Vegf antagonist formulations suitable for intravitreal administration

Patent metadata

Field	Value
Publication number	US-2025257118-A1
Application number	US-202519176527-A
Country	US
Kind code	A1
Filing date	Apr 11, 2025
Priority date	Jun 16, 2006
Publication date	Aug 14, 2025
Grant date	—

Abstract

Ophthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has an amino acid sequence of SEQ ID NO:4.

First claim

We claim:

1 . A prefilled glass syringe suitable for intravitreal administration containing a stable ophthalmic formulation comprising a vascular endothelial growth factor (VEGF) antagonist, an organic co-solvent, a buffer, and a stabilizing agent, wherein the VEGF antagonist is a protein produced in a Chinese Hamster Ovary (CHO) cell.

2 . The prefilled glass syringe of claim 1 , wherein 90% or more of the weight of the protein is not present as an aggregate.

3 . The prefilled glass syringe of claim 2 , wherein the protein is a fusion protein comprising the immunoglobulin-like (Ig) domain 2 of a first VEGF receptor and Ig domain 3 of a second VEGF receptor, and a multimerizing component.

4 . The prefilled glass syringe of claim 3 , wherein the first VEGF receptor is the human Flt1 and the second VEGF receptor is the human Flk1 or the human Flt4.

5 . The prefilled glass syringe of claim 4 , wherein the fusion protein comprises an amino acid sequence of SEQ ID NO:4.

6 . The prefilled glass syringe of claim 5 , wherein the VEGF antagonist is a dimer of the fusion protein.

7 . The prefilled syringe of claim 1 , wherein the organic co-solvent is selected from the group consisting of polysorbate 20, polysorbate 80, polyethylene glycol (PEG), PEG3350, and propylene glycol.

8 . The prefilled syringe of claim 1 , wherein the stabilizing agent is selected from the group consisting of sucrose, sorbitol, glycerol, trehalose, and mannitol.

9 . The prefilled syringe of claim 1 , wherein the buffer comprises phosphate.

10 . The prefilled syringe of claim 4 comprising (a) 1-100 mg/ml of the VEGF antagonist; (b) 0.01-5% of the organic co-solvent; (c) 5-40 mM of the buffer; and (d) 1.0-10% of the stabilizing agent.

11 . The prefilled syringe of claim 11 , wherein the organic co-solvent is polysorbate 20, the buffer is phosphate, and the stabilizing agent is sucrose.

Assignees

• Regeneron Pharma

Inventors

• Furfine Eric
• Dix Daniel
• Graham Kenneth
• Frye Kelly

Classifications

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K38/179

  for growth factors; for growth regulators · CPC title