ASSAYS FOR DETECTING NEUTRALIZING AUTOANTIBODIES TO BIOLOGIC THERAPY

摘要

The present invention provides assays for detecting and measuring the presence or level of neutralizing and non-neutralizing autoantibodies to biologics such as anti-TNFα drug therapeutics in a sample. The present invention is useful for monitoring the formation of neutralizing and/or non-neutralizing anti-drug antibodies over time while a subject is on biologic therapy. The present invention is also useful for predicting and/or determining the cross-reactivity of neutralizing anti-drug antibodies in a subject's sample with alternative biologic therapies. As such, the present invention provides information for guiding treatment decisions for those subjects receiving therapy with a biologic agent and improves the accuracy of optimizing therapy, reducing toxicity, and/or monitoring the efficacy of therapeutic treatment to biologic therapy.

主权项

1. A method for measuring the level or percent of a neutralizing form of an autoantibody to an anti-TNFα drug in a sample, the method comprising:
(a) contacting the sample with a labeled anti-TNFα drug and a labeled TNFα to form:
(i) a first labeled complex of the labeled anti-TNFα drug and the autoantibody; and/or(ii) a second labeled complex of the labeled anti-TNFα drug, the labeled TNFα, and the autoantibody; (b) subjecting the first labeled complex and/or the second labeled complex to size exclusion chromatography to separate them from free labeled TNFα, free labeled anti-TNFα drug, and/or a complex of labeled anti-TNFα drug and labeled TNFα; (c) measuring the level of free labeled TNFα after size exclusion chromatography; and (d) comparing the level of free labeled TNFα measured in step (c) to a normalized level or percent of free labeled TNFα in a control sample, wherein the normalized level or percent of the free labeled TNFα in the control sample corresponds to the level or percent of a neutralizing form of the autoantibody.