Details for Patent: 8,058,238

Title:	High purity lipopeptides
Abstract:	The invention discloses highly purified daptomycin and to pharmaceutical compositions comprising this compound. The invention discloses a method of purifying daptomycin comprising the sequential steps of anion exchange chromatography, hydrophobic interaction chromatography and anion exchange chromatography. The invention also discloses a method of purifying daptomycin by modified buffer enhanced anion exchange chromatography. The invention also discloses an improved method for producing daptomycin by fermentation of Streptomyces roseosporus. The invention also discloses high pressure liquid chromatography methods for analysis of daptomycin purity. The invention also discloses lipopeptide micelles and methods of making the micelles. The invention also discloses methods of using lipopeptide micelles for purifying lipopeptide antibiotics, such as daptomycin. The invention also discloses using lipopeptide micelles therapeutically.
Inventor(s):	Kelleher; Thomas (Weston, MA), Lai; Jan-Ji (Westborough, MA), DeCourcey; Joseph P. (Charlestown, MA), Lynch; Paul (Arlington, MA), Zenoni; Maurizio (Milan, IT), Tagliani; Auro (Pavia, IT)
Assignee:	Cubist Pharmaceuticals, Inc. (Lexington, MA)
Filing Date:	Apr 24, 2007
Application Number:	11/739,180
Claims:	1. A composition comprising essentially pure daptomycin purified by a process comprising the steps of: (a) subjecting daptomycin to conditions forming a daptomycin aggregate; and (b) obtaining the essentially pure daptomycin from the daptomycin aggregate. 2. The composition of claim 1, wherein the daptomycin has greater than 98% purity measured by HPLC analysis. 3. A composition comprising daptomycin that is substantially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin, the daptomycin being purified by a process comprising the steps of: (a) subjecting daptomycin to conditions forming a daptomycin aggregate; and (b) obtaining the daptomycin that is substantially free of anhydro-daptomycin or substantially free of .beta.-isomer of daptomycin from the daptomycin aggregate. 4. The composition according to claim 3 that is essentially free of anhydro-daptomycin, wherein the step of obtaining the daptomycin that is essentially free of anhydro-daptomycin from the daptomycin aggregate further comprises the steps of: (c) subjecting the daptomycin aggregate to conditions to form monomeric daptomycin; and (d) obtaining the daptomycin that is essentially free of anhydro-daptomycin from the monomeric daptomycin. 5. The composition of claim 4, wherein the daptomycin has greater than or about 93% purity measured by HPLC analysis. 6. The composition according to claim 3 that is free of anhydro-daptomycin. 7. The composition of claim 3, wherein the daptomycin has greater than or about 93% purity measured by HPLC analysis. 8. A composition comprising purified daptomycin that is substantially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12, the purified daptomycin being obtained by a process comprising the steps of: (a) subjecting daptomycin to conditions forming a daptomycin aggregate; (b) subjecting the daptomycin aggregate to conditions forming monomeric daptomycin; and (c) obtaining the daptomycin from the monomeric daptomycin, the daptomycin aggregate or a combination thereof. 9. The composition according to claim 8, wherein the purified daptomycin is essentially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 10. A pharmaceutical composition comprising essentially pure daptomycin purified by a process comprising the steps of: (a) forming micelles comprising daptomycin; (b) converting the micelles to a non-micellar daptomycin composition comprising daptomycin in a non-micellar state; and (c) obtaining the purified daptomycin from the micelles, the non-micellar daptomycin composition, or a combination thereof. 11. The pharmaceutical composition of claim 10 comprising daptomycin of at least 98% purity measured relative to daptomycin impurities 1-14 defined by peaks 1-14 shown in FIG. 12. 12. The pharmaceutical composition of claim 10 wherein the daptomycin is at least 99% pure. 13. The composition of claim 10, wherein the purified daptomycin is obtained from the non-micellar daptomycin. 14. The composition of claim 10, wherein the daptomycin micelles are converted to the non-micellar state by altering one or more of: temperature, pH, electrolyte concentration and daptomycin concentration. 15. The composition of claim 10, wherein the daptomycin is purified by a process further comprising the steps of: i) filtering the daptomycin micelles under conditions in which the daptomycin micelles are retained on the filter; and ii) collecting the daptomycin micelles. 