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US 12,656,343 B2Granted
Biomarkers of early osteoarthritis
AssigneeCD Diagnostics, Inc.
InventorsKrista Toler, James W. Stave, Michael Brown, Carolina Sepulveda, Tony Joaquim
Life of this patent
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Abstract
Biomarkers are used in compositions, combinations, systems, and methods for diagnosing, staging, and monitoring and/or treatment of osteoarthritis. The biomarkers discriminate osteoarthritis from rheumatoid arthritis, crystalline arthritis, septic arthritis, and/or traumatic injury, and can be used in a differential diagnosis of joint pain and/or joint inflammation.
Claims20
A method of evaluating a synovial fluid, comprising:
- extracting a synovial fluid sample from a painful or inflamed joint of a subject;
- determining a level of a first biomarker in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA) or mass spectrometry, the first biomarker selected from cartilage oligomeric matrix protein (COMP), osteopontin (OPN), osteoprotegerin (O1G), and osteocalcin (OC);
- determining a level of a second biomarker in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric assay, or mass spectrometry, the second biomarker selected from interleukin-8 (IL-8), interleukin-6 (IL-6), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3), neutrophil gelatinase-associated lipocalin (NGAL), and a platelet-derived growth factor (PDGF);
- determining a sample biomarker ratio of the levels of the first biomarker and the second biomarker in the synovial fluid sample;
- comparing the sample biomarker ratio to a reference ratio of the levels of the first biomarker and the second biomarker in a reference synovial fluid;
- and
- and
- administering a treatment to the subject based on the comparing step, wherein when the sample biomarker ratio is greater than or equal to the reference ratio, the treatment comprises a therapy for osteoarthritis selected from the group consisting of:
- viscosupplementation, hyaluronic acid, platelet-rich plasma, a disease-modifying osteoarthritis drug, and a corticosteroid, and wherein when the sample biomarker ratio is less than the reference ratio, the treatment comprises a therapy for inflammatory arthropathy selected from the group consisting of:
- a disease-modifying antirheumatic drug, a biologic response modifier, a corticosteroid, and a nonsteroidal anti-inflammatory drug.
7 more elements
A method of evaluating a synovial fluid, comprising:
- extracting a synovial fluid sample from a painful or inflamed joint of a subject;
- determining a level of a first biomarker in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA) or mass spectrometry, the first biomarker selected from cartilage oligomeric matrix protein (COMP), osteopontin (OPN), osteoprotegerin (O1G), and osteocalcin (OC);
- comparing the level of the first biomarker in the synovial fluid sample to a reference level of the first biomarker;
- determining a level of a second biomarker in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA) or mass spectrometry when the level of the first biomarker is greater than or equal to the reference level of the first biomarker, the second biomarker selected from interleukin-8 (IL-8), interleukin-6 (IL-6), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3), neutrophil gelatinase-associated lipocalin (NGAL), and a platelet-derived growth factor (PDGF);
- and
- administering a treatment to the subject, wherein when the level of the first biomarker is greater than or equal to the reference level of the first biomarker, the treatment comprises a therapy for osteoarthritis selected from the group consisting of:
- viscosupplementation, hyaluronic acid, platelet-rich plasma, a disease-modifying osteoarthritis drug, and a corticosteroid, and wherein when the level of the first biomarker is less than the reference level of the first biomarker, the treatment comprises a therapy for inflammatory arthropathy selected from the group consisting of:
- a disease-modifying antirheumatic drug, a biologic response modifier, a corticosteroid, and a nonsteroidal anti-inflammatory drug.
5 more elements
A method of evaluating joint pain or joint inflammation in a subject, comprising:
- extracting a synovial fluid sample from the joint;
- determining a level of cartilage oligomeric matrix protein (COMP) in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric assay, or mass spectrometry;
- and
- determining a level of interleukin-8 (IL-8) in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA) or mass spectrometry when the level of COMP is greater than or equal to 1,500 ng/ml and administering a therapy for osteoarthritis selected from the group consisting of:
- viscosupplementation, hyaluronic acid, platelet-rich plasma, a disease-modifying osteoarthritis drug, and a corticosteroid to the subject, or determining the presence of anti-cyclic citrullinated peptide (anti-CCP1) or rheumatoid factor (RF) in the synovial fluid sample using an analytical technique selected from enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric assay, or mass spectrometry when the level of COMP is less than 1,500 ng/mL and administering a therapy for inflammatory arthropathy selected from the group consisting of:
- a disease-modifying antirheumatic drug, a biologic response modifier, a corticosteroid, and a nonsteroidal anti-inflammatory drug to the subject.
3 more elements
Dependencies are inferred from the claim text.