Patent ID: 8575198

Claim:
A method for manufacturing glatiramer acetate drug substance having a Mp of 5000-9000 Da, the method comprising: (a) polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid protected L-lysine and L-tyrosine to generate a composition comprising intermediate-1; (b) treating the composition comprising intermediate-1 to partially depolymerize intermediate-1 and to deprotect benzyl-protected L-glutamic acid; (c) intermittently or continuously measuring the viscosity of the composition during step (b); (d) ending step (b) when the viscosity of the composition measured during step (b) is at a predetermined level that informs that step (f) will yield glatiramer acetate with a Mp of 5000-9000 Da, thereby generating a composition comprising intermediate-2; (e) treating the composition comprising intermediate-2 to deprotect trifluoroacetic acid protected L-lysine, thereby generating a composition comprising intermediate-3; and (f) processing the composition comprising intermediate-3 to generate glatiramer acetate drug substance having a Mp of 5000-9000 Da.