Morphic forms of trilaciclib and methods of manufacture thereof

Patent metadata

Field	Value
Publication number	US-12168666-B2
Application number	US-202117236687-A
Country	US
Kind code	B2
Filing date	Apr 21, 2021
Priority date	Jun 15, 2020
Publication date	Dec 17, 2024
Grant date	Dec 17, 2024

Abstract

An advantageous isolated morphic form of trilaciclib which is 2′-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-7′,8′-dihydro-6′H-spiro[cyclohexane-1,9′-pyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyrimidin]-6′-one, for example in the form of a di-hydrochloride salt or a dihydrochloride, dihydrate.

First claim

We claim:

1. A crystalline compound of structure:

which is a dihydrochloride.

2. The crystalline compound of claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three 2theta values selected from 9.6±0.2°, 21.3±0.2°, 19.8±0.2°, 12.2±0.2°, 24.0±0.2°, 26.1±0.2°, 19.3±0.2°, 17.6±0.2°, and 28.6±0.2°.

3. The crystalline compound of claim 2 , wherein the XRPD pattern comprises at least four 2theta values selected from 9.6±0.2°, 21.3±0.2°, 19.8±0.2°, 12.2±0.2°, 24.0±0.2°, 26.1±0.2°, 19.3±0.2°, 17.6±0.2°, and 28.6±0.2°.

4. The crystalline compound of claim 2 , wherein the XRPD pattern comprises at least five 2theta values selected from 9.6±0.2°, 21.3±0.2°, 19.8±0.2°, 12.2±0.2°, 24.0±0.2°, 26.1±0.2°, 19.3±0.2°, 17.6±0.2°, and 28.6±0.2°.

5. The crystalline compound of claim 2 , wherein the XRPD pattern comprises at least six 2theta values selected from 9.6±0.2°, 21.3±0.2°, 19.8±0.2°, 12.2±0.2°, 24.0±0.2°, 26.1±0.2°, 19.3±0.2°, 17.6±0.2°, and 28.6±0.2°.

6. The crystalline compound of claim 2 , wherein the XRPD pattern comprises at least the 2theta value of 9.6±0.2°.

7. The crystalline compound of claim 2 , wherein the XRPD pattern comprises at least the 2theta values of 9.6±0.2°, 19.8±0.2°, and 21.3±0.2°.

8. A composition comprising the crystalline compound of claim 1 , mannitol and citric acid.

9. A pharmaceutical composition comprising the crystalline compound of claim 1 and a pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutically acceptable excipient comprises mannitol.

11. The pharmaceutical composition of claim 9 , wherein the pharmaceutically acceptable excipient comprises citric acid.

12. The pharmaceutical composition of claim 9 , wherein the pharmaceutically acceptable excipient comprises mannitol and citric acid.

13. The pharmaceutical composition of claim 9 comprising about 200-600 milligrams of the crystalline compound.

14. The pharmaceutical composition of claim 9 comprising about 300 milligrams of the crystalline compound.

15. The pharmaceutical composition of claim 9 comprising about 349 milligrams of the crystalline compound.

16. The pharmaceutical composition of claim 10 comprising about 250-350 mg of mannitol.

17. The pharmaceutical composition of claim 10 comprising about 300 mg of mannitol.

18. The pharmaceutical composition of claim 11 comprising about 50-100 mg of citric acid.

19. The pharmaceutical composition of claim 11 comprising about 76 mg of citric acid.

20. The pharmaceutical composition of claim 12 comprising about 250-350 mg of mannitol.

21. The pharmaceutical composition of claim 12 comprising about 300 mg of mannitol.

22. The pharmaceutical composition of claim 12 comprising about 50-100 mg of citric acid.

23. The pharmaceutical composition of claim 12 comprising about 76 mg of citric acid.

24. The pharmaceutical composition of claim 12 comprising about 300 mg of mannitol and about 76 mg of citric acid.

25. The pharmaceutical composition of claim 24 comprising about 300 milligrams of the crystalline compound.

26. The pharmaceutical composition of claim 12 comprising a dose of about 150 mg/m 2 to about 350 mg/m 2 of the crystalline compound.

27. The pharmaceutical composition of claim 12 comprising a dose of about 240 mg/m 2 of the crystalline compound.

Assignees

• G1 Therapeutics Inc

Inventors

• Schneider Stephen
• Smith Alexander
• White Hannah S
• Strum Jay Copeland
• Mazurek Jaroslaw

Classifications

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title