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).

1 .- 92 . (canceled) 
     
     
         93 . A method for treating a vascular eye disease, the method comprising sequentially administering one or more doses of a pharmaceutical composition comprising therapeutically active amount of an anti-Ang-2 inhibitor and a VEGF antagonist to a subject in need thereof. 
     
     
         94 . The method of  claim 93 , wherein the pharmaceutical composition comprises about 10 mg/mL to about 120 mg/mL of the anti-Ang-2 inhibitor. 
     
     
         95 . The method of  claim 93 , wherein the pharmaceutical composition comprises about 40 mg/mL of the VEGF antagonist. 
     
     
         96 . The method of  claim 93 , wherein the pharmaceutical composition comprises about 10 mg/mL to about 120 mg/mL of the anti-Ang-2 inhibitor and about 40 mg/mL of the VEGF antagonist. 
     
     
         97 . The method of  claim 93 , wherein the pharmaceutical composition comprises 10 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         98 . The method of  claim 93 , wherein the pharmaceutical composition comprises 20 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         99 . The method of  claim 93 , wherein the pharmaceutical composition comprises 60 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         100 . The method of  claim 93 , wherein the pharmaceutical composition comprises 120 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         101 . The method of  claim 93  comprising administering an initial dose of the pharmaceutical composition to the subject; followed by administering one or more secondary doses of the pharmaceutical composition to the subject, wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose. 
     
     
         102 . The method of  claim 101 , wherein at least 2 secondary doses are administered to the subject and each secondary dose is administered 4 weeks after the immediately preceding dose. 
     
     
         103 . The method of  claim 102  further comprising administering one or more tertiary doses of the pharmaceutical composition to the subject wherein each tertiary dose is administered 5 to 12 weeks after the immediately preceding dose. 
     
     
         104 . The method of  claim 103 , wherein each tertiary dose is administered 8 weeks after the immediately preceding dose. 
     
     
         105 . The method of  claim 93 , wherein each dose of the pharmaceutical composition comprises about 0.5 mg to about 10 mg of the anti-Ang-2 inhibitor and about 2 mg of the VEGF antagonist. 
     
     
         106 . The method of  claim 105 , wherein each dose of the pharmaceutical composition comprises 10 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         107 . The method of  claim 105 , wherein each dose of the pharmaceutical composition comprises 20 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         108 . The method of  claim 105 , wherein each dose of the pharmaceutical composition comprises 60 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         109 . The method of  claim 105 , wherein each dose of the pharmaceutical composition comprises 120 mg/mL of the anti-Ang-2 inhibitor and 40 mg/mL of the VEGF antagonist. 
     
     
         110 . The method of  claim 93 , wherein each dose of the pharmaceutical composition is intravitreally administered to the subject. 
     
     
         111 . The method of  claim 93 , wherein the vascular eye disease is selected from the group consisting of diabetic retinopathy, diabetic macular edema, age-related macular degeneration, central retinal vein occlusion, branched retinal vein occlusion, and polypoidal choroidal vasculopathy. 
     
     
         112 . The method of  claim 111 , wherein the vascular eye disease is age-related macular degeneration. 
     
     
         113 . The method of  claim 111 , wherein the vascular eye disease is diabetic macular edema. 
     
     
         114 . The method of  claim 93 , wherein the Ang-2 inhibitor is an anti-Ang-2 antibody or antigen binding fragment thereof. 
     
     
         115 . The method of  claim 114 , wherein the antibody or antigen binding fragment comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO: 1 and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO: 2. 
     
     
         116 . The method of  claim 114 , wherein the antibody or antigen binding fragment comprises a heavy chain CDR1 (HCDR1) having the amino acid sequence of SEQ ID NO: 3, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, a HCDR3 having the amino acid sequence of SEQ ID NO: 5, a light chain CDR1 (LCDR1) having the amino acid sequence of SEQ ID NO: 6, a LCDR2 having the amino acid sequence of SEQ ID NO: 7, and a LCDR3 having the amino acid sequence of SEQ ID NO: 8. 
     
     
         117 . The method of  claim 116 , wherein the antibody or antigen binding fragment thereof comprises a HCVR having the amino acid sequence of SEQ ID NO: 1 and a LCVR having the amino acid sequence of SEQ ID NO: 2. 
     
     
         118 . The method of  claim 93 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap). 
     
     
         119 . The method of  claim 118 , wherein the VEGF Trap comprises one or more immunoglobulin (Ig)-like domains of VEGFR1, one or more Ig-like domains of VEGFR2, and a multimerizing domain. 
     
     
         120 . The method of  claim 119 , wherein the VEGF Trap comprises Ig-like domain 2 of VEGFR1, Ig-like domain 3 of VEGFR2, and a multimerizing domain. 
     
     
         121 . The method of  claim 120 , wherein the VEGF Trap is aflibercept. 
     
     
         122 . The method of  claim 93 , wherein the VEGF antagonist consists of a dimer of two polypeptides consisting of amino acids 27-457 of SEQ ID NO: 11.