IP Library › Granted Patent US 9,726,677
Granted Patent B2
US 9,726,677 · App. 14/213,970 · Granted Aug 8, 2017

Proteomic IPF markers

Inventors: Karl Kossen (Burlingame, CA); Xiaoli Qin (San Mateo, CA); Sharlene R. Lim (San Mateo, CA); Scott S. Seiwert (Half Moon Bay, CA); Donald Ruhrmund (San Francisco, CA)
Assignee: INTERMUNE, INC.
G01N33/6893C12Q1/6883G01N33/6854C12Q2600/118C12Q2600/158G01N2800/12
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Quick Facts
Patent No.
US 9,726,677
App. No.
14/213,970
Granted
Aug 8, 2017
Kind
B2
Abstract

Provided herein are novel biomarkers for the identification, prediction or monitoring of fibrotic pulmonary diseases (e.g. idiopathic pulmonary fibrosis (IPF)). The biomarkers provided herein may further be used for therapeutic treatment of IPF.

Claims (36)

1. A method of determining an expression level of each of a plurality of fibrotic pulmonary disease marker proteins in a subject that has or is at risk for developing a fibrotic pulmonary disease, said method comprising:

(i) obtaining a biological sample from said subject;

(ii) contacting each of said plurality of fibrotic pulmonary disease marker proteins with a marker protein binding agent for each of said plurality of fibrotic pulmonary disease marker proteins in said biological sample thereby forming disease marker protein-binding agent complexes; and

(iii) detecting said disease marker protein-binding agent complexes thereby determining an expression level of each of said plurality of fibrotic pulmonary disease marker proteins in said biological sample,

wherein said plurality of fibrotic pulmonary disease marker proteins consists of TIMP-1, MMP-7, PTN, Activin A, HGF, Midkine, SIEGE-121, PDE3A, SBDS, DKK-4, SICAM-5, SREC-I, ERIK-1, DKK-1, α2-Macroglobulin, NAGK, UFC1 and SGTA.

2. The method of claim 1 , further comprising selecting a subject that has or is at risk for developing a fibrotic pulmonary disease for treatment of said fibrotic pulmonary disease when said expression level of one or more of said plurality of pulmonary disease marker proteins as set forth in claim 1 is elevated relative to a standard control.

3. The method of claim 1 , wherein said fibrotic pulmonary disease is idiopathic pulmonary fibrosis or familial interstitial pneumonia.

4. The method of claim 1 , wherein said subject has or is at risk for developing a progressive fibrotic pulmonary disease.

5. The method of claim 4 , wherein said progressive fibrotic pulmonary disease is progressive idiopathic pulmonary fibrosis.

6. The method of claim 1 , wherein said biological sample is a blood-derived biological sample of said subject.

7. The method of claim 1 , wherein said expression level of one or more of said plurality of fibrotic pulmonary disease marker proteins as set forth in claim 1 is elevated relative to a standard control.

8. The method of claim 1 , wherein said expression level of one or more of said plurality of fibrotic pulmonary disease marker proteins as set forth in claim 1 is decreased relative to a standard control.

9. A method of treating a fibrotic pulmonary disease in a subject said method comprising:

(i) obtaining a biological sample from said subject;

(ii) contacting one or more fibrotic pulmonary disease marker proteins with a marker protein binding agent for each of said one or more of fibrotic pulmonary disease marker proteins in said biological sample thereby forming one or more disease marker protein-binding agent complexes;

(iii) detecting said one or more disease marker protein-binding agent complexes thereby detecting an expression level of said one or more fibrotic pulmonary disease marker proteins in said subject;

(iv) determining whether said expression level of said one or more fibrotic pulmonary marker proteins is increased or decreased relative to a standard control, wherein an elevated expression level of said one or more fibrotic pulmonary disease marker proteins or a decreased expression level of said one or more fibrotic pulmonary disease marker proteins relative to said standard control indicates that said subject has or is at risk of developing a fibrotic pulmonary disease; and

