Granted Patent
B2
US 12,269,829 · App. 18/236,095 · Granted Apr 8, 2025
Polymorphs of sepiapterin and salts thereof
Assignee:
PTC Therapeutics MP, Inc.
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Abstract
Disclosed are crystalline forms of sepiapterin free base selected from polymorphs A, B, C, D, E, F, and G, and combinations thereof, as well as crystalline polymorphs of salts of sepiapterin. Also disclosed are pharmaceutical compositions containing one or more such polymorphs and methods for preparing such polymorphs. Sepiapterin is useful in the treatment of a number diseases associated with low cellular levels of BH4, for example, phenylketonuria.
Claims (14)
1. A pharmaceutical composition comprising crystalline Form G of sepiapterin free base having peaks at diffraction angle 2θ(°) of 10.0°±0.5, 10.6°±0.5, and 25.7°±0.5° as measured by X-ray diffractometry by irradiation with Cu Kα X-rays or calculated from X-ray diffractometry and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1 , wherein the crystalline Form G is present in an amount of at least 90 percent by weight of the composition.
3. The pharmaceutical composition of claim 1 , wherein the crystalline Form G is formulated as particles less than 100 μm in size.
4. The pharmaceutical composition of claim 1 , wherein the crystalline Form G has peaks at diffraction angle 2θ (°) of 10.0°±0.5, 10.6°±0.5, 15.3° ±0.5, 24.4°±0.5, 25.7°±0.5, and 26.6°±0.5 as measured by X-ray diffractometry by irradiation with Cu Kα X-rays or calculated from X-ray diffractometry.
5. A method of treating a tetrahydrobiopterin (BH4)-related disorder in a subject in need thereof, the method comprising administering an effective amount of the pharmaceutical composition of claim 1 to the subject, wherein the BH4-related disorder is selected from primary BH4 deficiency and phenylketonuria.
6. The method of claim 5 , wherein the pharmaceutical composition is a liquid suspension.
7. A method of treating a tetrahydrobiopterin (BH4)-related disorder in a subject in need thereof, the method comprising administering an effective amount of crystalline Form G of sepiapterin free base having peaks at diffraction angle 2θ (°) of 10.0°±0.5, 10.6°±0.5, and 25.7°±0.5° as measured by X-ray diffractometry by irradiation with Cu Kα X-rays or calculated from X-ray diffractometry to the subject, wherein the BH4-related disorder is selected from primary BH4 deficiency and phenylketonuria.
8. The method of claim 7 , wherein the crystalline Form G of sepiapterin free base is administered as a liquid suspension.
9. The method of claim 7 , wherein the crystalline Form G has peaks at diffraction angle 2θ (°) of 10.0°±0.5, 10.6°±0.5, 15.3°±0.5, 24.4°±0.5, 25.7°±0.5, and 26.6°±0.5 as measured by X-ray diffractometry by irradiation with Cu Kα X-rays or calculated from X-ray diffractometry.
10. A method for decreasing phenylalanine levels in a subject in need thereof, the method comprising administering to the patient an effective amount of the pharmaceutical composition of claim 1 to the subject.
11. The method of claim 10 , wherein the pharmaceutical composition is a liquid suspension.
12. A method for decreasing phenylalanine levels in a subject in need thereof, the method comprising administering an effective amount of crystalline Form G of sepiapterin free base having peaks at diffraction angle 2θ (°) of 10.0°±0.5, 10.6°±0.5, and 25.7°±0.5° as measured by X-ray diffractometry by irradiation with Cu Kα X-rays or calculated from X-ray diffractometry to the subject.
13. The method of claim 12 , wherein the crystalline Form G of sepiapterin free base is administered as a liquid suspension.
14. The method of claim 12 , wherein the crystalline Form G has peaks at diffraction angle 2θ (°) of 10.0°±0.5, 10.6°±0.5, 15.3°±0.5, 24.4°±0.5, 25.7°±0.5, and 26.6°±0.5° as measured by X-ray diffractometry by irradiation with Cu Kα X-rays or calculated from X-ray diffractometry.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 20, 2023
From: LEVY, DANIEL E.
To: CENSA PHARMACEUTICALS INC.
Reel/Frame 064963/0163 →
CHANGE OF NAME
Recorded Sep 20, 2023
From: CENSA PHARMACEUTICALS INC.
To: PTC THERAPEUTICS, INC.
Reel/Frame 064963/0166 →
Continuity (5)
Continuation
16464771
Provisional Application
62546390
· Aug 16, 2017
Provisional Application
62427686
· Nov 29, 2016
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