Control of copolymer compositions

A method for preparing a composition comprising glatiramer acetate, the method comprising:

• polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid protected L-lysine and L-tyrosine to generate a sample comprising intermediate-1;
• treating the sample comprising intermediate-1 to partially depolymerize and deprotect benzyl-protected L-glutamic acid, thereby generating a sample comprising intermediate-2, wherein water is present for at least a portion of the treatment in a range of 4-25% weight/weight (w/w) against intermediate-1 present at the beginning of treatment;
• treating the sample comprising intermediate-2 to deprotect trifluoroacetic acid protected L-lysine, thereby generating intermediate-3;
• further processing the intermediate-3 to generate glatiramer acetate;
• and
• purifying the glatiramer acetate to generate purified glatiramer acetate.