Autoantibody enhanced immunoassays and kits

• US 8,574,858 B2
• Filed: 10/02/2012
• Issued: 11/05/2013
• Est. Priority Date: 12/03/2009
• Status: Active Grant

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Adamczyk, Maciej, Brashear, Roy Jeffrey, Mattingly, Phillip G.
• Primary Examiner(s): COOK, LISA V
• Application Number:
  US13/633,551
• Publication Number:
  US 20130029353A1
• Time in Patent Office: 399 Days
• Field of Search: None
• US Class Current: 435/7.21
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays

Abstract

The present disclosure provides immunoassays and kits for detection or quantification of an analyte of interest in a test sample that potentially contains endogenously produced autoantibodies reactive with the analyte.

Claims

1. An immunodetection composition comprising:

a) a first detection complex comprising a first antibody reactive with an analyte of interest and bound to a solid phase, the analyte of interest, and a second antibody reactive with the analyte of interest, wherein the second antibody has a detectable label; and

b) a second detection complex comprising an autoantibody reactive with the analyte of interest and bound to the solid phase, the analyte of interest, and the second antibody,

wherein the first and second complexes generate a measurable optical, electrical, or change-of-state signal from the detectable label.

2. The composition according to claim 1, wherein the first detection complex is bound to the second detection complex on the solid phase.

3. The composition of claim 1, wherein the second antibody is conjugated to a detectable label, wherein the detectable label is an enzyme, oligonucleotide, nanoparticle chemiluminophore, fluorophore, fluorescence quencher, chemiluminescence quencher, or biotin.

4. The composition of claims 1 or 2, wherein the optical signal is measured as an analyte concentration dependent change in chemiluminescence, fluorescence, phosphorescence, electrochemiluminescence, ultraviolet absorption, visible absorption, infrared absorption, refraction, surface plasmon resonance.

5. The composition of claims 1 or 2, wherein the electrical signal is measured as an analyte concentration dependent change in current, resistance, potential, mass to charge ratio, or ion count.

6. The composition of claims 1 or 2, wherein the change-of-state signal is measured as an analyte concentration dependent change in size, solubility, mass, or resonance.

7. The composition of claim 1, wherein the analyte of interest is a cardiac troponin, thyroid stimulating hormone (TSH), beta human chorionic gonadotropin (beta-HCG);

myeloperoxidase (MPO), prostate specific antigen (PSA), human B-type natriuretic peptide (BNP), myosin light chain 2, myosin-6 or myosin-7.

8. The composition of claim 1, wherein the test sample is whole blood, serum, plasma.

9. The composition of claim 3, wherein the detectable label is an acridinium-9-carboxamide having a structure according to formula I:

10. The composition of claim 3, wherein the detectable label is an acridinium-9-carboxylate aryl ester having a structure according to formula II:

11. The composition of claim 1, wherein the solid phase is selected from the group consisting of a magnetic particle, bead, test tube, microtiter plate, cuvette, membrane, a scaffolding molecule, quartz crystal, film, filter paper, disc and chip.

12. The composition of claim 1, wherein the first antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a human antibody, and an affinity maturated antibody.

13. The composition of claim 1, wherein the second antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a human antibody, and an affinity maturated antibody.