Polypeptide formulation
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.
1. A method of treating a mammal suffering from rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and/or psoriasis, the method comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition that is a stable aqueous formulation comprising a polypeptide that is an extracellular ligand-binding portion of a human p75 tumor necrosis factor receptor fused to the Fc region of a human IgG1 and an aggregation inhibitor, wherein the aggregation inhibitor in the pharmaceutical composition is L-arginine at a concentration of from about 10 mM to about 200 mM.
2. The method of claim 1 , wherein the pharmaceutical composition further comprises a buffer.
3. The method 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 method of claim 3 , wherein the L-arginine in the pharmaceutical composition is at a concentration of from about 10 mM to about 75 mM.
5. The method of claim 4 , wherein the pharmaceutical composition further comprises a tonicity modifier.
6. The method 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 method of claim 6 , wherein the tonicity modifier is sodium chloride.
8. The method of claim 1 , wherein the pharmaceutical composition further comprises an excipient.
9. The method of claim 7 , wherein the pharmaceutical composition further comprises an excipient.
10. The method 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.
11. The method of claim 10 , wherein the excipient is sucrose.
12. A method of treating a mammal suffering from rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and/or psoriasis, the method comprising administering to the mammal a therapeutically effective amount of a stable pharmaceutical composition comprising from about 10 mg/ml to about 100 mg/ml etanercept, and further comprising L-arginine, sodium phosphate, sodium chloride and sucrose.
13. The method of claim 12 , wherein the L-arginine in the pharmaceutical composition is at a concentration of from about 10 mM to about 75 mM.
14. The method of claim 12 , wherein the sodium phosphate in the pharmaceutical composition is at a concentration of from about 5 mM to about 100 mM.
15. The method of claim 12 , wherein the sodium chloride in the pharmaceutical composition is at a concentration of from about 5 mM to about 200 mM.
16. The method of claim 12 , wherein the sucrose in the pharmaceutical composition is at a concentration of from about 0.5% to about 1.5%.
17. The method of claim 12 , wherein the pH of the pharmaceutical composition is from about 5.5 to about 7.8.
18. The method of claim 12 , comprising from 25 to 50 mg/ml etanercept, about 25 mM L-arginine, about 25 mM sodium phosphate, about 100 mM sodium chloride, about 1% sucrose, and at about pH 6.0 to about pH 7.0 in the pharmaceutical composition.
19. The method of claim 18 , wherein the pharmaceutical composition further comprises polysorbate 20.
20. The method of claim 18 , wherein the pharmaceutical composition has been in a frozen state and is unfrozen prior to administering.