Assay for measurement of antibodies binding to a therapeutic monoclonal antibody
AssigneeRoche Diagnostics Operations, Inc.
InventorsVeit Peter Grunert, Ursula Klause, Pavel Kubalec, Matthias Rothfuss, Barbara Upmeier
Life of this patent
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Abstract
Methods and system for determination of an anti-<therapeutic monoclonal antibody> antibody (anti-<TmAB>AB) in vitro in a sample from a patient treated with a therapeutic monoclonal antibody (TmAB). Also, methods and systems for the determination of antigen specific antibodies of a particular immunoglobulin class and for the identification of a patient who is at risk of developing an adverse drug reaction (ADR) during treatment with a TmAB.
Claims20
A method for determination of an anti-<therapeutic monoclonal antibody> antibody (anti <TmAB> AB) in a sample from a patient treated with a therapeutic monoclonal antibody (TmAB), the method comprising:
- a) providing a F(ab) fragment of the TmAB bound to a solid phase;
- b) incubating the solid phase with the sample, whereby the anti <TmAB>AB binds to the F(ab) fragment bound to the solid phase;
- c) incubating the solid phase with a monoclonal antibody <h-Agg.-IgG>, whereby the monoclonal antibody binds to the anti <TmAB> AB bound to the F(ab) fragment;
- and
- d) detecting the monoclonal antibody <h-Agg.-IgG> bound in to anti <TmAB> AB bound to the F(ab) fragment bound to the solid phase.
A method for facilitating a therapeutic decision in a subject, comprising:
- a) obtaining a sample from a subject being treated with a first therapeutic monoclonal antibody (TmAB);
- b) providing a F(ab) fragment of the first TmAB bound to a solid phase;
- c) incubating the solid phase with the sample, whereby an anti <first TmAB> AB binds to the F(ab) fragment bound to the solid phase;
- d) incubating the solid phase with a monoclonal antibody <h-Agg.-IgG>, whereby the monoclonal antibody binds to the anti <first TmAB> AB bound to the F(ab) fragment;
- e) detecting the monoclonal antibody <h-Agg.-IgG> bound to the anti <first TmAB> AB bound to the F(ab) fragment bound to the solid phase;
- and
- f) selecting a second TmAB for future therapy of the subject, if anti <first TmAB> AB is detected in said step of detecting.
The method according to 11, wherein the second TmAB is selected from the group consisting of an anti-<TNFα> monoclonal antibody and rituximab.
A system for facilitating a therapeutic decision in a subject being treated with a therapeutic monoclonal antibody (TmAB), comprising:
- an array having a solid phase and a plurality of test areas spatially separated by inert area of the solid phase, at least one of the plurality of test areas having a F(ab) fragment of the TmAB bound thereto;
- a binding buffer for facilitating the binding of an anti <therapeutic monoclonal antibody> antibody (anti <TmAB> AB) in a sample from the subject with the F(ab) fragment;
- a monoclonal antibody <h-Agg.-IgG> having specific binding affinity for the anti <TmAB> AB bound to the F(ab) fragment;
- a wash buffer for aiding in the removal of monoclinal antibody <h-Agg.-IgG> exposed to the array which is not bound to the anti <TmAB> AB;
- and
- a detection means for detection of the monoclinal antibody <h-Agg.-IgG> bound to the anti <TmAB> AB bound to the F(ab) fragment bound to the solid phase of the array.
Dependencies are inferred from the claim text.