Methods and formulations for treating vascular eye diseases

Abstract

The present invention provides methods for treating, preventing or reducing the severity of an eye disease. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an angiopoietin-2 (Ang-2) inhibitor such as an anti-Ang-2 antibody in combination with a vascular endothelial growth factor (VEGF) antagonist (e.g., aflibercept).

What is claimed is: 
     
         1 .- 70 . (canceled) 
     
     
         71 . A stable liquid formulation comprising: (i) a vascular endothelial growth factor (VEGF) antagonist; (ii) an antibody that binds specifically to human angiopoietin-2 (hAng-2); (iii) a buffer at pH of 6.2±0.3; (iv) a non-ionic detergent; (v) a tonicity agent; and (vi) a stabilizer; wherein the VEGF antagonist is a VEGF receptor-based chimeric molecule (“VEGF Trap”). 
     
     
         72 . The formulation of  claim 71 , wherein the antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) wherein HCDR1 has SEQ ID NO: 3, HCDR2 has SEQ ID NO: 4, HCDR3 has SEQ ID NO: 5, and three light chain CDRs (LCDR1, LCDR2 and LCDR3), wherein LCDR1 has SEQ ID NO: 6, LCDR2 has SEQ ID NO: 7, and LCDR3 has SEQ ID NO: 8. 
     
     
         73 . The formulation of  claim 72 , wherein the antibody comprises a heavy chain variable region (HCVR) of SEQ ID NO: 1 and a light chain variable region (LCVR) of SEQ ID NO: 2. 
     
     
         74 . The formulation of  claim 73 , wherein the VEGF antagonist concentration is about 40 mg/mL±1.5 mg/mL. 
     
     
         75 . The formulation of  claim 74 , comprising about 10-120 mg/mL of the antibody. 
     
     
         76 . The formulation of  claim 75 , comprising the antibody at a concentration selected from the group consisting of 10 mg/mL, 20 mg/mL, 60 mg/mL, and 120 mg/mL. 
     
     
         77 . The formulation of  claim 71 , comprising about 5-100 mg/mL of the VEGF antagonist; about 10-120 mg/mL of the anti-Ang-2 antibody; about 5-50 mM sodium phosphate, pH about 6.2; about 0.01-0.1% (w/v) polysorbate; about 10-50 mM sodium chloride; and about 1-20% (w/v) sucrose. 
     
     
         78 . The formulation of  claim 77 , comprising the antibody at a concentration selected from the group consisting of 10 mg/ml, 20 mg/ml, 60 mg/ml, and 120 mg/ml. 
     
     
         79 . The formulation of  claim 76 , wherein the buffer is sodium phosphate. 
     
     
         80 . The formulation of  claim 79 , wherein the sodium phosphate concentration is 10 mM±1.5 mM. 
     
     
         81 . The formulation of  claim 76 , wherein the non-ionic detergent is polysorbate  20 . 
     
     
         82 . The formulation of  claim 81 , wherein the polysorbate 20 concentration is about 0.03% w/v±0.0045%. 
     
     
         83 . The formulation of  claim 76 , wherein the tonicity agent is sodium chloride. 
     
     
         84 . The formulation of  claim 83 , wherein the sodium chloride concentration is about 40 mM±6.0 mM. 
     
     
         85 . The formulation of  claim 76 , wherein the stabilizer is sucrose. 
     
     
         86 . The formulation of  claim 85 , wherein the sucrose concentration is about 5%±0.75% (w/v). 
     
     
         87 . The formulation of  claim 71 , wherein the VEGF antagonist concentration is 40 mg/mL±6.0 mg/mL, the antibody concentration is 10 mg/mL±1.5 mg/mL, the buffer is 10 mM±1.5 mM sodium phosphate, pH 6.2±0.3, the non-ionic detergent is 0.03% w/v±0.0045% polysorbate 20, the tonicity agent is 40 mM sodium chloride, and the stabilizer is 5% w/v±1.5% sucrose. 
     
     
         88 . The formulation of  claim 71 , wherein the VEGF antagonist concentration is 40 mg/mL±6.0 mg/mL, the antibody concentration is 20 mg/mL±3.0 mg/mL, the buffer is 10 mM±1.5 mM sodium phosphate, pH 6.2±0.3, the non-ionic detergent is 0.03% w/v±0.0045% polysorbate 20, the tonicity agent is 40 mM sodium chloride, and the stabilizer is 5% w/v±1.5% sucrose. 
     
     
         89 . The formulation of  claim 71 , wherein the VEGF antagonist concentration is 40 mg/mL±6.0 mg/mL, the antibody concentration is 60 mg/mL±9.0 mg/mL, the buffer is 10 mM±1.5 mM sodium phosphate, pH 6.2±0.3, the non-ionic detergent is 0.03% w/v±0.0045% polysorbate 20, the tonicity agent is 40 mM sodium chloride, and the stabilizer is 5% w/v±1.5% sucrose. 
     
     
         90 . The formulation of  claim 71 , wherein the VEGF antagonist concentration is 40 mg/mL±6.0 mg/mL, the antibody concentration is 120 mg/mL±18.0 mg/mL, the buffer is 10 mM±1.5 mM sodium phosphate, pH 6.2±0.3, the non-ionic detergent is 0.03% w/v±0.0045% polysorbate 20, the tonicity agent is 40 mM sodium chloride, and the stabilizer is 5% w/v±1.5% sucrose. 
     
     
         91 .- 122 . (canceled) 
     
     
         123 . The formulation of  claim 71 , wherein the VEGF Trap consists of a dimer of two polypeptides consisting of amino acids 27-457 of SEQ ID NO:11. 
     
     
         124 . The formulation of  claim 123 , wherein the VEGF Trap is aflibercept.