Combination therapy for the treatment of ocular neovascular disorders

Abstract

The invention features methods for treating a patient diagnosed with, or at risk of developing, a neovascular disorder by administering a PDGF antagonist and a VEGF antagonist to the patient. The invention also features a pharmaceutical composition containing a PDGF antagonist and a VEGF antagonist for the treatment or prevention of a neovascular disorder.

1 .- 18 . (canceled) 
     
     
         19 . A method for ameliorating wet type age-related macular degeneration, comprising administering to a mammal in need thereof:
 (a) a PDGF-B antagonist, wherein the PDGF-B antagonist is a pegylated aptamer having the sequence of SEQ ID NO: 23, and   (b) a VEGF antagonist, wherein the VEGF antagonist is a chimeric VEGF receptor protein comprising immunoglobulin (Ig)-like domains from two or more different VEGF receptor molecules, wherein said chimeric VEGF receptor protein comprises an Ig-like domain 2 of flt-1 receptor or an Ig-like domain 2 of KDR receptor,   wherein the PDGF-B antagonist and the VEGF antagonist are administered simultaneously or within 90 days of each other, and wherein the PDGF-B antagonist and the VEGF antagonist are administered in an amount effective to ameliorate the wet type age-related macular degeneration, and wherein the mammal is a human or mouse.   
     
     
         20 . The method of  claim 19 , wherein the PDGF-B antagonist and the VEGF antagonist are administered within 10 days of each other. 
     
     
         21 . The method of  claim 19 , wherein the PDGF-B antagonist and the VEGF antagonist are administered within 5 days of each other. 
     
     
         22 . The method of  claim 19 , wherein the PDGF-B antagonist and the VEGF antagonist are administered within 24 hours of each other. 
     
     
         23 . The method of  claim 19 , wherein the PDGF-B antagonist and the VEGF antagonist are administered simultaneously. 
     
     
         24 . The method of  claim 19 , wherein the PDGF-B antagonist and VEGF antagonist are administered separately in individual dosage amounts. 
     
     
         25 . The method of  claim 24 , wherein the PDGF-B antagonist and VEGF antagonist are administered sequentially. 
     
     
         26 . The method of  claim 19 , wherein the PDGF-B antagonist and VEGF antagonist are administered together in the same composition. 
     
     
         27 . The method of  claim 19 , wherein the mammal is a human. 
     
     
         28 . The method of  claim 19 , wherein the Ig-like domain 2 comprises an amino acid sequence of SEQ ID NO: 39. 
     
     
         29 . The method of  claim 19 , wherein the chimeric VEGF receptor protein further comprises an Ig-like domain 3 of a flt-1 receptor or a KDR receptor. 
     
     
         30 . The method of  claim 29 , wherein the Ig-like domain 3 comprises an amino acid sequence of SEQ ID NO: 47. 
     
     
         31 . The method of  claim 29 , wherein the Ig-like domain 2 comprises an amino acid sequence of SEQ ID NO: 39 and the Ig-like domain 3 comprises an amino acid sequence of SEQ ID NO: 47. 
     
     
         32 . The method of  claim 19 , wherein the chimeric VEGF receptor protein is fused to an immunoglobulin sequence. 
     
     
         33 . The method of  claim 32 , wherein the immunoglobulin sequence comprises an IgG heavy chain sequence. 
     
     
         34 . The method of  claim 33 , wherein the chimeric VEGF receptor protein is fused to an immunoglobulin sequence. 
     
     
         35 . The method of  claim 34 , wherein the immunoglobulin sequence comprises an IgG heavy chain sequence. 
     
     
         36 . The method of  claim 19 , wherein the dosage of the PDGF antagonist or the VEGF antagonist is about 0.1 mg to about 250 mg per day. 
     
     
         37 . The method of  claim 36 , wherein the dosage of the PDGF antagonist or the VEGF antagonist is about 1 mg to about 20 mg per day. 
     
     
         38 . The method of  claim 37 , wherein the dosage of the PDGF antagonist or the VEGF antagonist is about 3 mg to about 5 mg per day. 
     
     
         39 . The method of  claim 19 , wherein the dosage of the VEGF antagonist is about 0.15 mg to about 3.0 mg per day. 
     
     
         40 . The method of  claim 39 , wherein the dosage of the VEGF antagonist is about 0.3 mg to about 3.0 mg per day. 
     
     
         41 . The method of  claim 19 , wherein the dosage of the VEGF antagonist is about 0.1 mg to 1.0 mg per day.