Anti-il - 23p19 antibodies modulation of genes involved in ulcerative cholitis

Abstract

To provide alternative compositions and methods for diagnosing and treating inflammatory bowel diseases such as ulcerative colitis.SOLUTION: It was concluded that the expression of a number of genes (determined by measuring changes in gene transcript biomarkers in colonic or rectal tissue samples) occurs in response to treatment with anti-IL-23pl9 antibodies in patients with or suspected of having ulcerative colitis. This gene transcript may be used as a biomarker for diagnosing ulcerative colitis, symptoms of ulcerative colitis, bowel frequency associated with ulcerative colitis, and bowel urgency associated with ulcerative colitis. Genetic transcripts may also be used as biomarkers of successful response to treatment with anti-IL - 23p19 antibodies.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Background technology The present disclosure relates generally to pharmaceuticals. More particularly, the present disclosure relates to pharmaceuticals for treating ulcerative colitis. The method relates to a method for diagnosing ulcerative colitis in a patient having or suspected of having ulcerative colitis. The method is particularly suitable for treating and diagnosing specific subgroups of patients with ulcers. US201301226333A1 - Treating and diagnosing urgency in patients with or suspected of having idiopathic colitis - Google Patents The method is also particularly suitable for administering to patients with or suspected of having ulcerative colitis. It is particularly suitable for treating and diagnosing bowel frequency and bowel urgency in children.

[0002] Ulcerative colitis (UC) is a chronic, relapsing disease characterized by mucosal inflammation of the colon. It is a chronic, immune-mediated inflammatory bowel disease (IBD). Significant morbidity and reduced quality of life result from typical symptoms such as diarrhea, rectal bleeding, and urgency. The goals of treatment are to achieve symptom control (clinical remission) and mucosal healing (endoscopic These include suppressing intestinal inflammation to achieve remission and maintaining intestinal function. Current treatment options include 5-aminosalicylates, glucocorticoids, and thiopurine. and the Janus-Associated Kinase (JAK) inhibitor tofacitinib. , as well as TNFα, the p-40 subunit of IL-12 / IL-23, and α4b7 in However, up to one-third of patients experience induced leukemia. Approximately 40% of patients who initially benefit from induction therapy subsequently lose their response. Therapy has recently been shown to be associated with potentially serious side effects. blocking the IL-1 receptor, thereby reducing lymphocyte trafficking to the intestinal mucosa and reducing mucosal inflammation; Newer classes of biologics present more favorable safety profiles. Vedolizumab, an α4β7 integrin blocker, is effective in treating moderate to severe UC. and was shown to be more effective than the TNF inhibitor adalimumab.

[0003] Interleukin-23 (IL-23) is a novel therapeutic target in IBD. It is a heterodimer consisting of the p19 and p40 subunits shared with L-12. IL-23 receptor binding is mediated by JAKs (mainly TYK2 and JAK2) ) and transcription factors 3 and 4 (STAT3 and STAT4) signal transduction transducers and activity IL-23 induces the transcription of multiple pro-inflammatory factors and downstream target genes. cytokines (e.g., interferon-γ, IL-17A, IL-17F, and IL- -22) and the differentiation, maintenance, and stabilization of pathogenic T cell lineages, including populations that simultaneously produce Promotes activation and induction of effector functions of innate lymphoid cells. Therapeutic blockade of p40 is effective in both UC and CD, and drugs targeting p19 are effective in both UC and CD. Both have been studied.

[0004] Data from single-cell RNASeq studies demonstrate that inflamed mucosal fibroblasts, tissue-resident The monocytes and dendritic cells in UC patients were significantly higher in anti-TNF resistant ( TNF R These studies suggest that Smi Illie et al. analyzed varicella-positive and varicella-negative leukemia (VLLE) data from 60 responders and 57 non-responders to anti-TNF therapy. Based on a meta-analysis of TNF expression data, R Gene signature of Cell subsets were scored for characteristics (atures, gene expression patterns) and sensitivity. TNF R Immune Associated Fibroblasts (I AF), inflammatory mononuclear cells, and DC2 cells. In contrast, favorable responses to anti-TNF therapy prevailed in UC patients in remission. This is evident in the transcriptome signature of epithelial cells representing healthy mucosa. It was.

