METHODS OF REDUCING PHOSPHATE ABSORPTION

• US 20100166760A1
• Filed: 10/23/2007
• Published: 07/01/2010
• Est. Priority Date: 10/25/2006
• Status: Active Grant

• Current Assignee: Cytochroma Inc. (Opko Health, Inc.), Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Cook, Mark, Helvig, Christian, Crawford, Keith, Petkovich, Martin, Hellestad, Erica
• Granted Patent: US 8,802,094 B2
• Time in Patent Office: Days
• US Class Current: 424/139.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

A method for reducing phosphate absorption in a human or non-human animal subject at risk of developing or having developed hyperphosphatemia is disclosed. The method includes the step of administering orally to the subject an anti-intestinal sodium phosphate cotransporter type 2B (Npt2B) antibody in an amount effective to reduce or maintain the serum phosphate concentration in the subject.

Claims

1. A method of reducing phosphate absorption in a human or non-human animal subject at risk of developing or having developed hyperphosphatemia, the method comprising the step of:

administering orally to the subject an IgY anti-intestinal sodium phosphate cotransporter type 2B (Npt2B) antibody that binds to Npt2B of SEQ ID NO;

1 in an amount effective to reduce or maintain the serum phosphate concentration in the subject.

2. The method of claim 1, wherein the subject is a human subject.

3. The method of claim 1, wherein the subject has a kidney disease.

4. The method of claim 3, wherein the kidney disease is selected from end stage renal disease, acute renal failure, chronic renal failure, polycystic kidney disease, chronic kidney disease, acute tubular necrosis, an infection that reduces kidney function, and a urinary tract obstruction.

5. The method of claim 1, wherein the subject is receiving a vitamin D compound.

6. The method of claim 1, wherein the antibody is obtained from an avian egg.

7. The method of claim 1, wherein the antibody is administered with a phosphate binder.

8. The method of claim 1, further comprising the steps of measuring the serum phosphate concentration after the anti-intestinal Npt2B antibody is administered and comparing the concentration to that before the anti-intestinal Npt2B antibody is administered.

9. A method of reducing phosphate absorption in a human or non-human animal subject at risk of developing or having developed hyperphosphatemia, the method comprising the step of:

administering orally to the subject an anti-intestinal sodium phosphate cotransporter type 2B (Npt2B) antibody that binds to an epitope within amino acids 234-362 of SEQ ID NO;

1 in an amount effective to reduce or maintain the serum phosphate concentration in the subject.

10. The method of claim 9, wherein the anti-intestinal Npt2B antibody binds to an epitope within amino acids 245-340 of SEQ ID NO:

1.

11. The method of claim 9, wherein the anti-intestinal Npt2B antibody binds to an epitope within amino acids 252-330 of SEQ ID NO:

1.

12. The method of claim 9, wherein the subject is a human subject.

13. The method of claim 9, wherein the subject has a kidney disease.

14. The method of claim 13, wherein the kidney disease is selected from end stage renal disease, acute renal failure, chronic renal failure, polycystic kidney disease, chronic kidney disease, acute tubular necrosis, an infection that reduces kidney function, and a urinary tract obstruction.

15. The method of claim 9, wherein the subject is receiving a vitamin D compound.

16. The method of claim 9, wherein the antibody is an IgY antibody.

17. The method of claim 9, wherein the antibody is administered with a phosphate binder.

18. The method of claim 9, further comprising the steps of measuring the serum phosphate concentration after the anti-intestinal Npt2B antibody is administered and comparing the concentration to that before the anti-intestinal Npt2B antibody is administered.

19. A method of reducing phosphate absorption in a human or non-human animal subject at risk of developing or having developed hyperphosphatemia, the method comprising the step of:

administering orally to the subject an anti-intestinal sodium phosphate cotransporter type 2B (Npt2B) antibody that binds to an epitope within amino acids 429-485 of SEQ ID NO;

1 in an amount effective to reduce or maintain the serum phosphate concentration in the subject.

20. The method of claim 19, wherein the anti-intestinal Npt2B antibody binds to an epitope within amino acids 445-480 of SEQ ID NO:

1.

21. The method of claim 19, wherein the anti-intestinal Npt2B antibody binds to an epitope within amino acids 455-474 of SEQ ID NO:

1.

22. The method of claim 19, wherein the subject is a human subject.

23. The method of claim 19, wherein the subject has a kidney disease.

24. The method of claim 23, wherein the kidney disease is selected from end stage renal disease, acute renal failure, chronic renal failure, polycystic kidney disease, chronic kidney disease, acute tubular necrosis, an infection that reduces kidney function, and a urinary tract obstruction.

25. The method of claim 19, wherein the subject is receiving a vitamin D compound.

26. The method of claim 19, wherein the antibody is an IgY antibody.

27. The method of claim 19, wherein the antibody is administered with a phosphate binder.

28. The method of claim 19, further comprising the steps of measuring the serum phosphate concentration after the anti-intestinal Npt2B antibody is administered and comparing the concentration to that before the anti-intestinal Npt2B antibody is administered.

29. A method of reducing side effects of vitamin D therapy in a human comprising the step of:

administering orally to the subject (a) a vitamin D compound and (b) an anti-intestinal sodium phosphate cotransporter type 2B (Npt2B) antibody that binds to Npt2B of SEQ ID NO;

1 in an amount effective to reduce hyperphosphatemia induced by vitamin D therapy.

30. The method of claim 29, wherein the subject has a kidney disease.

31. The method of claim 29, wherein the human has a vitamin D deficiency.

32. The method of claim 29, wherein the antibody is administered with a phosphate binder.

33. The method of claim 29, further comprising the steps of measuring the serum phosphate concentration after the anti-intestinal Npt2B antibody is administered and comparing the concentration to that before the anti-intestinal Npt2B antibody is administered.