Stabilized Polypeptide Formulations

• US 20090060861A1
• Filed: 05/22/2006
• Published: 03/05/2009
• Est. Priority Date: 05/25/2005
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Poulsen, Christian
• Application Number:
  US11/914,564
• Publication Number:
  US 20090060861A1
• Time in Patent Office: Days
• US Class Current: 424/85.200
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention relates to a pharmaceutical formulation comprising a polypeptide and a buffer selected from the group consisting of diethylmalonic acid, trimellitic acid, shikimic acid, glycinamid, 2-amino-2-methyl-1,3-propanediol (AMPD) and tetraethylammonium (T.E.A.) or salts thereof. Further more the invention relates to a method for improving stability of a polypeptide in a purification process comprising the step of applying a buffer selected from the group consisting of diethylmalonic acid, trimellitic acid, shikimic acid, glycinamid, AMPD and T.E.A. or salts thereof to said purification process.

Claims

1. A pharmaceutical formulation comprising a polypeptide and a buffer or a combination of buffers is selected from the group consisting of diethylmalonic acid, trimellitic acid, shikimic acid, glycinamid, 2-amino-2-methyl-1,3-propanediol (AMPD) and tetraethylammonium (T.E.A.) or salts thereof.

2. A pharmaceutical formulation according to claim 1, wherein the buffer or the combination of buffers is selected from the group consisting of diethylmalonic acid, trimellitic acid and glycinamid or salts thereof.

3. A pharmaceutical formulation according to claim 1, wherein the buffer or the combination of buffers is selected from the group consisting of shikimic acid, 2-amino-2-methyl-1,3-propanediol (AMPD) and tetraethylammonium (T.E.A.) or salts thereof.

4. A pharmaceutical formulation according to claim 1, wherein the concentration of buffer or combination of buffers is in the range from 0.01-100 mM

5. A pharmaceutical formulation according to claim 4, wherein the concentration of buffer or combination of buffers is in the range from 0.1-50 mM.

6. A pharmaceutical formulation according to claim 5, wherein the concentration of buffer or combination of buffers is in the range from 3-25 mM.

7. A pharmaceutical formulation according to claim 6, wherein the concentration of buffer or combination of buffers is in the range from 5-16 mM.

8. A pharmaceutical formulation according to claim 1, wherein the polypeptide is selected from the group comprising of insulin, human growth hormone, glucagon, GLP-1, exendin-4, FVII, FXIII, a mixture of FVII and FXIII, IL-20, IL-21, IL-28a, IL-29, IL-31 or analogues or derivatives thereof.

9. The pharmaceutical formulation according to claim 8, wherein the polypeptide is insulin or an analogue or a derivative thereof.

10. A method for improving the stability of a polypeptide in a purification process or in a pharmaceutical formulation comprising the step of applying a buffer or a combination of buffers selected from the group consisting of diethylmalonic acid, trimellitic acid, shikimic acid, glycinamid, AMPD and T.E.A. or salts thereof to said purification process or pharmaceutical formulation.