16. The composition of claim 15, wherein the daptomycin micelles collected in step (ii) are converted to the non-micellar daptomycin in step (b). 17. The composition of claim 16, wherein the purified daptomycin is obtained from the non-micellar daptomycin in step (c). 18. The composition of claim 17, wherein the purified daptomycin is obtained by a process further comprising the step of lyophilizing the purified daptomycin. 19. The composition of claim 18, wherein the purified daptomycin is substantially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 20. The composition of claim 15, wherein the daptomycin micelles are formed by a process comprising one or more steps selected from the group consisting of: adjusting the pH of a daptomycin preparation to a pH of about 2.5 to 5.0, combining daptomycin with 300 to 500 mM NaCl in an aqueous solution; and providing a daptomycin preparation at a temperature of 2-15 degrees C. 21. A composition comprising daptomycin of greater than or about 93% purity relative to daptomycin impurities that arise in fermentation or purification of daptomycin, and wherein the daptomycin impurities comprise impurities 1-14 defined by peaks 1-14 shown in FIG. 12, and the daptomycin is obtained by a process comprising the step of forming a micelle comprising daptomycin. 22. The composition of claim 21, wherein the daptomycin impurities arise in fermentation. 23. The composition of claim 21, wherein the purity of daptomycin is at least 93%. 24. The composition of claim 23, wherein the daptomycin impurities arise in fermentation. 25. The composition of claim 21 wherein impurity 1 is present in an amount no more than 1%. 26. The composition of claim 25 wherein impurity 8 is present in an amount no more than 1%. 27. The composition of claim 21 wherein impurity 2 is present in an amount no more than 0.5%. 28. The composition of claim 21 wherein impurity 3 is present in an amount no more than 1%. 29. The composition of claim 21 wherein impurity 4 is present in an amount no more than 0.5%. 30. The composition of claim 21 wherein impurity 5 is present in an amount no more than 0.5%. 31. The composition of claim 21 wherein impurity 6 is present in an amount no more than 1%. 32. The composition of claim 21 wherein impurity 7 is present in an amount no more than 1%. 33. The composition of claim 21 wherein impurity 8 is present in an amount no more than 4%. 34. The composition of claim 33 wherein impurity 8 is present in an amount no more than 1%. 35. The composition of claim 21 wherein impurity 12 is present in an amount no more than 0.5%. 36. The composition of claim 21 wherein impurity 14 is present in an amount no more than 0.1%. 37. The composition of claim 21, wherein the daptomycin is obtained by a process comprising a) separating daptomycin from high molecular weight contaminants; b) subjecting the daptomycin of step a) to conditions forming the micelle comprising daptomycin; and c) separating the micelle comprising daptomycin from low molecular weight contaminants. 38. The composition of claim 37, wherein the micelle comprising daptomycin of step c) is separated from the low molecular weight contaminants by a size selection technique. 39. The composition of claim 38, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 40. The composition of claim 39, further comprising subjecting the micelle comprising daptomycin of step c) to conditions in which the micelle comprising daptomycin dissociates into daptomycin monomers. 41. The composition of claim 37, wherein the micelle consists of daptomycin. 42. The composition of claim 21, wherein the daptomycin is obtained by a process comprising a) subjecting a daptomycin solution to conditions forming a daptomycin micelle; b) filtering the daptomycin micelle under conditions in which the daptomycin micelle is retained on the filter; and c) collecting the daptomycin micelle. 43. The composition of claim 21, wherein the daptomycin is obtained by subjecting a daptomycin solution to conditions effective to form daptomycin micelles. 44. The composition of claim 21, wherein the micelle comprising daptomycin is obtained by adjusting any one or more of temperature, salt concentration, daptomycin concentration, and pH of the solution to cause a concentration of the daptomycin in the solution to be above a critical micelle concentration. 45. The composition of claim 21, wherein the micelle comprising daptomycin is obtained by subjecting a daptomycin solution to a pH of 2.5 to 5.0. 