Patent ID: 6737401
Filing Date: 2004-05-18
Classification: A61K,A61M,G01N

Abstract:
A method of evaluating the physical stability of a protein formulation, wherein the protein is susceptible to changes in its native conformation that yield non-native conformers of the protein that are preferentially bound by a spectroscopic agent, the method comprising:(a) preparing a statistically relevant number of identical samples of a protein formulation to yield a first sample type, wherein the protein within the protein formulation is susceptible to changes in its native conformation yielding non-native conformers of the protein; (b) preparing a statistically relevant number of identical samples of at least one other protein formulation that differs from the first sample type to yield a second, or more, sample types, wherein the protein within at least one other protein formulation is susceptible to a changes in its native conformation yielding non-native conformers of the protein; wherein the samples prepared in steps (a) and (b) further comprise a spectroscopic agent that exhibits a change in spectra when bound to a non-native conformer of the protein; (c) applying a controlled stress on all sample types, wherein the controlled stress applied is an interfacial tension or a physical, photochemical or thermal stress which causes the protein to exhibit a change in its native conformation; (d) monitoring the observable signal produced by the spectroscopic agent in the samples types to yield time-dependent data that are related to a degree of protein conformational change for each sample type; (e) applying a survival analysis to the data obtained for each sample type; and (f) comparing the survival analysis for each sample type to determine the relative physical stability of the protein formulations under evaluation.