Assays for the detection of anti-TNF drugs and autoantibodies
Inventors
Singh, Sharat • Wang, Shui-Long • Ohrmund, Linda
Assignees
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Publication Number
US-10386366-B2
Publication Date
2019-08-20
Expiration Date
Abstract
The present invention provides assays for detecting and measuring the presence or level of anti-TNFα drug therapeutics and autoantibodies in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNFα drug therapeutics to detect the presence or level of autoantibodies (e.g., HACA and/or HAHA) against the drug.
Core Innovation
A method is described for optimizing therapy and/or reducing toxicity to an anti-TNFα drug in a subject receiving therapy with the anti-TNFα drug. The method includes measuring the level of the anti-TNFα drug in a first sample and measuring the level of an autoantibody to the anti-TNFα drug in a second sample, and determining a subsequent course of therapy based on both measured levels.
The anti-TNFα drug level is measured by contacting the first sample with labeled TNFα to form a first complex comprising the labeled TNFα with the anti-TNFα drug, detecting the amount of the first complex by size exclusion chromatography, and comparing the detected amount to a standard curve of known amounts of the anti-TNFα drug. The autoantibody level is measured in the second sample, and the subsequent course of therapy is determined based on the levels of the anti-TNFα drug and the autoantibody.
The assay format is a homogeneous mix-and-read mobility shift detection approach implemented using size exclusion chromatography with fluorescent labels, and it separates bound versus free labeled TNFα/anti-TNFα complexes without wash steps. The method supports use during ongoing therapy when drug is present and enables standard-curve quantitation, optionally including internal controls, to support therapy optimization and reduce toxicity by adjusting dose or switching anti-TNFα therapy based on measured drug and autoantibody levels.
Claims Coverage
The document provides one independent claim that defines a method for optimizing therapy and/or reducing toxicity using two measurements, anti-TNFα drug level and anti-TNFα autoantibody level, followed by determination of a subsequent course of therapy. The anti-TNFα drug level is measured by a labeled TNFα size-exclusion chromatography assay with a standard curve. Dependent claims refine the method by specifying autoantibody classes, measurement formats, sample types, and decision rules.
Optimizing therapy and/or reducing toxicity using measured anti-TNFα drug and autoantibody levels
A method for optimizing therapy and/or reducing toxicity to an anti-TNFα drug in a subject receiving therapy with said anti-TNFα drug by measuring the level of said anti-TNFα drug in a first sample and measuring the level of an autoantibody to said anti-TNFα drug in a second sample, then determining a subsequent course of therapy based upon the levels of said anti-TNFα drug and said autoantibody.
Measuring anti-TNFα drug level by labeled TNFα complex detection with size exclusion chromatography and standard curve
Measuring the level of said anti-TNFα drug in said first sample by contacting said first sample with an amount of a labeled TNFα to form a first complex comprising said labeled TNFα with said anti-TNFα drug; detecting an amount of said first complex by size exclusion chromatography; and comparing the amount detected to a standard curve of known amounts of the anti-TNFα drug.
Determining subsequent course of therapy based on measured anti-TNFα drug and autoantibody levels
Determining a subsequent course of therapy for said subject based upon the levels of said anti-TNFα drug and said autoantibody, thereby optimizing therapy and/or reducing toxicity to said anti-TNFα drug.
Using specified autoantibody classes (HAMA, HACA, HAHA)
Selecting the autoantibody to be measured from HAMA, HACA, HAHA, or combinations thereof.
Measuring autoantibody level via labeled anti-TNFα drug–autoantibody complex detected by size exclusion chromatography
Measuring an autoantibody level by forming a labeled anti-TNFα drug–autoantibody complex from a second sample and detecting that complex by size exclusion chromatography.
Refining therapy course based on high anti-TNFα levels and low autoantibody levels with immunosuppressive co-administration
Providing a therapy in which an immunosuppressive drug is co-administered with an anti-TNFα drug when anti-TNFα levels are high and autoantibody levels are low.
Using serum samples for both measurements
Performing the method using both a first and a second sample that are serum samples.
Overall claim coverage centers on using a dual measurement strategy, anti-TNFα drug level and anti-TNFα autoantibody level, to determine a subsequent course of anti-TNFα therapy aimed at optimizing therapy and/or reducing toxicity, with the anti-TNFα drug level measured by detecting labeled TNFα/anti-TNFα complexes using size exclusion chromatography and a standard curve. Dependent refinements include specified autoantibody classes, autoantibody measurement via labeled anti-TNFα drug–autoantibody complex detection by size exclusion chromatography, serum sampling, and therapy decision rules such as immunosuppressive co-administration under high drug and low autoantibody conditions.
Stated Advantages
Optimizing therapy and/or reducing toxicity to an anti-TNFα drug in a subject receiving therapy.
Enabling measurement of anti-TNFα drug level using a size exclusion chromatography assay with a standard curve.
Allowing determination of a subsequent course of therapy based on both anti-TNFα drug and autoantibody levels.
Documented Applications
Therapy optimization and/or reducing toxicity to an anti-TNFα drug in a subject receiving anti-TNFα therapy based on measured anti-TNFα drug and autoantibody levels.
Therapy decision support including dose adjustment or switching anti-TNFα therapy based on measured drug and autoantibody levels.
Reducing toxicity by co-administering an immunosuppressive drug with an anti-TNFα drug when anti-TNFα levels are high and autoantibody levels are low.
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