Granted Patent B2

US 12,618,111 · App. 17/513,693 · Granted May 5, 2026

Inventors: Rebecca Gonsky (Los Angeles, CA); Stephan R. Targan (Santa Monica, CA); Richard L. Deem (Azusa, CA); Philip Fleshner (Los Angeles, CA); Dermot P. Mcgovern (Los Angeles, CA); Janine Bilsborough (Los Angeles, CA)

Assignee: CEDARS-SINAI MEDICAL CENTER

C12Q1/6883C12Q1/6806C12Q1/6834C12Q1/686C12Q2600/106C12Q2600/154C12Q2600/156G01N2800/065

Abstract

Claims (28)

1 . A method of treating inflammatory bowel disease (IBD) in a subject,

the method comprising administering a therapeutically effective amount of an anti-Tumor Necrosis Factor Ligand 1 (anti-TL1A) antibody to the subject,

wherein the subject has been identified as having one or more RNase T2 (RNASET2) gene alleles selected from the group consisting of an “A” allele of rs1819333, a “T” allele of rs2149092, a “G” allele of rs9355610, a “T” allele of rs2149085, a “G” allele of rs1410295, and a “G” allele of rs9366093, and

wherein methylation of the RNASET2 gene of the subject is increased as compared to a control subject who has not been diagnosed with IBD.

2 . The method of claim 1 , wherein the inflammatory bowel disease (IBD) is Crohn's disease (CD).

3 . The method of claim 1 , wherein the subject is refractory to one or both of thiopurine and anti-Tumor Necrosis Factor (anti-TNF) therapy.

4 . The method of claim 1 , wherein the subject is determined to need surgical intervention for disease management or wherein the subject has undergone surgical intervention for disease management.

5 . The method of claim 4 , wherein the surgical intervention is intestinal resection.

6 . A method of identifying a subject having inflammatory bowel disease (IBD) who is likely to benefit from treatment with an anti-Tumor Necrosis Factor Ligand 1 (anti-TL1A) antibody, wherein the method comprises:

a) assessing a biological sample from the subject to determine the presence or absence of one or more RNase T2 (RNASET2) gene alleles selected from the group consisting of an “A” allele of rs1819333, a “T” allele of rs2149092, a “G” allele of rs9355610, a “T” allele of rs2149085, a “G” allele of rs1410295, and a “G” allele of rs9366093; and

b) assessing the biological sample from the subject to determine a level of methylation of RNASET2;

wherein the presence of one or more of the alleles and/or increased methylation of RNASET2 indicates that the subject is likely to benefit from treatment with the anti-TL1A antibody.

7 . The method of claim 6 , wherein the inflammatory bowel disease (IBD) is Crohn's disease (CD).

8 . The method of claim 6 , wherein the subject is refractory to one or both of thiopurine and anti-Tumor Necrosis Factor (anti-TNF) therapy.

9 . The method of claim 6 , wherein the subject is determined to need surgical intervention for disease management or wherein the subject had surgical intervention for disease management.

10 . The method of claim 9 , wherein the surgical intervention is intestinal resection.

11 . A method of treating inflammatory bowel disease (IBD) in a subject,

the method comprising administering a therapeutically effective amount of an anti-Tumor Necrosis Factor Ligand 1 (anti-TL1A) antibody to the subject,

wherein the subject has been identified as having each of an “A” RNase T2 (RNASET2) gene allele of rs1819333, a “G” RNASET2 allele of rs9355610, and a “T” RNASET2 allele of rs2149085.

12 . The method of claim 1 , wherein the inflammatory bowel disease (IBD) is ulcerative colitis (UC) or medically refractive ulcerative colitis (mrUC).

13 . The method of claim 6 , wherein the inflammatory bowel disease (IBD) is ulcerative colitis (UC) or medically refractive ulcerative colitis (mrUC).

14 . The method of claim 1 , wherein the anti-TL1A antibody comprises a neutralizing TL1A antibody.

15 . The method of claim 6 , wherein the anti-TL1A antibody comprises a neutralizing TL1A antibody.

16 . The method of claim 1 , wherein the subject is anti-neutrophil cytoplasmic antibody (ANCA) seropositive.

17 . The method of claim 1 , wherein the subject is identified as having the one or more RNASET2 gene alleles by analysis of samples isolated from the peripheral T cells and/or small bowel surgical resections of the subject.

18 . The method of claim 6 , wherein the subject is identified as having the one or more RNASET2 gene alleles by analysis of samples isolated from the peripheral T cells and/or small bowel surgical resections of the subject.

19 . The method of claim 1 , wherein the subject has been identified as having one or more of the “T” allele of rs2149085, the “T” allele of rs2149092, and the “A” allele of rs1819333.

20 . The method of claim 6 , wherein the subject has been identified as having one or more of the “T” allele of rs2149085, the “T” allele of rs2149092, and the “A” allele of rs1819333.

Assignments (1)

Continuity (4)

References Cited (400)