46. The composition of claim 21, wherein the daptomycin is obtained by a process comprising: a) adjusting the pH of a daptomycin preparation to a pH of 2.5 to 5.0; b) filtering the daptomycin preparation of step a) on an ultrafiltration membrane; c) adjusting the pH of the daptomycin preparation of step b) to a pH of 6.5. 47. The composition of claim 46, wherein the daptomycin preparation of step a) that comprises micelle has a pH of 2.5 to 4.7, and the preparation further comprises 300 to 500 mM NaCl and is at a temperature of 2-15 degrees C. 48. The composition of claim 21 wherein the daptomycin is obtained by a process comprising: a) subjecting a solution of daptomycin to anion exchange chromatography to obtain an enriched daptomycin preparation; b) subjecting the enriched daptomycin preparation to hydrophobic interaction chromatography to obtain a semi-purified daptomycin preparation; and c) subjecting the semi-purified daptomycin preparation to anion exchange chromatography. 49. A purified daptomycin composition comprising daptomycin of greater than or about 93% purity relative to impurities 1-14 defined by peaks 1-14 shown in FIG. 12, the daptomycin being obtained by a process comprising the step of forming an aggregate comprising daptomycin. 50. A composition comprising purified daptomycin obtained from a daptomycin aggregate, the purified daptomycin selected from the group consisting of: (a) essentially pure daptomycin, (b) daptomycin that is substantially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin, (c) daptomycin that is essentially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin, (d) daptomycin that is free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin, (e) daptomycin that is substantially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12, and (f) daptomycin that is essentially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 51. The composition of claim 49, wherein daptomycin purity is measured by HPLC. 52. The composition of claim 49 further comprising a pharmaceutically acceptable carrier or excipient. 53. The pharmaceutical composition according to claim 52, further comprising one or more antibiotics, one or more antifungal agents, or both an antibiotic and an antifungal agent. 54. The pharmaceutical composition of claim 52 comprising essentially pure daptomycin. 55. The pharmaceutical composition of claim 52 comprising daptomycin that is substantially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 56. The pharmaceutical composition of claim 52 comprising daptomycin that is essentially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 57. The pharmaceutical composition of claim 52 comprising daptomycin that is free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 58. The pharmaceutical composition of claim 52 comprising daptomycin that is substantially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 59. The pharmaceutical composition of claim 52 comprising daptomycin that is essentially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 60. The pharmaceutical composition of claim 52 wherein the composition is essentially pure daptomycin. 61. The pharmaceutical composition of claim 52 wherein the composition is daptomycin that is substantially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 62. The pharmaceutical composition of claim 52 wherein the composition is daptomycin that is essentially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 63. The pharmaceutical composition of claim 52 wherein the composition is daptomycin that is free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 64. The pharmaceutical composition of claim 52 wherein the composition is daptomycin that is substantially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 65. The pharmaceutical composition of claim 52 wherein the composition is daptomycin that is essentially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 66. The composition according to claim 49 or 50 wherein the daptomycin is purified by a process comprising the steps of: a) supplying a fermentation broth; b) fermenting Streptomyces roseosporus with a feed of n-decanoic acid to produce daptomycin in the fermentation broth; c) clarifying the fermentation broth to obtain a clarified solution; d) subjecting the clarified solution to anion exchange chromatography to obtain an enriched daptomycin preparation; e) subjecting the enriched daptomycin preparation to hydrophobic interaction chromatography to obtain a semi-purified daptomycin preparation; and f) subjecting the semi-purified daptomycin preparation to anion exchange chromatography to obtain the composition. 67. The composition according to claim 66, wherein the feed of n-decanoic acid is regulated to achieve a residual concentration of n-decanoic acid of no more than 50 parts per million (ppm) during fermentation. 