Methods of treating eye disorders with APLNR antagonists and VEGF inhibitors
The present disclosure provides methods for treating, preventing or reducing the severity of an eye disease. The methods of the present disclosure comprise administering to a subject in need thereof a therapeutic composition comprising an APLNR antagonist such as an anti-APLNR antibody in combination with a vascular endothelial growth factor (VEGF) antagonist (for example, aflibercept).
1. A method for treating a vascular eye disease or disorder, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
2. The method of claim 1 , wherein the eye disease or disorder is selected from the group consisting of diabetic retinopathy, proliferative diabetic retinopathy, diabetic macular edema, age-related macular degeneration, retinal neovascularization, central retinal vein occlusion, branched retinal vein occlusion, polypoidal choroidal vasculopathy, choroidal neovascularization (CNV), degenerative myopia (myopic CNV), neovascular glaucoma, and retinopathy of prematurity.
3. The method of claim 2 , wherein the eye disease or disorder is age-related macular degeneration.
4. The method of claim 2 , wherein the eye disease or disorder is diabetic macular edema.
5. The method of claim 1 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
6. The method of claim 1 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
7. The method of claim 6 , wherein the VEGF Trap is aflibercept.
8. A method for inhibiting retinal angiogenesis, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
9. The method of claim 8 , wherein the subject has been diagnosed with an eye disease or disorder selected from the group consisting of diabetic retinopathy, proliferative diabetic retinopathy, diabetic macular edema, age-related macular degeneration, retinal neovascularization, central retinal vein occlusion, branched retinal vein occlusion, polypoidal choroidal vasculopathy, choroidal neovascularization (CNV), degenerative myopia (myopic CNV), neovascular glaucoma, and retinopathy of prematurity.
10. The method of claim 9 , wherein the eye disease or disorder is age-related macular degeneration.
11. The method of claim 9 , wherein the eye disease or disorder is diabetic macular edema.
12. The method of claim 8 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
13. The method of claim 8 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
14. The method of claim 13 , wherein the VEGF Trap is aflibercept.
15. A method of inhibiting retinal neovascularization, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
16. The method of claim 15 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
17. The method of claim 15 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
18. The method of claim 17 , wherein the VEGF Trap is aflibercept.
19. A method for inhibiting choroidal neovascularization, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
20. The method of claim 19 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
21. The method of claim 19 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
22. The method of claim 21 , wherein the VEGF Trap is aflibercept.
23. A method for improving vascular regrowth and decreasing abnormal neovascularizations, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
24. The method of claim 23 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
25. The method of claim 23 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
26. The method of claim 25 , wherein the VEGF Trap is aflibercept.
27. A method for promoting revascularization of a retina, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
28. The method of claim 27 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
29. The method of claim 27 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
30. The method of claim 29 , wherein the VEGF Trap is aflibercept.
31. A method for promoting uniform regrowth of retinal vessels, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
32. The method of claim 31 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
33. The method of claim 31 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
34. The method of claim 33 , wherein the VEGF Trap is aflibercept.
35. A method of improving vessel outgrowth in a retina, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
36. The method of claim 35 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
37. The method of claim 35 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
38. The method of claim 37 , wherein the VEGF Trap is aflibercept.
39. A method for promoting uniform blood vessel growth in a retina, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
40. The method of claim 39 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
41. The method of claim 39 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
42. The method of claim 41 , wherein the VEGF Trap is aflibercept.
43. A method for improving blood vessel organization of a retina, comprising:
administering a therapeutically effective amount of an apelin receptor (APLNR) antagonist to a subject in need thereof, wherein the APLNR antagonist comprises an anti-APLNR antibody or antigen binding fragment thereof that specifically binds human APLNR, and wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 3-4-5-8-9-10 and 14-15-16-19-20-21; and
administering a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, to the subject.
44. The method of claim 43 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/7 and 13/18.
45. The method of claim 43 , wherein the VEGF antagonist comprises a VEGF receptor-based chimeric molecule (VEGF Trap).
46. The method of claim 45 , wherein the VEGF Trap is aflibercept.