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1. (WO2005100302) SOLID STATE FORMS OF (-)-(1R,2S)-2-AMINO-4-METHYLENE-CYCLOPENTANECARBOXYLIC ACID
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WHAT CLAIMED IS:

1. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized by the monoclmic space group P 2\, and displaying unit cell parameters comprising: crystal axis lengths of a = 6.38(18) A, b = 5.98 (18) A, and c — 9.69 (19) A, and an angle between the crystal axes of β= 96.60(1)°.

2. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic x-ray powder diffraction peaks, designated by 2© and expressed in degrees, at 9.2+0.2°, 14.0+0.2°, 15.8+0.2°, 17.5+0.2, 20.4+0.2°, 21.7+0.2°, 28.6+0.2°, and 32.0+0.2°.

3. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having a characteristic DSC endothermic maximum at about 176 °C (onset at about 174 °C) (heating rate of 10 °C/min).

A. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic FT-Raman absoφtion bands at 3076, 2979, 2921, 2900, 1542, 1427, 826, 545, and 403 cm"1.

5. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized in that when heated above about 176 °C, transfer to high temperature solid state form αl is characterized by the following data: x-ray powder diffraction peaks, designated by 2© and expressed in degrees, at 8.2+0.2°, 14.0±0.2°, 14.4+0.2°, 15.3+0.2°, 17.4+0.2°, 20.4±0.2°, 28.2+0.2°, and 30.9+0.2°; and
a DSC characteristic endothermic maximum at about 237 °C (onset at about 233 °C) at heating rate of 10 °C/mm.

6. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized in that when cooled to about -173 °C, transfer to low temperature solid state form α2 characterized by the following data:
monoclmic space group P2 with unit cell parameters comprising: crystal axis lengths of a = 6.34(1) A, b = 5.95 (1) A, and c = 9.51 (1) A, and an angle between the crystal axes of β= 96.5 (1)°.

7. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, characterized in that it does not contain water.

8. A solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, characterized in that it does not contain solvent.

9. A process for the preparation of the solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, characterized in that a solution of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid and organic solvents or mixtures of organic solvents is subjected to crystallization at a temperature of -20 °C to 80 °C.

10. A process for the preparation of the solid state form o of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, characterized in that a solution of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid and organic solvents or mixtures of organic solvents and water is subjected to crystallization at a temperature of -20 °C to 80 °C.

11. A process for the preparation of the solid state form oc of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, characterized in that (-)-(li<-JS)-2-amino-4-methylene-cyclopentanecarboxylic acid is subjected to a sublimation.

12. The solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a polymoφhic purity greater than 95.0 %.

13. The solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a polymoφhic purity greater than 99.0 %.

14. The solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a polymoφhic purity greater than 99.5 %.

15. T-he solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a polymoφhic purity greater than 99.9 %.

16. T_he solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, which is polymoφhic pure.

17. T-he solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a purity of greater than about 90.0 %.

18. T-he solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a purity of greater than about 95.0 %.

19. T-he solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a purity of greater than about 99.0 %.

20. Trie solid state form α (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, having a purity of greater than about 99.9 %.

21. A pharmaceutical composition comprising the solid state form oc (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, and one or more pharmaceutically acceptable carriers or excipients.

22. A method of treating fungal infections in a human, comprising administering to a patient in need of such treatment an effective amount of the solid state form α of (-)-(lR,l»S -2-amino-4-methylene-cyclopentatιecarboxylic acid according to claims 1 to 6.

23. A solid state form β of (-)-(lR3lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized by the orthorhombic space group P 212121, and displaying unit cell parameters comprising: crystal axis lengths of a = 6.04(1) A, b = 6.42(1) A, and c -18.720) A.

24. A solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid -having characteristic x-ray powder diffraction peaks, designated by 2© and expressed in degrees, at 9.0+0.2°, 14.4+0.2°, 15.6+0.2°, 17.5+0.2°, 20.3+0.2°, 20.8+0.2°, 22.2+0.2°, 23.6+0.2°, 27.3+0.2°, 28.9+0.2°, and 30.5+0.2°.

