Claims for Patent: 8,821,865

Summary for Patent: 8,821,865

Title:	High concentration anti-TNF.alpha. antibody liquid formulations
Abstract:	The invention provides a liquid aqueous pharmaceutical formulation comprising a human anti-TNFa antibody, or antigen-binding portion thereof, which reduces pain associated with injection in a subject by at least about 50% when compared to injecting an otherwise identical formulation comprising at least one salt and/or at least one buffer. The invention also provides a liquid aqueous pharmaceutical formulation comprising a human anti-TNFa antibody, or antigen-binding portion thereof, having increased bioavailability upon subcutaneous administration into a subject. The formulation may comprise a therapeutic protein, such as a human anti-TNF-alpha antibody, or an antigen-binding portion thereof, or a biosimilar thereof.
Inventor(s):	Neu; Michael (Edingen-Neckarahuasen, DE), Tschoepe; Markus (Hessheim, DE), Weber; Carsten (Maxdorf, DE), Fraunhofer; Wolfgang (Gurnee, IL), Redden; Laura (Glenview, IL), Gastens; Martin (Wachenheim, DE), Feick; Alexander (Allschwil, CH)
Assignee:	Abbvie Biotechnology Ltd. (Hamilton, BM)
Application Number:	13/294,692
Patent Claims:	1. A liquid aqueous formulation comprising: (1) 100 mg/ml of adalimumab; (2) 1.0 mg/ml of polysorbate-80; and, (3) 42 mg/ml of mannitol; wherein the formulation has a pH of 4.7 to 5.7 and does not contain a buffer or a salt, and wherein injection of the formulation into a human subject results in a Pain Visual Analog Scale (VAS) score of less than 1.0. 2. A liquid aqueous formulation comprising: (1) 100 mg/ml of adalimumab; (2) 1.0 mg/ml of polysorbate-80; and, (3) 42 mg/ml of mannitol; wherein the formulation has a pH of 4.7 to 5.7 and does not contain a buffer or a salt, and wherein injection of the formulation reduces pain associated with the injection in a human subject by at least about 50% when compared to injection of an otherwise identical formulation that comprises a salt and/or a buffer. 3. A liquid aqueous formulation consisting essentially of: (1) 100 mg/ml of adalimumab; (2) 1.0 mg/ml of polysorbate-80; and (3) 42 mg/ml of mannitol, wherein the formulation has a pH of 4.7 to 5.7, and wherein injection of the formulation into a human subject results in a Pain Visual Analog Scale (VAS) score of less than 1.0. 4. The formulation of claim 2, wherein the pain associated with the injection is assessed using a Pain Visual Analog Scale (VAS). 5. The formulation of claim 2, wherein the otherwise identical formulation comprises a citrate phosphate buffer and sodium chloride. 6. A liquid aqueous formulation comprising: (1) 100 mg/ml of adalimumab; (2) 1.0 mg/ml of polysorbate-80; and, (3) 42 mg/ml of mannitol; wherein the formulation has a pH of 4.7 to 5.7, and wherein the formulation is stable up to about 30.degree. C. for at least 6 days. 7. The formulation of claim 6, wherein the formulation is stable up to about 30.degree. C. for 10 days. 8. A liquid aqueous formulation comprising: (1) 100 mg/ml of adalimumab; (2) 1.0 mg/ml of polysorbate-80; and, (3) 42 mg/ml of mannitol; wherein the formulation has a pH of 4.7 to 5.7, and wherein the formulation has a characteristic selected from the group consisting of: a) a conductivity of less than about 2 mS/cm; b) a hydrodynamic diameter (D.sub.h) which is at least about 50% less than the D.sub.h of the protein in a buffered solution at a given concentration; and c) a hydrodynamic diameter (D.sub.h) of less than about 4 nm. 9. A liquid aqueous formulation consisting essentially of 1.0 mg/ml of polysorbate-80 and 40 mg of adalimumab, wherein the concentration of adalimumab is 100 mg/ml, and wherein the formulation has a pH of 4.7 to 5.7, and wherein the formulation provides increased bioavailability of the adalimumab to a human subject upon subcutaneous injection of the formulation relative to a formulation comprising a citrate phosphate buffer, sodium chloride, and mannitol. 10. A liquid aqueous formulation consisting essentially of 1.0 mg/ml of polysorbate-80 and 40 mg of adalimumab, wherein the formulation has an adalimumab concentration of 100 mg/ml a pH of 4.7-5.7, and wherein the formulation provides increased bioavailability of adalimumab in a human subject upon subcutaneous injection of the formulation, such that adalimumab has an area under the curve, 0-360 minutes (AUC.sub.0-360) greater than 1300 .mu.g/hr/ml. 11. A pre-filled syringe or autoinjector device, comprising the formulation of any one of claims 1-7, 8, 9 and 10.

Details for Patent 8,821,865

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2030-11-11
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2030-11-11
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2030-11-11