Stable protein solution formulation containing high concentration of an anti-VEGF antibody
The present invention provides anti-VEGF antibodies formulated as high concentration, aqueous pharmaceutical compositions, suitable for an injection, preferably an intravitreal injection. The aqueous pharmaceutical compositions are useful for delivery of a high concentration of the antibody active ingredient to a patient without high levels of antibody aggregation and without a high level of sub-visible particulate matter. An aqueous composition of the invention comprises an antibody having a concentration of at least 50 mg/ml. An aqueous pharmaceutical composition of the invention includes a sugar, a buffering agent, and a surfactant.
1. An aqueous ophthalmic pharmaceutical composition, comprising (i) at least 60 mg/ml of an anti-VEGF antibody that comprises the sequences of SEQ ID NO: 1 and SEQ ID NO: 2, (ii) about 6.75% (w/v) sucrose, (iii) a citrate buffer comprising about 0.01% (w/v) citric acid and about 0.428% (w/v) trisodium citrate dehydrate, and (iv) about 0.05% (w/v) polysorbate 80 as a surfactant, wherein the maximum number of particles ≥10 μm diameter in the aqueous ophthalmic pharmaceutical composition is 50 per mL.
2. The aqueous ophthalmic pharmaceutical composition of claim 1 , wherein the antibody comprises the sequence of SEQ ID NO: 3.
3. The aqueous ophthalmic pharmaceutical composition of claim 1 , wherein the concentration of the anti-VEGF antibody is about 60 mg/ml.
4. The aqueous ophthalmic pharmaceutical composition of claim 3 , wherein the anti-VEGF antibody comprises the sequence of SEQ ID NO: 3, and the pH is about 6.8.
5. The aqueous ophthalmic pharmaceutical composition of claim 1 , wherein the concentration of the anti-VEGF antibody is about 120 mg/ml.
6. The aqueous ophthalmic pharmaceutical composition of claim 5 , wherein the anti-VEGF antibody comprises the sequence of SEQ ID NO: 3, and the pH is about 6.8.
7. A delivery device including the aqueous ophthalmic pharmaceutical composition of claim 1 .
8. The delivery device of claim 7 , which is a pre-filled syringe.
9. A delivery device including the aqueous ophthalmic pharmaceutical composition of claim 5 .
10. The delivery device of claim 9 , which is a pre-filled syringe.
11. A lyophilized formulation prepared by lyophilizing the aqueous ophthalmic pharmaceutical composition of claim 1 .
12. A lyophilized formulation prepared by lyophilizing the aqueous ophthalmic pharmaceutical composition of claim 5 .
13. A method for delivering an anti-VEGF antibody to a subject, comprising a step of administering to the subject an aqueous pharmaceutical composition of claim 1 .
14. A method of treating an ocular disease or disorder that is mediated by VEGF, comprising administering to a subject in need thereof, an aqueous pharmaceutical composition of claim 1 .
15. The method of claim 14 , wherein said ocular disease or disorder is an ocular neovascular disease.
16. A method for delivering an anti-VEGF antibody to a subject, comprising a step of administering to the subject an aqueous pharmaceutical composition of claim 5 .
17. A method of treating an ocular disease or disorder that is mediated by VEGF, comprising administering to a subject in need thereof, an aqueous pharmaceutical composition of claim 5 .
18. The method of claim 17 , wherein said ocular disease or disorder is an ocular neovascular disease.