68. The composition according to claim 66, wherein said clarifying comprises filtration or centrifugation and depth filtration. 69. The composition according to claim 66, wherein the anion exchange chromatography in d) is performed using a resin comprising a copolymer of 2-methacrylic acid and ethyleneglycol dimethacrylate (EDGM). 70. The composition according to claim 66, wherein the hydrophobic interaction chromatography is performed using a resin comprising a co-polymer of cross-linked divinylbenzene/stryene. 71. The composition according to claim 70, wherein the hydrophobic interaction chromatography is performed at neutral pH and a solvent concentration that is reduced compared to the solvent concentration used when performing the hydrophobic interaction chromatography at acidic pH. 72. The composition according to claim 71, wherein the resin is recycled by loading the column at an acidic pH and eluting the column at a neutral pH. 73. The composition according to claim 66, wherein the anion exchange chromatography in f) is performed using a resin comprising a copolymer of 2-methacrylic acid and ethyleneglycol dimethacrylate (EDGM). 74. The composition according to claim 66, wherein the anion exchange chromatography is used to reduce the level of solvent in the clarified solution. 75. The composition according to claim 66, wherein the anion exchange chromatography is performed via continuous flow chromatography. 76. The composition according to claim 66, wherein the process further comprises the step of filtering daptomycin. 77. The composition according to claim 66, wherein the process further comprises the step of depyrogenating daptomycin using ultrafiltration. 78. The composition according to claim 77, wherein said depyrogenating comprises the steps of: i) providing a daptomycin solution under conditions in which the daptomycin is in a monomeric and nonmicellar state; ii) filtering the daptomycin solution under conditions in which the daptomycin passes through the filter but pyrogens do not pass through the filter; iii) subjecting the daptomycin solution to conditions forming a daptomycin aggregate; iv) filtering the daptomycin aggregate under conditions in which the daptomycin aggregate is retained on the filter; and v) collecting the daptomycin aggregate. 79. The composition according to claim 77, wherein the process further comprises the step of lyophilizing daptomycin. 80. The composition according to claim 77, wherein the anion exchange chromatography is performed via radial flow chromatography. 81. The composition according claim 66, wherein said clarifying comprises microfiltration or centrifugation. 82. The composition according to claim 66, wherein the process further comprises the steps of filtering and concentrating daptomycin. 83. The composition according to claim 66, wherein the process further comprises the step of separating the enriched daptomycin from low molecular weight material by ultrafiltration. 84. The composition according to claim 83, wherein the process further comprises the step of depyrogenating the daptomycin. 85. A method for preparing a pharmaceutical composition comprising combining the composition of claim 49 with a pharmaceutically acceptable carrier or excipient. 86. The method of claim 85 wherein the composition is essentially pure daptomycin. 87. The method of claim 85 wherein the composition is daptomycin that is substantially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 88. The method of claim 85 wherein the composition is daptomycin that is essentially free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 89. The method of claim 85 wherein the composition is daptomycin that is free of anhydro-daptomycin and substantially free of .beta.-isomer of daptomycin. 90. The method of claim 85 wherein the composition is daptomycin that is substantially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 91. The method of claim 85 wherein the composition is daptomycin that is essentially free of each of impurities 1 to 14 defined by peaks 1-14 shown in FIG. 12. 92. The composition of claim 49, wherein the purity of daptomycin is at least 93%. 93. The composition of claim 92, wherein the daptomycin is obtained by a process comprising: a) subjecting a daptomycin solution to conditions forming a daptomycin aggregate; b) separating the daptomycin aggregate from low molecular weight contaminants; and c) subjecting the daptomycin aggregate to conditions in which the daptomycin aggregate dissociates into daptomycin monomers. 94. The composition of claim 93, wherein the daptomycin aggregate of step b) is separated from the low molecular weight contaminants by a size selection technique. 