# US 2025/0164480 A1 · Biomarkers and methods for assessing response to inflammatory disease therapy

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- Number: US 2025/0164480 A1
- Document ID: US20250164480A1
- Status: Published application
- Kind: A1
- Application number: 19/027,907
- Filed: 2025-01-17
- Published: 2025-05-22
- Earliest claimed: 2016-04-20
- Assignees: Laboratory Corporation of America Holdings
- Applicants: Laboratory Corporation of America Holdings
- Inventors: Paul Scott Eastman; William Manning
- Web page: https://patentgrep.com/patent/US20250164480A1

## CPC

- 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}
- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B 40/20: Supervised data analysis
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G16H 50/50: for simulation or modelling of medical disorders
- C12Q 2600/00: Oligonucleotides characterized by their use
- G01N 2800/102: Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
- 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 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis
- 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)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Provided herein are methods for assessing response to inflammatory disease therapy. The methods include performing immunoassays to generate scores based on quantitative data for expression of biomarkers relating to inflammatory biomarkers to assess disease activity in inflammatory diseases, e.g., rheumatoid arthritis. Also provided are uses of inflammatory biomarkers for guiding treatment decisions.

## Claims

### Claim 1

A method for assessing rheumatoid arthritis (RA) disease activity in a subject, the method comprising:
performing at least one immunoassay on a first blood sample from the subject to generate a first dataset comprising protein level data for at least two protein markers, wherein the at least two protein markers comprise at least two markers selected from Serum Amyloid P-component (SAP), Cathepsin D (CPSD), Chemerin (TIG2), alpha-1-Microglobulin (AIM), Haptoglobin (Hp), Pigment Epithelium Derived Factor (PEDF), Clusterin (CLU), Tissue type Plasminogen activator (tPA), C-reactive protein (CRP), Monocyte Chemotactic Protein 4 (MCP-4), Alpha-I-acid glycoprotein 1 (AGP-1), Connecting Peptide (C-Peptide), Complement Factor H (CFH), Pulmonary and Activation-Regulated chemokine (PARC), growth-regulated alpha protein (GRO-alpha), Sex Hormone-Binding Globulin (SHBG), Matrix Metalloproteinase-7 (MMP-7), Growth/differentiation factor 15 (GDF-15), Fibroblast Growth Factor 21 (FGF-21), Angiopoietin-related protein 3 (ANGPTL3), Hemopexin (HPX), FASLG Receptor (FAS), Receptor for Advanced Glycosylation End products (RAGE), CD5 Antigen-like (CD5L), Endoglin (ENG), von Willebrand Factor (vWF), Apolipoprotein C-III (Apo C-III), Interleukin-1 receptor antagonist (IL-1ra), Ficolin-3 (FCN3), Peroxiredoxin-4 (Prx-IV), ST2 cardiac biomarker (ST2), Sortilin (SORT1), Tumor necrosis factor ligand superfamily member 12 (Tweak), Phosphoserine Aminotrasferase (PSAT), Heparin-Binding EGF-Like Growth Factor (HB-EGF), Interleukin-8 (IL-8), Beta-2-Microglobulin (B2M), Apolipoprotein E (Apo E), Urokinase-type Plasminogen Activator (uPA), Adrenomedullin (ADM), Urokinase-type plasminogen, activator receptor (uPAR), Tetranectin (TN), E-Selectin (ESEL), Monokine Induced by Gamma Interferon (MIG), Glucagon-like Peptide 1, total (GLP-1 total), Interleukin-12 Subunit p40 (IL-12p40), Cartilage Oligomeric Matric protein (COMP), Apolipoprotein H (Apo H), Factor VII (F7), Interferon-inducible T-cell alpha chemoattractant (ITAC), Antileukoproteinase (ALP), Thymus and activation-regulated chemokine (TARC), Plasminogen Activator Inhibitor 1 (PAI-1), Ceruloplasmin (CP), Complement Factor H-Related Protein 1 (CFHR1), Protein DJ-1 (DJ-1), Alpha-Fetoprotein (AFP), Chemokine CC-4 (HCC-4), Ferritin (FRTN), Interleukin-15 (IL-15), Immunoglobulin A (IgA), thrombin-Activatable Fibrinolysis (TAFI), Cystatin-B (CSTB), Alpha-1-Antichymotrypsin (AACT) Pancreatic Polypeptide (PPP), Heat-Shock Protein 70 (HSP-70), Transferrin Receptor Protein (TFR1), Tamm-Horsfall Urinary Glycoprotein (THP) Tenascin-C (TN-C), pepsinogen 1 (PG1), Hepatocyte Growth Factor (HGF), T-Cell-Specific Pro-tein RANTES (RANTES), Tumor Necrosis Factor Receptor 2 (TNFR2), Macrophage Colony-Stimulating Factor 1 (M-CSF), Beta Amyloid 1-40 (AB-40), cystatin-C, Tissue Inhibitor of Metalloproteinases 3 (TIMP-3), Insulin-like Growth Factor binding Protein 4 (IGFBP4), Gastric Inhibitory Polypeptide (GIP), Midkine (MDK), Angiogenin (ANG), Stem Cell Factor (SCF), Myeloid Progenitor Inhibitory Factor 1 (MPIF-1), Osteoprotegerin (OPG), CD 40 antigen (CD40), Monocyte Chemotactic Protein 2 (MCP-2), Insulin-like Growth Factor-binding Protein 1 (IGFBP-1), Vitamin K-Dependent Protein S (VKDPS), Hepatocyte Growth Factor Receptor (HGFR), Brain-Derived Neurotrophic Factor (BDNF), Macrophage-Stimulating Protein (MSP), or Monocyte Chemotactic Protein 1 (MCP-1); and
determining a first RA disease activity score from the first dataset using an interpretation function, wherein said first RA disease activity score provides a quantitative measure of RA disease activity in said subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the at least two protein markers comprise at least two markers selected from CPSD, SAP, PEDF, C-Peptide, tPA, TIG2, or FAS.

