SNS-595 and methods of using the same

1. A pharmaceutical composition comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and an acid, wherein the pH of the composition is 2-3.5 when measured in an aqueous solution in which the (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is present in an amount of 10 mg per mL.

2. The pharmaceutical composition of claim 1 , wherein the acid is selected from acetic acid, ascorbic acid, benzenesulfonic acid, ethanesulfonic acid, glycolic acid, hydrogen bromide, hydroxyethanesulfonic acid, lactic acid, maleic acid, propionic acid, succinic acid, sulfuric acid, trifluoroacetic acid and toluenesulfonic acid.

3. The pharmaceutical composition of claim 1 , wherein the pH of the composition is 2.3-2.7 when measured in aqueous solution.

4. The pharmaceutical composition of claim 1 further comprising a tonicity agent.

5. The pharmaceutical composition of claim 4 , wherein the tonicity agent is selected from the group consisting of amino acids, electrolytes, monosaccharides, disaccharides, and hexahydric alcohols.

6. The pharmaceutical composition of claim 5 , wherein the tonicity agent comprises sorbitol.

7. The pharmaceutical composition of claim 1 , wherein the pH of the composition is 2-3 when measured in aqueous solution.

8. The pharmaceutical composition of claim 1 , wherein the pH of the composition is about 2.5 when measured in aqueous solution.

9. The pharmaceutical composition of claim 1 that is formulated for intravenous administration.

10. The pharmaceutical composition of claim 1 further comprising water.

11. The pharmaceutical composition of claim 10 , wherein (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is present in an amount of 10 mg/mL.

12. The pharmaceutical composition of claim 10 further comprising sorbitol in an amount of 45 mg per ml.

13. The pharmaceutical composition of claim 10 , wherein the composition comprises about 100 mg of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and about 450 mg of sorbitol per 10 mL of the composition.

14. The pharmaceutical composition of claim 13 , wherein the pH of the composition is about 2.5 when measured in aqueous solution.

15. A powder consisting essentially of the composition of claim 1 .

16. A lyophilized powder consisting essentially of the composition of claim 1 .

17. A lyophilized powder consisting essentially of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid and an acid, wherein the lyophilized powder is suitable for reconstitution in sterile water to obtain a composition at pH 2-3.5 in which the (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid is present in an amount of 10 mg per mL.

18. An aqueous pharmaceutical composition comprising about 10 mg/mL of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, about 45 mg/mL of sorbitol, and an acid, wherein the pH of the composition is about 2.3 to about 2.7.

19. The aqueous pharmaceutical composition of claim 18 , wherein the pH of the composition is about 2-3.5.

20. The aqueous pharmaceutical composition of claim 19 , wherein the pH of the composition is about 2.3-2.7.

21. The aqueous pharmaceutical composition of claim 20 , wherein the pH of the composition is about 2.5.

22. A product formed by a process of contacting about 100 mg of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, about 450 mg of sorbitol and an acid in 10 mL aqueous solvent, wherein the pH of the product is about 2.3 to about 2.7.

23. A method of treating cancer comprising administering the composition of claim 1 to a patient in need of treatment of cancer.

24. A method of treating cancer comprising administering the composition of claim 14 to a patient in need of treatment of cancer.

25. A method of treating cancer comprising administering the composition of claim 18 to a patient in need of treatment of cancer.

26. The pharmaceutical composition of claim 1 , wherein the acid is an organic acid.