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 . A method for ameliorating wet type age-related macular degeneration, comprising administering to a mammal in need thereof:
 (a) a PDGF antagonist, wherein the PDGF antagonist is ST157 or a pharmaceutically acceptable salt thereof; and   (b) a VEGF antagonist, wherein the VEGF antagonist is a humanized anti-VEGF antibody or binding fragment thereof that binds to VEGF-A,   wherein the PDGF antagonist and the VEGF antagonist are administered simultaneously or within 90 days of each other, and wherein the PDGF antagonist and the VEGF antagonist are administered in an amount effective to ameliorate the wet type age-related macular degeneration.   
     
     
         2 . The method of  claim 1 , wherein the PDGF antagonist and the VEGF antagonist are administered within 10 days of each other. 
     
     
         3 . The method of  claim 1 , wherein the PDGF antagonist and the VEGF antagonist are administered within 5 days of each other. 
     
     
         4 . The method of  claim 1 , wherein the PDGF antagonist and the VEGF antagonist are administered within 24 hours of each other. 
     
     
         5 . The method of  claim 1 , wherein the PDGF antagonist and the VEGF antagonist are administered simultaneously. 
     
     
         6 . The method of  claim 1 , wherein the PDGF antagonist and VEGF antagonist are administered separately in individual dosage amounts. 
     
     
         7 . The method of  claim 1 , wherein the PDGF antagonist and VEGF antagonist are administered together in the same composition. 
     
     
         8 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         9 . The method of  claim 1 , wherein the VEGF antagonist is a humanized anti-VEGF antibody having a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 26 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 27, or an anti-VEGF antibody binding fragment having a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 25 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 24. 
     
     
         10 . The method of  claim 9 , wherein the VEGF antagonist is a humanized anti-VEGF antibody binding fragment having a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 24 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 25. 
     
     
         11 . The method of  claim 9 , wherein the VEGF antagonist is a humanized anti-VEGF antibody having a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 26 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 27. 
     
     
         12 . The method of  claim 1 , wherein the dosage of the PDGF antagonist or the VEGF antagonist is about 0.1 mg to about 250 mg per day. 
     
     
         13 . The method of  claim 12 , wherein the dosage of the PDGF antagonist or the VEGF antagonist is about 1 mg to about 20 mg per day. 
     
     
         14 . The method of  claim 13 , wherein the dosage of the PDGF antagonist or the VEGF antagonist is about 3 mg to about 5 mg per day. 
     
     
         15 . The method of  claim 12 , wherein the dosage of the VEGF antagonist is about 0.15 mg to about 3.0 mg per day. 
     
     
         16 . The method of  claim 15 , wherein the dosage of the VEGF antagonist is about 0.3 mg to about 3.0 mg per day. 
     
     
         17 . The method of  claim 16 , wherein the dosage of the VEGF antagonist is about 0.1 mg to 1.0 mg per day.