Stable liquid formulations of dimer VEGF antagonists

Patent metadata

Field	Value
Publication number	US-9416167-B2
Application number	US-201414550385-A
Country	US
Kind code	B2
Filing date	Nov 21, 2014
Priority date	Mar 25, 2005
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

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.

First claim

We claim:

1. A stable pharmaceutical formulation comprising: (a) 50-100 mg/mL of a vascular endothelial growth factor (VEGF) antagonist fusion protein dimer consisting of two identical fusion polypeptides consisting essentially of (i) the immunoglobulin-like domain 2 of the human Flt1 VEGF receptor, (ii) the immunoglobulin-like domain 3 of the human Flk1 or the human Flt4 VEGF receptor, and (iii) an immunoglobulin Fc domain; (b) 5-50 mM histidine; (c) 0.1-3.0% polyethylene glycol (PEG) 3350; (d) 0.24-3.0% glycine; and (e) 0.5-6.0% sucrose, pH 6.3-6.5.

2. The stable pharmaceutical formulation of claim 1 , wherein the two identical fusion polypeptides consist of amino acids 27-457 of SEQ ID NO:4.

3. The stable pharmaceutical formulation of claim 2 , wherein the VEGF antagonist fusion protein dimer is at a concentration of 50 mg/mL.

4. The stable pharmaceutical formulation of claim 3 , wherein the histidine is at a concentration of 10 mM.

5. The stable pharmaceutical formulation of claim 4 , wherein the PEG 3350 is at a concentration of 1.5%.

6. The stable pharmaceutical formulation of claim 5 , wherein the glycine is at a concentration of 0.75%.

7. The stable pharmaceutical formulation of claim 6 , wherein the sucrose is at a concentration of 2.5%.

8. The stable pharmaceutical formulation of claim 2 , wherein (a) the VEGF antagonist fusion protein dimer is at a concentration of 50 mg/mL; (b) the histidine is at a concentration of 10 mM; (c) the PEG 3350 is at a concentration of 1.5%; (d) the glycine is at a concentration of 0.75%; and (e) the sucrose is at a concentration of 2.5%.

Assignees

• Regeneron Pharma

Inventors

• Dix Daniel
• Frye Kelly
• Kautz Susan

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title