95. The composition of claim 94, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 96. The composition of claim 95 further comprising separating the daptomycin monomers obtained from step c) from high molecular weight contaminants. 97. The composition of claim 96, wherein the daptomycin monomers are separated from the high molecular weight contaminants by a size selection technique. 98. The composition of claim 97, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 99. The composition of claim 93, wherein the aggregate is a micelle. 100. The composition of claim 92, wherein the daptomycin is obtained by a process comprising a) separating daptomycin from high molecular weight contaminants, b) subjecting the daptomycin of step a) to conditions forming a daptomycin aggregate; and c) separating the daptomycin aggregate from low molecular weight contaminants. 101. The composition of claim 100, wherein the daptomycin aggregate of step c) is separated from the low molecular weight contaminants by a size selection technique. 102. The composition of claim 101, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 103. The composition of claim 102, further comprising subjecting the daptomycin aggregate of step c) to conditions in which the daptomycin aggregate dissociates into daptomycin monomers. 104. The composition of claim 100, wherein the aggregate is a micelle. 105. The composition of claim 92, wherein the daptomycin is obtained by a process comprising a) subjecting a daptomycin solution to conditions forming a daptomycin aggregate; b) filtering the daptomycin aggregate under conditions in which the daptomycin aggregate is retained on the filter; and c) collecting the daptomycin aggregate. 106. The composition of claim 105, wherein the aggregate is a micelle. 107. The composition of claim 92, wherein the daptomycin is obtained by subjecting a daptomycin solution to conditions effective to forming micelles. 108. The composition of claim 92, wherein the daptomycin is obtained by adjusting any one or more of temperature, salt concentration, daptomycin concentration, and pH of the solution to cause a concentration of the daptomycin in the solution to be above a critical micelle concentration. 109. The composition of claim 92, wherein the daptomycin is obtained by subjecting a daptomycin solution to a pH of 2.5 to 5.0. 110. The composition of claim 92, wherein the daptomycin is obtained by a process comprising: a) adjusting the pH of a daptomycin preparation to a pH of 2.5 to 5.0; b) filtering the daptomycin preparation of step a) on an ultrafiltration membrane; c) adjusting the pH of the daptomycin preparation of step b) to a pH of 6.5. 111. The composition of claim 110, wherein the daptomycin preparation of step a) is at a pH of 2.5 to 4.7, and the preparation further comprises 300 to 500 mM NaCl and is at a temperature of 2-15 degrees C. 112. The composition of claim 92 wherein the daptomycin is obtained by a process comprising: a) subjecting a solution of daptomycin to anion exchange chromatography to obtain an enriched daptomycin preparation; b) subjecting the enriched daptomycin preparation to hydrophobic interaction chromatography to obtain a semi-purified daptomycin preparation; and c) subjecting the semi-purified daptomycin preparation to anion exchange chromatography. 113. The composition of claim 92 wherein impurity 1 is present in an amount no more than 1%. 114. The composition of claim 113 wherein impurity 8 is present in an amount no more than 1%. 115. The composition of claim 92 wherein impurity 2 is present in an amount no more than 0.5%. 116. The composition of claim 92 wherein impurity 3 is present in an amount no more than 1%. 117. The composition of claim 92 wherein impurity 4 is present in an amount no more than 0.5%. 118. The composition of claim 92 wherein impurity 5 is present in an amount no more than 0.5%. 119. The composition of claim 92 wherein impurity 6 is present in an amount no more than 1%. 120. The composition of claim 92 wherein impurity 7 is present in an amount no more than 1%. 121. The composition of claim 92 wherein impurity 8 is present in an amount no more than 4%. 122. The composition of claim 121 wherein impurity 8 is present in an amount no more than 1%. 123. The composition of claim 92 wherein impurity 12 is present in an amount no more than 0.5%. 124. The composition of claim 92 wherein impurity 14 is present in an amount no more than 0.1%. 125. The composition of claim 49, wherein the daptomycin is obtained by a process comprising: a) subjecting a daptomycin solution to conditions forming a daptomycin aggregate; b) separating the daptomycin aggregate from low molecular weight contaminants; and c) subjecting the daptomycin aggregate to conditions in which the daptomycin aggregate dissociates into daptomycin monomers. 