Crystalline forms of tenofovir alafenamide

Patent metadata

Field	Value
Publication number	US-10287307-B2
Application number	US-201815882784-A
Country	US
Kind code	B2
Filing date	Jan 29, 2018
Priority date	Jan 31, 2017
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The present invention relates to novel crystalline forms of salts and/or co-crystals of tenofovir alafenamide, the pharmaceutical formulations, and the therapeutic uses thereof in treating viral infections.

First claim

What is claimed:

1. Crystalline Tenofovir Alafenamide Sebacate Form I, characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 5.3°, 6.6°, 9.4°, 9.6°, and 19.8° 2-θ±0.2° 2-θ.

2. The crystalline form of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 14.8°, 15.7°, 18.7°, 19.3°, and 22.1° 2-θ±0.2° 2-θ.

3. The crystalline form of claim 2 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 11.7°, 12.6°, 20.9°, 23.4°, 23.8°, 26.2°, 28.2°, and 29.0° 2-θ±0.2° 2-θ.

4. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern as set forth in FIG. 5 .

5. The crystalline form of claim 1 , characterized by a differential scanning calorimetry (DSC) pattern as set forth in FIG. 6 .

6. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline Tenofovir Alafenamide Sebacate of claim 1 and a pharmaceutically acceptable excipient.

7. The pharmaceutical composition of claim 6 , further comprising one to three additional therapeutic agents.

8. The pharmaceutical composition of claim 7 , wherein the additional therapeutic agents are each active against HIV.

9. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is in a unit dosage form.

10. The pharmaceutical composition of claim 9 , wherein the unit dosage form is a subcutaneous injection.

11. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an injection.

12. The pharmaceutical composition of claim 9 , wherein the unit dosage form is an intramuscular injection.

13. The pharmaceutical composition of claim 9 , wherein the crystalline Tenofovir Alafenamide Sebacate is in a suspension.

14. A method for treating a viral infection in a human, the method comprising administering to a human in need thereof a therapeutically effective amount of the crystalline Tenofovir Alafenamide Sebacate of claim 1 .

15. The method of claim 14 wherein the viral infection is caused by HIV.

16. The method of claim 14 , wherein the crystalline Tenofovir Alafenamide Sebacate is administered by injection.

17. The method of claim 14 , wherein the crystalline Tenofovir Alafenamide Sebacate is administered by intramuscular injection.

18. The method of claim 14 , wherein the crystalline Tenofovir Alafenamide Sebacate is administered by subcutaneous injection.

19. The method of claim 18 , wherein the crystalline Tenofovir Alafenamide Sebacate is in a suspension.

20. The method of claim 15 , wherein the crystalline Tenofovir Alafenamide Sebacate is in a long-acting formulation.

21. The method of claim 20 , wherein the long-acting formulation is active for at least 30 days.

22. The method of claim 21 , wherein the long-acting formulation maintains a concentration minimum (Cmin) above the efficacious level for HIV treatment.

Assignees

• Gilead Sciences Inc

Inventors

• Lai Chiajen
• Shi Bing
• Strickley Robert G

Classifications

• A61P31/18

  for HIV · CPC title

• A61P31/20

  for DNA viruses · CPC title

• C07F9/65616 Primary

  containing the ring system [IMAGE cpc-sch-C07F-1006.gif] having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title