Granted Patent
B2
US 12,398,087 · App. 18/657,105 · Granted Aug 26, 2025
Methods of making bempedoic acid and compositions of the same
Inventors:
Richard Copp (Pinckney, MI); Mohamed Abdelnasser (New City, NY); Christopher M. Cimarusti (Clementon, NJ); Jonathan Lane (Longmont, CO); Michael Barkman (Louisville, CO); Rasidul Amin (Cary, NC); Arthur John Cooper (Mentor, OH); Damodaragounder Gopal (Highland Heights, OH); Philipp Selig (Linz, AT)
Assignee:
Esperion Therapeutics, Inc.
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Abstract
The invention provides methods of preparing 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid and methods of making a pharmaceutical material comprising a purified amount of 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid. Also provided are compositions and pharmaceutical materials including a purified amount of 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid as well as methods of treating various diseases and conditions using the compositions and pharmaceutical materials.
Claims (30)
1. A pharmaceutical material comprising a compound of formula (V):
wherein the pharmaceutical material comprises the compound of formula (V) in an amount greater than 98% by weight based on the total weight of the pharmaceutical material and the pharmaceutical material comprises 0.001% to 0.15% of a compound of formula (VI):
or a pharmaceutically acceptable salt thereof, based on the total weight of the pharmaceutical material.
2. The pharmaceutical material of claim 1 , wherein the compound of formula (V) is a crystalline form of the compound of formula (V), which exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.4±0.2, 17.9±0.2, 18.8±0.2, 19.5±0.2, and 20.7±0.2.
3. The pharmaceutical material of claim 2 , wherein the crystalline form of the compound of formula (V) is characterized by an X-ray powder diffraction pattern substantially the same as shown in FIG. 4 .
4. The pharmaceutical material of claim 2 , wherein the crystalline form of the compound of formula (V) has a melting point onset as determined by differential scanning calorimetry in the range of from 90° C. to 94° C.
5. The pharmaceutical material of claim 2 , wherein the pharmaceutical material comprises the compound of formula (V) in an amount greater than 99.5% by weight based on the total weight of the pharmaceutical material.
6. The pharmaceutical material of claim 2 , wherein the pharmaceutical material comprises the compound of formula (V) in an amount greater than 99.7% by weight based on the total weight of the pharmaceutical material.
7. The pharmaceutical material claim 2 , wherein the pharmaceutical material comprises the compound of formula (V) in an amount greater than 99.9% by weight based on the total weight of the pharmaceutical material.
8. A pharmaceutical material comprising the compound of formula (V):
in an amount of from about 98% to about 102% by weight based on the total weight of the pharmaceutical material, as determined by a high performance liquid chromatography (HPLC) assay, and less than or equal to 0.15% of a compound of formula (VI):
or a pharmaceutically acceptable salt thereof, based on the total weight of the pharmaceutical material,
wherein the total batch weight of the pharmaceutical material is at least 100 kg.
9. The pharmaceutical material of claim 8 , wherein the HPLC assay uses a C18 column (4.6 mm i.d.×150 mm, 2.5 μm) at a temperature of about 40° C., with isocratic elution of a mobile phase comprising about 0.05% phosphoric acid in water/acetonitrile (about 50:50) at a flow rate of about 1.2 mL/minute, and detection at 215 nm, wherein the retention time of the compound of formula (V) is about 4.6 minutes.
10. The pharmaceutical material of claim 1 , further comprising 0.001% to 0.15% of a compound of formula (VIII):
or a pharmaceutically acceptable salt thereof, based on the total weight of the pharmaceutical material.
11. A pharmaceutical formulation comprising:
a pharmaceutical material comprising:
the compound of formula (V):
and
a compound of formula (VI):
or a pharmaceutically acceptable salt thereof, wherein the compound of formula (VI) is present in an amount between 0.001% to 0.15% based on the total weight of the pharmaceutical material; and
a pharmaceutically acceptable excipient,
wherein the pharmaceutical formulation is prepared using a crystalline form of the compound of formula (V).
12. The pharmaceutical formulation of claim 11 , wherein the compound of formula (V) is present in a therapeutically effective amount.
13. The pharmaceutical formulation of claim 11 , wherein the compound of formula (V) is present in the pharmaceutical material in an amount greater than 98% by weight based on the total weight of the pharmaceutical material.
14. The pharmaceutical formulation of claim 11 , wherein the compound of formula (V) is present in the pharmaceutical material in an amount greater than 99% by weight based on the total weight of the pharmaceutical material.
15. The pharmaceutical formulation of claim 11 , wherein the crystalline form of the compound of formula (V) exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.4±0.2, 17.9±0.2, 18.8±0.2, 19.5±0.2, and 20.7±0.2.
16. The pharmaceutical formulation of claim 11 , wherein the pharmaceutical formulation is formulated for administration as an oral dosage form.
17. The pharmaceutical formulation of claim 16 , wherein the oral dosage form is a tablet.
Assignments (11)
RELEASE OF SECURITY INTEREST
Recorded Jul 14, 2026
From: GLAS AMERICAS LLC
To: ESPERION THERAPEUTICS INC.
Reel/Frame 075267/0816 →
PATENT SECURITY AGREEMENT
Recorded Jul 13, 2026
From: ESPERION THERAPEUTICS, INC.; RESQ PHARMACEUTICALS LLC
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 075952/0812 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: SELIG, PHILIPP
To: PATHEON AUSTRIA GMBH & CO KG
Reel/Frame 070307/0139 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: PATHEON AUSTRIA GMBH & CO KG
To: ESPERION THERAPEUTICS, INC.
Reel/Frame 070307/0171 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: CORDEN PHARMA COLORADO, INC.
To: ESPERION THERAPEUTICS, INC.
Reel/Frame 070307/0561 →
EMPLOYEE NON-COMPETITION, NON-SOLICITATION, CONFIDENTIALITY AND ASSIGNMENT AGREEMENT
Recorded Feb 24, 2025
From: ABDELNASSER, MOHAMED
To: ESPERION THERAPEUTICS, INC.
Reel/Frame 070306/0567 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: COOPER, ARTHUR JOHN; GOPAL, DAMODARAGOUNDER
To: OLON RICERCA BIOSCIENCE LLC
Reel/Frame 070307/0573 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: LANE, JONATHAN; BARKMAN, MICHAEL; AMIN, RASIDUL; FRANK, MICHELLE
To: CORDEN PHARMA COLORADO, INC.
Reel/Frame 070312/0339 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: OLON RICERCA BIOSCIENCE LLC
To: ESPERION THERAPEUTICS, INC.
Reel/Frame 070307/0567 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 24, 2025
From: COPP, RICHARD; CIMARUSTI, CHRISTOPHER M.
To: ESPERION THERAPEUTICS, INC.
Reel/Frame 070307/0132 →
SECURITY INTEREST
Recorded Dec 13, 2024
From: ESPERION THERAPEUTICS, INC.
To: GLAS AMERICAS LLC
Reel/Frame 069582/0756 →
Continuity (5)
Continuation
PCTUS2020038622
· Jun 19, 2020
Provisional Application
62864873
· Jun 21, 2019
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