[0005] Alternative compositions and methods for diagnosing and treating inflammatory bowel diseases, such as ulcerative colitis, include: It is still needed. Summary of the Invention

[0006] The present disclosure relates generally to methods of treating and diagnosing ulcerative colitis. It is particularly suitable for treating and diagnosing specific subgroups of patients with colitis. The method is also particularly suitable for treating and diagnosing urgency in patients with ulcerative colitis. The method is also suitable for treating bowel frequency and bowel urgency in patients with ulcerative colitis. It is particularly suitable for therapeutic and diagnostic purposes.

[0007] The present inventors have performed a quantitative analysis of gene transcript biomarkers in colon or rectal tissue samples. The expression of a number of genes (determined by measuring changes) is associated with ulcerative colitis. that occurs in response to treatment of patients with or suspected of having IL-23p19 antibodies. We concluded that this gene transcript is involved in ulcerative colitis, ulcerative colitis symptoms, and ulcerative colitis-related diseases. and biomarkers for diagnosing bowel urgency associated with ulcerative colitis. The gene transcripts may also be used as a test for the response to treatment with anti-IL-23p19 antibodies. , may be used as a biomarker of a successful response.

[0008] Thus, in a first aspect of the present invention, a subject having or suspected of having ulcerative colitis is A method of treating ulcerative colitis in a patient is provided, the method comprising: Obtaining a first sample from the patient and analyzing the first sample to detect CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. detecting a number of administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. and detecting a plurality of signals (possibly multiple signals), wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the wherein a change in the expression level of the IL-23p19 gene is indicative of a response to the anti-IL-23p19 antibody.

[0009] A further aspect of the invention provides an anti-IL-23p19 antibody for use in the treatment of ulcerative colitis. The body is provided, but this treatment Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1 P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIG D1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRP M6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, T One or more selected from MEM236, CD177P1, SLC17A4, and ZG16 detecting one or more gene transcript biomarker(s) of the gene; administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. and detecting a plurality of signals (possibly multiple signals), wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0010] In a still further aspect of the invention, a method for the manufacture of a medicament for use in the treatment of ulcerative colitis is provided. The present invention provides the use of an anti-IL-23p19 antibody in Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1 P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIG D1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRP M6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, T One or more selected from MEM236, CD177P1, SLC17A4, and ZG16 detecting one or more gene transcript biomarker(s) of the gene; administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. and detecting a plurality of signals (possibly multiple signals), wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0011] In a further aspect of the invention, in a patient having or suspected of having ulcerative colitis A method of treating ulcerative colitis is provided, the method comprising: Obtaining a first sample from a patient; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C Detecting gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C detecting gene transcript biomarker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0012] In a still further aspect of the present invention there is provided an anti-IL-2 antibody for use in the treatment of ulcerative colitis. 3p19 antibodies are provided, but this treatment: Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C Detecting gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C detecting gene transcript biomarker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0013] In a still further aspect of the invention, a method for the manufacture of a medicament for use in the treatment of ulcerative colitis is provided. The present invention provides a use of an anti-IL-23p19 antibody for the treatment of Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C Detecting gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C detecting gene transcript biomarker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0014] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is

[0013] A method of treating symptoms associated with ulcerative colitis in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1 P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIG D1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRP M6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, T One or more selected from MEM236, CD177P1, SLC17A4, and ZG16 detecting one or more gene transcript biomarker(s) of the gene; administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. and detecting a plurality of signals (possibly multiple signals), wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the wherein a change in the expression level of the IL-23p19 gene is indicative of a response to the anti-IL-23p19 antibody.

[0015] In a still further aspect of the invention, a compound comprising: The anti-IL-23p19 antibody for this purpose is provided, but this treatment is Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1 P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIG D1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRP M6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, T One or more selected from MEM236, CD177P1, SLC17A4, and ZG16 detecting one or more gene transcript biomarker(s) of the gene; administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. and detecting a plurality of signals (possibly multiple signals), wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the wherein a change in the expression level of the IL-23p19 gene is indicative of a response to the anti-IL-23p19 antibody.

[0016] In a still further aspect of the invention, a compound comprising: The present invention provides the use of an anti-IL-23p19 antibody for the manufacture of a medicament for the treatment of Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1 P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIG D1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRP M6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, T One or more selected from MEM236, CD177P1, SLC17A4, and ZG16 detecting one or more gene transcript biomarker(s) of the gene; administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and one or more gene transcript biomarkers (multiple) of one or more genes selected from ZG16 and ZG17. and detecting a plurality of signals (possibly multiple signals), wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the wherein a change in the expression level of the IL-23p19 gene is indicative of a response to the anti-IL-23p19 antibody.

