Granted Patent B2

US 12,516,015 · App. 17/516,591 · Granted Jan 6, 2026

Inventors: Keith Anderson (San Diego, CA); Jim Behling (Eagle River, WI); Christine Henderson Dougan (Glasgow, GB); Stephen William Watt (Tranent, GB); Peter Manini (Giubiasco, CH); Attilia Figini (Mendrisio, CH)

Assignee: Amalive Limited

C07C227/40A61K31/198A61K31/205C07C51/42C07C57/32C07C227/42C07C229/26

Abstract

Claims (24)

1 . An amorphous form of L-ornithine phenylacetate, prepared by a process comprising:

intermixing an L-ornithine salt, a benzoate salt and a solvent to form an intermediate solution;

intermixing phenylacetate with said intermediate solution; and

isolating a composition comprising at least 70% by weight of the amorphous form of L-ornithine phenylacetate, wherein the composition comprises at least about 0.1% by weight benzoate salt.

2 . The amorphous form of claim 1 , wherein the process further comprises removing at least a portion of a salt from said intermediate solution before intermixing the phenylacetate, wherein said salt is not an L-ornithine salt.

3 . The amorphous form of claim 2 , wherein the process further comprises adding hydrochloric acid before removing at least a portion of the salt.

4 . The amorphous form of claim 1 , wherein the composition comprises no more than 5% by weight benzoate salt.

5 . The amorphous form of claim 1 , wherein the L-ornithine salt is L-ornithine hydrochloride.

6 . The amorphous form of claim 5 , wherein the composition comprises no more than 0.1% by weight chloride.

7 . The amorphous form of claim 1 , wherein the benzoate salt is silver benzoate.

8 . The amorphous form of claim 7 , wherein the composition comprises at least 10 ppm silver.

9 . The amorphous form of claim 8 , wherein said composition comprises no more than 600 ppm silver.

10 . The amorphous form of claim 1 , wherein the phenylacetate is in an alkali metal salt.

11 . The amorphous form of claim 10 , wherein the alkali metal salt is sodium phenylacetate.

12 . The amorphous form of claim 11 , wherein said composition comprises no more than 100 ppm sodium.

13 . An amorphous form of L-ornithine phenylacetate, prepared by a process comprising:

increasing the pH value of a solution comprising an L-ornithine salt at least until an intermediate salt precipitates, wherein said intermediate salt is not an L-ornithine salt;

isolating the intermediate salt from said solution;

intermixing phenyl acetic acid with said solution; and

isolating a composition comprising an amorphous form of L-ornithine phenylacetate from said solution, wherein the L-ornithine phenylacetate salt is L-ornithine hydrochloride, and wherein the composition comprises at least about 0.005% by weight of chloride.

14 . The amorphous form of claim 13 , wherein the pH value is increased to at least 8.0.

15 . The amorphous form of claim 14 , wherein the pH value is increased to at least 9.0.

16 . The amorphous form of claim 13 , wherein increasing the pH value comprises adding a pH modifier selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium methoxide, potassium t-butoxide, sodium carbonate, calcium carbonate, dibutylamine, tryptamine, sodium hydride, calcium hydride, butyllithium, ethylmagnesium bromide, and combinations thereof.

17 . The amorphous form of claim 13 , wherein the composition comprises no more than 1% by weight of chloride.

Assignments (14)

Continuity (10)

References Cited (321)