Long lasting synthetic glucagon like peptide (GLP-1)

• US 20040127398A1
• Filed: 11/25/2003
• Published: 07/01/2004
• Est. Priority Date: 05/17/1999
• Status: Abandoned Application

• Current Assignee: ConjuChem, Inc. (Colabor Group, Inc.)
• Original Assignee: ConjuChem, Inc. (Colabor Group, Inc.)
• Inventors: LʼArcheveque, Benoit, Bridon, Dominique P., Ezrin, Alan M., St. Pierre, Serge, Leblanc, Anouk, Holmes, Darren L.
• Application Number:
  US10/722,733
• Publication Number:
  US 20040127398A1
• Time in Patent Office: Days
• US Class Current: 514/3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.

Claims

1. A modified insulinotropic peptide or derivative thereof comprising a reactive group which reacts with amino groups, hydroxyl groups or thiol groups on blood components to form a stable covalent bond.

2. The peptide of claim 1 wherein said reactive group is selected from the group consisting of succinimidyl and maleimido groups.

3. A peptide according to claim 2, wherein the derivative is reactive with a thiol group on a blood protein.

4. A peptide according to claim 1 wherein the peptide is selected from the group consisting of SEQ ID NO:

2 SEQ ID NO;

3, SEQ ID NO;

11, SEQ ID NO;

13, SEQ ID NO;

14 and SEQ ID NO;

15.

5. A peptide according to claim 1 wherein the peptide is selected from the group consisting of SEQ ID:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.

6. A composition comprising a derivative of insulinotropic peptide or analog thereof, said derivative comprising a reactive group which reacts with amino groups, hydroxyl groups or thiol groups on blood components to form stable covalent bonds wherein said reactive group is selected from the group consisting of succinimidyl and maleimido groups for use in a method of treating diabetes in a human.

7. The composition of claim 6 wherein said derivative is reactive with blood components.

8. The composition of claim 6 wherein said peptide is selected from the group consisting of SEQ ID NO:

2 SEQ ID NO;

3, SEQ ID NO;

11, SEQ ID NO;

13, SEQ ID NO;

14 and SEQ ID NO;

15.

9. The composition of claim 6 wherein said peptide is selected from the group consisting of SEQ ID:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.

11. The derivative of claim 9 wherein said peptide is selected from the group consisting of SEQ ID NO:

2 SEQ ID NO;

3, SEQ ID NO;

11, SEQ ID NO;

13, SEQ ID NO;

14 and SEQ ID NO;

15.

12. The derivative of claim 9 wherein said peptide is selected from the group consisting of SEQ ID:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.

10. A derivative of an insulintropic peptide, said derivative comprising a maleimido group which reacts with a thiol group on human serum albumin to form a covalent bond.

13. A composition comprising a derivative of an insulinotropic peptide, said derivative comprising a maleimido group which reacts with a thiol group on human serum albumin to form a covalent bond for use in a method of treating diabetes in a human.

14. The composition of claim 13 wherein the peptide is selected from the group consisting of SEQ ID NO:

2 SEQ ID NO;

3, SEQ ID NO;

11, SEQ ID NO;

13, SEQ ID NO;

14 and SEQ ID NO;

15.

15. The compositions of claim 13 wherein the peptide is selected from the group consisting of SEQ ID:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.

16. Use of a composition for the manufacturer of a medicament extending the in vivo half-life of an insulinotropic peptide in a diabetes patient the composition comprising a derivative of an insulinotropic peptide or analog thereof, said derivative comprising a reactive group which reacts with amino groups, hydroxo gropus, or thiol groups on blood components to form stable covalent bonds, wherein the reactive group is selected from the group consisting of succinimidyl and maleimido groups.

17. Use of a composition according to claim 16, wherein the derivative is reacted with blood proteins.

18. Use of the composition of claim 16 wherein said peptide is selected from the group consisting of SEQ ID NO:

2 SEQ ID NO;

3, SEQ ID NO;

11, SEQ ID NO;

13, SEQ ID NO;

14 and SEQ ID NO;

15.

19. An insulinotropic peptide selected from the group consisting of GLP-1(1-36)-Lys³⁷(ε

-MPA)-NH², GLP-1(1-36)-Lys³⁷(ε

-AEEA-AEEA-MPA)-NH², GLP-1(7-36)-Lys³⁷ (ε

-MPA)-NH², GLP-1(7-36)-Lys³⁷ (ε

-AEEA-AEEA-MPA)-NH², D-Ala² GLP-1(7-36)-Lys³⁷-(C-MPA)-NH², D-Ala² GLP-1(7-36)-Lys³⁷ (ε

-AEEA-AEEA-MPA)-NH², exendin-4 (1-39)-Lys⁴⁰ (ε

-MPA)-NH², exendin-4(1-39)-Lys⁴⁰ (ε

-AEEA-AEEA-MPA)-NH², exendin-3(1-39)-Lys⁴⁰ (ε

-MPA)-NH² and exendin-3(1-39)-Lys⁴⁰ (ε

-AEEA-AEEA-MPA).