COMBINATION THERAPY FOR THE TREATMENT OF OCULAR NEOVASCULAR DISORDERS
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.