 22, 26, 30, 34 and 36 of GLP-1 is substituted with an oligosaccharide chain added amino acid. 
 
     
     
         3 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein:
 said oligosaccharide chain added amino acid is oligosaccharide chain added Asn;   in said oligosaccharide chain added amino acid, the oligosaccharide chain is linked to the amino acid without a linker;   said oligosaccharide chain consists of four or more sugars; and   said oligosaccharide chain is selected from the group consisting of disialo, monosialo, asialo, diGlcNAc and   
       dimannose oligosaccharide chains. 
     
     
         4 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein said oligosaccharide chain added amino acid is oligosaccharide chain added Asn or oligosaccharide chain added Cys. 
     
     
         5 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein in said oligosaccharide chain added amino acid, the oligosaccharide chain is linked to the amino acid without a linker. 
     
     
         6 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein said oligosaccharide chain consists of four or more sugars. 
     
     
         7 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein said oligosaccharide chain is selected from the group consisting of disialo, monosialo, asialo, diGlcNAc and dimannose oligosaccharide chains. 
     
     
         8 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , wherein said oligosaccharide chain is represented by the following formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 and R2 are the same or different and each represents 
 
       
         
           
           
               
               
           
         
         Ac represents an acetyl group. 
       
     
     
         9 . The oligosaccharide chain added GLP-1 peptide according to  claim 1 , having at least one of the following properties:
 higher stability in blood than that of GLP-1;   activity of controlling blood-sugar levels at least 10 times that of GLP-1 in OGTT (Oral Glucose Tolerance Test); and   DPP-IV resistance at least 30 times that of GLP-1.   
     
     
         10 . A pharmaceutical composition comprising the oligosaccharide chain added GLP-1 peptide according to  claim 1  for treating or preventing disease associated with GLP-1. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein said disease associated with GLP-1 is diabetes. 
     
     
         12 . The pharmaceutical composition according to  claim 11  wherein said oligosaccharide chain has at least 90% uniformity. 
     
     
         13 . A method for treating or preventing disease associated with GLP-1 comprising administering an effective amount of the oligosaccharide chain added GLP-1 peptide according to  claim 1 . 
     
     
         14 . The method according to  claim 13 , wherein said disease associated with GLP-1 is diabetes. 
     
     
         15 . An oligosaccharide chain added glucagon-like peptide-1 (GLP-1) peptide having GLP-1 activity, wherein two amino acids are each substituted with oligosaccharide chain added amino acids, wherein said oligosaccharide chains are not O-linked oligosaccharide chains, in
 (a) GLP-1;   (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or   (c) a GLP-1 analog.   
     
     
         16 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein:
 at least one of said oligosaccharide chain added amino acids is oligosaccharide chain added Asn;   in at least one of said oligosaccharide chain added amino acids, the oligosaccharide chain is linked to the amino acid without a linker;   at least one of said oligosaccharide chains consists of four or more sugars; and   at least one of said oligosaccharide chains is selected from the group consisting of disialo, monosialo, asialo, diGlcNAc and dimannose oligosaccharide chains.   
     
     
         17 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein the oligosaccharide chain added GLP-1 peptide is an oligosaccharide chain added GLP-1 peptide wherein an amino acid at at least one site selected from positions 18, 20, 22, 26, 30, 34 and 36 of GLP-1 is substituted with an oligosaccharide chain added amino acid. 
     
     
         18 . The oligosaccharide chain added GLP-1 peptide according to  claim 17 , wherein:
 each of said oligosaccharide chain added amino acids is oligosaccharide chain added Asn;   in said oligosaccharide chain added amino acids, the oligosaccharide chain is linked to the amino acid without a linker;   said oligosaccharide chains each consist of four or more sugars; and   each of said oligosaccharide chains is independently selected from the group consisting of disialo, monosialo, asialo, diGlcNAc and dimannose oligosaccharide chains.   
     
     
         19 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein each of said oligosaccharide chain added amino acids is oligosaccharide chain added Asn or oligosaccharide chain added Cys. 
     
     
         20 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein in said oligosaccharide chain added amino acids, the oligosaccharide chain is linked to the amino acid without a linker. 
     
     
         21 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein said oligosaccharide chains each consist of four or more sugars. 
     
     
         22 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein each of said oligosaccharide chains is independently selected from the group consisting of disialo, monosialo, asialo, diGlcNAc and dimannose oligosaccharide chains. 
     
     
         23 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , wherein said oligosaccharide chains are represented by the following formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 and R2 are the same or different and each represents 
 
       
         
           
           
               
               
           
         
       
       and
 Ac represents an acetyl group. 
 
     
     
         24 . The oligosaccharide chain added GLP-1 peptide according to  claim 15 , having at least one of the following properties:
 higher stability in blood than that of GLP-1;   activity of controlling blood-sugar levels at least 10 times that of GLP-1 in OGTT (Oral Glucose Tolerance Test); and   DPP-IV resistance at least 30 times that of GLP-1.   
     
     
         25 . A pharmaceutical composition comprising the oligosaccharide chain added GLP-1 peptide according to  claim 15  for treating or preventing disease associated with GLP-1. 
     
     
         26 . The pharmaceutical composition according to  claim 25 , wherein said disease associated with GLP-1 is diabetes. 
     
     
         27 . The pharmaceutical composition according to  claim 26  wherein said oligosaccharide chain has at least 90% uniformity. 
     
     
         28 . A method for treating or preventing disease associated with GLP-1 comprising administering an effective amount of the oligosaccharide chain added GLP-1 peptide according to  claim 15 . 
     
     
         29 . The method according to  claim 28 , wherein said disease associated with GLP-1 is diabetes.

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