Marker panels for idiopathic pulmonary fibrosis diagnosis and evaluation
Inventors
Kaminski, Naftali • Gibson, Kevin F. • Gochuico, Bernadette R. • Richards, Thomas J. • Rosas, Ivan • Konishi, Kazuhisa • Selman, Moises • Herazo-Maya, Jose David • Noth, Imre
Assignees
INSTITUTO NACIONAL DE ENFERMEDADES RESPIRATORIAS ISMAEL COSIO VILLEGAS • Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas DF • University of Chicago • University of Pittsburgh • US Department of Health and Human Services
Publication Number
US-8846341-B2
Publication Date
2014-09-30
Expiration Date
2029-09-04
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention relates to the discovery that of a panel of serum or plasma markers may be used to diagnose Idiopathic Pulmonary Fibrosis (“IPF”) and distinguish this condition from other lung ailments. It further relates to the identification of markers associated with IPF disease progression.
Core Innovation
The invention relates to the discovery that panels of serum or plasma markers may be used to diagnose Idiopathic Pulmonary Fibrosis (IPF) and distinguish this condition from other lung diseases. It further relates to the identification of markers associated with IPF disease progression.
IPF is a progressive fibrotic interstitial lung disease characterized by alveolar epithelial cell injury and activation, fibroblast/myofibroblast foci formation, and exaggerated accumulation of extracellular matrix in the lung parenchyma. Existing diagnostic approaches such as surgical lung biopsy and high-resolution computed tomography (HRCT) can be invasive or lack molecular assessment. Peripheral blood biomarkers have not been well established to facilitate diagnosis, follow-up, or therapeutic intervention. Existing markers examined were limited in scope or not specific to IPF.
The invention is based on discovering that increases in plasma levels of MMP7, MMP1, and MMP8, as well as IGFBP1 and/or TNFRSF1A, indicate a diagnosis of IPF with high sensitivity and specificity, and a decrease in AGER further confirms diagnosis. Additional markers such as increased SFTPD, MEG3, ID-1 and decreased IL-4, ICOS, or CCR7 support diagnosis. Further, specific markers including increases in plasma MMP7, DEFA-1, DEFA-2, DEFA-3, S100A12, CCNA2, and IL12P40 are associated with progression of IPF.
Claims Coverage
The patent contains several independent claims relating to methods of identifying progression of IPF, evaluation of lung transplant recommendations, and kits for diagnosing or evaluating IPF progression by measuring specific markers.
Method of identifying progression of IPF by measuring specific markers
A method of identifying progression of idiopathic pulmonary fibrosis in a subject by measuring serum or plasma levels of MMP7, DEFA-1, DEFA-2, DEFA-3, S100A12, and IL12P40 mRNA or protein using a kit that does not contain means for determining more than twenty other markers, wherein increases in these markers indicate progression of IPF.
Method of evaluating lung transplant recommendation based on marker levels
A method of evaluating whether a lung transplant is recommended or should be performed by identifying progression of IPF through measuring the levels of the aforementioned markers (MMP7, DEFA-1, DEFA-2, DEFA-3, S100A12, and IL12P40 mRNA or protein) and recommending transplant if increases are detected.
Kit for evaluating progression of IPF comprising means for specific markers
A kit comprising means for determining serum or plasma levels of MMP7, DEFA-1, DEFA-2, DEFA-3, S100A12, and IL12P40, excluding means for more than twenty other markers.
Measurement modalities employing nucleic acid hybridization or amplification assays
Methods where mRNA levels of the markers are measured by nucleic acid hybridization assays, including microarray assays, or nucleic acid amplification assays, such as quantitative reverse transcriptase-PCR.
Measurement modalities employing immunoassays for protein detection
Methods where protein levels of the markers are measured via immunoassays including enzyme-linked immunosorbent assays (ELISA).
Use of capture agents on solid supports in kits
Kits where each molecule is detected by capture agents such as antibodies, antibody portions, single chain antibodies, non-immunoglobulin receptors, peptide or oligonucleotide ligands, optionally bound to solid supports like beads.
Inclusion of control markers and detection reagents in kits
Kits that may further include means for determining control serum or plasma markers and reagents for detection, such as labeled secondary antibodies, enzymes, avidin, or streptavidin.
The claims broadly cover methods and kits for diagnosing and evaluating progression of IPF by measuring specific biomarker panels consisting of defined markers at mRNA or protein levels using various detection methods and reagents, emphasizing the exclusion of more than twenty other marker measurements in certain kits, and include applications for prognosis and lung transplant recommendation.
Stated Advantages
Provides blood-based biomarkers capable of diagnosing IPF and distinguishing it from other chronic lung diseases with high sensitivity and specificity.
Enables non-invasive monitoring of disease progression and evaluation of prognosis through measurement of specific plasma markers.
Allows early detection of sub-clinical and familial pulmonary fibrosis and can inform clinical decision-making including lung transplant recommendations.
Documented Applications
Diagnostic assays and kits for identifying idiopathic pulmonary fibrosis by measuring panels of plasma or serum markers.
Methods and kits for evaluating progression of idiopathic pulmonary fibrosis using specific marker panels.
Prognostic evaluation of IPF patients to assess survival likelihood and disease progression.
Methods for guiding clinical decisions such as lung transplant recommendation or performance based on biomarker levels.
Interested in licensing this patent?