# US 2019/0170732 A1 · Targeting fibroblast invasion for pulmonary fibrosis

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- Number: US 2019/0170732 A1
- Document ID: US20190170732A1
- Status: Published application
- Kind: A1
- Application number: 15/761,404
- Filed: 2016-09-26
- Published: 2019-06-06
- Earliest claimed: 2015-09-25
- Assignees: Cedars-Sinai Medical Center
- Applicants: Cedars-Sinai Medical Center
- Inventors: Paul W. Noble; Dianhua Jiang; Carol Jiurong Liang
- Web page: https://patentgrep.com/patent/US20190170732A1

## CPC

- G01N 33/5044: {involving specific cell types}
- A61P 11/00: Drugs for disorders of the respiratory system
- G01N 2500/02: Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
- G01N 2800/12: Pulmonary diseases
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The described invention provides a method for identifying a therapeutic compound effective to reduce invasiveness of fibroblasts characterized by a highly invasive phenotype obtained from a subject with idiopathic pulmonary fibrosis.

## Claims

### Claim 1

A method for identifying a therapeutic compound effective to reduce invasiveness of fibroblasts characterized by a highly invasive phenotype obtained from a subject with idiopathic pulmonary fibrosis, comprising
a. Purifying a population of the fibroblasts characterized by a highly invasive phenotype by:
i. Confirming expression of cell surface markers Krtap2-3′high and Patched1negative by the invasive fibroblasts by flow cytometry;
ii. isolating and establishing single cell clones based on expression of the cell surface markers;
iii. Transfecting into IPF fibroblasts one or more mammalian expression pcDNA3-XFP vectors selected from the group of Krtap23-GFP, PODXL-RFP, CD127-CFP and PTCH1-mCherry comprising a promoter of Krtap23, PODXL, CD127, or Patched1 inserted upstream of the fluorescent protein tag;
iv. Selecting positive cells of XFP expression; and
v. Determining cell marker expression, matrix production, proliferation, survival, migration and invasive capacity of the transfected cells,
b. Contacting the population of fibroblasts characterized by the highly invasive phenotype with a prospective therapeutic compound; and
c. Reducing invasiveness of the fibroblasts as measured in an invasiveness assay, with minimal impact on normal lung fibroblasts with a non-invasive phenotype.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the highly invasive phenotype comprises differential expression of one or more of genes Krtap2-3, Involucrin, PODXL, IL7R, GPNMB, VAMP1, Patched1.

### Claim 3 (depends on 1)

The method according to claim 1, wherein transcriptional control of the invasive phenotype comprises upregulation of one or more transcriptional factors selected from TAF12, MGA2, and BNC1 and downregulation of one or more transcriptional factors selected from NR4A2 and NEAT1.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the therapeutic compound is a short hairpin RNA.
