GLP-1 Fusion Peptides

• US 8,853,159 B2
• Filed: 05/29/2012
• Issued: 10/07/2014
• Est. Priority Date: 09/22/2005
• Status: Expired due to Fees

• Current Assignee: Biocompatibles UK Limited (Boston Scientific Corporation)
• Original Assignee: Biocompatibles UK Limited (Boston Scientific Corporation)
• Inventors: Geigle, Peter, Wallrapp, Christine, Thoenes, Eric
• Primary Examiner(s): STOICA, ELLY GERALD
• Application Number:
  US13/482,354
• Publication Number:
  US 20120238497A1
• Time in Patent Office: 861 Days
• US Class Current: 514/11.7
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

The present invention provides fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV. The fusion peptide comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) C-terminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. Component (II) is preferably a full or partial version of IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2/GLP-1(7-35, 36 or 37) or GLP-2. The fusion peptide may be produced in engineered cells or synthetically and may be used for preparing a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.

Claims

1. A fusion peptide comprising

a component (I) N-terminally having a sequence according to formula I:

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-X(I) (SEQ ID NO;

     43), wherein X is NH₂ or Gly-OH, or a sequence having 95% sequence identity with SEQ ID NO;

43;

a component (II) C-terminally having a peptide sequence containing SEQ ID NO;

22 or sequence having 90% sequence identity with SEQ ID NO;

22 (RRDFPEEVAI); and

a component (III) C-terminally having a sequence according to formula I (SEQ ID NO;

     43) or a sequence having 95% sequence identity with SEQ ID NO;

43;

and its pharmaceutically active salts.

2. The fusion peptide according to claim 1, wherein the component (II) is a peptide sequence containing a sequence selected from a group consisting of SEQ ID NO:

23 (RRDFPEEVAIVEEL) and SEQ ID NO;

24 (RRDFPEEVAIAEEL), or a sequence having at least 90% sequence identity with any of SEQ ID NO;

23 or 24.

3. The fusion peptide according to claim 1, wherein the component (II) is a peptide sequence containing a sequence selected from the group consisting of SEQ ID NO:

2 (RRDFPEEVAIVEELG), SEQ ID NO;

3 (RRDFPEEVAIAEELG), or a sequence having at least 90% sequence identity with SEQ ID NO;

2 or 3.

4. The fusion peptide according to claim 1, wherein the fusion peptide contains a sequence selected from the group consisting of:

SEQ ID NO;

8 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIAEELG),

SEQ ID NO;

12 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELG),

SEQ ID NO;

32 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFAEEVAIAEELG),

SEQ ID NO;

36 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVA),

SEQ ID NO;

37 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIAEELGR RHAC),

SEQ ID NO;

39 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFAEEVAIVEELG), and

SEQ ID NO;

42 (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELGR RHAC), or a sequence having at least 95% sequence identity with SEQ ID NO;

8 or 12.

5. The fusion peptide according to claim 1, wherein the fusion peptide contains a peptide sequence selected from a group consisting of:

SEQ ID NO;

6 or SEQ ID NO;

10 or a sequence having at least 95% sequence identity with SEQ ID NO;

6 or 10.

6. The fusion peptide according to claim 1, wherein the fusion peptide consists of SEQ ID NO:

6 or SEQ ID NO;

10.

7. The fusion peptide according to claim 1, wherein the N-terminal His residue of formula I of the fusion peptide is chemically modified at its NH₂ terminus and/or at its histidyl side chain by a hydrophobic moiety.

8. The fusion peptide according to claim 1, wherein the fusion peptide further comprises a carrier protein, comprising transferrin or albumin, as component (IV).

9. The fusion peptide according to claim 1, wherein the fusion peptide further comprises a leader or a signal peptide sequence upstream of component (I).

10. A nucleic acid encoding a fusion peptide according to claim 1.

11. A vector comprising a nucleic acid according to claim 9.

12. A pharmaceutical composition comprising the fusion peptide according to claim 1, or according to claim 6.