Granted Patent B2

US 12,618,855 · App. 17/766,556 · Granted May 5, 2026

Inventors: William D. Hardie (Lebanon, OH); Assem Ziady (Newport, KY); Bethany Moore (Ann Arbor, MI)

Assignees: Children's Hospital Medical Center; University of Michigan

G01N33/6893G01N2800/12G01N2800/52

Abstract

Claims (23)

1 . A method for assessing stable versus progressive pulmonary fibrosis disease status in an individual in need thereof, comprising

a. detecting a level of one or more biomarkers in a biomarker panel comprising Ephrin B2, Epidermal Growth Factor, Ferritin-heavy chain, Apotransferrin, Phosphoinositide 3-kinase, Mdm2-binding protein isoform X3, Tubulin polyglutamylase TTLL13 isoform X7, Heparin sulfate glucosamine 3-O-sulfotransferase 2, in a biological sample obtained from the individual;

b. comparing the level of the one or more biomarkers to that of a control value;

c. based on a comparison of the one or more biomarker level to a control value, characterizing the disease status in said individual as either progressive or stable; and

d. where the disease status is determined to be progressive, administering a treatment to the individual selected from one or more of a PI3K pathway inhibitor, an EGF pathway inhibitor, Pirfenidone, and Nintendanib.

2 . The method of claim 1 , the biomarker panel further comprising a biomarker selected from pregnancy zone protein, serotransferrin, alpha-2-macroglobulin, immunoglobulin lambda-like polypeptide 5, ceruloplasmin, alpha-1-antitrypsin precursor, complement C3 preproprotein, coiled-coil domain-containing protein 144A, cytochrome P450 3A43, myosin phosphatase Rho-interacting protein, collagen alpha-6 (IV) chain protein FAM110A, DNA polymerase epsilon catalytic subunit A, semaphorin-5B ephrin type-B receptor 1, zinc finger protein 532, tyrosine—tRNA ligase (cytoplasmic), mismatch repair endonuclease PMS2, cadherin EGF LAG seven-pass G-type receptor, cytoskeleton-associated protein 2, tyrosine—tRNA ligase (cytoplasmic), zinc finger protein 618, cytoskeleton-associated protein 2, alpha-2-macroglobulin, serine/threonine-protein kinase OSR1, collagen alpha-1 (XII) chain, zinc finger ZZ-type and EF-hand domain-containing protein 1, iporin, phospholipid-transporting ATPase IG, collagen alpha-6 (IV) chain, spatacsin, short stature homeobox protein 2, collagen alpha-1 (XII) chain, ubiquitin carboxyl-terminal hydrolase 28, phospholipid-transporting ATPase IG, cyclin-dependent kinase 13, A-kinase anchor protein 9, zinc finger protein 417, sorting nexin-13, hemoglobin subunit beta, hemoglobin subunit delta, hemoglobin subunit alpha, cytochrome P450 3A4 isoform, filamin-C, apolipoprotein A-IV, nebulin, SAA2-SAA2 protein precursor, plasminogen isoform 1 precursor, ATPase family AAA domain-containing protein 5, DNA damage-induced apoptosis suppressor protein, E3 ubiquitin-protein ligase Midline-1, mitogen-activated protein kinase kinase kinase kinase 1, mucin-16, probable E3 ubiquitin-protein ligase HECTD4, protein RRP5 homolog, retrotransposon Gag-like protein 9, serine/threonine-protein phosphatase 2A regulatory subunit B″ subunit gamma, and uncharacterized protein C12orf42.

3 . The method of claim 1 , further comprising identifying said individual as having improved disease, progressing disease, or a plateau in disease.

4 . The method of claim 1 , wherein an alteration in the biomarker level compared to the control level indicates the presence of disease or progression of disease.

5 . The method of claim 1 , wherein a second comparison step is carried out following administration of the treatment, wherein a return to the biomarker level to that of a control value indicates an improvement in disease.

6 . The method of claim 1 , wherein the pulmonary fibrosis disease is selected from progressive pulmonary fibrosis, interstitial lung disease (ILD), and idiopathic pulmonary fibrosis (IPF).

7 . The method of claim 1 , wherein the treatment is selected from erlotinib, cetuximab, panitumumab, lapatinib, and canertinib.

8 . The method of claim 1 , wherein the individual has one or more predispositions selected from a familial history of IPF, age of 60 years or greater, and a history of chronic smoking.

9 . A method of diagnosing and treating a pulmonary disease in an individual in need thereof, comprising

a) establishing, using a computing system, a model for characterizing a disease state of an individual having or likely to have a pulmonary disease, by using expression level data of a biomarker panel comprising Ephrin B2, Epidermal Growth Factor, Ferritin-heavy chain, Apotransferrin, Phosphoinositide 3-kinase, Mdm2-binding protein isoform X3, Tubulin polyglutamylase TTLL13 isoform X7, and Heparin sulfate glucosamine 3-O-sulfotransferase 2;

b) contacting a biological sample from said individual with at least one detection agent capable of specifically binding to one or more biomarkers of the biomarker panel;

c) acquiring an expression level from the one or more biomarkers measured from said biological sample;

d) characterizing the individual as one or more of likely to have a lung disease, having stable lung disease, having progressive lung disease, or having improving lung disease; and

e) administering a therapy to said individual based on the characterization, wherein the therapy is selected from one or more of a PI3K pathway inhibitor, an EGF pathway inhibitor, Pirfenidone, and Nintendanib.

10 . The method of claim 9 , wherein said disease is idiopathic pulmonary fibrosis (IPF).

11 . The method of claim 1 , wherein the biological sample is a plasma sample.

12 . The method of claim 9 , wherein the biological sample is a plasma sample.

13 . The method of claim 1 , wherein each of the one or more biomarkers is a protein biomarker.

14 . The method of claim 9 , wherein each of the one or more biomarkers is a protein biomarker.

Assignments (1)

Continuity (3)

References Cited (390)