Claims for Patent: 7,648,702

Summary for Patent: 7,648,702

Title:	Stable aqueous formulation of a soluble TNF receptor and arginine
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.
Inventor(s):	Gombotz; Wayne R. (Kenmore, WA), Remmele, Jr.; Richard L. (Camarillo, CA)
Assignee:	Immunex Corporation (Thousand Oaks, CA)
Application Number:	11/784,538
Patent Claims:	1. 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 Fe region of a human IgG1 and an aggregation inhibitor, wherein the aggregation inhibitor is L-arginine at a concentration of from about 10 mM to about 200 mM. 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 75 mM. 5. The composition of claim 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 claim 1, further comprising an excipient. 9. The composition of claim 7, further comprising an excipient. 10. 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. 11. The composition of claim 10, wherein the excipient is sucrose. 12. 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 composition of claim 12, wherein the L-arginine is at a concentration of from about 10 mM to about 75 mM. 14. The composition of claim 12, wherein the sodium phosphate is at a concentration of from about 5 mM to about 100 mM. 15. The composition of claim 12, wherein the sodium chloride is at a concentration of from about 5 mM to about 200 mM. 16. The composition of claim 12, wherein the sucrose is at a concentration of from about 0.5% to about 1.5%. 17. The composition of claim 12, wherein the pH of the composition is from about 5.5 to about 7.8. 18. The composition 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. 19. The composition of claim 18, further comprising polysorbate 20. 20. The composition of claim 18, wherein the composition is in a frozen state. 21. A method of formulating a composition comprising combining an isolated polypeptide that is an extracellular ligand-binding portion of a human p75 tumor necrosis factor receptor fused to the Fe region of a human IgG1with L-arginine at a concentration of from about 10 mM to about 200 mM. 22. The method of claim 21, further comprising the steps of combining a buffer, a tonicity modifier, and an excipient with the composition. 23. The method of claim 22, wherein the buffer is sodium phosphate, the tonicity modifier is sodium chloride at a concentration of from 5 mM to 200 mM, and the exipient is sucrose at a concentration of from 0.5% to 1.5%. 24. The method of claim 23, further comprising adding polysorbate 20. 25. The method of claim 21, further comprising freezing the composition. 26. The method of claim 23, further comprising freezing the composition.

Details for Patent 7,648,702

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2022-02-27
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2022-02-27
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2022-02-27
Immunex Corporation	ENBREL	etanercept	Injection	103795	02/01/2007		2022-02-27