Methods of treating ocular conditions by administering humanized monoclonal antibodies that target VE-PTP (HPTP-beta)
The disclosure provides compositions and methods for the treatment of ocular conditions associated with angiogenesis comprising administering an antibody that targets a tyrosine phosphatase inhibitor in a subject.
1. A method of treating an ocular condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody, the antibody comprising:
a) a heavy chain that comprises: a sequence that is SEQ ID NO: 54; a sequence that is SEQ ID NO: 55; and a sequence that is SEQ ID NO: 56, wherein the sequence that is SEQ ID NO: 54; the sequence that is SEQ ID NO: 55; and the sequence that is SEQ ID NO: 56 are contained within a sequence that is at least 91% identical to any one of SEQ ID NOs: 9-12; and
b) a light chain that comprises: a sequence that is SEQ ID NO: 57; a sequence that is SEQ ID NO: 58; and a sequence that is SEQ ID NO: 59,
wherein the antibody binds human protein tyrosine phosphatase-beta (HPTP-β).
2. The method of claim 1 , wherein the condition is diabetic retinopathy.
3. The method of claim 1 , wherein the condition is neovascularization.
4. The method of claim 1 , wherein the condition is vascular leak.
5. The method of claim 1 , wherein the condition is increased intraocular pressure.
6. The method of claim 1 , wherein the condition is ocular edema.
7. The method of claim 1 , wherein the condition is diabetic macular edema.
8. The method of claim 1 , wherein the condition is ocular hypertension.
9. The method of claim 1 , wherein the condition is ocular inflammation.
10. The method of claim 1 , wherein the administration is to an eye of the subject.
11. The method of claim 1 , wherein the administration is intravitreal.
12. The method of claim 1 , wherein the administration is subcutaneous.
13. The method of claim 1 , wherein the administration is topical.
14. The method of claim 1 , wherein the subject is a human.
15. The method of claim 1 , wherein the therapeutically effective amount of the antibody is from about 0.25 mg to about 200 mg.
16. The method of claim 1 , wherein the therapeutically effective amount of the antibody is from about 1 mg/kg to about 10 mg/kg.
17. The method of claim 1 , wherein the therapeutically effective amount of the antibody is from about 1 mg to about 50 mg.
18. The method of claim 1 , wherein the antibody inhibits HPTP-β in the subject.
19. The method of claim 1 , wherein the antibody binds a first fibronectin type III (FN3) repeat of an extracellular domain of HPTP-β in the subject.
20. The method of claim 1 , wherein the condition is glaucoma.
21. The method of claim 1 , wherein the condition is proliferative retinopathy.
22. The method of claim 1 , wherein the administration is intravenous.
23. The method of claim 1 , wherein the sequence that is SEQ ID NO: 54; the sequence that is SEQ ID NO: 55; and the sequence that is SEQ ID NO: 56 are contained within a sequence that is any one of SEQ ID NOs: 9-12.
24. A method of treating an ocular condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody, the antibody comprising:
a) a heavy chain that comprises: a sequence that is SEQ ID NO: 54; a sequence that is SEQ ID NO: 55; and a sequence that is SEQ ID NO: 56; and
b) a light chain that comprises: a sequence that is SEQ ID NO: 57; a sequence that is SEQ ID NO: 58; and a sequence that is SEQ ID NO: 59, wherein the sequence that is SEQ ID NO: 57; the sequence that is SEQ ID NO: 58; and the sequence that is SEQ ID NO: 59 are contained within a sequence that is at least 83% identical to any one of SEQ ID NOs: 20-23,
wherein the antibody binds HPTP-β.
25. The method of claim 24 , wherein the condition is diabetic retinopathy.
26. The method of claim 24 , wherein the condition is neovascularization.
27. The method of claim 24 , wherein the condition is vascular leak.
28. The method of claim 24 , wherein the condition is increased intraocular pressure.
29. The method of claim 24 , wherein the condition is ocular edema.
30. The method of claim 24 , wherein the condition is diabetic macular edema.
31. The method of claim 24 , wherein the condition is ocular hypertension.
32. The method of claim 24 , wherein the condition is ocular inflammation.
33. The method of claim 24 , wherein the condition is glaucoma.
34. The method of claim 24 , wherein the condition is proliferative retinopathy.
35. The method of claim 24 , wherein the administration is to an eye of the subject.
36. The method of claim 24 , wherein the administration is intravitreal.
37. The method of claim 24 , wherein the administration is intravenous.
38. The method of claim 24 , wherein the administration is subcutaneous.
39. The method of claim 24 , wherein the administration is topical.
40. The method of claim 24 , wherein the subject is a human.
41. The method of claim 24 , wherein the therapeutically effective amount of the antibody is from about 0.25 mg to about 200 mg.
42. The method of claim 24 , wherein the therapeutically effective amount of the antibody is from about 1 mg/kg to about 10 mg/kg.
43. The method of claim 24 , wherein the therapeutically effective amount of the antibody is from about 1 mg to about 50 mg.
44. The method of claim 24 , wherein the antibody inhibits HPTP-β in the subject.
45. The method of claim 24 , wherein the antibody binds a first FN3 repeat of an extracellular domain of HPTP-β in the subject.
46. The method of claim 24 , wherein the sequence that is SEQ ID NO: 57; the sequence that is SEQ ID NO: 58; and the sequence that is SEQ ID NO: 59 are contained within a sequence that is any one of SEQ ID NOs: 20-23.