Humanized monoclonal antibodies that target protein tyrosine phosphatase-beta (HPTP-β/VE-PTP)
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 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 antibody of claim 1 , wherein the antibody inhibits HPTP-β.
3. The antibody of claim 1 , wherein the antibody binds a first fibronectin type III (FN3) repeat of an extracellular domain of HPTP-β.
4. The antibody 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.
5. The antibody 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 at least 91% identical to SEQ ID NO: 9.
6. The antibody 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 at least 91% identical to SEQ ID NO: 10.
7. The antibody 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 at least 91% identical to SEQ ID NO: 11.
8. The antibody 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 at least 91% identical to SEQ ID NO: 12.
9. A pharmaceutical composition comprising a therapeutically effective amount of an 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; and
a pharmaceutically-acceptable carrier,
wherein the antibody binds HPTP-β.
10. The pharmaceutical composition of claim 9 , wherein the composition is formulated for ophthalmic administration.
11. The pharmaceutical composition of claim 9 , wherein the composition is formulated for intravitreal administration.
12. The pharmaceutical composition of claim 9 , wherein the composition is formulated for intravenous administration.
13. The pharmaceutical composition of claim 9 , wherein the composition is formulated for subcutaneous administration.
14. The pharmaceutical composition of claim 9 , wherein the composition is formulated for topical administration.
15. The pharmaceutical composition of claim 9 , wherein the therapeutically effective amount of the antibody is from about 0.25 mg to about 200 mg.
16. The pharmaceutical composition of claim 9 , wherein the therapeutically effective amount of the antibody is from about 1 mg to about 50 mg.
17. The pharmaceutical composition of claim 9 , wherein the therapeutically effective amount of the antibody is from about 1 mg/kg to about 10 mg/kg.
18. The pharmaceutical composition of claim 9 , 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.
19. An 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.
20. The antibody of claim 19 , wherein the antibody inhibits HPTP-β.
21. The antibody of claim 19 , wherein the antibody binds a first FN3 repeat of an extracellular domain of HPTP-β.
22. The antibody of claim 19 , 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.
23. The antibody of claim 19 , 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 SEQ ID NO: 20.
24. The antibody of claim 19 , 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 SEQ ID NO: 21.
25. The antibody of claim 19 , 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 SEQ ID NO: 22.
26. The antibody of claim 19 , 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 SEQ ID NO: 23.
27. A pharmaceutical composition comprising a therapeutically effective amount of an 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; and
a pharmaceutically-acceptable carrier,
wherein the antibody binds HPTP-β.
28. The pharmaceutical composition of claim 27 , wherein the composition is formulated for ophthalmic administration.
29. The pharmaceutical composition of claim 27 , wherein the composition is formulated for intravitreal administration.
30. The pharmaceutical composition of claim 27 , wherein the composition is formulated for intravenous administration.
31. The pharmaceutical composition of claim 27 , wherein the composition is formulated for subcutaneous administration.
32. The pharmaceutical composition of claim 27 , wherein the composition is formulated for topical administration.
33. The pharmaceutical composition of claim 27 , wherein the therapeutically effective amount of the antibody is from about 0.25 mg to about 200 mg.
34. The pharmaceutical composition of claim 27 , wherein the therapeutically effective amount of the antibody is from about 1 mg to about 50 mg.
35. The pharmaceutical composition of claim 27 , wherein the therapeutically effective amount of the antibody is from about 1 mg/kg to about 10 mg/kg.
36. The pharmaceutical composition of claim 27 , 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.