VEGF antagonist formulations for intravitreal administration

1. A stable liquid ophthalmic formulation of a vascular endothelial growth factor (VEGF) antagonist, comprising:

(a) between 50 mg/ml to about 10 mg/ml of a VEGF antagonist comprising amino acids 27-475 of SEQ ID NO:4;

(b) about 0.03% to about 0.1% polysorbate;

(c) about 5-40 mM of sodium phosphate buffer, pH of about 5.8 to about 7.0; and

(d) either:

(i) about 5% sucrose and about 40 to about 50 mM NaCl, or

(ii) about 135 mM NaCl,

wherein at least 99% of the VEGF antagonist is present in native conformation following storage at 5° C. for 2 months as measured by size exclusion chromatography.

2. The formulation of claim 1 , comprising between 50 mg/ml to about 10 mg/ml of the VEGF antagonist, about 10 mM sodium phosphate buffer, about 40 mM NaCl, about 0.03% polysorbate, and about 5% sucrose, pH about 6.2-6.3.

3. The formulation of claim 2 , comprising about 10 to about 40 mg/ml of the VEGF antagonist.

4. The formulation of claim 3 , comprising VEGF antagonist at a concentration of about 10 mg/ml.

5. The formulation of claim 3 , comprising VEGF antagonist at a concentration of about 40 mg/ml.

6. The formulation of claim 1 , comprising between 50 mg/ml to about 10 mg/ml of the VEGF antagonist, about 10 mM sodium phosphate buffer, about 135 mM NaCl and about 0.03% polysorbate, pH about 6.2-6.3.

7. The formulation of claim 6 , comprising about 10 to about 40 mg/ml of the VEGF antagonist.

8. The formulation of claim 7 , comprising VEGF antagonist at a concentration of about 10 mg/ml.

9. The formulation of claim 7 , comprising VEGF antagonist at a concentration of about 40 mg/ml.

10. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 1 .

11. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 4 .

12. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 5 .

13. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 6 .

14. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 8 .

15. A pre-filled syringe suitable for intravitreal administration comprising the formulation of claim 9 .

16. 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 5-50 mg/ml of the VEGF antagonist, comprising amino acids 27-475 of SEQ ID NO:4;

(ii) about 5-25 mM of sodium phosphate buffer, pH about 5.8-7.0;

(iii) about 0.01-0.15% of an organic co-solvent, selected from the group consisting of polysorbate, polyethylene glycol (PEG), propylene glycol, and a combination thereof; and

(iv) about 1-10% of a stabilizing agent selected from the group consisting of sucrose, sorbitol, glycerol, trehalose, and mannitol; and

(b) lyophilizing the combination of step (a),

wherein at least about 99% of the VEGF antagonist is present in native conformation as measured by size exclusion chromatography following storage at 5° C. for 2 months.

17. The non-liquid formulation of claim 16 , wherein about 20 mg/ml of the VEGF antagonist, about 5 mM sodium phosphate buffer, about 0.015% polysorbate, about 2.5% sucrose, and about 20 mM sodium chloride, pH about 6.2-6.3 are combined at step (a).

18. The non-liquid formulation of claim 16 , wherein about 20 mg/ml of the VEGF antagonist, about 5 mM sodium phosphate buffer, about 0.015% polysorbate, and about 67.5 mM sodium chloride, pH about 6.2-6.3 are combined at step (a).

19. The non-liquid formulation of claim 16 , wherein the formulation can be reconstituted in about 0.7 minutes or less.