Granted Patent B2

US 12,642,815 · App. 17/878,192 · Granted Jun 2, 2026

Inventors: Gerrit Klaerner (Hillsborough, CA); Eric F. Connor (Los Gatos, CA); Randi K. Gbur (Brisbane, CA); Matthew J. Kade (Berkeley, CA); Paul H. Kierstead (Oakland, CA); Jerry M. Buysse (Los Altos, CA); Michael J. Cope (Berkeley, CA); Kalpesh N. Biyani (Dublin, CA); Son H. Nguyen (Milpitas, CA); Scott M. Tabakman (Palo Alto, CA)

Assignee: Renibus Therapeutics, Inc.

A61K31/785A61K9/0053A61K9/14A61K33/00A61P3/12A61P13/12A61P43/00C08F8/02C08F226/02C08F226/04

Abstract

Claims (18)

1 . A method of treating an individual afflicted with chronic kidney disease (CKD) and metabolic acidosis characterized by a baseline serum bicarbonate value of less than 22 mEq/l, the method comprising oral administration of a pharmaceutical composition to increase the individual's serum bicarbonate levels wherein:

(i) the pharmaceutical composition binds HCl in the individual's digestive system when given orally;

(ii) the pharmaceutical composition increases the serum bicarbonate level by at least 3 mEq/I in a placebo controlled study, said increase being the difference between the cohort average serum bicarbonate level in a first cohort at the end of the study, relative to the cohort average serum bicarbonate level in a second cohort at the end of the study, wherein the first cohort's subjects receive the pharmaceutical composition and the second cohort's subjects receive a placebo, wherein the first and second cohorts each comprise at least 25 subjects, each cohort is prescribed the same diet during the study and the study lasts at least two weeks; and

(iii) the pharmaceutical composition comprise a crosslinked amine polymer that is a copolymer comprising the residues of (1) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof.

2 . The method of claim 1 , wherein the oral administration is as frequent as at least weekly, is as frequent as at least semi-weekly, or is as frequent as at least daily within the treatment period.

3 . The method of claim 1 , wherein the metabolic acidosis is characterized by a baseline serum bicarbonate value of less than 18 mEq/l.

4 . The method of claim 1 , wherein the method increases the serum bicarbonate value from the baseline serum bicarbonate value to an increased serum bicarbonate value of at least 22 mEq/l.

5 . The method of claim 1 , wherein the clinically significant increase is achieved within a treatment period of less than one month, 25 days, or 3 weeks.

6 . The method of claim 1 , wherein the individual's serum bicarbonate value returns to the baseline value ±2 mEq/I within 1 month, 3 weeks or 2 weeks of the cessation of treatment.

7 . The method of claim 1 , wherein the baseline serum bicarbonate value is the mean value of at least two serum bicarbonate concentrations for serum samples drawn on different days.

8 . The method of claim 2 , wherein the daily dose has the capacity to remove at least 7.5 mEq of HCl as it transits the digestive system.

9 . The method of claim 2 , wherein the daily dose is less than 100 g/day, 30 g/day or 10 g/day.

10 . The method of claim 1 , wherein the individual is treated for at least several months.

11 . The method of claim 1 , wherein the crosslinked amine polymer has a theoretical binding capacity for HCl in the range of 2 to 25 mEq/g.

12 . The method of claim 1 , wherein the crosslinked amine polymer is characterized by a chloride ion binding capacity of at least 1 mEq/g, 1.5 mEq/g, 2 mEq/g, 2.5 mEq/g, 3 mEq/g, 3.5 mEq/g, 4 mEq/g, 4.5 mEq/g, 5 mEq/g, 5.5 mEq/g, or 6 mEq/g, in a SIB assay.

13 . The method of claim 1 , wherein the crosslinked amine polymer is characterized by a ratio of an amount of bound chloride to bound phosphate in a SIB assay that is at least 0.3:1, 0.5:1, or at least 1:1, respectively.

14 . The method of claim 1 , wherein the crosslinked amine polymer is prepared in two steps, (i) the first step comprising a concurrent polymerization and crosslinking reaction between (a) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof, to produce a preformed crosslinked amine polymer in which the crosslinks are primarily carbon-carbon crosslinks, and a second step in which the preformed amine polymer is further crosslinked in a substitution reaction in which a carbon-nitrogen bond is formed.

15 . The method of claim 1 , wherein the pharmaceutical composition comprises a crosslinked amine polymer prepared in two steps, (i) the first step comprising a concurrent polymerization and crosslinking reaction between (a) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof to produce a preformed amine polymer, and (ii) a second step in which the preformed amine polymer is further crosslinked in a substitution reaction with dichlorethane.

Assignments (3)

Continuity (6)

References Cited (324)