Crystalline forms of tenofovir alafenamide

Patent metadata

Field	Value
Publication number	US-11440928-B2
Application number	US-201916360763-A
Country	US
Kind code	B2
Filing date	Mar 21, 2019
Priority date	Jan 31, 2017
Publication date	Sep 13, 2022
Grant date	Sep 13, 2022

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 is:

1. A crystalline form of Tenofovir Alafenamide Hemipamoate, wherein the crystalline form is crystalline Tenofovir Alafenamide Hemipamoate Form I, characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 7.4°, 8.4°, 10.6°, 14.8°, and 22.3°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 17.4°, 19.0°, 20.1°, 23.8°, and 25.7° 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 11.2°, 13.1°, 13.8°, 15.8°, 21.0°, and 28.8° 2-θ±0.2° 2-θ.

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

5. The crystalline form of claim 1 , characterized by differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 2 .

6. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline Tenofovir Alafenamide Hemipamoate Form I 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. A method for treating a virus infection in a human, the method comprising administering to a human in need thereof a therapeutically effective amount of the crystalline Tenofovir Alafenamide Hemipamoate Form I of claim 1 .

12. The method for treating a virus infection in a human of claim 11 , wherein the virus infection is caused by HIV.

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

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

15. The pharmaceutical composition of claim 9 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is in a suspension.

16. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is administered by injection.

17. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is administered by intramuscular injection.

18. The method of claim 11 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I is administered by subcutaneous injection.

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

20. The method of claim 12 , wherein the crystalline Tenofovir Alafenamide Hemipamoate Form I 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

• 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

• A61P31/18

  for HIV · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P31/20

  for DNA viruses · CPC title