Stabilized formulations of peptides and proteins protecting against non-enzymatic degradation

摘要

Stabilization of water-containing solutions or lyophilizates of proteins and peptide against non-enzymatic deamidation degradation reactions at asparaginyl or glutaminyl residues is achieved using organic anions, such as saccharin, benzenesulfonic acid, gentisic acid or N-acetyltryptophan which have a pKa within the range of 0.5 to 3.5.

主权项

1. A peptide or protein composition, comprising:
a. at least one peptide or protein which contains one or more asparaginyl or glutaminyl residues with at least one deamidation prone sequence of -Asn-Gly- protected against non-enzymatic deamidation at at least said deamidation prone sequence, where the peptides or proteins are present in aqueous formulations or lyophilizates; and b. one or more stabilizing anions to form a mixture wherein said stabilizing anions are present in a molar excess to the total number of asparaginyl or glutaminyl residues in said peptides or proteins and are in a molar excess to any destabilizing anions in said mixture, wherein said stabilizing anions are organic compounds that are not zwitterionic where each protic group of said stabilizing anion has a pKa ranging from 0.5 to 3.5, wherein destabilizing anions have at least one protic group that has a pKa of less than 0.5 or greater than 3.5, and wherein said stabilizing anions are selected from the group consisting of saccharin, benzenesulfonic acid, gentisic acid, and N-acetyltryptophan; wherein said mixture includes at least one destabilizing anion and said stabilizing anions are present at a molar excess of at least 3:1 relative to said at least one destabilizing anion.