### Claim 3 (depends on 1)

The method of claim 1, wherein the at least two protein markers comprise at least two markers selected from CPSD, A1M, TIG2, C-Peptide, tPA, SHBG, GDF-15, Hp, CD5L, AGP-1, CLU, FAS, CRP, CFH, RAGE, FGF-21, vWF, CRP, AACT, CSTB, ST2, TAFI, uPA, TN, Prx-IV, Tweak, PSAT, GLP-1 total, or IL-15.

### Claim 4 (depends on 1)

The method of claim 1, wherein the at least two protein markers comprise at least two markers selected from CPSD, PEDF, SAP, SHBG, A1M, tPA, AGP-1, TIG2, CD5L, FAS, C-Peptide, CRP, PSAT, uPA, GIP, Prx-IV, HGF, or IL-15.

### Claim 5 (depends on 1)

The method of claim 1, wherein performance of the at least one immunoassay comprises:
obtaining the first blood sample, wherein the first blood sample comprises the protein markers;
contacting the first blood sample with a plurality of distinct reagents;
generating a plurality of distinct complexes between the reagents and markers; and
detecting the complexes to generate the data.

### Claim 6 (depends on 1)

The method of claim 1, wherein the at least one immunoassay comprises a multiplex assay.

### Claim 7 (depends on 1)

The method of claim 1, wherein the interpretation function is based on a predictive model.

### Claim 8 (depends on 1)

The method of claim 1, further comprising:
receiving a second dataset associated with a second sample obtained from said subject, wherein said first sample and said second sample are obtained from said subject at different times;
determining a second RA disease activity score from said second dataset using said interpretation function; and comparing said first RA disease activity score and said second disease activity score to determine a change in said first and second RA disease activity scores, wherein said changes indicates a change in said RA disease activity in said subject.

### Claim 9 (depends on 8)

The method of claim 8, wherein said change in said first and second RA disease activity scores indicates the presence, absence, or extent of the subject's response to a therapeutic regimen.

