IP Library › Granted Patent US 12,491,160
Granted Patent B2
US 12,491,160 · App. 17/906,585 · Granted Dec 9, 2025

Formulations of a farnesoid X receptor agonist

Inventors: Nicholas D. Smith (San Diego, CA); Robert Mansfield (San Diego, CA)
Assignee: ELI LILLY AND COMPANY
A61K9/1635A61K9/1652A61K9/2009A61K9/2013A61K9/2018A61K9/2027A61K9/2054A61K31/4439
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Quick Facts
Patent No.
US 12,491,160
App. No.
17/906,585
Granted
Dec 9, 2025
Kind
B2
Abstract

Described herein are pharmaceutical formulations of a farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, and methods of using such pharmaceutical formulations in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.

Claims (20)

1 . A spray-dried solid dispersion, comprising: (a) 4-((4-(1-(tert-butyl)-1H-pyrazol -4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, and (b) a pharmaceutically acceptable polymer; wherein 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate is dispersed in a polymer matrix formed from the pharmaceutically acceptable polymer.

2 . The spray-dried solid dispersion of claim 1 , wherein the pharmaceutically acceptable polymer is selected from PVP/VA 64, PVP 30, HPMCAS-L, HPMCAS-M, HPMCAS-H, HPMC E15,HPMC E3, HPMC E5, and HPMCP-HP55.

3 . The spray-dried solid dispersion of claim 2 , wherein the pharmaceutically acceptable polymer is selected from PVP/VA 64 and HPMCAS-M.

4 . The spray-dried solid dispersion of claim 3 , wherein the pharmaceutically acceptable polymer is PVP/VA 64.

5 . The spray-dried solid dispersion of claim 3 , wherein the pharmaceutically acceptable polymer is HPMCAS-M.

6 . The spray-dried solid dispersion of claim 1 , wherein the weight ratio of 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine -trans-1-carboxylate to the pharmaceutically acceptable polymer is from 9:1 to 1:9.

7 . The spray-dried solid dispersion of claim 6 , wherein the weight ratio of 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine -trans-1-carboxylate to the pharmaceutically acceptable polymer is from 3:1 to 1:3.

8 . The spray-dried solid dispersion of claim 7 , wherein the weight ratio of 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine -trans-1-carboxylate to the pharmaceutically acceptable polymer is about 2:1, about 1.5:1, or about 1:1.

9 . The spray-dried solid dispersion of claim 1 , further comprising a non-aqueous solvent.

10 . The spray-dried solid dispersion of claim 9 , wherein the non-aqueous solvent is selected from the group consisting of tert-butanol, n-propanol, n-butanol, isopropanol, ethanol, methanol, acetone, ethyl acetate, dimethyl carbonate, acetonitrile, dichloromethane, methyl ethyl ketone, methyl isobutyl ketone, 1-pentanol, methyl acetate, carbon tetrachloride, dimethyl sulfoxide, hexafluoroacetone, chlorobutanol, dimethyl sulfone, acetic acid, cyclohexane, and mixtures thereof.

11 . The spray-dried solid dispersion of claim 10 , wherein the non-aqueous solvent is a mixture of dichloromethane and methanol.

12 . A pharmaceutical formulation comprising a spray-dried solid dispersion of claim 1 and optionally one or more pharmaceutical acceptable ingredients selected from the group consisting of one or more diluents, one or more disintegrants, one or more binders, one or more lubricants, one or more glidants, and one or more surfactants.

13 . The pharmaceutical formulation of claim 12 , wherein the one or more pharmaceutical acceptable ingredients are selected from the group consisting of microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, colloidal silicon dioxide, mannitol, crospovidone, and sodium stearyl fumarate.

14 . The pharmaceutical formulation of claim 13 , wherein the one or more pharmaceutical acceptable ingredients are selected from the group consisting of microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and colloidal silicon dioxide.

15 . The pharmaceutical formulation of claim 12 , wherein the pharmaceutical formulation is in tablet form.

16 . The pharmaceutical formulation of claim 15 , wherein the tablet comprises about 1% by weight to about 30% by weight of the spray-dried solid dispersion.

17 . The pharmaceutical formulation of claim 15 , wherein the tablet comprises about 5% by weight to about 25% by weight of the spray-dried solid dispersion.

18 . The pharmaceutical formulation of claim 15 , wherein the tablet comprises about 1% by weight to about 20% by weight of 4-((4-(1-(tert-butyl)-1H-pyrazol -4-yl) pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate.

19 . The pharmaceutical formulation of claim 15 , wherein the tablet comprises about 1 mg, about 5 mg, about 12 mg, or about 25 mg of 4-((4-(1-(tert-butyl)-1H -pyrazol-4-yl) pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate.

20 . A method of treating or preventing a gastrointestinal disease or condition in a mammal, comprising administering to the mammal a spray-dried solid dispersion of claim 1 .

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2025
From: ORGANOVO, INC.
To: ELI LILLY AND COMPANY
Reel/Frame 070892/0218 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 14, 2023
From: SMITH, NICHOLAS D.; MANSFIELD, ROBERT
To: METACRINE, INC.
Reel/Frame 064263/0821 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2023
From: METACRINE, INC.
To: ORGANOVO, INC.
Reel/Frame 063355/0402 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2023
From: METACRINE, INC.
To: ORGANOVO, INC.
Reel/Frame 063357/0508 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2023
From: SMITH, NICHOLAS D.; MANSFIELD, ROBERT
To: METACRINE, INC.
Reel/Frame 062347/0083 →
Continuity (2)
Provisional Application 62991216 · Mar 18, 2020
Related Publication 20230120914A1 · Apr 20, 2023
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