Claims for Patent: 11,123,363

Summary for Patent: 11,123,363

Title:	Potassium-binding agents for treating hypertension and hyperkalemia
Abstract:	The present invention generally relates to methods of treating hypertension (HTN) in patients in need thereof wherein the patient optionally further suffers from chronic kidney disease (CKD) or Type II diabetes mellitus (T2DM). The invention also relates to methods of treating hyperkalemia in a patient in need thereof, wherein the patient suffers from CKD, T2DM or HTN and are optionally being treated with an effective amount of a renin-angiotensin-aldosterone system (RAAS) agent. The invention also relates to methods of treating kidney disease in a patient in need thereof, wherein the patient is optionally being treated with an effective amount of a renin-angiotensin-aldosterone system (RAAS) agent. The methods can comprise administering an effective amount of a potassium-binding agent to the patient to lower the patient's blood pressure and/or increase or stabilize the patient's kidney function.
Inventor(s):	Klaerner; Gerrit (Los Gatos, CA), Berman; Lance (San Francisco, CA)
Assignee:	VIFOR (INTERNATIONAL) LTD. (St. Gallen, CH)
Application Number:	15/916,617
Patent Claims:	1. A method of treating hyperkalemia in a human patient in need thereof optionally being treated with an effective amount of a renin-angiotensin-aldosterone system (RAAS) agent, the method comprising: administering to the human patient sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer at a once daily dose of between 10 g and 40 g wherein the dose is calculated by determining the amount of calcium 2-fluoroacrylate-divinylbenzene-1,7-octadiene copolymer anion plus the amount of calcium counterion; wherein the human patient was hyperkalemic before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer; wherein the human patient was normokalemic after 4 weeks of treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer; and wherein the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer is prepared by slurrying cross-linked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer with a sorbitol solution. 2. The method of claim 1, further comprising observing an increase or stabilization of estimated glomerular filtration rate (eGFR) as compared to the patient's eGFR before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 3. The method of claim 1, further comprising observing a decrease in the patient's serum creatinine level as compared to the patient's serum creatinine level before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 4. The method of claim 1, further comprising observing an increase in the time to progression of end stage renal disease as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 5. The method of claim 1, further comprising observing an increase in survival as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 6. The method of claim 2, wherein the increase or stabilization of eGFR is maintained over more than 12 weeks during which the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer is administered to the patient daily. 7. The method of claim 2, wherein the increase or stabilization of eGFR is maintained over more than 24 weeks during which the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer is administered to the patient daily. 8. The method of claim 2, wherein the increase or stabilization of eGFR is maintained over 52 weeks or more during which the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer is administered to the patient daily. 9. The method of claim 8, wherein the patient's eGFR after treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer increased by at least 4 mL/min/1.73 m.sup.2 or more as compared to the patient's eGFR before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 10. The method of claim 1, wherein the patient's serum potassium level is decreased after 2 days or more of treatment as compared to the patient's serum potassium level before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer, and the decreased serum potassium level is maintained over the 52 weeks or more of treatment. 11. The method of claim 2, further comprising observing a decrease in the patient's serum creatinine level as compared to the patient's serum creatinine level before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 12. The method of claim 2, further comprising observing an increase in the time to progression of end stage renal disease as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 13. The method of claim 11, further comprising observing an increase in the time to progression of end stage renal disease as compared a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 14. The method of claim 2, further comprising observing an increase in survival as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 15. The method of claim 11, further comprising observing an increase in survival as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 16. The method of claim 12, further comprising observing an increase in survival as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 17. The method of claim 13, further comprising observing an increase in survival as compared to a patient in need of treatment for hyperkalemia wherein the patient has chronic kidney disease optionally treated with a RAAS agent but not treated with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 18. The method of claim 1, wherein the patient's albumin:creatinine ratio is stabilized after 3 months or more of treatment. 19. The method of claim 1, wherein the patient is being treated with a RAAS agent. 20. The method of claim 1, wherein the patient had a serum potassium level of greater than 5.0 mEq/L before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 21. The method of claim 1, wherein the patient had a serum potassium level of greater than or equal to 5.1 mEq/L before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 22. The method of claim 1, wherein the patient had a serum potassium level of greater than or equal to 5.5 mEq/L before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 23. The method of claim 20, wherein the patient had a serum potassium level of less than or equal to 5.0 mEq/L after 4 weeks of treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 24. The method of claim 1, wherein the patient had a serum potassium level of less than or equal to 5.0 mEq/L after 4 weeks of treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 25. A method of treating hyperkalemia in a human patient in need thereof optionally being treated with an effective amount of a renin-angiotensin-aldosterone system (RAAS) agent, the method comprising: administering to the human patient sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer; wherein the starting dose of sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer is 8.4 grams anion daily; wherein the human patient was hyperkalemic before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer; and wherein the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer is prepared by slurrying cross-linked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer with a sorbitol solution. 26. The method of claim 25, wherein the patient was normokalemic after 4 weeks of treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 27. The method of claim 25, wherein the patient had a serum potassium level of greater than 5.0 mEq/L before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 28. The method of claim 25, wherein the patient had a serum potassium level of greater than or equal to 5.1 mEq/L before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 29. The method of claim 25, wherein the patient had a serum potassium level of greater than or equal to 5.5 mEq/L before treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 30. The method of claim 25, wherein the patient had a serum potassium level of less than or equal to 5.0 mEq/L after 4 weeks of treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 31. The method of claim 29, wherein the patient had a serum potassium level of less than or equal to 5.0 mEq/L after 4 weeks of treatment with the sorbitol-loaded, crosslinked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer. 32. The method of claim 1, wherein cross-linked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer was slurried with 25 wt.% to 30% wt.% aqueous sorbitol solution at ambient temperature. 33. The method of claim 25, wherein cross-linked (calcium 2-fluoroacrylate)-divinylbenzene-1,7-octadiene copolymer was slurried with 25 wt.% to 30% wt.% aqueous sorbitol solution at ambient temperature.