Compositions Comprising an Anti-PDGF Aptamer and a VEGF Antagonist

1 . A composition comprising an effective amount of:

(a) about 0.3 mg/mL to about 30 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 0.5 mg/mL to about 20 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof; and one or both of:

(c) a buffer capable of achieving or maintaining the pH of the composition at about pH 5.0 to about pH 8.0; and

(d) a tonicity modifier.

2 . The composition of claim 1 , wherein-the buffer is about 1 mM to about 20 mM L-histidine or about 1 mM to about 20 mM sodium phosphate; and the tonicity modifier is about 10 mM to about 200 mM NaCl, about 1% to about 20% (w/v) sorbitol, or about 1% to about 20% (w/v) trehalose.

3 . The composition of claim 2 , wherein-the buffer is about 1 mM to about 20 mM L-histidine; and the tonicity modifier is about 10 mM to about 200 mM NaCl.

4 . The composition of claim 1 , further comprising:

(e) about 0.001% (w/v) to about 0.05% (w/v) surfactant.

5 . The composition of claim 2 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof;

(c) about 10 mM L-histidine; and

(d) about 130 mM NaCl,

wherein the pH of the composition is about pH 6.0.

6 . The composition of claim 5 , further comprising:

(e) about 0.01% (w/v) polysorbate 20.

7 . The composition of claim 2 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof;

(c) about 10 mM sodium phosphate; and

(d) about 5% (w/v) sorbitol,

wherein the pH of the composition is about pH 7.0.

8 . The composition of claim 7 , further comprising:

(e) about 0.01% (w/v) polysorbate 20.

9 . The composition of claim 2 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof;

(c) about 10 mM sodium phosphate; and

(d) about 130 mM NaCl,

wherein the pH of the composition is about pH 7.0.

10 . The composition of claim 9 , further comprising:

(e) about 0.01% (w/v) polysorbate 20.

11 . The composition of claim 2 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof;

(c) about 5 mM sodium phosphate;

(d) about 5 mM histidine HCl;

(e) about 75 mM NaCl; and

(f) about 5% (w/v) trehalose),

wherein the pH of the composition is about pH 6.5.

12 . The composition of claim 11 , further comprising:

(g) about 0.005% (w/v) polysorbate 20.

13 . A composition comprising an effective amount of:

(a) about 0.3 mg/mL to about 30 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof; and

(b) about 0.5 mg/mL to about 25 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof; and one or both of:

(c) a buffer capable of achieving or maintaining the pH of the composition at about pH 5.0 to about pH 8.0; and

(d) a tonicity modifier.

14 . The composition of claim 13 , wherein the buffer is about 5 mM to about 200 mM sodium phosphate or about 5 mM to about 200 mM Tris.HCl; and the tonicity modifier is about 10 mM to about 200 mM NaCl, about 1% to about 20% (w/v) sorbitol, or about 1% to about 20% (w/v) trehalose.

15 . The composition of claim 14 , wherein the buffer is about 5 mM to about 200 mM sodium phosphate; and the tonicity agent is about 10 mM to about 200 mM NaCl, wherein the pH of the composition is about pH 5.0 to about pH 7.0.

16 . The composition of claim 13 , further comprising:

(e) about 0.001% (wiv) to about 0.05% (w/v) surfactant.

17 . The composition of claim 14 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 50 mM sodium phosphate; and

(d) about 130 mM NaCl,

wherein the pH of the composition is about pH 6.0.

18 . The composition of claim 17 , further comprising:

(e) about 0.02% (w/v) polysorbate 20.

19 . The composition of claim 14 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 50 mM sodium phosphate; and

(d) about 5% (w/v) sorbitol,

wherein the pH of the composition is about pH 6.0.

20 . The composition of claim 19 , further comprising:

(e) about 0.02% (w/v) polysorbate 20.

21 . The composition of claim 14 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 50 mM sodium phosphate; and

(d) about 5% (w/v) sorbitol,

wherein the pH of the composition is about pH 7.0.

22 . The composition of claim 21 , further comprising:

(e) about 0.02% (w/v) polysorbate 20.

23 . The composition of claim 14 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 50 mM sodium phosphate; and

(d) about 150 mM NaCl,

wherein the pH of the composition is about pH 7.0.

24 . The composition of claim 23 , further comprising:

(e) about 0.02% (w/v) polysorbate 20.

25 . The composition of claim 14 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 50 mM Tris.HCl; and

(d) about 130 mM NaCl,

wherein the pH of the composition is about pH 8.0.

26 . The composition of claim 25 , further comprising:

(e) about 0.02% (w/v) polysorbate 20.

27 . The composition of claim 14 , wherein the composition comprises:

(a) about 15 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 30 mM sodium phosphate;

(d) about 75 mM NaCl; and

(e) about 3% (w/v) trehalose,

wherein the pH of the composition is about pH 6.3.

