Derivatives of GLP-1 analogs

• US 8,097,698 B2
• Filed: 11/26/2007
• Issued: 01/17/2012
• Est. Priority Date: 08/30/1996
• Status: Expired due to Fees

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Knudsen, Liselotte Bjerre, Huusfeldt, Per Olaf, Nielsen, Per Franklin, Kaarsholm, Niels C., Olsen, Helle Birk, Bjorn, Soren Erik, Pedersen, Freddy Zimmerdahl, Madsen, Kjeld
• Primary Examiner(s): Lukton, David
• Application Number:
  US11/944,757
• Publication Number:
  US 20090176700A1
• Time in Patent Office: 1,513 Days
• Field of Search: 530/399, 530/324, 530/308, 514/21.3
• US Class Current: 530/324
• 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 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C11D 3/0063 Photo- activating compounds
• CPC Class Codes: C11D 3/168 Organometallic compounds or orgometallic complexes

Abstract

The present invention relates to a pharmaceutical composition comprising a GLP-1 derivative having a lipophilic substituent; and a surfactant.

Claims

1. A glucagon-like peptide 1 (GLP-1) derivative, said derivative containing a single lipophilic substituent of from 8 to 40 carbon atoms attached, optionally via a spacer, to the C-terminal amino acid residue of a parent polypeptide where i) the parent polypeptide is selected from the group consisting of GLP-1 (7-35), GLP-1 (7-36), GLP-1 (7-37), GLP-1 (7-38), GLP-1 (7-39), GLP-1 (7-40), GLP-1 (7-41) and an analogue of any of GLP-1 (7-35), GLP-1 (7-36), GLP-1 (7-37), GLP-1 (7-38), GLP-1 (7-39), GLP-1 (7-40) and GLP-1 (7-41) where the total number of different amino acids between said analogue and the corresponding native form of GLP-1 does not exceed five, and ii) the lipophilic substituent is selected from the group consisting of an acyl group of a straight-chain alkane α

,ω

-dicarboxylic acid, an acyl group of an alkyl group, and a straight chain alkyl group.

2. The GLP-1 derivative of claim 1, wherein the lipophilic substituent is an acyl group of a straight-chain alkane α

,ω

-dicarboxylic acid.

3. The GLP-1 derivative of claim 2, wherein the acyl group is from 8 to 25 carbons in length.

4. The GLP-1 derivative of claim 2, wherein the acyl group is HOOC(CH₂)_mCO—

, wherein m is 6-38.

5. The GLP-1 derivative of claim 4, wherein the acyl group is selected from the group consisting of HOOC(CH₂)₁₄CO—

, HOOC(CH₂)₁₆CO—

, HOOC(CH₂)₁₈CO—

, HOOC(CH₂)₂₀CO—

, and HOOC(CH₂)₂₂CO—

.

6. The GLP-1 derivative of claim 1, wherein the lipophilic substituent is a straight chain alkyl group.

7. The GLP-1 derivative of claim 6, wherein the alkyl group is from 8 to 25 carbon atoms.

8. The GLP-1 derivative of claim 1, wherein the parent polypeptide is selected from the group consisting of Arg²⁶-GLP-1 (7-37);

Arg³⁴-GLP-1 (7-37);

Lys³⁶-GLP-1 (7-37);

Arg^26,34Lys³⁶-GLP-1 (7-37);

Arg^26,34Lys³⁹-GLP-1 (7-39);

Arg^26,34Lys⁴⁰-GLP-1 (7-40);

Arg²⁶Lys³⁶-GLP-1(7-37);

Arg³⁴Lys³⁶-GLP-1 (7-37);

Arg²⁶Lys³⁹-GLP-1 (7-39);

Arg³⁴Lys⁴⁰-GLP-1 (7-40);

Arg^26,34Lys^36,39-GLP-1 (7-39);

Arg^26,34Lys^36,40-GLP-1 (7-40);

Gly⁸Arg²⁶-GLP-1(7-37);

Gly⁸Arg³⁴-GLP-1 (7-37);

Gly⁸Lys³⁶-GLP-1 (7-37);

Gly⁸Arg^26,34Lys³⁶-GLP-1 (7-37);

Gly⁸Arg^26,34Lys³⁹-GLP-1 (7-39);

Gly⁸Arg^26,34Lys⁴⁰-GLP-1 (7-40);

Gly⁸Arg²⁶Lys³⁶-GLP-1(7-37);

Gly⁸Arg³⁴Lys³⁶-GLP-1 (7-37);

Gly⁸Arg²⁶Lys³⁹-GLP-1 (7-39);

Gly⁸Arg³⁴Lys⁴⁰-GLP-1 (7-40);

Gly⁸Arg^26,34Lys^36,39-GLP-1 (7-39); and

Gly⁸Arg^26,34Lys^36,40-GLP-1 (7-40).

9. The GLP-1 derivative of claim 8, wherein the lipophilic substituent is an acyl group of a straight-chain alkane α

,ω

-dicarboxylic acid.

10. The GLP-1 derivative of claim 9, wherein the acyl group is from 8 to 25 carbons in length.

11. The GLP-1 derivative of claim 9, wherein the acyl group is HOOC(CH₂)_mCO—

, wherein m is 6-38.

12. The GLP-1 derivative of claim 11, wherein the acyl group is selected from the group consisting of HOOC(CH₂)₁₄CO—

, HOOC(CH₂)₁₆CO—

, HOOC(CH₂)₁₈CO—

, HOOC(CH₂)₂₀CO—

, and HOOC(CH₂)₂₂CO—

.

13. The GLP-1 derivative of claim 8, wherein the lipophilic substituent is a straight chain alkyl group.

14. The GLP-1 derivative of claim 13, wherein the alkyl group is from 8 to 25 carbon atoms.

15. A GLP-1 derivative according to claim 1, wherein the spacer is an amino acid residue except Cys or a dipeptide.