US 8,575,198 B1Granted

In-process control for the manufacture of glatiramer acetate

AssigneeMomenta Pharmaceuticals, Inc.

InventorsMani S. Iyer, Harper Kaminski

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Abstract

The present disclosure provides methods for manufacturing or producing glatiramer acetate having a Mp of 5000-9000 Da. These methods include: polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA)-protected L-lysine, and L-tyrosine to generate a sample comprising intermediate-1; treating the sample comprising intermediate-1 to partially depolymerize the protected copolymer and deprotect benzyl-protected L-glutamic acid, measuring the viscosity of the sample comprising intermediate-1 during the treatment, and ending the treatment when the viscosity of the sample is within an endpoint range, thereby generating a sample comprising intermediate-2; treating the sample comprising intermediate-2 to deprotect TFA-protected L-lysine, thereby generating intermediate-3; further processing the intermediate-3 to generate a sample glatiramer acetate; and purifying the glatiramer acetate to generate a composition comprising purified glatiramer acetate having a Mp of 5000-9000 Da.

Claims30

Dependent claims

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.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/607,625Filed 7 Sep 2012 · us provisional application
Priority: 7 Sep 2011
Granted: 5 Nov 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07K 14/001
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: by chemical synthesis
C07K 1/02
General methods for the preparation of peptides , i.e. processes for the organic chemical preparation of peptides or proteins of any length: in…
C07K 1/06
General methods for the preparation of peptides , i.e. processes for the organic chemical preparation of peptides or proteins of any length: using…
C07K
Peptides