126. The composition of claim 125, wherein the daptomycin aggregate of step b) is separated from the low molecular weight contaminants by a size selection technique. 127. The composition of claim 126, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 128. The composition of claim 127 further comprising separating the daptomycin monomers obtained from step c) from high molecular weight contaminants. 129. The composition of claim 128, wherein the daptomycin monomers are separated from the high molecular weight contaminants by a size selection technique. 130. The composition of claim 129, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 131. The composition of claim 125, wherein the aggregate is a micelle. 132. The composition of claim 49, wherein the daptomycin is obtained by a process further comprising: a) separating the daptomycin aggregate from low molecular weight contaminants; and b) subjecting the daptomycin aggregate to conditions in which the daptomycin aggregate dissociates into daptomycin monomers. 133. The composition of claim 132, wherein the daptomycin aggregate of step a) is separated from the low molecular weight contaminants by a size selection technique. 134. The composition of claim 133, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 135. The composition of claim 134 further comprising separating the daptomycin monomers obtained from step b) from high molecular weight contaminants. 136. The composition of claim 135, wherein the daptomycin monomers are separated from the high molecular weight contaminants by a size selection technique. 137. The composition of claim 136, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 138. The composition of claim 132, wherein the aggregate is a micelle. 139. The composition of claim 48, wherein the daptomycin is obtained by a process comprising a) separating daptomycin from high molecular weight contaminants. b) subjecting the daptomycin of step a) to conditions forming a daptomycin aggregate; and c) separating the daptomycin aggregate from low molecular weight contaminants. 140. The composition of claim 139, wherein the daptomycin aggregate of step c) is separated from the low molecular weight contaminants by a size selection technique. 141. The composition of claim 140, wherein the size selection technique is ultrafiltration or size exclusion chromatography. 142. The composition of claim 141, further comprising subjecting the daptomycin aggregate of step c) to conditions in which the daptomycin aggregate dissociates into daptomycin monomers. 143. The composition of claim 139, wherein the aggregate is a micelle. 144. The composition of claim 49, wherein the daptomycin is obtained by a process comprising a) subjecting a daptomycin solution to conditions forming a daptomycin aggregate; b) filtering the daptomycin aggregate under conditions in which the daptomycin aggregate is retained on the filter; and c) collecting the daptomycin aggregate. 145. The composition of claim 144, wherein the daptomycin aggregate is a micelle comprising daptomycin. 146. The composition of claim 49, wherein the daptomycin is obtained by subjecting a daptomycin solution to conditions effective to form the aggregate comprising daptomycin micelles. 147. The composition of claim 49, wherein the daptomycin is obtained by adjusting any one or more of temperature, salt concentration, daptomycin concentration, and pH of the solution to cause a concentration of the daptomycin in the solution to be above a critical micelle concentration. 148. The composition of claim 49, wherein the daptomycin is obtained by subjecting a daptomycin solution to a pH of 2.5 to 5.0. 149. The composition of claim 49, wherein the daptomycin is obtained by a process comprising: a) adjusting the pH of a daptomycin preparation to a pH of 2.5 to 5.0; b) filtering the daptomycin preparation of step a) on an ultrafiltration membrane; c) adjusting the pH of the daptomycin preparation of step b) to a pH of 6.5. 150. The composition of claim 149, wherein the daptomycin preparation of step a) is at a pH of 2.5 to 4.7, and the preparation further comprises 300 to 500 mM NaCl and is at a temperature of 2-15 degrees C. 151. The composition of claim 49 wherein impurity 1 is present in an amount no more than 1%. 152. The composition of claim 151 wherein impurity 8 is present in an amount no more than 1%. 153. The composition of claim 49 wherein impurity 2 is present in an amount no more than 0.5%. 154. The composition of claim 49 wherein impurity 3 is present in an amount no more than 1%. 