Claims for Patent: 8,404,638

Summary for Patent: 8,404,638

Title:	Dimer VEGF antagonist formulations
Abstract:	Formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.
Inventor(s):	Dix; Daniel (LaGrangeville, NY), Frye; Kelly (Mendham, NJ), Kautz; Susan (Albany, NY)
Assignee:	Regeneron Pharmaceuticals, Inc. (Tarrytown, NY)
Application Number:	13/343,214
Patent Claims:	1. A non-liquid formulation of a vascular endothelial growth factor (VEGF) antagonist made according to the steps of: (a) combining in a liquid solution the following excipients: (i) about 50 mg/mL of a VEGF antagonist, which is a dimer consisting of two identical polypeptides consisting of amino acids 27-457 of SEQ ID NO:4; (ii) about 10 mM histidine, pH about 6.3-6.5; (iii) about 1.5% polyethylene glycol (PEG) 3350; (iv) about 5% sucrose; and (v) about 1.5% glycine; and (b) lyophilizing the combination of step (a), wherein, following storage of the lyophilized combination obtained after step (b) at 5.degree. C. for about 6 months, at least 98% of the VEGF antagonist is present in native conformation as measured by size exclusion chromatography upon reconstitution. 2. The non-liquid formulation of claim 1, wherein, following storage of the lyophilized combination obtained after step (b) at 5.degree. C. for about 3 months, the VEGF antagonist comprises at least 65% of maximum biological activity. 3. The non-liquid formulation of claim 2, wherein the biological activity is the ability of the VEGF antagonist to inhibit the biological effects of human VEGF on a mouse Baf/2 VEGFR1/EpoR cell line reported as IC.sub.50. 4. The non-liquid formulation of claim 1, wherein, following storage of the lyophilized combination obtained after step (b) at 5.degree. C. for about 3 months, the VEGF antagonist binds VEGF at a level of at least 94% of maximum binding. 5. The non-liquid formulation of claim 4, wherein the binding of the VEGF antagonist to VEGF is expressed as IC.sub.50 as determined by ELISA. 6. A method of producing a liquid formulation of a VEGF-specific fusion protein antagonist, comprising reconstituting the lyophilized formulation of claim 1 with liquid, wherein a liquid formulation is generated. 7. The method of claim 6, wherein the liquid is sterile water or bacteriostatic water. 8. A liquid formulation made according to the method of claim 7.

Details for Patent 8,404,638

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2025-03-25