Analysis of amino acid copolymer compositions
AssigneeMomenta Pharmaceuticals, Inc.
InventorsXiangping Zhu, Zachary Shriver, Yanjie Jiang, Corinne Bauer, James Eric Anderson, Peter James Ahern
Life of this patent
Estimating the term…
Abstract
Methods for analyzing, selecting, characterizing or classifying compositions of a co-polymer, e.g., glatiramer acetate are described. The methods entail analysis of pyro-glutamate in the composition, and, in some methods, comparing the amount of pyro-glutamate present in a composition to a reference standard. In some cases, the methods entail treating the co-polymer with pyro-glutamate aminopeptidase to cleave N-terminal pyro-glutamate residues.
Claims37
A method of selecting a batch of a composition comprising glatiramer acetate for use in preparation of a pharmaceutical composition, the method comprising:
- providing a batch of a composition comprising glatiramer acetate manufactured by a method 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;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotect TFA-protected lysines to generate glatiramer acetate;
- measuring the amount of pyro-glutamate (pyro-Glu) produced during manufacture of glatiramer acetate in a sample of the batch;
- and
- selecting the batch when the amount of pyro-Glu in the sample of the batch is less than 7000 ppm, thereby selecting a batch of a composition comprising glatiramer acetate.
A method of preparing a pharmaceutical composition comprising glatiramer acetate, the method comprising:
- providing a batch of a composition comprising glatiramer acetate manufactured by a method 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;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotect TFA-protected lysines to generate glatiramer acetate,
- measuring the amount of pyroglutamate (pyro-Glu) produced during manufacture of glatiramer acetate in a sample of the batch;
- selecting the batch for use in the preparation of a pharmaceutical composition when the amount of pyro-Glu in the sample of the batch is less than 7000 ppm;
- and
- preparing a pharmaceutical composition comprising at least a portion of the selected batch.
A method for preparing a pharmaceutical composition comprising
- glatiramer acetate, 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;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotect TFA-protected lysines to generate glatiramer acetate;
- and purifying the glatiramer acetate,
- wherein the improvement comprises:
- measuring the amount of pyro-glutamate (pyro-Glu) in the purified glatiramer acetate,
- selecting the purified glatiramer acetate for use in the preparation of a pharmaceutical composition when the amount of pyro-Glu in the purified glatiramer acetate is less than 7000 ppm, and
- preparing a pharmaceutical composition comprising at least a portion of the selected purified glatiramer acetate.
Dependencies are inferred from the claim text.