[0017] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is

[0013] A method of treating symptoms associated with ulcerative colitis in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C Detecting gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, and ADH1C detecting one or more gene transcript biomarker(s) of one or more genes involved in the and from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to the anti-IL-23p19 antibody.

[0018] In a still further aspect of the invention, a compound comprising: The anti-IL-23p19 antibody for this purpose is provided, but this treatment is Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C Detecting gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, and ADH1C detecting one or more gene transcript biomarker(s) of one or more genes involved in the and from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to the anti-IL-23p19 antibody.

[0019] In a still further aspect of the invention, a compound comprising: There is provided the use of an anti-IL-23p19 antibody in the manufacture of a medicament for the treatment of Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to determine the expression of CXCL8, AQP9, IL1B, S100A9, and TREM1. , MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A 14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, One or more genes selected from AQP8, SLC26A2, and ADH1C Detecting gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; Obtaining a second sample from the patient and analyzing the second sample for CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, and ADH1C detecting one or more gene transcript biomarker(s) of one or more genes involved in the and from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to the anti-IL-23p19 antibody.

[0020] Preferably, symptoms include abdominal pain / discomfort, bloody stool, pus in stool, fever, weight loss, rectal discharge One or more of the following symptoms: bloody diarrhea, frequent diarrhea, recurrent diarrhea, fatigue, loss of appetite, and tenesmus (urgency) Above.

[0021] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis and having an anti- Anti-Tumor Necrosis Factor (anti-TNF) therapy resistance R ) Methods for treating patients with or suspected of having IL-23p19 with anti-IL-23p19 antibodies are provided. However, this method Samples were obtained from patients and analyzed for OSMR, FCGR3, CXCL6, interleukin-11, Interleukin-24, interleukin-13RA2, FAP, TWIST1, and one or more anti-tumor necrosis factor (anti-TNF) therapies of one or more genes selected from WNT2 Resistance (anti-TNF R3.) Analyzing the sample for gene transcript biomarker(s). By this, patients are anti-TNF R determining whether If the patient is anti-TNF R treating the patient with an anti-IL-23p19 antibody if include.

[0022] In a still further aspect of the present invention there is provided an anti-IL-2 antibody for use in the treatment of ulcerative colitis. 3p19 antibodies are provided, but this treatment: Patients with or suspected of having ulcerative colitis and who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF R a sample is obtained from a patient having or suspected of having anti-TNF R determining whether OSMR, FCGR3, CXCL6, interleukin-11, interleukin-2 4, interleukin-13RA2, FAP, TWIST1, and WNT2 Resistance to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) in one or more genes R ) legacy analyzing the sample for gene transcript biomarker(s); If the patient is anti-TNF R treating the patient with an anti-IL-23p19 antibody if include.

[0023] In a still further aspect of the invention, a method for the manufacture of a medicament for use in the treatment of ulcerative colitis is provided. The present invention provides the use of an anti-IL-23p19 antibody for the treatment of Patients with or suspected of having ulcerative colitis and who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF R a sample is obtained from a patient having or suspected of having anti-TNF Rdetermining whether OSMR, FCGR3, CXCL6, interleukin-11, interleukin-2 4, interleukin-13RA2, FAP, TWIST1, and WNT2 Resistance to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) in one or more genes R ) legacy analyzing the sample for gene transcript biomarker(s); If the patient is anti-TNF R treating the patient with an anti-IL-23p19 antibody if include.

[0024] Preferably, the method or treatment comprises administering to the patient a therapeutically effective amount of CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, O TOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1 , REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2 , TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A 3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B- AS1, TMEM236, CD177P1, SLC17A4, and ZG16 One or more gene transcript biomarkers for one or more genes involved in the anti-IL-1 Analyzing samples obtained before and after administration of anti-IL-23p19 antibody further including: one or more of the following: Expression levels of gene transcript biomarkers revealed that the efficacy of anti-IL-23p19 antibody was significantly improved after administration of the antibody. The expression levels of one or more gene transcript biomarker(s) detected in the selected samples The changes in the anti-TNF R 1 shows the response to anti-IL-23p19 antibodies in patients.