25. A solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having a characteristic DSC endothermic maximmn at about 85 °C (onset at about 83 °C) (heating rate of 10 °C/min).

26. A solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic FT-Raman absoφtion bands at 3074, 2981, 2950, 2911, 1658, 1431, 1315, 818, 605, 541, and 422 cm"1.

27. A solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized in that when heated above about 85 °C, transfer to high temperature solid state form βl is characterized "by the following data:
x-ray powder diffraction peaks, designated by 2© and expressed in degrees, at 5.9+0.2°, 8.6(2) +0.2°, 14.4+0.2°, 15.6+0.2°, 16.2+0.2°, 17.4+0.2°, 18.9+0.2°, 20.4±0.2°, 20.8+0.2°, 22.2+0.2°, 28.9+0.2°, and 30.6(2)+0.2°; and
a DSC characteristic endothermic maximum at about 236 °C (onset at about 232 °C) at heating rate of 10 °C/min.

28. A solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, c-haracterized in that it does not contain water.

29. A solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, c-haracterized in that it does not contain solvent.

30. A process for the preparation of the solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, characterized in that (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid is subjected to spray drying.

31. A process for the preparation of the solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, characterized in that a frozen solution of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid and water is subjected to a lyophilization.

32. The solid state form β (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a polymoφhic purity greater than 95.0 %.

33. The solid state form β (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a polymoφhic purity greater than 99.0 %.

34. The solid state form β (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a polymoφhic purity greater than 99.5 % .

35. The solid state form β (-)-(lR,lS)-2-an-tino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a polymoφhic purity greater than 99.9 %.

36. The solid state form β (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, which is polymoφhic pure.

37. The solid state form β (-)-(lR,lS)-2-anιino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a purity of greater than about 90.0 %.

38. The solid state form β (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a purity of greater than about 95.0 %.

39. The solid state form β (-)-(lR,l/-S)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a purity of greater than about 99.0 %.

40. The solid state form β (-)-(lR,l<S)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, having a purity of greater than about 99.9 %.

41. A pharmaceutical composition comprising the solid state form β (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarbox lic acid according to claims 23 to 27, and one or more pharmaceutically acceptable carriers or excipients.

42. A method of treating fungal infections in a human, comprising administering to a patient in need of such treatment an effective amount of the solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopenta.necarboxylic acid according to claims 23 to 27.

43. A pharmaceutical composition comprising any mixture of the solid state form α of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 1 to 6, and the solid state form β of (-)-(lR,l<S)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27, and one or more pharmaceutically acceptable carriers or excipients.

44. A method of treating fungal infections in a human, comprising aα-tninistering to a patient in need of such treatment an effective amount of any mixture of the solid state form α of (-)-(lR,lS)-2-amino-4-rα.ethylene-cyclopentanecarboxylic acid of claim 1 to claim 6, and the solid state form β of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 23 to 27.

45. Solid state form δ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic x-ray powder diffraction peaks, designated by 2Θ and expressed in degrees, at 7.6+0.2°, 8.2.0+0.2°, 9.2+0.2°, 18.4+0.221.2+0.2° and 29.7+0.2°.

46. Solid state form δ of (-)-( lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic DSC endothermic maximum at about 147 °C (onset at about 145 °C) and another one at about 158 °C (onset at about 150 °C) (heating rate of 10 °C/min).

47. Solid state form δ of (-)-(lR,lS)-2-aιrιino-4-methylene-cyclopentanecarboxylic acid characterized in that when is heating above about 158 °C transfer to high temperature solid state form δl of (-)-(lR,l-?)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized by the following data:
X-ray powder diffraction peaks, designated by 2© and expressed in degrees, at 8.5±0.2°, 14.3+0.2°, 18.2+0.2°, 19.7-t0.2°, 20.8+0.2°, and 29.3+0.2°
and DSC characteristic endothermic maximum at about 211 °C (onset at about 202 °C) and exothermic maximum at about 232 °C (onset at about 230 °C) at heating rate of 10 °C/min.