(v) based at least in part on said expression level detected in step (iii) and the presence of one or more additional characteristics of fibrotic pulmonary disease in said subject determining said subject has or is at risk for developing a fibrotic pulmonary disease; and

(vi) administering to said subject that has or is at risk for developing a fibrotic pulmonary disease an effective amount of a steroid or a TGF-β inhibitor;

wherein said one or more fibrotic pulmonary disease marker proteins is selected from the group consisting of:

(a) a plurality of fibrotic pulmonary disease marker proteins consisting of TIMP-1, MMP-7, PTN, Activin A, HGF, Midkine, VEGF-121, PDE3A, SBDS, DKK-4, SICAM-5, SREC-I, ERK-1, DKK-1, α2-Macroglobulin, NAGK, UFC1 and SGTA wherein the expression level of each of said plurality of fibrotic pulmonary disease marker proteins is determined;

(b) SREC-I; and

(c) PTN.

10. The method of claim 9 , wherein said subject has or is at risk for developing a progressive fibrotic pulmonary disease.

11. The method of claim 10 , wherein said progressive fibrotic pulmonary disease is progressive idiopathic pulmonary fibrosis.

12. A method of treating a fibrotic pulmonary disease in a subject in need thereof the method comprising:

(i) obtaining a biological sample from said subject;

(ii) contacting one or more fibrotic pulmonary disease marker proteins with a marker protein binding agent for each of said one or more of fibrotic pulmonary disease marker proteins in said biological sample forming thereby one or more disease marker protein-binding agent complexes;

(iii) detecting said one or more disease marker protein-binding agent complexes thereby detecting an expression level of said one or more fibrotic pulmonary disease marker proteins in said fibrotic pulmonary disease patient;

(iv) determining whether said expression level of said one or more fibrotic pulmonary marker proteins is modulated relative to a standard control, wherein a modulated expression level of said one or more fibrotic pulmonary disease marker protein relative to said standard control indicates that said fibrotic pulmonary disease patient is at risk for progression of said fibrotic pulmonary disease; and

(v) based at least in part on said expression level in step (iv) and the presence of one or more additional characteristics of fibrotic pulmonary disease in said subject, determining said fibrotic pulmonary disease patient is at risk for progression of said fibrotic pulmonary disease; and

(vi) administering to said subject that has or is at risk for developing a fibrotic pulmonary disease an effective amount of a steroid or a TGF-β inhibitor,

wherein said one or more fibrotic pulmonary disease marker proteins is selected from the group consisting of:

(a) a plurality of fibrotic pulmonary disease marker proteins consisting of TIMP-1, MMP-7, PTN, Activin A, HGF, Midkine, VEGF-121, PDE3A, SBDS, DKK-4, SCAM-5, SREC-I, ERK-1, DKK-1, α2-Macroglobulin, NAGK, UFC1 and SGTA wherein the expression level of each of said plurality of fibrotic pulmonary disease marker proteins is determined;

(b) SREC-I; and

(c) PTN.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2024
From: INTERMUNE, INC.
To: GENENTECH, INC.
Reel/Frame 066998/0231 →
CHANGE OF ASSIGNEE ADDRESS Recorded Dec 20, 2018
From: INTERMUNE, INC.
To: INTERMUNE, INC.
Reel/Frame 047969/0276 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 7, 2014
From: KOSSEN, KARL; QIN, XIAOLI; LIM, SHARLENE R.; SEIWERT, SCOTT S.; RUHRMUND, DONALD
To: INTERMUNE, INC.
Reel/Frame 033486/0001 →
Continuity (4)
Provisional Application 61801290 · Mar 15, 2013
Provisional Application 61801476 · Mar 15, 2013
Provisional Application 61874947 · Sep 6, 2013
Related Publication 20140286929A1 · Sep 25, 2014