[0025] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is A method of treating bowel frequency in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample is analyzed to identify one or more gene transcript biomarkers of a gene selected from Table 8. detecting the target(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; The second sample is analyzed to detect one or more gene transcription factors of one or more genes selected from the above. and detecting the biological biomarker(s); from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to anti-IL-23p19 antibodies.

[0026] In a still further aspect of the invention, a method for treating bowel frequency associated with ulcerative colitis is provided. The treatment involves the use of an anti-IL-23p19 antibody. Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample is analyzed to identify one or more gene transcript biomarkers of a gene selected from Table 8. detecting the target(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; The second sample is analyzed to detect one or more gene transcription factors of one or more genes selected from Table 8. and detecting the biological biomarker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0027] In a still further aspect of the invention, a method for treating bowel frequency associated with ulcerative colitis is provided. The present invention provides the use of an anti-IL-23p19 antibody for the manufacture of a medicament for treating IL-23p19, the treatment comprising: Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample is analyzed to identify one or more gene transcript biomarkers of a gene selected from Table 8. detecting the target(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; The second sample is analyzed to detect one or more gene transcription factors of one or more genes selected from Table 8. and detecting the biological biomarker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0028] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is A method of treating bowel frequency in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, Platelet activating factor factor receptor), apoptosis (cell suicide, apoptosis-inducing factor mitochondrial Doria-related 3, Fc fragment of IgG receptor IIb, colony stimulating factor factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane protein 2, calpain 13, RNA polymerase elongation factor of ATPase II2, prokineficin 2, aquaporin 9, and interleukin 1 -leukin-1 alpha, Fc fragment of IgG receptor IIa, TIMP metallopeptidase inhibitor one of the genes selected from cytotoxic substance 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, and Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) for one or more genes selected from and from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to anti-IL-23p19 antibodies.

[0029] In a still further aspect of the invention, a method for treating bowel frequency associated with ulcerative colitis is provided. The treatment involves the use of an anti-IL-23p19 antibody. Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) of a gene selected from and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, and Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) for one or more genes selected from and from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to anti-IL-23p19 antibodies.

[0030] In a still further aspect of the invention, a method for treating bowel frequency associated with ulcerative colitis is provided. The treatment involves the use of an anti-IL-23p19 antibody. Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) of a gene selected from and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, and Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) for one or more genes selected from and from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to anti-IL-23p19 antibodies.

[0031] In a still further aspect of the invention, a method for treating bowel frequency associated with ulcerative colitis is provided. The present invention provides the use of an anti-IL-23p19 antibody for the manufacture of a medicament for treating IL-23p19, the treatment comprising: Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) of a gene selected from and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, and Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B detecting one or more gene transcript biomarker(s) for one or more genes selected from and wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0032] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is

[0013] A method of treating bowel urgency in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample is analyzed to detect one or more gene transcription factors of one or more genes selected from Table 9. Detecting the biological biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; The second sample is analyzed to identify one or more gene transcript biomarkers for one or more genes from Table 9. detecting the marker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0033] In a still further aspect of the invention, a method for treating bowel urgency associated with ulcerative colitis is provided. The treatment involves the use of an anti-IL-23p19 antibody. Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample is analyzed to detect one or more gene transcription factors of one or more genes selected from Table 9. Detecting the biological biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; The second sample is analyzed to identify one or more gene transcript biomarkers for one or more genes from Table 9. detecting the marker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0034] In a still further aspect of the invention, a method for treating bowel urgency associated with ulcerative colitis is provided. The present invention provides the use of an anti-IL-23p19 antibody for the manufacture of a medicament for treating IL-23p19, the treatment comprising: Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample is analyzed to detect one or more gene transcription factors of one or more genes selected from Table 9. Detecting the biological biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; The second sample is analyzed to identify one or more gene transcript biomarkers for one or more genes from Table 9. detecting the marker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0035] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is

