Polypeptide formulation

• US 20030180287A1
• Filed: 02/27/2003
• Published: 09/25/2003
• Est. Priority Date: 02/27/2002
• Status: Abandoned Application

• Current Assignee: Immunex Corporation (Amgen Inc.)
• Original Assignee: Immunex Corporation (Amgen Inc.)
• Inventors: Remmele, Richard L. Jr., Gombotz, Wayne R.
• Application Number:
  US10/376,576
• Publication Number:
  US 20030180287A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: Y10S 435/81 Packaged device or kit

Abstract

The present invention relates to an aqueous pharmaceutical composition suitable for long-term storage of polypeptides containing an Fc domain of an immunoglobulin, methods of manufacture, methods of administration and kits containing same.

Claims

1. A pharmaceutical composition that is a stable aqueous formulation comprising an Fc domain containing polypeptide and an aggregation inhibitor, wherein the aggregation inhibitor is L-arginine.

2. The composition of claim 1, further comprising a buffer.

3. The composition of claim 2, wherein the buffer is selected from the group consisting of sodium phosphate, histidine, potassium phosphate, sodium or potassium citrate, maleic acid, ammonium acetate, tris-(hydroxymethyl)-aminomethane (tris), acetate and diethanolamine.

4. The composition of claim 3, wherein the L-arginine is at a concentration of from about 10 mM to about 100 mM.

5. The composition of any one of claims 1, 2, 3 or 4, further comprising a tonicity modifier.

6. The composition of claim 5, wherein the tonicity modifier is selected from the group consisting of arginine, cysteine, histidine, glycine, sodium chloride, potassium chloride, sodium citrate, sucrose, glucose and Mannitol.

7. The composition of claim 6, wherein the tonicity modifier is sodium chloride.

8. The composition of any one of claims 1, 2, 3, or 4, further comprising an excipient.

9. The composition of claim 6, further comprising an excipient.

10. The composition of claim 7, further comprising an excipient.

11. The composition of claim 8, wherein the excipient is selected from the group consisting of sucrose, lactose, glycerol, xylitol, sorbitol, Mannitol, maltose, inositol, trehalose, glucose, bovine serum albumin (BSA), human SA or recombinant HA, dextran, PVA, hydroxypropyl methylcellulose (HPMC), polyethyleneimine, gelatin, polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC), polyethylene glycol, ethylene glycol, glycerol, dimethysulfoxide (DMSO), dimethylformamide (DMF), proline, L-serine, sodium glutamic acid, alanine, glycine, lysine hydrochloride, sarcosine, gamma-aminobutyric acid, Tween-20, Tween-80, SDS, polysorbate, polyoxyethylene copolymer, potassium phosphate, sodium acetate, ammonium sulfate, magnesium sulfate, sodium sulfate, trimethylamine N-oxide, betaine, zinc ions, copper ions, calcium ions, manganese ions, magnesium ions, CHAPS, sucrose monolaurate, and 2-O-beta-mannoglycerate.

12. The composition of claim 11, wherein the excipient is sucrose.

20. The composition of any one of claims 1, 13 or 19, wherein the composition is liquid.

21. The composition of claim 20, wherein the composition is frozen.

13. A stable pharmaceutical composition comprising about 10 mg/ml to about 100 mg/ml TNFR:

Fc, L-arginine, sodium phosphate, sodium chloride and sucrose.

14. The composition of claim 13, wherein L-arginine is about 10 mM to about 75 mM.

15. The composition of claim 13, wherein sodium phosphate is about 5 mM to about 100 mM.

16. The composition of claim 13, wherein sodium chloride is about 5 mM to about 200 mM.

17. The composition of claim 13, wherein sucrose is about 0.5% to about 1.5%.

18. The composition of claim 13, wherein pH is about 5.5 to about 7.8.

19. The composition of claim 13, having 25 mg/ml TNFR:

Fc, 25 mM L-arginine, 25 mM sodium phosphate, 98 mM sodium chloride, 1% sucrose at pH 6.2.

29. A method of treating a mammal in need thereof comprising administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 4 or 13.

22. A method of formulating a composition comprising combining isolated TNFR:

Fc with L-arginine.

23. The method of claim 22, further comprising the steps of combining a buffer, a tonicity modifier, and an excipient with the composition.

24. The method of claim 22 or 23, wherein the composition is liquid.

25. A kit comprising a composition comprising an Fc domain containing polypeptide and L-arginine, and instructions for use of said composition.

26. The kit of claim 25, wherein the composition is liquid.

27. The kit of claim 25 or 26, wherein the composition is stored in a pre-filled sterile syringe.

28. The kit of claim 27, wherein the syringe is stored at about −

20°

C. to about −

70°

C.

30. A method of accelerated stability testing of an Fc domain containing polypeptide in a pharmaceutical composition, wherein the composition comprises L-arginine, the steps of the method comprising storing the composition at 37°

C. and measuring the stability of the polypeptide after at least one month at 37°

C.