IP Library Granted Patent US 10,119,168
Granted Patent B2
US 10,119,168 · App. 15/124,450 · Granted Nov 6, 2018

Methods for the treatment of kidney fibrosis

Inventors: Vishal S. Vaidya (Cambridge, MA); Florin Craciun (Wellesley, MA); Amrendra K. Ajay (Boston, MA)
Assignee: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
C12Q1/6883A61K31/519C12Q1/68C12Q2600/106C12Q2600/118C12Q2600/158
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Quick Facts
Patent No.
US 10,119,168
App. No.
15/124,450
Granted
Nov 6, 2018
Kind
B2
Abstract

The technology described herein is directed to the diagnosis, prognosis, and treatment of kidney fibrosis, e.g., chronic kidney disease.

Claims (32)

1. A method of treatment for kidney fibrosis or chronic kidney disease comprising;

selecting a subject determined to have

i. an increased level of expression of at least one gene selected from the group consisting of:

ADAM metallopeptidase with thrombospondin type 1 motif 16 (Adamts16); C-C motif chemokine ligand 2 (Ccl2); C-C motif chemokine ligand 6 (Ccl6); C-C motif chemokine ligand 15 (Ccl15); C-C motif chemokine ligand 9 (Ccl9); C-C motif chemokine receptor 2 (Ccr2); claudin 3 (Cldn3); Collagen type III alpha 1 chain (Col3a1); Collagen type VIII alpha 1 chain (Col8a1); caboxypeptidase N subunit 1 (Cpn1); Endothelin 1 (Edn1); adhesion G protein-coupled receptor E1 (Emr1); fibronectin 1 (Fn1); gamma-aminobutyric acid type A receptor pi subunit (Gabrp); histocompatibility 2, class II, locus Mb1 (H2-Dmb1); major histocompatibility complex, class II, DM beta (HLA-DMB); integrin subunit alpha M (Itgam); lipopolysaccharide binding protein (Lbp); lysozyme 2 (Lyz2); lysozyme (Lyz); matrix Gla protein (Mgp); matrix metallopeptidase 7 (Mmp7); mannose receptor C-type 1 (Mrc1); NFAT activating protein with ITAM motif 1 (Nfam1); neuropeptide Y receptor Y6 (Npy6r); podoplanin (Pdpn); phospholipase D family member 4 (Pld4); phospholipid transfer protein (Pltp); sodium voltage-gated channel, alpha subunit alpha (Scn7a); semaphorin 3D (Sema3d); serpin family E member 2 (Serpine2); SPARC related modular calcium binding 2 (Smoc2); stimulated by retinoic acid 6 (Stra6); synaptotagmin like 2 (Sytl2); tenascin C (Tnc); and TYRO protein tyrosine kinase binding protein (Tyrobp)

as compared to a reference level, in a urine sample obtained from the subject;

ii. normal levels of a) serum creatine orb) urinary albumin or protein; administering to the subject at least one of:

a) a dialysis treatment; and

b) at least one compound selected from the group consisting of:

an ACE inhibitor; an angiotensin II receptor blocker (ARB); D vitamin supplementation; or an antagonist of the at least one selected gene.

2. The method of claim 1 , wherein the at least one gene is selected from the group consisting of:

Gabrp; Mgp; Pld4; Smoc2; Mrc1; Sytl2; Stra6; Scn7a; Sema3d; Pdpn; and Pltp.

3. The method of claim 1 , wherein the at least one gene is selected from the group consisting of:

Gabrp; Mgp; Pld4; Smoc2; Mrc1; Sytl2; Stra6; Scn7a; and Pltp.

4. The method of claim 1 , wherein the at least one gene is selected from the group consisting of:

Mrc1; Pltp; Smoc2 and MGP.

5. The method of claim 1 , wherein the kidney fibrosis is chronic progressive fibrosis.

6. The method of claim 1 , wherein the expression level of the at least one gene is the level of a nucleic acid.

7. The method of claim 1 , wherein the expression level of the at least one gene is the level of the gene's polypeptide expression product.

8. The method of claim 1 , wherein the reference level is the expression level in a prior sample obtained from the subject.

9. The method of claim 1 , wherein the at least one gene includes at least two genes from the group consisting of:

Adamts16; Ccl2; Ccl6; Ccl15; Ccl9; Ccr2; Cldn3; Col3a1; Col8a1; Cpn1; Edn1; Emr1; Fn1; Gabrp; H2-Dmb1; HLA-DMB; Itgam; Lbp; Lyz2; Lyz; Mgp; Mmp7; Mrc1; Nfam1; Npy6r; Pdpn; Pld4; Pltp; Scn7a; Sema3d; Serpine2; Smoc2; Stra6; Sytl2; Tnc; and Tyrobp.

10. The method of claim 1 , wherein the at least one gene is selected from the group

consisting of:

Pltp; Smoc2 and MGP.

11. The method of claim 1 , wherein the at least one gene is Smoc2.

12. A method of treatment for kidney fibrosis or chronic kidney disease comprising;

selecting a subject determined to have

i. an increased level of expression of SPARC related modular calcium binding 2 (Smoc2); as compared to a reference level, in a urine sample obtained from the subject; and

ii. normal levels of a) serum creatine or b) urinary albumin or protein; administering to the subject

at least one of

a) a dialysis treatment; and

b) at least one compound selected from the group consisting of: an ACE inhibitor; an angiotensin II receptor blocker (ARB); D vitamin supplementation; or an antagonist of Smoc2.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 11, 2018
From: BRIGHAM AND WOMEN'S HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 047768/0566 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 19, 2016
From: VAIDYA, VISHAL S; CRACIUN, FLORIN; AJAY, AMRENDRA K
To: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
Reel/Frame 040066/0569 →
Continuity (2)
Provisional Application 61951778 · Mar 12, 2014
Related Publication 20170037472A1 · Feb 9, 2017
Cited By (2)
US 12,338,437 US 12,577,561