[0013] A method of treating bowel urgency in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. detecting one or more gene transcript biomarker(s) of one or more genes involved in the and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. one or more gene transcript biomarkers for one or more genes to be and detecting one or more gene transcript biomarker(s) of the gene; wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0036] In a still further aspect of the invention, a method for treating bowel urgency associated with ulcerative colitis is provided. The treatment involves the use of an anti-IL-23p19 antibody. Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. detecting one or more gene transcript biomarker(s) of one or more genes involved in the and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. one or more gene transcript biomarkers for one or more genes to be and detecting one or more gene transcript biomarker(s) of the gene; wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0037] In a still further aspect of the invention, a method for treating bowel urgency associated with ulcerative colitis is provided. The present invention provides the use of an anti-IL-23p19 antibody for the manufacture of a medicament for treating IL-23p19, the treatment comprising: Obtaining a first sample from a patient having or suspected of having ulcerative colitis; The first sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. detecting one or more gene transcript biomarker(s) of one or more genes involved in the and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. one or more gene transcript biomarkers for one or more genes to be and detecting one or more gene transcript biomarker(s) of the gene; wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0038] In a preferred embodiment of the method, treatment and use of the present invention, the method, treatment or use comprises administering to a patient a suitable In such cases, prior to and after administration of anti-IL-23p19 antibodies, at least one of the aforementioned genes Both involve detecting the expression levels of two gene transcript biomarkers.

[0039] In a further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or use comprises , if appropriate, prior to and after administration of the anti-IL-23p19 antibody, The method includes detecting the expression levels of at least three gene transcript biomarkers.

[0040] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The method includes detecting the expression levels of at least four gene transcript biomarkers of the genes. nothing.

[0041] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The method includes detecting the expression levels of at least five gene transcript biomarkers of the genes. nothing.

[0042] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The method includes detecting the expression levels of at least six gene transcript biomarkers of the genes. nothing.

[0043] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The method includes detecting the expression levels of at least seven gene transcript biomarkers of the genes. nothing.

[0044] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The method includes detecting the expression levels of at least eight gene transcript biomarkers of the genes. nothing.

[0045] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The method includes detecting the expression levels of at least nine gene transcript biomarkers of the genes. nothing.

[0046] In a still further preferred embodiment of the method, treatment and use of the present invention, the method, treatment or This use may be accompanied by, where appropriate, the administration of an anti-IL-23p19 antibody, as described above, both prior to and after administration of the anti-IL-23p19 antibody. The aim is to detect the expression levels of at least 10 gene transcript biomarkers of the genes include.

[0047] In a still further preferred embodiment of the methods, treatments and uses of the present invention, in the first sample and detecting in a second sample the expression of one or more gene transcript biomarkers detected in the first sample. The changes in expression of one or more gene transcript biomarkers detected by the anti-IL-23p19 antibody This indicates that administration of

[0048] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 9. After administration of the antibody, one or more gene transcript biomarker(s) are increased, and one or more The gene transcript biomarker(s) are GUCA2B, OTOP2, AQP8, SL C26A2, ADH1C, ABCG2, HMGCS2, TMIGD1, GUCA2A, L OC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SL C16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD17 7P1, SLC17A4 and ZG16.

[0049] In a still further preferred embodiment of the methods, treatments and uses of the present invention, one or more genes The transcript biomarker(s) are decreased after anti-IL-23p19 antibody treatment, and one or more Gene transcript biomarker(s) include CXCL8, AQP9, IL1B, and S100A 9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA 2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, R EG1A, IDO1, NOS2, MMP10, CXCL1 and PTGS2.

[0050] In a still further preferred embodiment of the methods, treatments and uses of the present invention, one or more genes The expression levels of the transcript biomarker(s) are determined by methods of gene expression profiling. It is decided that:

[0051] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the gene expression profile The filing method is PCR (Polymerase Chain Reaction, It is a polymerase chain reaction (PCR)-based method.

[0052] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the gene expression profile The method of filing is immunohistochemistry.

[0053] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the gene expression profile The filing method is a proteomic technique.

[0054] In a still further preferred embodiment of the methods, treatments and uses of the present invention, one or more genes The expression level of the transcript biomarker(s) is correlated with the expression level of one or more reference genes. The expression levels of the proteins are normalized to the expression levels of the proteins or their expression products.

[0055] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the sample is colon tissue. Biopsy-derived or rectal tissue biopsy-derived.

[0056] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the colon tissue biopsy comprises: from tissues selected from the group consisting of the terminal ileum, the ascending colon, the descending colon, and the sigmoid colon. That is why.

[0057] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the colon tissue biopsy comprises: It originates from a non-inflamed area of ​​the colon.

