IP Library › Granted Patent US 8,404,638
Granted Patent B2
US 8,404,638 · App. 13/343,214 · Granted Mar 26, 2013

Dimer VEGF antagonist formulations

Inventors: Daniel Dix (LaGrangeville, NY); Kelly Frye (Mendham, NJ); Susan Kautz (Albany, NY)
Assignee: Regeneron Pharmaceuticals, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,404,638
App. No.
13/343,214
Granted
Mar 26, 2013
Kind
B2
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.

Claims (8)

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° 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° 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 50 .

4. The non-liquid formulation of claim 1 , wherein, following storage of the lyophilized combination obtained after step (b) at 5° 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 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 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 26, 2012
From: DIX, DANIEL; FRYE, KELLY; KAUTZ, SUSAN
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 028643/0036 →
Continuity (4)
Division 12835065 · Jul 13, 2010
Continuation 11387256 · Mar 22, 2006
Provisional Application 60665125 · Mar 25, 2005
Related Publication 20120101035A1 · Apr 26, 2012