155. The composition of claim 49 wherein impurity 4 is present in an amount no more than 0.5%. 156. The composition of claim 49 wherein impurity 5 is present in an amount no more than 0.5%. 157. The composition of claim 49 wherein impurity 6 is present in an amount no more than 1%. 158. The composition of claim 49 wherein impurity 7 is present in an amount no more than 1%. 159. The composition of claim 49 wherein impurity 8 is present in an amount no more than 4%. 160. The composition of claim 159 wherein impurity 8 is present in an amount no more than 1%. 161. The composition of claim 49 wherein impurity 12 is present in an amount no more than 0.5%. 162. The composition of claim 49 wherein impurity 14 is present in an amount no more than 0.1%. 163. The composition of claim 49 wherein the daptomycin is obtained by a process comprising: a) subjecting a solution of daptomycin to anion exchange chromatography to obtain an enriched daptomycin preparation; b) subjecting the enriched daptomycin preparation to hydrophobic interaction chromatography to obtain a semi-purified daptomycin preparation; and c) subjecting the semi-purified daptomycin preparation to anion exchange chromatography. 164. The composition of claim 49, wherein the daptomycin has greater than 93% purity measured by HPLC analysis. 165. The composition of claim 50, wherein the daptomycin aggregate comprises a daptomycin micelle. 166. The composition of claim 165, wherein the daptomycin is purified by a process comprising the steps of: (a) subjecting a daptomycin solution to conditions forming the daptomycin aggregate; (b) separating the daptomycin aggregate from low molecular weight contaminants; and c) subjecting the daptomycin aggregate to conditions in which the daptomycin micelle dissociates into daptomycin monomers. 167. The composition of claim 166, wherein the daptomycin aggregate consists of daptomycin micelles. 168. The composition of claim 167, wherein the step of subjecting a daptomycin solution to conditions forming daptomycin micelles includes subjecting the daptomycin solution to a pH of about 3.0 to 4.8 and a temperature of about 2-15 degrees C. 169. The composition of claim 166, wherein the step of subjecting the daptomycin solution to conditions forming a daptomycin aggregate includes adjusting one or more of temperature, salt concentration, daptomycin concentration, and pH of the daptomycin solution to form the daptomycin aggregate. 170. The composition of claim 169, wherein the daptomycin aggregate comprises daptomycin micelles. 171. The composition of claim 166, wherein the step of subjecting the daptomycin solution to conditions forming the daptomycin aggregate results in a concentration of the daptomycin in the daptomycin solution at or above the critical micelle concentration. 172. The composition of claim 166, wherein the step of subjecting a daptomycin solution to conditions forming a daptomycin aggregate includes one or more of the following: (a) the daptomycin solution having a pH of about 2.5 to 5.0, (b) the daptomycin solution having a temperature of about 2-15 degrees C., and (c) the daptomycin solution having a daptomycin concentration at or above the critical micelle concentration. 173. The composition of claim 166, wherein the step of subjecting the daptomycin aggregate to conditions in which the daptomycin aggregate dissociate into daptomycin monomers includes one or more of the following: (a) raising the pH of the daptomycin aggregate to about 6.0 or higher; (b) adjusting the daptomycin concentration to below the critical micelle concentration; (c) contacting the daptomycin aggregate with an organic solvent; and (d) raising the temperature of the daptomycin aggregate above about 15 degrees C. 174. The composition of claim 173, wherein the organic solvent is selected from the group consisting of: n-butanol, isopropyl alcohol, acetonitrile, and a combination thereof. 175. The composition of claim 50, wherein the daptomycin has greater than or about 93% purity measured by HPLC analysis. 176. A purified daptomycin composition of greater than or 93% purity relative to impurities 1-14 defined by peaks 1-14 shown in FIG. 12, the purified daptomycin composition obtained by a process comprising the steps of: (a) subjecting daptomycin to conditions forming daptomycin micelles and (b) obtaining the purified daptomycin from the daptomycin micelles. 177. The purified daptomycin composition of claim 176, wherein the step of obtaining the purified daptomycin from the daptomycin micelles further comprises the steps of: (c) subjecting the daptomycin micelles to conditions forming monomeric daptomycin from the daptomycin micelles; and (d) obtaining the purified daptomycin from the monomeric daptomycin. 