[0058] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the colon tissue biopsy comprises: It originates from an inflamed area of ​​the colon.

[0059] In a still further preferred embodiment of the methods, treatments and uses of the present invention, the first sample comprises an antibody The second sample is taken prior to or concurrently with administration of an IL-23p19 antibody, wherein the second sample is taken prior to or concurrently with administration of an anti-IL-23p19 antibody. At least 2 weeks, at least 4 weeks, or at least After 8 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, At least 24 weeks later, at least 28 weeks later, at least 30 weeks later, at least 32 weeks later weeks, at least 36 weeks, at least 40 weeks, at least 44 weeks, at least Both will be collected after 48 weeks or at least 52 weeks.

[0060] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 9 The antibodies are mirikizumab, guselkumab, risankizumab, tildrakizumab, or bradykinin. It is zikumab.

[0061] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 9The antibody is mirikizumab.

[0062] Preferably, the method, treatment or use comprises: a) Patients will receive three induction doses of mirikizumab via intravenous infusion at 4-week intervals. administering each induction dose containing 300 mg of mirikizumab; b) Patients receive maintenance doses of mirikizumab by subcutaneous injection every 4 or 12 weeks. The first maintenance dose is administered 2 to 8 weeks after the last induction dose. and administering a maintenance dose of 200 mg of mirikizumab to a patient receiving the treatment, wherein each maintenance dose contains 200 mg of mirikizumab.

[0063] More preferably, the first maintenance dose of mirikizumab is administered within 4 to 12 days after the last induction dose. It is administered after 6 weeks.

[0064] More preferably, subsequent maintenance dose(s) of mirikizumab are administered at a dose that is shorter than the dose of the first maintenance dose. The drug is then administered at 4-week intervals.

[0065] Alternatively, preferably, subsequent maintenance dose(s) of mirikizumab are administered at a dose equal to or greater than the initial maintenance dose. After the initial dose, the drug is administered at 12-week intervals.

[0066] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 The 9 antibody is guselkumab.

[0067] Preferably, the method, treatment or use comprises: a) Patients will receive three induction doses of guselkumab via intravenous infusion, four weeks apart. wherein each induction dose contains 100 to 500 mg of guselkumab. and, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or Administer to a patient by subcutaneous injection at 12-week intervals, the first maintenance dose being and administering the same 2 to 8 weeks after the administration of the induction dose of

[0068] More preferably, each induction dose contains 200 mg of guselkumab.

[0069] Alternatively preferably, each induction dose contains 400 mg of guselkumab.

[0070] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 The 9 antibody is risankizumab.

[0071] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 9The antibody is tildrakizumab.

[0072] In a still further preferred embodiment of the methods, treatments and uses of the present invention, an anti-IL-23p1 The 9 antibody is brazikumab.

[0073] In a further aspect of the invention, a subject receiving anti-IL-23p19 antibody treatment for ulcerative colitis is As candidate patients for this study, we have identified patients who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF R ) A method for identifying a patient suspected of having a pulmonary embolism is provided, the method comprising: Obtaining a sample from a patient; OSMR, FCGR3, CXCL6, interleukin-11, interleukin-2 4, interleukin-13RA2, FAP, TWIST1, and WNT2 Resistance to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) in one or more genes R ) legacy analyzing the sample for gene transcript biomarker(s); Based on the analysis of gene transcript biomarkers, patients were selected to receive anti-IL-23p19 antibody treatment. and identifying the patient as a candidate patient for treatment with the HER2 gene.

[0074] Preferably, a candidate patient for receiving anti-IL-23p19 antibody treatment for ulcerative colitis. As a result, patients with anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF R ) have or have Methods for identifying suspected patients include CXCL8, AQP9, IL1B, S100A9, TR EM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SL C6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTO P2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, R EG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, ID O1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, T MIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS 1. One selected from TMEM236, CD177P1, SLC17A4 and ZG16 Gene transcript biomarker(s) from one or more of the above genes are obtained from the patient. The method further includes analyzing a sample of each of the samples obtained.

