# US 2013/0157892 A1 · Assay for measurement of antibodies binding to a therapeutic monoclonal antibody > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0157892 A1 - Document ID: US20130157892A1 - Status: Published application - Kind: A1 - Application number: 13/766,130 - Filed: 2013-02-13 - Published: 2013-06-20 - Earliest claimed: 2010-08-19 - Assignees: Roche Diagnostics Operations, Inc. - Inventors: Veit Peter Grunert; Ursula Klause; Pavel Kubalec; Matthias Rothfuss; Barbara Upmeier - Web page: https://patentgrep.com/patent/US20130157892A1 ## CPC - G01N 33/6854: {Immunoglobulins} - C40B 30/04: by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60) ## Abstract Methods and system for determination of an anti- antibody (anti-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. ## Claims ### Claim 1 A method for determination of an anti- antibody (anti 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 AB binds to the F(ab) fragment bound to the solid phase; c) incubating the solid phase with a monoclonal antibody , whereby the monoclonal antibody binds to the anti AB bound to the F(ab) fragment; and d) detecting the monoclonal antibody bound in to anti AB bound to the F(ab) fragment bound to the solid phase. ### Claim 2 (depends on 1) The method according to claim 1, wherein the sample is selected from the group consisting of whole blood, serum and plasma. ### Claim 3 (depends on 1) The method according to claim 1, wherein the TmAB is selected from the group consisting of chimeric antibodies (CA) and humanized antibodies (HA). ### Claim 4 (depends on 1) The method according to claim 1, wherein the TmAB is selected from the group consisting of infliximab, adalimumab, certolizumab and rituximab. ### Claim 5 (depends on 1) The method according to claim 1, wherein the F(ab) fragment is bound to the solid phase by a binding system selected from the group consisting of biotin/steptavidin, biotin/avidin, and biotin/anti- antibody. ### Claim 6 (depends on 1) The method according to claim 1, wherein the monoclonal antibody is an antibody having a dissociation constant (KD) value of between approximately 10−6 mol/l-10−8 mol/l. ### Claim 7 (depends on 1) The method according to claim 1, wherein the monoclonal antibody is labeled. ### Claim 8 (depends on 7) The method according to claim 7, wherein the monoclonal antibody is labeled with Dig. ### Claim 9 (depends on 8) The method according to claim 8, wherein the Dig-labeled monoclonal antibody is detected by incubating with an anti- antibody conjugated to a detectable label. ### Claim 10 (depends on 9) The method according to claim 9, wherein the detectable label is selected from the group consisting of luminescent labels, chemiluminescent labels, electrochemiluminescent labels, fluorescent labels, and radioactive labels. ### Claim 11 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 AB binds to the F(ab) fragment bound to the solid phase; d) incubating the solid phase with a monoclonal antibody , whereby the monoclonal antibody binds to the anti AB bound to the F(ab) fragment; e) detecting the monoclonal antibody bound to the anti 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 AB is detected in said step of detecting. ### Claim 12 (depends on 11) The method according to claim 11, wherein the sample is obtained from the subject no later than 14 weeks after first administration of the first TmAB. ### Claim 13 The method according to 11, wherein the second TmAB is selected from the group consisting of an anti- monoclonal antibody and rituximab. ### Claim 14 (depends on 11) The method according to claim 11, wherein the second TmAB is selected from the group consisting of infliximab, adalimumab, and certolizumab. ### Claim 15 (depends on 11) The method according to claim 11, wherein the first TmAB is an anti- monoclonal antibody and the second TmAB is rituximab. ### Claim 16 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 antibody (anti AB) in a sample from the subject with the F(ab) fragment; a monoclonal antibody having specific binding affinity for the anti AB bound to the F(ab) fragment; a wash buffer for aiding in the removal of monoclinal antibody exposed to the array which is not bound to the anti AB; and a detection means for detection of the monoclinal antibody bound to the anti AB bound to the F(ab) fragment bound to the solid phase of the array. ### Claim 17 (depends on 16) The system of claim 16, wherein the solid phase is comprised of polysterene. ### Claim 18 (depends on 16) The system of claim 16, wherein the monoclonal antibody comprises a digoxigenin label. ### Claim 19 (depends on 18) The system of claim 18, wherein the detection means comprises an anti antibody with a detectable label. ### Claim 20 (depends on 19) The system of claim 19, wherein the detectable label is selected from the group consisting of a fluorescent label, a peroxidase enzyme, and a ruthenium label.