### Claim 10

A method for determining the presence or absence of rheumatoid arthritis (RA) in a subject, the method comprising:
performing at least one immunoassay on a first blood sample from the subject to generate a first dataset comprising protein level data for at least two protein markers, wherein the at least two protein markers comprise at least two markers selected from Serum Amyloid P-component (SAP), Cathepsin D (CPSD), Chemerin (TIG2), alpha-1-Microglobulin (AIM), Haptoglobin (Hp), Pigment Epithelium Derived Factor (PEDF), Clusterin (CLU), Tissue type Plasminogen activator (tPA), C-reactive protein (CRP), Monocyte Chemotactic Protein 4 (MCP-4), Alpha-I-acid glycoprotein 1 (AGP-1), Connecting Peptide (C-Peptide), Complement Factor H (CFH), Pulmonary and Activation-Regulated chemokine (PARC), growth-regulated alpha protein (GRO-alpha), Sex Hormone-Binding Globulin (SHBG), Matrix Metalloproteinase-7 (MMP-7), Growth/differentiation factor 15 (GDF-15), Fibroblast Growth Factor 21 (FGF-21), Angiopoietin-related protein 3 (ANGPTL3), Hemopexin (HPX), FASLG Receptor (FAS), Receptor for Advanced Glycosylation End products (RAGE), CD5 Antigen-like (CD5L), Endoglin (ENG), von Willebrand Factor (vWF), Apolipoprotein C-III (Apo C-III), Interleukin-1 receptor antagonist (IL-1ra), Ficolin-3 (FCN3), Peroxiredoxin-4 (Prx-IV), ST2 cardiac biomarker (ST2), Sortilin (SORT1), Tumor necrosis factor ligand superfamily member 12 (Tweak), Phosphoserine Aminotrasferase (PSAT), Heparin-Binding EGF-Like Growth Factor (HB-EGF), Interleukin-8 (IL-8), Beta-2-Microglobulin (B2M), Apolipoprotein E (Apo E), Urokinase-type Plasminogen Activator (uPA), Adrenomedullin (ADM), Urokinase-type plasminogen, activator receptor (uPAR), Tetranectin (TN), E-Selectin (ESEL), Monokine Induced by Gamma Interferon (MIG), Glucagon-like Peptide 1, total (GLP-1 total), Interleukin-12 Subunit p40 (IL-12p40), Cartilage Oligomeric Matric protein (COMP), Apolipoprotein H (Apo H), Factor VII (F7), Interferon-inducible T-cell alpha chemoattractant (ITAC), Antileukoproteinase (ALP), Thymus and activation-regulated chemokine (TARC), Plasminogen Activator Inhibitor 1 (PAI-1), Ceruloplasmin (CP), Complement Factor H-Related Protein 1 (CFHR1), Protein DJ-1 (DJ-1), Alpha-Fetoprotein (AFP), Chemokine CC-4 (HCC-4), Ferritin (FRTN), Interleukin-15 (IL-15), Immunoglobulin A (IgA), thrombin-Activatable Fibrinolysis (TAFI), Cystatin-B (CSTB), Alpha-1-Antichymotrypsin (AACT) Pancreatic Polypeptide (PPP), Heat-Shock Protein 70 (HSP-70), Transferrin Receptor Protein (TFR1), Tamm-Horsfall Urinary Glycoprotein (THP) Tenascin-C (TN-C), pepsinogen 1 (PG1), Hepatocyte Growth Factor (HGF), T-Cell-Specific Pro-tein RANTES (RANTES), Tumor Necrosis Factor Receptor 2 (TNFR2), Macrophage Colony-Stimulating Factor 1 (M-CSF), Beta Amyloid 1-40 (AB-40), cystatin-C, Tissue Inhibitor of Metalloproteinases 3 (TIMP-3), Insulin-like Growth Factor binding Protein 4 (IGFBP4), Gastric Inhibitory Polypeptide (GIP), Midkine (MDK), Angiogenin (ANG), Stem Cell Factor (SCF), Myeloid Progenitor Inhibitory Factor 1 (MPIF-1), Osteoprotegerin (OPG), CD 40 antigen (CD40), Monocyte Chemotactic Protein 2 (MCP-2), Insulin-like Growth Factor-binding Protein 1 (IGFBP-1), Vitamin K-Dependent Protein S (VKDPS), Hepatocyte Growth Factor Receptor (HGFR), Brain-Derived Neurotrophic Factor (BDNF), Macrophage-Stimulating Protein (MSP), or Monocyte Chemotactic Protein 1 (MCP-1);
determining a first RA disease score from the first dataset using an interpretation function;
determining an aggregate RA disease score from subjects in a population wherein said subjects are negative for RA;
comparing the first RA disease score from the first dataset to the aggregate RA disease score; and
determining a presence or absence of RA in said subject based on said comparison.

### Claim 11 (depends on 10)

The method of claim 10, wherein the at least two protein markers comprise at least two markers selected from CPSD, SAP, PEDF, C-Peptide, tPA, TIG2, or FAS.

### Claim 12 (depends on 10)

The method of claim 10, wherein the at least two protein markers comprise at least two markers selected from CPSD, A1M, TIG2, C-Peptide, tPA, SHBG, GDF-15, Hp, CD5L, AGP-1, CLU, FAS, CRP, CFH, RAGE, FGF-21, vWF, CRP, AACT, CSTB, ST2, TAFI, uPA, TN, Prx-IV, Tweak, PSAT, GLP-1 total, or IL-15.

### Claim 13 (depends on 10)

The method of claim 10, wherein the at least two protein markers comprise at least two markers selected from CPSD, PEDF, SAP, SHBG, A1M, tPA, AGP-1, TIG2, CD5L, FAS, C-Peptide, CRP, PSAT, uPA, GIP, Prx-IV, HGF, or IL-15.

### Claim 14 (depends on 10)

The method of claim 10, wherein performance of the at least one immunoassay comprises:
obtaining the first blood sample, wherein the first blood sample comprises the protein markers;
contacting the first blood sample with a plurality of distinct reagents;
generating a plurality of distinct complexes between the reagents and markers; and
detecting the complexes to generate the data.

### Claim 15 (depends on 10)

The method of claim 10, wherein the at least one immunoassay comprises a multiplex assay.

### Claim 16 (depends on 10)

The method of claim 10, wherein the interpretation function is based on a predictive model.

### Claim 17 (depends on 10)

The method of claim 10, further comprising: receiving a second dataset associated with a second sample obtained from said subject, wherein said first sample and said second sample are obtained from said subject at different times;
determining a second RA activity score from said second dataset using said interpretation function; and
comparing said first RA disease activity score and said second disease activity score to determine a change in said presence or absence of RA.

### Claim 18 (depends on 17)

The method of claim 17, wherein said change in said RA activity score indicates the presence, absence, or extent of the subject's response to a therapeutic regimen.