[0075] In a further aspect of the invention, in a patient having or suspected of having ulcerative colitis A method for diagnosing ulcerative colitis is provided, the method comprising: In samples obtained from patients, CXCL8, AQP9, IL1B, S100A9, T REM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, S LC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OT OP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, I DO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3 , TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-A S1, TMEM236, CD177P1, SLC17A4, and ZG16 Determining the expression level of one or more gene transcript biomarker(s) for one or more genes To do, The determined expression levels of one or more gene transcript biomarker(s) are compared with CXCL 8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7 , TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, R EG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH 1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D- 40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1 , PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101 928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9 , ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, S one or more gene transcript biomarkers selected from LC17A4, and ZG16 and comparing the expression level of the gene to a reference expression level of the gene (e.g., a gene encoding a gene for which the gene is a nucleotide sequence). If the biomarker expression level in the patient is increased compared to the reference expression level or the biomarker expression level in the patient is decreased compared to the reference expression level. and if so, providing a diagnosis of ulcerative colitis.

[0076] In a further aspect of the invention, a patient having or suspected of having ulcerative colitis is treated with anti-I Methods for determining whether a patient is cured in response to treatment with an L-23p19 antibody are provided. However, this method (a)(i)CXCL8, AQP9, IL1B, S100A9, TREM1, MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6, CD177P1, SLC17A4, and ZG16 For one or more gene transcript biomarker(s), patients are screened for anti-IL-23p19 antibodies. analyzing a sample obtained from the patient prior to receiving the treatment; (b)(i)CXCL8, AQP9, IL1B, S100A9, TREM1, MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6, CD177P1, SLC17A4, and ZG16 For one or more gene transcript biomarker(s), patients are screened for anti-IL-23p19 antibodies. analyzing a sample obtained from the patient after the patient has undergone the treatment; (c)(i) one or more gene transcription factors after the patient receives anti-IL-23p19 antibody treatment If a change in the expression level of the biomarker(s) is detected, ulcerative colitis is diagnosed. Patients with or suspected of having IL-23p19 have been cured in response to anti-IL-23p19 antibody treatment and determining that: or (a)(ii)CXCL8, AQP9, IL1B, S100A9, TREM1, MMP 12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, V NN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8 , SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S1 00A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2 , MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, G UCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, N XPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM2 36, CD177P1, SLC17A4, and ZG16 One or more gene transcript biomarkers of Analyze samples obtained from patients with or suspected of having ulcerative colitis who have not undergone surgery. To do, (b)(ii)CXCL8, AQP9, IL1B, S100A9, TREM1, MMP 12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, V NN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8 , SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S1 00A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2 , MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, G UCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, N XPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM2 36, CD177P1, SLC17A4, and ZG16 and wherein the patient has a IL-23p19 antibody or IL-23p20 antibody with respect to one or more gene transcript biomarker(s). analyzing a sample obtained from the patient after receiving the antibody treatment; (c)(ii) one or more gene transcription factors after the patient receives anti-IL-23p19 antibody treatment Changes in expression levels of the target biomarker(s) are determined in response to anti-IL-23p19 antibody treatment. Expression levels of one or more gene transcript biomarker(s) in patients who did not receive When detected compared to anti-I, patients with or suspected of having ulcerative colitis are and determining that the patient is cured in response to the L-23p19 antibody treatment.

[0077] In a further aspect of the invention, a patient having or suspected of having ulcerative colitis is provided with a method of administering to a subject the claimed Determine whether the patient is cured in response to treatment with the anti-IL-23p19 antibody of paragraph 151. A method is provided, the method comprising: (a)(i)GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C For one or more gene transcript biomarker(s) of one or more genes selected from In this case, a sample obtained from the patient is analyzed before the patient receives anti-IL-23p19 antibody treatment. And, (b)(i)GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C For one or more gene transcript biomarker(s) of one or more genes selected from In this study, samples obtained from patients were analyzed after the patients received anti-IL-23p19 antibody treatment. And, (c)(i) one or more gene transcription factors after the patient receives anti-IL-23p19 antibody treatment If the expression level of the biomarker(s) is increased, the patient has ulcerative colitis. Patients suspected of having IL-23p19 are determined to be cured in response to anti-IL-23p19 antibody treatment. And, or (a)(ii) GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1 C. to one or more gene transcript biomarker(s) of one or more genes selected from Patients with ulcerative colitis who have not received anti-IL-23p19 antibody treatment analyzing a sample obtained from a patient suspected of having (b)(ii) GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1 C. to one or more gene transcript biomarker(s) of one or more genes selected from To investigate this, samples obtained from patients were analyzed after they received anti-IL-23p19 antibody treatment. To do, (c)(ii) one or more genes in patients who did not receive anti-IL-23p19 antibody treatment and comparing the expression levels of gene transcript biomarker(s) to determine whether the patient has anti-IL-23p19. after receiving antibody treatment, the expression level of one or more gene transcript biomarker(s) If increased, patients with or suspected of having ulcerative colitis should be treated with anti-IL-23p1 and determining that the patient is cured in response to the antibody treatment.

