Granted Patent
B2
US 12,325,706 · App. 17/486,421 · Granted Jun 10, 2025
Polymorphic form of sepiapterin
Inventors:
Hiroshi Yoshino (Narashino, JP); Taichi Komoda (Narashino, JP); Yuichi Shiro (Narashino, JP); Shunichi Murata (Narashino, JP); Takayoshi Matsumoto (Narashino, JP); Kaito Kishimoto (Narashino, JP); Daniel E. Levy (San Mateo, CA)
Assignee:
PTC Therapeutics MP, Inc.
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Abstract
Disclosed is a crystalline form of sepiapterin, a method of preparing the crystalline form, pharmaceutical compositions containing the crystalline form, and a method for treating patients with a disease associated with low intracellular BH4 levels or with dysfunction of various BH4 dependent metabolic pathways, which involves administering to the patient an effective amount of the crystalline form.
Claims (16)
1. Crystalline Form 1 of the hydrochloride salt of sepiapterin having peaks at diffraction angle 2θ (°) of 7.8°±0.5, 12.9°±0.5, and 26.2°±0.5 as measured by X-ray diffractometry by irradiation with Cu Kα X-rays.
2. Crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 peaks at diffraction angle 2θ (°) of 7.8°±0.5, 12.9°±0.5, 17.9°±0.5, 21.1°±0.5, 23.6±0.5, 25.2°±0.5, 26.2°±0.5, 27.6°±0.5, and 30.3°±0.5 as measured by X-ray diffractometry by irradiation with Cu Kα X-rays.
3. Crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 an X-Ray powder diffraction spectrum as shown in FIG. 10 .
4. Crystalline Form 1 of the hydrochloride salt of claim 1 having an endotherm at 225.9° C. in differential scanning calorimetry (DSC) profile.
5. A pharmaceutical composition comprising crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 and a pharmaceutically acceptable carrier.
6. The pharmaceutical composition of claim 5 , wherein the crystalline Form 1 of the hydrochloride salt of sepiapterin is present in an amount of at least 90 percent by weight of the composition.
7. The pharmaceutical composition of claim 5 , wherein the crystalline Form 1 of the hydrochloride salt of sepiapterin is formulated as particles less than 100 μm in size.
8. A method of preparing the crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 comprising:
(1) preparing a slurry of a first crystalline form of sepiapterin in acetone/water, adding hydrochloric acid, stirring the resulting suspension, and isolating the resulting solids; and
(2) dispersing the solids obtained in step (1) in acetone/water, adding hydrochloric acid, and isolating the resulting solids.
9. The method of claim 8 , wherein the solids resulting from step (2) are isolated by vacuum filtration.
10. The method of claim 8 , wherein the solids resulting from step (2) are dried in vacuum.
11. The method of claim 10 , wherein the solids are dried overnight at room temperature.
12. A method of treating primary tetrahydrobiopterin deficiency in a patient in need thereof, the method comprising administering to the patient an effective amount of the crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 .
13. A method of decreasing phenylalanine levels in a patient in need thereof, the method comprising administering to the patient an effective amount of the crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 .
14. A method of treating phenylketonuria in a patient in need thereof, the method comprising administering to the patient an effective amount of the crystalline Form 1 of the hydrochloride salt of sepiapterin of claim 1 .
Assignments (6)
TERMINATION AND RELEASE OF PATENT SECURITY AGREEMENT @ REEL 061584 AND FRAME 0377
Recorded Oct 23, 2023
From: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS ADMINISTRATIVE AGENT
To: PTC THERAPEUTICS MP, INC.
Reel/Frame 065321/0025 →
SECURITY INTEREST
Recorded Oct 28, 2022
From: PTC THERAPEUTICS MP, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 061584/0377 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 13, 2022
From: LEVY, DANIEL E.
To: CENSA PHARMACEUTICALS INC.
Reel/Frame 058641/0422 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 13, 2022
From: YOSHINO, HIROSHI; KOMODA, TAICHI; SHIRO, YUICHI; MURATA, SHUNICHI; MATSUMOTO, TAKAYOSHI; KISHIMOTO, KAITO
To: SHIRATORI PHARMACEUTICALS CO., LTD.
Reel/Frame 058641/0494 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 13, 2022
From: SHIRATORI PHARMACEUTICALS CO., LTD.
To: CENSA PHARMACEUTICALS INC.
Reel/Frame 058641/0505 →
CHANGE OF NAME
Recorded Jan 13, 2022
From: CENSA PHARMACEUTICALS INC.
To: PTC THERAPEUTICS MP, INC.
Reel/Frame 058733/0505 →
Continuity (3)
Continuation
16464916
Provisional Application
62427686
· Nov 29, 2016
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