IP Library Granted Patent US 8,765,669
Granted Patent B2
US 8,765,669 · App. 12/999,654 · Granted Jul 1, 2014

Glycosylated GLP-1 peptide

Inventors: Yasuhiro Kajihara (Toyonaka, JP); Takashi Tsuji (Nagareyama, JP); Izumi Sakamoto (Tokushima, JP); Yuri Nambu (Tokushima, JP); Naohiro Hayashi (Tokushima, JP); Kazuyuki Ishii (Tokushima, JP); Kazuhiro Fukae (Tokushima, JP); Katsunari Tezuka (Tokushima, JP); Hiroaki Asai (Tokushima, JP)
Assignee: Glytech, Inc.
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Quick Facts
Patent No.
US 8,765,669
App. No.
12/999,654
Granted
Jul 1, 2014
Kind
B2
Abstract

Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.

Claims (32)

1. An oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least two amino acids are each substituted with an oligosaccharide chain added amino acid, wherein the GLP-1 peptide is:

(a) GLP-1; or

(b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of 1-3 amino acids,

wherein each of the substituted sites is selected from the group consisting of the positions 18, 20, 22, 26, 30, 34, and 36 of GLP-1,

and

wherein each of said oligosaccharide chains is independently a biantennary complex-type oligosaccharide chain and represented by the following formula:

wherein

R 1 and R 2 are the same or different and each represents

and Ac represents an acetyl group;

or a pharmaceutically acceptable salt thereof.

2. The oligosaccharide chain added GLP-1 peptide according to claim 1 , wherein each of said oligosaccharide chain added amino acids is independently oligosaccharide chain added Asn and/or oligosaccharide chain added Cys.

3. 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.

4. The oligosaccharide chain added GLP-1 peptide according to claim 1 , wherein said oligosaccharide chain is substantially uniform.

5. The oligosaccharide chain added GLP-1 peptide according to to claim 1 , wherein:

each of said oligosaccharide chain added amino acids 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 chains each consist of four or more sugars;

and

said oligosaccharide chain is substantially uniform.

6. The oligosaccharide chain added GLP-1 peptide according to claim 1 , having at least one of the following properties:

a higher stability in blood than that of GLP-1;

an 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.

7. A pharmaceutical composition comprising the oligosaccharide chain added GLP-1 peptide according to claim 1 as an active ingredient.

8. The pharmaceutical composition according to claim 7 for treating or preventing disease associated with GLP-1.

9. The pharmaceutical composition according to claim 8 , wherein said disease associated with GLP-1 is diabetes.

10. A method for treating or preventing disease associated with GLP-1 comprising administering effective amount of the oligosaccharide chain added GLP-1 peptide according to claim 1 .

11. An oligosaccharide chain added GLP-1 peptide having GLP-1 activity according to claim 1 , wherein, in said oligosaccharide chain added amino acid, the oligosaccharide chain is linked to the amino acid via a linker, and said linker contains an amino acid at the terminal bound to said oligosaccharide chain.

12. The oligosaccharide chain added GLP-1 peptide according to claim 11 , the amino acid bound to said linker is Lys.

13. The oligosaccharide chain added GLP-1 peptide according to claim 11 , wherein the amino acid contained in said linker is Asn.

14. The oligosaccharide chain added GLP-1 peptide according to claim 11 , wherein the oligosaccharide chain is substantially uniform.

15. A pharmaceutical composition comprising the oligosaccharide chain added GLP-1 peptide according to claim 11 as an active ingredient.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2013
From: OTSUKA CHEMICAL CO., LTD.
To: GLYTECH, INC.
Reel/Frame 030358/0048 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2011
From: TSUJI, TAKASHI; SAKAMOTO, IZUMI; NAMBU, YURI; HAYASHI, NAOHIRO; ISHII, KAZUYUKI; FUKAE, KAZUHIRO; TEZUKA, KATSUNARI; ASAI, HIROAKI
To: OTSUKA CHEMICAL CO., LTD.
Reel/Frame 025915/0830 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2011
From: KAJIHARA, YASUHIRO
To: PUBLIC UNIVERSITY CORPORATION YOKOHAMA CITY UNIVERSITY
Reel/Frame 025915/0863 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2011
From: PUBLIC UNIVERSITY CORPORATION YOKOHAMA CITY UNIVERSITY
To: OTSUKA CHEMICAL CO., LTD.
Reel/Frame 025915/0972 →
Priority Claims (2)
JP 2008-157583 · Jun 17, 2008 · national
JP 2008-326609 · Dec 22, 2008 · national
Continuity (1)
Related Publication 20110195897A1 · Aug 11, 2011