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Methods of prognosing, diagnosing and treating idiopathic pulmonary fibrosis

A pulmonary fibrosis, idiopathic technology, applied in chemical instruments and methods, biochemical equipment and methods, disease diagnosis, etc., can solve problems such as inconsistent, sub-optimal, targetable molecular mechanisms to understand limited disease trajectories, etc.

Inactive Publication Date: 2015-02-04
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, many of these biomarker studies were conducted in small, nonreplicated cohorts and utilized suboptimal, inconsistent, and / or unvalidated biomarker detection techniques
[0009] Due to the limited understanding of targetable molecular mechanisms, the variability of disease trajectories, and the time and expense of conducting survival studies in unselected IPF patient populations, designing appropriately powered clinical studies to evaluate candidate therapeutics in IPF prolongs The potential for survival is extremely challenging

Method used

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  • Methods of prognosing, diagnosing and treating idiopathic pulmonary fibrosis
  • Methods of prognosing, diagnosing and treating idiopathic pulmonary fibrosis
  • Methods of prognosing, diagnosing and treating idiopathic pulmonary fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0153] Example 1: Identification of Systemic Biomarkers for Survival Prediction in IPF

[0154]To identify molecular biomarkers that could be used to predict survival in IPF, we first performed microarray and qPCR in lung tissues from 40 IPF patients and 8 unused donor controls (“Cohort 1”). gene expression analysis. We then identified candidate predictive serum biomarkers from the gene expression results. Serum levels of candidate predictive serum biomarkers and lung function were assessed in a separate cohort of 80 IPF patients ("Cohort 2") attending the Interstitial Lung Disease Clinic at the University of California, San Francisco when collected. The vital status was followed for 2-8 years after sample collection.

[0155] method

[0156] human lung tissue

[0157] At the University of California, San Francisco Lung Center collects tissue from IPF patients at the time of biopsy or lung transplantation. Non-IPF controls were collected from donor lungs. Additional det...

Embodiment 3II

[0300] Example 3. Phase II Clinical Study

[0301] Research Principle

[0302] IPF is characterized by varying degrees of interstitial fibrosis. The fibrotic process in IPF patients involves several extracellular matrix proteins, including collagen types I, III, and IV, fibronectin, and tenascin-C, with abnormal proliferation of mesenchymal cells, distortion of lung architecture, and subepithelial formation. Generation of fibroblastic foci. IL-13 and IL-4 are strong inducers of tissue fibrosis. In a nonclinical model, transgenic overexpression of IL-13 in mouse lung was sufficient to induce collagen gene expression and severe subepithelial fibrosis (Lee et al. 2001, J Exp Med 194:809-22; Zhu et al. 1999, J Clin Invest 103 :779-88). In contrast, mice targeted for disruption of IL-13 and mice treated with a blocking antibody specific for IL-13 showed reduced extracellular Matrix deposition (Belperio et al. 2002, Am J Respir Cell Mol Biol 27:419-27; Kolodsick et al. 2004, J ...

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Abstract

Compositions, kits and methods for assessing the prognosis of idiopathic pulmonary fibrosis in patients are provided. In addition, compositions, kits and methods for diagnosing subtypes of idiopathic pulmonary fibrosis are provided. Also provided are methods for treating idiopathic pulmonary fibrosis.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 61 / 616,394, filed March 27, 2012, and U.S. Provisional Application No. 61 / 707,411, filed September 28, 2012, both of which are hereby incorporated in their entirety incorporated herein by reference. [0003] sequence listing [0004] This application contains a Sequence Listing which has been submitted in ASCII form via the Electronic Submission System (EFS-Web), and is hereby incorporated by reference in its entirety. This ASCII copy, created on March 6, 2013, is named P4841R1_SequenceListing.txt and is 22,866 bytes in size. technical field [0005] Compositions, kits and methods for assessing the prognosis of idiopathic pulmonary fibrosis in a patient are provided. Additionally, compositions, kits and methods for diagnosing subtypes of idiopathic pulmonary fibrosis are provided. Also provided are methods for treating idiopathic pulmonary fibrosis....

Claims

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Application Information

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IPC IPC(8): C12Q1/68G01N33/53A61K38/00A61K39/395C07K16/00
CPCC12Q1/6883G01N33/6893C12Q2600/158C07K16/244A61K38/00G01N2800/12G01N2800/52C12Q2600/118A61K45/00C07K2317/56C07K2317/565C07K2317/51C07K2317/515C07K2317/76G01N2333/96494G01N2333/775G01N2333/521C12Q2600/112A61P11/00A61K2039/505A61K2039/54A61K2039/545
Inventor A·R·阿巴斯J·R·阿罗恩S·钱德里阿尼G·贾N·J·I·卢因-科赫D·德皮安托
Owner F HOFFMANN LA ROCHE & CO AG
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