Combination therapy for the treatment of ocular neovascular disorders
View Patent ↗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 pharmaceutical composition comprising:
(i) a PDGF-B antagonist, wherein the PDGF-B antagonist is a pegylated aptamer whose sequence is that of SEQ ID NO: 23;
(ii) a VEGF antagonist, wherein the VEGF antagonist is a humanized anti-VEGF antibody or a binding fragment thereof that binds to human VEGF-A; and
(iii) a pharmaceutically acceptable carrier, wherein the PDGF-B antagonist and the VEGF antagonist are present in an effective amount effective to improve vision in a human having wet type age-related macular degeneration.
2. The composition of claim 1 , wherein the VEGF antagonist is an 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.
3. The composition of claim 1 , wherein the VEGF antagonist is an 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.
4. The composition of claim 1 , wherein the VEGF antagonist is an 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.
5. A drug delivery device comprising:
(i) a PDGF-B antagonist, wherein the PDGF-B antagonist is a pegylated aptamer whose sequence is that of SEQ ID NO: 23; and
(ii) a VEGF antagonist, wherein the VEGF antagonist is a humanized anti-VEGF antibody or a binding fragment thereof that binds to human VEGF-A,
wherein the PDGF-B antagonist and the VEGF antagonist are present in an amount effective to improve vision in a human having wet type age-related macular degeneration.
6. A pharmaceutical pack comprising:
(a) a PDGF-B antagonist, wherein the PDGF-B antagonist is a pegylated aptamer whose sequence is that of SEQ ID NO: 23; and
(b) a VEGF antagonist, wherein the VEGF antagonist is a humanized anti-VEGF antibody or a binding fragment thereof that binds to human VEGF-A,
wherein the PDGF-B antagonist and the VEGF antagonist are present in an amount effective to improve vision in a human having wet type age-related macular degeneration.
7. The pharmaceutical pack of claim 6 , wherein the VEGF antagonist is an 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.
8. The pharmaceutical pack of claim 6 , wherein the VEGF antagonist is an 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.
9. The pharmaceutical pack of claim 6 , wherein the VEGF antagonist is an 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.
10. The pharmaceutical pack of claim 6 , further comprising a pharmaceutically acceptable carrier or diluent.
11. A pharmaceutical pack comprising:
(a) a composition comprising a PDGF-B antagonist, wherein the PDGF-B antagonist is a pegylated aptamer whose sequence is that of SEQ ID NO: 23, and a pharmaceutically acceptable carrier; and
(b) a composition comprising a VEGF antagonist, wherein the VEGF antagonist is a humanized anti-VEGF antibody or a binding fragment thereof that binds to human VEGF-A, and a pharmaceutically acceptable carrier,
wherein the amount of PDGF-B antagonist and VEGF antagonist are present in an amount effective to improve vision in a human having wet type age-related macular degeneration.
12. The pharmaceutical pack of claim 11 , wherein the VEGF antagonist is an 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.
13. The pharmaceutical pack of claim 11 , wherein the VEGF antagonist is an 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 sequence of SEQ ID NO: 25.
14. The pharmaceutical pack of claim 11 , wherein the VEGF antagonist is an 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.
15. The drug delivery device of claim 5 , wherein the VEGF antagonist is an 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.
16. The drug delivery device of claim 5 , wherein the VEGF antagonist is an 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.
17. The drug delivery device of claim 5 , wherein the VEGF antagonist is an 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.
18. The drug delivery device of claim 5 , further comprising a pharmaceutically acceptable carrier.
19. The drug delivery device of claim 5 , in the form of an intraocular implant.
20. The composition of claim 1 , wherein the PDGF-B antagonist is present at a concentration of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, 10 mg/mL, 20 mg/mL, or 30 mg/mL.
21. The drug delivery device of claim 5 , wherein the PDGF-B antagonist is present at a concentration of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, 10 mg/mL, 20 mg/mL, or 30 mg/mL.
22. The pharmaceutical pack of claim 6 or 11 , wherein the PDGF-B antagonist is present at a concentration of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, 10 mg/mL, 20 mg/mL, or 30 mg/mL.