Claims for Patent: 11,944,612

Summary for Patent: 11,944,612

Title:	Dosing regimens for 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde
Abstract:	Provided herein are methods for treating sickle cell disease, comprising administering to a subject 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)-methoxy)benzaldehyde (Compound 1), or a polymorph thereof, in certain dosing regimens.
Inventor(s):	Eleanor L. Ramos, Joshua Eli Lehrer-Graiwer, Athiwat Hutchaleelaha, Naveen Bejugam
Assignee:	Global Blood Therapeutics Inc
Application Number:	US17/881,874
Patent Claims:	1. A capsule dosage form comprising: (i) from about 65% to about 93% w/w of Compound 1; (ii) from about 2% to about 10% w/w a binder; wherein w/w is relative to the total weight of the formulation, excluding the weight of the capsule, and wherein the compound 1 is in a crystalline ansolvate form that is characterized by at least four X-ray powder diffraction peaks (Cu Kα radiation) at 13.37°, 14.37°, 19.95° and 23.92° 2θ, each peak is ±0.2° 2θ. 2. The capsule dosage form of claim 1, further comprising from about 2% to about 10% a disintegrant. 3. The capsule dosage form of claim 1, further comprising from about 2% to about 10% a disintegrant and about 2% to 35% a filler. 4. A capsule dosage form comprising: (i) from about 65% to about 86% w/w of Compound 1; (ii) from about 2% to about 6% w/w a binder; (iii) from about 6% to about 25% w/w a filler; (iv) from about 2% to 6% w/w a disintegrant; and (iv) from about 0.5% to about 1.5% w/w a lubricant; wherein w/w is relative to the total weight of the formulation, excluding the weight of the capsule; and wherein the compound 1 is in a crystalline ansolvate form that is characterized by at least four X-ray powder diffraction peaks (Cu Kα radiation) at 13.37°, 14.37°, 19.95° and 23.92° 2θ, each peak is ±0.2° 2θ. 5. The capsule dosage form of claim 4 comprising: (i) from about 65% to about 86% w/w of the crystalline ansolvate form compound 1; (ii) from about 2% to about 6% w/w a binder; (iii) from about 3.5% to about 25% w/w an insoluble filler, or 2.5% to 25% w/w of soluble filler, or 2.5% to 25% of a combination of soluble or insoluble filler; (iv) from about 2% to 6% w/w a disintegrant; and (iv) from about 0.5% to about 1.5% w/w a lubricant. 6. The capsule dosage form of claim 5 comprising: (i) about 86% w/w of the crystalline ansolvate form compound; (ii) about 4% w/w a binder; (iii) about 3.5% w/w an insoluble filler and 2.5% w/w of soluble filler; (iv) about 3.5% w/w a disintegrant; and (iv) about 0.5% w/w a lubricant. 7. The capsule dosage form of claim 6 comprising: (i) 85.71% w/w of the crystalline ansolvate form compound; (ii) 4% w/w a binder; (iii) 3.64% w/w an insoluble filler and 2.65% w/w of soluble filler; (iv) 2.65% w/w a disintegrant; and (iv) 0.5% w/w a lubricant. 8. The capsule dosage form of claim 6 wherein: the compound 1 is in a crystalline ansolvate form characterized by at least four X-ray powder diffraction peaks (Cu Kα radiation) at 13.37°, 14.37°, 19.950 and 23.92° 2θ, each peak is ±0.2° 2θ, the binder is hypromellose; the insoluble filler is microcrystalline cellulose; the soluble filler is lactose monohydrate; the disintregrant is croscarmellose sodium; and the lubricant is magnesium stearate. 9. The capsule dosage form of claim 8, wherein the capsule contains 300 mg+/−5% of the crystalline ansolvate form compound; wherein the crystalline ansolvate form of compound 1 is substantially free of Form I and/or N; wherein Form I is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 12.820, 15.740, 16.030, 16.630, 17.60°, 25.14°, 25.820 and 26.44020 (each X0.2 020); and wherein Form N is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 11.650, 11.850, 12.080, 16.700, 19.650 and 23.48020 (each ±0.2 020). 10. A method for treating sickle cell disease in a patient comprising administering to the patient Compound 1: wherein Compound 1 is administered in a dose of about 500 mg/day to about 1500 mg/day; and wherein the compound 1 is in a crystalline ansolvate form that is characterized by at least four X-ray powder diffraction peaks (Cu Kα radiation) at 13.37°, 14.37°, 19.95° and 23.92° 2θ, each peak is ±0.2° 2θ. 11. The method of claim 10, wherein the crystalline ansolvate form compound 1 is administered in a dose of from about 600 mg/day to about 900 mg/day. 12. The method of claim 10, wherein the crystalline ansolvate form compound 1 is administered in a dose of about 600 mg/day. 13. The method of claim 10, wherein the crystalline ansolvate form compound 1 is administered in a dose of about 900 mg/day, or about 1200 mg/day, or about 1500 mg/day. 14. The method of claim 10, wherein the crystalline ansolvate form compound 1 is administered in a dose of 600 mg/day. 15. The method of claim 10, wherein the crystalline ansolvate form compound 1 is administered in a dose of 900 mg/day, 1200 mg/day or 1500 mg/day. 16. The method of claim 10, wherein the crystalline ansolvate form compound 1 is administered once daily. 17. The method of claim 14, wherein the crystalline ansolvate form compound 1 is administered once daily. 18. The method of claim 15, wherein the crystalline ansolvate form compound 1 is administered once daily. 19. The method of claim 10, wherein the crystalline ansolvate form of Compound 1 is substantially free of Form I and/or Form N; wherein Form I is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 12.820, 15.740, 16.030, 16.630, 17.600, 25.140, 25.820 and 26.44020 (each ±0.2 020); and wherein Form N is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 11.65°, 11.850, 12.080, 16.700, 19.65″ and 23.48° 20 (each ±0.2 20). 20. The method of claim 14, wherein the compound 1 is a crystalline ansolvate form that characterized by at least four X-ray powder diffraction peaks (Cu Ka radiation) at 13.370, 14.370, 19.950, and 23.92° 2θ, (each peak is ±0.2° 2θ). 21. The method of claim 20, wherein the crystalline ansolvate form of Compound 1 is substantially free of Form I and/or Form N; wherein Form I is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 12.820, 15.740, 16.03°, 16.630, 17.600, 25.140, 25.820 and 26.44020 (each 0.2 020); and wherein Form N is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 11.650, 11.85°, 12.08°, 16.700, 19.650 and 23.48020 (each ±0.2 020). 22. The method of claim 15, wherein the compound 1 is a crystalline ansolvate form that is characterized by at least four X-ray powder diffraction peaks (Cu Ka radiation) at 13.370, 14.370, 19.950, and 23.92° 2θ, (each peak is ±0.2° 2θ). 23. The method of claim 22, wherein the crystalline ansolvate form of Compound 1 is substantially free of Form I and/or Form N; wherein Form I is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 12.820, 15.740, 16.03°, 16.630, 17.600, 25.140, 25.820 and 26.44020 (each ±0.2 020); and wherein Form N is characterized by at least three X-ray powder diffraction peaks (Cu Ka radiation) selected from 11.650, 11.850, 12.080, 16.700, 19.650 and 23.48020 (each ±0.2 020).