Extendin derivatives

• US 7,226,990 B2
• Filed: 06/21/2001
• Issued: 06/05/2007
• Est. Priority Date: 02/27/1998
• Status: Expired due to Fees

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Knudsen, Liselotte Bjerre, Nielsen, Per Franklin, Madsen, Kjeld, Huusfeldt, Per Olaf
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): Mohamed; Abdel A.
• Application Number:
  US09/886,311
• Publication Number:
  US 20010047084A1
• Time in Patent Office: 2,175 Days
• Field of Search: 530/308, 530/300, 530/303, 530/322, 530/324, 530/345, 530/399, 530/402, 514/2, 514/3, 514/12, 514/23, 514/866
• US Class Current: 530/308
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

The present invention relates to novel derivatives of exendin-4 or exendin-4 fragments, wherein the derivatives have a lipophilic substituent attached, optionally via a spacer, to an amino acid residue, which is not the N-terminal or C-terminal amino acid residue of the derivative.

Claims

1. A derivative of exendin-4 or a fragment thereof, wherein said derivative has one lipophilic substituent attached, optionally via a spacer, to an amino acid residue of said exendin-4 or fragment thereof, which is not the N-terminal or C-terminal amino acid residue of said exendin-4 or fragment thereof, wherein said fragment has insulinotropic activity.

2. A pharmaceutical composition comprising a derivative of claim 1 and a pharmaceutically acceptable vehicle or carrier.

3. A method of treating insulin dependent or non-insulin dependent diabetes mellitus in a patient in need of such a treatment, comprising administering to the patient a therapeutically effective amount of a derivative of claim 1 and a pharmaceutically acceptable carrier.

4. The derivative of claim 1, wherein the lipophilic substituent has 4 to 40 carbon atoms.

5. The derivative of claim 4, wherein the lipophilic substituent has 8 to 25 carbon atoms.

6. The derivative of claim 4, wherein the lipophilic substituent is attached by means of a spacer.

7. The derivative of claim 6, wherein the spacer is an unbranched alkane α

,ω

-dicarboxylic acid group having from 1 to 7 methylene groups.

8. The derivative of claim 4, wherein the lipophilic substituent is a straight-chain or branched acyl group.

9. The derivative of claim 8, wherein the acyl group is of the formula CH₃(CH₂)_nCO—

, wherein n is 4 to 38.

10. The derivative of claim 9, wherein the acyl group is CH₃(CH₂)₆CO—

, CH₃(CH₂)₈CO—

, CH₃(CH₂)₁₀CO—

, CH₃(CH₂)₁₂CO—

, CH₃(CH₂)₁₄CO—

, CH₃(CH₂)₁₆CO—

, CH₃(CH₂)₁₈CO—

, CH₃(CH₂)₂₀CO—

or CH₃(CH₂)₂₂CO—

.