48. Process for the preparation of the solid state form δ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 45 to 47, characterized in that suspension of (-)-(lR3lS)-2-amino-4-methylene-cyclopentanecarboxylic acid and chloroform is stirred at about 61 °C.

49. A pharmaceutical composition comprising the solid state form δ of (-)--(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 45 to 47 , and one or more pharmaceutically acceptable carriers or excipients.

50. A method of treating fungal infections in a human which comprises adrninistering to a patient in need of such treatment an effective amount of the solid state form δ of (-)-(lR,lS)-2-amirιo-4-methylene-cyclopentanecarboxylic acid according to claims 45 to 47 .

51. Solid state form ε of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic DSC endothermic maximum at about 81 °C (onset at about 79 °C) (heating rate of 10 °C/min).

52. Solid state form ε of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized in that when is heating above about 81 °C transfer to high temperature solid state form δl of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid characterized by the following data:

X-ray powder diffraction peaks, designated by 2© and expressed in degrees, at 8.5+0.2°,

14.3+0.2°, 18.2+0.2°, 19.7+0.2°, 20.8+0.2°, and 29.3±0.2°
and DSC characteristic endothermic maximum at about 210 °C (onset at about 204 °C) and exothermic maximum at about 232 °C (onset at about 230 °C) at heating rate of 10

°C/min.;

53. Process for the preparation of the solid state form ε of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid that includes heating of solid state form δ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid up to about 158 °C and cooling to about 75 °C.

54. Process for the preparation of the solid state form ε of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid that includes heating of solid state form δ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid up to about 158 °C and cooling to room temperature.

55. A pharmaceutical composition comprising the solid state form ε of (-)-(lR,lS)-2-ammo-4-memylerre-cyclopentanecarboxylic acid according to claims 51 to 52, and one or more pharmaceutically acceptable carriers or excipients.

56. A method of treating fungal infections in a human which comprises adm-tnistering to a patient in need of such treatment an effective amount of the solid state form ε of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claims 51 to 52 .

57. Solid state form ζ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid having characteristic DSC endothermic maximum at about 234 °C (onset at about 229 °C) (heating rate of 10 °C/min).

58. Process for the preparation of the solid state form ζ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid that includes sublimation of icofungipen at about oil bath temperature 170 °C and pressure of about 0.05 mm Hg for 1 hour.

59. The solid state form ζ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claim 57, having a polymoφhic purity greater than about 95.0 %.

60. The solid state form ζ of (-)-(lR,lS)-2-amino-4-mefhylene-cyclopentanecarboxylic acid according to claim 57, having a polymoφhic purity greater than about 99.0 %.

61. The solid state form ζ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxylic acid according to claim 57, having a polymoφhic purity greater than about 99.5 %.

62. A pharmaceutical composition comprising the solid state form ζ of (-)-(lR,lS)-2-amino-4-methylene-cyclopentanecarboxyhc acid according to claim 57, and one or more pharmaceutically acceptable carriers or excipients.

63. A method of treating fungal infections in a human which, comprises administering to a patient in need of such treatment an effective amount of the solid state form ζ of (-)-(lR,l-S}-2-amino-4-methylene-cyclopentanecarboxylic acid according to claim 57.

64. A pharmaceutical composition comprising at least two solid state forms of (-)-(lR,lΛS)-2-amino-4-methylene-cyclopentanecarboxylic acid and one or more pharmaceutically acceptable carriers or excipients, wherein said solid state forms of (-)-(lR,l-S}-2-amino-4-methylene-cyclopentanecarboxylic acid are selected from the solid state form α according to claims 1 to 6, the solid state form β according to claims 23 to 27, the solid state form δ according to claims 45 to 47, the solid state form ε according to claims 51 to 52, and the solid state form ζ according to clai 57.