178. The purified daptomycin composition of claim 177, wherein the step of subjecting the daptomycin micelles to conditions to form monomeric daptomycin from the daptomycin micelles includes one or more of the following steps: (a) raising the pH of the daptomycin micelles to about 6.0 or higher; (b) adjusting the daptomycin concentration to below the critical micelle concentration; (c) contacting the daptomycin micelles with an organic solvent; and (d) raising the temperature of the daptomycin micelles above or about 15 degrees C. 179. The purified daptomycin composition of claim 176, wherein the step of obtaining the daptomycin from the daptomycin micelles further comprises the steps of: (c) filtering the daptomycin micelles under conditions in which the daptomycin micelles are retained on the filter; (d) collecting the daptomycin aggregate; (e) subjecting the daptomycin micelles to conditions to form monomeric daptomycin from the daptomycin micelles; and (f) obtaining the purified daptomycin from the monomeric daptomycin. 180. A purified daptomycin composition of greater than or about 93% purity relative to impurities 1-14 defined by peaks 1-14 shown in FIG. 12, the purified daptomycin composition obtained by a process comprising the steps of: (a) subjecting an aqueous solution comprising daptomycin at or above the critical daptomycin micelle concentration to a pH of 3.0 to 4.8 at a temperature of about 2-15 degrees C. to form a daptomycin preparation; and (b) obtaining the purified daptomycin from the daptomycin preparation obtained in step (a). 181. The composition of claim 180, wherein the daptomycin preparation comprises daptomycin aggregates, and wherein the process further comprises: (a) filtering the daptomycin preparation to obtain a filtered daptomycin material comprising the daptomycin aggregates; and (b) contacting the filtered daptomycin material with an organic solvent or a solvent having a pH of at least or about 6.0. 182. The composition of claim 181, wherein the purified daptomycin is obtained by contacting the filtered daptomycin material with a hydrophobic interaction chromatography (HIC) resin and eluted with a solvent at a pH of about 6.0-7.5. 183. A purified daptomycin composition of greater than or about 93% purity relative to impurities 1-14 defined by peaks 1-14 shown in FIG. 12, wherein the percent purity is measured by HPLC analysis, and the purified daptomycin composition is obtained from a lipopeptide aggregate comprising daptomycin. 184. The composition of claim 183, wherein the daptomycin is obtained by adjusting any one or more of temperature, salt concentration, daptomycin concentration, and pH of a daptomycin solution to cause a concentration of the daptomycin in the solution to be above a daptomycin critical micelle concentration. 185. The composition of claim 183, wherein the aggregate comprises daptomycin micelles formed by a process further comprising subjecting daptomycin micelles, daptomycin in a non-micellar state, or a combination thereof to anion exchange chromatography. 186. The composition of claim 183, wherein the daptomycin composition is at least or about 95% pure. 187. The composition of claim 183, wherein the daptomycin composition is at least or about 97% pure. 188. The composition of claim 183, wherein the daptomycin composition is at least or about 98% pure. 189. The composition of claim 183, wherein the daptomycin composition is at least 93% pure. 190. The composition of claim 183, wherein the daptomycin composition is essentially free of anhydro daptomycin. 191. A purified daptomycin composition of greater than or about 93% purity relative to impurities 1-14 defined by peaks 1-14 shown in FIG. 12, wherein the percent purity is measured by HPLC analysis, and the purified daptomycin composition is obtained by a process comprising the steps of: (a) fermenting a culture of Streptomyces roseosporus to produce daptomycin; (b) contacting the daptomycin from step (a) with an anion exchange resin; (c) eluting the daptomycin from the anion exchange resin in step (b) with a solvent having a pH of about 6.0-6.5 to obtain a daptomycin solution; (d) adjusting the pH of the daptomycin solution from step (c) to about 3.0 to 4.8 and a temperature to about 2-15 degrees C. to obtain a daptomycin aggregate solution comprising daptomycin aggregates; and (e) filtering the daptomycin aggregate solution to separate daptomycin aggregates from the daptomycin aggregate solution; and (f) obtaining the purified daptomycin from the daptomycin aggregates. 192. The composition of claim 191, wherein the daptomycin aggregates comprise daptomycin micelles.