Claims for Patent: 9,982,032

Summary for Patent: 9,982,032

Title:	Stable liquid formulation of fusion protein with IgG Fc domain
Abstract:	A stable liquid formulation includes a fusion protein having an Fc domain of a human immunoglobulin G (IgG), in particular, a protein in which an Fc domain of a human immunoglobulin G (IgG) and a soluble extracellular domain of a vascular endothelial growth factor (VEGF) receptor are fused (e.g., aflibercept)). A composition for stabilizing a protein and a method for stabilizing a protein in which an Fc domain of an IgG and a soluble extracellular domain of a VEGF receptor are fused are disclosed. The present invention improves therapeutic effects on various ophthalmic diseases (e.g., retinal vein occlusion, diabetic macular edema, choroidal neovascularization and wet age-related macular degeneration, etc.) caused by abnormal angiogenesis, while pursuing stabilization of bioactivity through a stable liquid formulation suitable for intravitreal injection of an anti-VEGF-Fc fusion protein including aflibercept.
Inventor(s):	Park; Soon Jae (Daejeon, KR), Chung; Hye-Shin (Daejeon, KR), Kim; Jin Hwan (Daejeon, KR), Kim; Yong Mo (Daejeon, KR), Kim; Jun Young (Daejeon, KR)
Assignee:	ALTEOGEN, INC. (Daejeon, KR)
Application Number:	15/190,378
Patent Claims:	1. A liquid formulation, consisting of: 10 to 100 mg/ml of a protein in which a soluble extracellular domain of a vascular endothelial growth factor (VEGF) receptor and an Fc domain of a human immunoglobulin G (IgG) are fused; a buffer consisting of a histidine salt and having pH ranging from 5.7 to 6.2; and a sugar selected from the group consisting of more than 6%, but not more than 10% of sucrose, trehalose, mannitol, and glucose; a surfactant selected from the group consisting of 0% to 0.1% of polysorbate 20 and polysorbate 80; wherein the soluble extracellular domain of the VEGF receptor comprises the immunoglobulin-like domain 2 of the human Flt1 VEGF receptor-1 and the immunoglobulin-like domain 3 of the human Flk1 VEGF receptor-2; and the histidine salt is 10 mM to 50 mM of histidine-HCl or histidine-acetate. 2. The liquid formulation of claim 1, comprising the fusion protein in an amount of 10 to 40 mg/ml. 3. A liquid formulation, consisting of: a buffer consisting of a histidine salt and having pH ranging from 5.7 to 6.2; a sugar selected from the group consisting of more than 6%, but not more than 10% of sucrose, trehalose, mannitol, and glucose; a surfactant selected from the group consisting of 0% to 0.1% of polysorbate 20 and polysorbate 80; and 10 to 100 mg/ml of aflibercept; wherein the histidine salt is 10 mM to 50 mM of histidine-HCl or histidine-acetate. 4. The liquid formulation of claim 1, wherein the liquid formulation is suitable for intravitreal injection.

Details for Patent 9,982,032

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Csl Behring Ag	CARIMUNE, CARIMUNE NF, PANGLOBULIN, SANDOGLOBULIN	immune globulin intravenous (human)	For Injection	102367	07/27/2000		2035-06-23
Csl Behring Ag	PRIVIGEN	immune globulin intravenous (human), 10% liquid	Injection	125201	07/26/2007		2035-06-23
Csl Behring Ag	PRIVIGEN	immune globulin intravenous (human), 10% liquid	Injection	125201	10/02/2009		2035-06-23
Csl Behring Ag	PRIVIGEN	immune globulin intravenous (human), 10% liquid	Injection	125201	02/07/2013		2035-06-23