Patent ID: 8617896

Claim:
A method of manufacturing an enoxaparin preparation comprising: esterification of carboxylate groups on uronic acid residues of a heparin preparation followed by beta-elimination to provide a LMWH preparation; providing a high performance liquid chromatography (HPLC) determination of whether a tetrasaccharide structure is present in the LMWH preparation in an amount provided in the following table: Range A Range B Range C % Area % Area % Area under under under Peak HPLC HPLC HPLC # Tetrasaccharide curve curve curve 1 Î”UH NS6S I 2S H NS6S 0.1 0.6 Present or Present or Detectable Detectable 2 Î”UH NS6S I 2S H NS6S 0.6 1.2 0.6 1.2 0.4 1.4 Î”U gal H NS6S I 2S Man NS6S 3 Î”U 2S H NS6S I 2S H NS (Î±) 0.6 1.2 0.4 1.0 0.2 1.2 4 Î”U 2S H NS6S I 2S H NS (Î²), 1.8 3.6 1.7 4.1 0.9 4.9 Î”U 2S H NS6S I 2S Man NS (Î²) 5 Î”U 2S H NS6S I 2S Man NS (Î±), 2.1 3.7 2.2 4.0 1.6 4.6 Î”U 2S H NS I 2S H NS6S (Î±) 6 Î”U 2S H NS I 2S H NS6S (Î²) 0.5 1.6 0.4 1.6 0.0 2.0 7 Î”U 2S H NS6S I 2S Man NS 5.9 9.0 5.6 9.2 4.4 10.4 (1,6 anhydro) 8 Î”U 2S H NS6S I 2S H NS 7.0 9.9 6.6 10.2 5.4 11.4 (1,6 anhydro) 9 Î”U 2S H NS6S G 2S H NS (Î±) 0.9 1.6 0.8 1.4 0.6 1.6 10 Î”U 2S H NS6S GH NS6S (Î±) 5.0 6.2 4.9 6.7 4.3 7.3 11 Î”U 2S H NS6S GMan NS6S 1.2 1.9 1.0 2.2 0.6 2.6 (Î±, Î²) 12 Î”U 2S H NS6S I 2S H NS6S (Î±), 39.7 48.0 38.1 48.9 34.5 52.5 Î”U 2S H NS6S I 2S Man NS6S (Î²) 13 Î”U 2S H NS6S I 2S H NS6S (Î²), 18.1 20.7 17.8 20.8 16.8 21.8 Î”U 2S H NS6S I 2S Man NS6S (Î±) 14 Î”U 2S H NS6S G 2S H NS6S (Î±) 2.3 4.0 1.9 4.3 1.1 5.1 15 Î”U 2S H NS6S G 2S H NS6S (Î²) 0.6 1.4 0.4 1.6 0.0 2.0 and if said structures are present in an amount provided in the table, processing said preparation into an enoxaparin drug product to thereby manufacture an enoxaparin preparation.