Control of Copolymer Compositions

Abstract

Methods of making copolymers are described.

What is claimed is: 
     
         1 . (canceled) 
     
     
         2 . A method for determining the pyro-glutamate content of a sample of glatiramer acetate, the method comprising:
 digesting a sample of glatiramer acetate with  Pyrococcus furiosus  pyroglutamate aminopeptidase to create an enzymatic hydrolysate; and   subjecting the enzymatic hydrolysate to reverse phase liquid chromatography to detect and measure the amount of pyroglutamate in the enzymatic hydrolysate thereby determining the pyro-glutamate content of the sample of glatiramer acetate.   
     
     
         3 . The method of  claim 2 , wherein the glatiramer acetate has a Mp of 5000- 9000 Da. 
     
     
         4 . A method for preparing glatiramer acetate comprising: comprising: polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA) protected L-lysine and L-tyrosine to generate a protected copolymer (Intermediate-1);
 treating the Intermediate-1 with HBr and acetic acid to partially depolymerize the protected copolymer and deprotect benzyl-protected L-glutamic acid thereby generating a partially depolymerized product;   treating the partially depolymerized product with piperidine to deprotect TFA-protected lysines thereby generating glatiramer acetate;   purifying the glatiramer acetate; and 
 measuring the pyro-glutamate content of a sample of the purified glatiramer acetate.