28 . The composition of claim 27 , further comprising:

(f) about 0.02% (w/v) polysorbate 20.

29 . The composition of claim 14 , wherein the composition comprises:

(a) about 3 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 12.5 mg/mL bevacizumab or a pharmaceutically acceptable salt thereof;

(c) about 30 mM sodium phosphate;

(d) about 75 mM NaCl; and

(e) about 3% (w/v) trehalose,

wherein the pH of the composition is about pH 6.3.

30 . The composition of claim 29 , further comprising:

(f) about 0.02% (w/v) polysorbate 20.

31 . A composition comprising an effective amount of:

(a) about 0.3 mg/mL to about 30 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL to about 40 mg/mL aflibercept or a pharmaceutically acceptable salt thereof; and one or more of:

(c) a buffer capable of achieving or maintaining the pH of the composition at about pH 5.0 to about pH 8.0;

(d) a tonicity modifier; and

(e) 0 to about 10% (w/v) sucrose.

32 . The composition of claim 31 , wherein the buffer is about 5 mM to about 50 mM phosphate; and the tonicity modifier is about 10 mM to about 200 mM NaCl.

33 . The composition of claim 32 , wherein the composition comprises:

(a) about 0.3 mg/mL to about 30 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL to about 40 mg/mL aflibercept or a pharmaceutically acceptable salt thereof;

(c) about 5 mM to about 50 mM phosphate;

(d) about 10 mM to about 200 mM NaCl; and

(e) 0 to about 10% (w/v) sucrose,

wherein the pH of the composition is about pH 6.0 to about pH 8.0.

34 . The composition of claim 31 , further comprising:

(f) about 0.001% (w/v) to about 0.05% (w/v) surfactant.

35 . The composition of claim 32 , wherein the composition comprises:

(a) about 6 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 40 mg/mL aflibercept or a pharmaceutically acceptable salt thereof;

(c) about 10 mM phosphate;

(d) about 40 mM NaCl; and

(e) about 5%/(w/v) sucrose,

wherein the pH of the composition is about pH 6.2.

36 . The composition of claim 35 , further comprising:

(f) about 0.03% (w/v) polysorbate 20.

37 . A composition comprising an effective amount of:

(a) about 3 mg/mL to about 90 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 1.0 mg/mL to about 30 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof; and one or both of:

(c) a buffer capable of achieving or maintaining the pH of the composition at about pH 5.0 to about pH 8.0; and

(d) a tonicity modifier.

38 . The composition of claim 37 , wherein the buffer comprises about 1 mM to about 100 mM sodium phosphate or about 1.0 mM to about 10 mM histidine.HCl; and the tonicity modifier is about 0.5% (w/v) to about 10% (w/v) trehalose.

39 . The composition of claim 38 , wherein the composition comprises:

(a) about 15 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 5 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof;

(c) about 5 mM phosphate;

(d) about 75 mM NaCl;

(e) about 5 mM histidine.HCl; and

(f) about 5% (w/v) trehalose.

40 . The composition of claim 39 , further comprising:

(g) about 0.005% (w/v) polysorbate 20.

41 . The composition of claim 38 , wherein the composition comprises:

(a) about 24 mg/mL Antagonist A or a pharmaceutically acceptable salt thereof;

(b) about 8 mg/mL ranibizumab or a pharmaceutically acceptable salt thereof;

(c) about 8 mM phosphate;

(d) about 120 mM NaCl;

(e) about 2 mM histidine.HCl; and

(f) about 2% (w/v) trehalose.

42 . The composition of claim 41 , further comprising:

(g) about 0.002% (w/v) polysorbate 20.

43 . A method for treating or preventing an ophthalmological disease, comprising administering to a mammal in need thereof the composition of claim 1 .

44 . The method of claim 43 , wherein the ophthalmological disease is age-related macular degeneration, polypoidal choroidal vasculopathy, condition associated with choroidal neovascularization, hypertensive retinopathy, diabetic retinopathy, sickle cell retinopathy, condition associated with peripheral retinal neovascularization, retinopathy of prematurity, venous occlusive disease, arterial occlusive disease, central serous chorioretinopathy, cystoid macular edema, retinal telangiectasia, arterial macroaneurysm, retinal angiomatosis, radiation-induced retinopathy, rubeosis iridis, or a neoplasm.

45 . The method of claim 43 , wherein the ophthalmological disease is wet age-related macular degeneration or dry age-related macular degeneration.

46 . The method of claim 43 , wherein the composition is present in a drug-delivery device.

47 . The method of claim 43 , wherein the composition is administered intraocularly.

48 . The method of claim 47 , wherein the intraocular administration is intravitreal administration or anterior chamber administration.

49 . (canceled)