Antibodies that target human protein tyrosine phosphatase-beta (HPTP-beta) and methods of use thereof to treat ocular conditions
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. An antibody comprising:
a) a heavy chain that comprises a sequence that is at least 80% identical to SEQ ID NO: 30, wherein the heavy chain comprises:
i) a sequence that is at least 90% identical to SEQ ID NO: 54; a sequence that is SEQ ID NO: 55; and a sequence that is SEQ ID NO: 56;
ii) a sequence that is SEQ ID NO: 54; a sequence that is at least 94% identical to SEQ ID NO: 55; and a sequence that is SEQ ID NO: 56; or
iii) a sequence that is SEQ ID NO: 54; a sequence that is SEQ ID NO: 55; and a sequence that is at least 92% identical to SEQ ID NO: 56; and
b) a light chain that comprises a sequence that is at least 80% identical to SEQ ID NO: 34, wherein the light chain comprises:
i) a sequence that is at least 90% identical to SEQ ID NO: 57; a sequence that is SEQ ID NO: 58; and a sequence that is SEQ ID NO: 59;
ii) a sequence that is SEQ ID NO: 57; a sequence that is at least 85% identical to SEQ ID NO: 58; and a sequence that is SEQ ID NO: 59; or
iii) a sequence that is SEQ ID NO: 57; a sequence that is SEQ ID NO: 58; and a sequence that is at least 88% identical to SEQ ID NO: 59,
wherein the antibody binds human protein tyrosine phosphatase-beta (HPTP-β).
2. The antibody of claim 1 , wherein the heavy chain is at least 85% identical to SEQ ID NO: 30; and the light chain is at least 85% identical to SEQ ID NO: 34.
3. The antibody of claim 1 , wherein the heavy chain is at least 90% identical to SEQ ID NO: 30; and the light chain is at least 90% identical to SEQ ID NO: 34.
4. The antibody of claim 1 , wherein the heavy chain is at least 95% identical to SEQ ID NO: 30; and the light chain is at least 95% identical to SEQ ID NO: 34.
5. The antibody of claim 1 , wherein the heavy chain is SEQ ID NO: 30 and the light chain is SEQ ID NO: 34.
6. The antibody of claim 1 , wherein the antibody inhibits a tyrosine phosphatase.
7. The antibody of claim 1 , wherein the antibody inhibits (HPTP-β).
8. The antibody of claim 1 , wherein the antibody further inhibits vascular endothelial protein tyrosine phosphatase (VE-PTP).
9. The antibody of claim 1 , wherein the antibody activates tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2(Tie2).
10. The antibody of claim 1 , wherein the antibody activates Akt.
11. The antibody of claim 1 , wherein the antibody binds an extracellular domain of HPTP-β.
12. The antibody of claim 1 , wherein the antibody binds a first FN3 repeat of an extracellular domain of HPTP-β.
13. The antibody of claim 12 , wherein a binding affinity (K D ) of the antibody to the extracellular domain of HPTP-β is about 70 pM to about 70 nM.
14. The antibody of claim 1 , wherein:
a) the heavy chain 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) the light chain 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.
15. 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 at least 80% identical to SEQ ID NO: 30, wherein the heavy chain comprises:
i) a sequence that is at least 90% identical to SEQ ID NO: 54; a sequence that is SEQ ID NO: 55; and a sequence that is SEQ ID NO: 56;
ii) a sequence that is SEQ ID NO: 54; a sequence that is at least 94% identical to SEQ ID NO: 55; and a sequence that is SEQ ID NO: 56; or
iii) a sequence that is SEQ ID NO: 54; a sequence that is SEQ ID NO: 55; and a sequence that is at least 92% identical to SEQ ID NO: 56;and
b) a light chain that comprises a sequence that is at least 80% identical to SEQ ID NO: 34, wherein the light chain comprises:
i) a sequence that is at least 90% identical to SEQ ID NO: 57; a sequence that is SEQ ID NO: 58; and a sequence that is SEQ ID NO: 59;
ii) a sequence that is SEQ ID NO: 57; a sequence that is at least 85% identical to SEQ ID NO: 58; and a sequence that is SEQ ID NO: 59;or
iii) a sequence that is SEQ ID NO: 57; a sequence that is SEQ ID NO: 58; and a sequence that is at least 88% identical to SEQ ID NO: 59;
wherein the antibody binds HPTP-β.
16. The method of claim 15 , wherein the condition is diabetic retinopathy.
17. The method of claim 15 , wherein the condition is neovascularization.
18. The method of claim 15 , wherein the condition is vascular leak.
19. The method of claim 15 , wherein the condition is increased intraocular pressure.
20. The method of claim 15 , wherein the condition is ocular edema.
21. The method of claim 15 , wherein the condition is diabetic macular edema.
22. The method of claim 15 , wherein the condition is ocular hypertension.
23. The method of claim 15 , wherein the condition is ocular inflammation.
24. The method of claim 15 , wherein the administration is to an eye of the subject.
25. The method of claim 15 , wherein the administration is intravitreal.
26. The method of claim 15 , wherein the administration is subcutaneous.
27. The method of claim 15 , wherein the administration is topical.
28. The method of claim 15 , wherein the subject is a human.
29. The method of claim 15 , wherein the therapeutically-effective amount of the antibody is from about 0.25 mg to about 200 mg.
30. The method of claim 15 , wherein the therapeutically-effective amount of the antibody is from about 1 mg/kg to about 10 mg/kg.
31. The method of claim 15 , wherein the therapeutically-effective amount of the antibody is from about 1 mg to about 50 mg.
32. The method of claim 15 , wherein the therapeutically-effective amount of the antibody is from about 50 mg to about 200 mg.
33. The method of claim 15 , wherein the heavy chain is at least 85% identical to SEQ ID NO: 30; and the light chain is at least 85% identical to SEQ ID NO: 34.
34. The method of claim 15 , wherein the heavy chain is at least 90% identical to SEQ ID NO: 30; and the light chain is at least 90% identical to SEQ ID NO: 34.
35. The method of claim 15 , wherein the heavy chain is at least 95% identical to SEQ ID NO: 30; and the light chain is at least 95% identical to SEQ ID NO: 34.
36. The method of claim 15 , wherein the heavy chain is SEQ ID NO: 30 and the light chain is SEQ ID NO: 34.
37. The method of claim 15 , wherein the antibody inhibits a tyrosine phosphatase in the subject.
38. The method of claim 15 , wherein the antibody inhibits HPTP-β in the subject.
39. The method of claim 15 , wherein the antibody inhibits VE-PTP in the subject.
40. The method of claim 15 , wherein the antibody activates Tie2 in the subject.
41. The method of claim 15 , wherein the antibody activates Akt in the subject.
42. The method of claim 15 , wherein the antibody binds an extracellular domain of HPTP-β in the subject.
43. The method of claim 15 , wherein the antibody binds a first FN3 repeat of an extracellular domain of HPTP-β in the subject.
44. The method of claim 43 , wherein a binding affinity (K D ) of the antibody to the extracellular domain of HPTP-β is about 70 pM to about 70 nM.
45. The method of claim 15 , wherein:
a) the heavy chain 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) the light chain 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.