[0078] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is A method for diagnosing bowel frequency in a subject is provided, the method comprising: One or more gene transcript biomarker(s) of one or more genes selected from Table 8 determining the expression level of The determined expression level of one or more gene transcript biomarker(s) can be selected from the table above. Reference to one or more gene transcript biomarker(s) of one or more genes selected from and comparing the expression levels of If the biomarker expression level in the patient is altered compared to the reference expression level and providing a diagnosis of bowel frequency.

[0079] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is A method for diagnosing bowel frequency in a subject is provided, the method comprising: A second sample was analyzed to detect S100 calcium binding protein 8, S100 calcium binding protein 9, and Synaptic protein A12, cadherin-related family member 1, S100 calcium-binding protein Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor Mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, L YN proto-oncogene, Src family tyrosine kinase, interferon-inducible transmembrane protein Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinephysin 2 , aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TI MP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B expression of one or more gene transcript biomarker(s) of one or more genes selected from Determining the current level; S100 calcium-binding protein 8, S100 calcium-binding protein A12, Adherin-related family member 1, S100 calcium-binding protein A9, Trip les pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane protein 2, calpain 1 3, RNA polymerase II2 elongation factor, prokinephrine 2, aquaporin 9, and insulin tialleukin-1 alpha, Fc fragment of IgG receptor IIa, TIMP metallopeptidase one or more selected from inhibitor 1, transcobalamin 1, and creatine kinase B a reference expression level of one or more gene transcript biomarker(s) of the gene(s) and one or more and comparing the determined expression levels of the gene transcript biomarker(s) with , If the biomarker expression level in the patient is altered compared to the reference expression level and providing a diagnosis of bowel frequency.

[0080] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is

[0013] A method of treating bowel urgency in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample is analyzed to detect one or more gene transcription factors of one or more genes selected from Table 9. Detecting the biological biomarker(s); administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample is analyzed to identify one or more gene transcript biomarkers for one or more genes from the table above. and detecting the marker(s); wherein the expression levels of one or more gene transcript biomarkers detected in the first sample are one or more gene transcript biomarkers (multiple) detected in the second sample from the Changes in expression levels of IL-23p19 indicate a response to anti-IL-23p19 antibodies.

[0081] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is

[0013] A method of treating bowel urgency in a subject is provided, the method comprising: Obtaining a first sample from a patient; The first sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. detecting one or more gene transcript biomarker(s) of one or more genes involved in the and, administering to the patient an anti-IL-23p19 antibody; obtaining a second sample from the patient; A second sample was analyzed to identify the multicoil domain-containing 175, TNF receptor superfamily Member 17, complement factor B, containing the F-box and WD-repeat regions; member 7, lipase A, lysosomal enzyme somatic acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interf Receptor subunit 2 of interferon alpha and interferon beta, phosphoserine amino otransferase 1, sortin nexin 25, heat shock protein family A ( Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, Signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasm Polyadenylation element binding protein 4, phosphoenolpyruvate carboxykinase 1 , an elongation factor of RNA polymerase II2, cathepsin H, and calpain 13. one or more gene transcript biomarkers for one or more genes to be and detecting one or more gene transcript biomarker(s) of the gene; from the expression levels of one or more gene transcript biomarkers detected in the first sample. of the expression of one or more gene transcript biomarker(s) detected in the second sample. Changes in current levels indicate a response to anti-IL-23p19 antibodies.

[0082] In a still further aspect of the invention, CXCL8, AQP9, IL1B, S100A9 , TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2 , SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT 1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A , IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS 2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2 A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B - selected from AS1, TMEM236, CD177P1, SLC17A4 and ZG16 a gene transcript biomarker comprising one or more gene transcript biomarkers for one or more genes A marker panel is provided.

[0083] In a still further aspect of the invention, GUCA2A, OTOP2, AQP8, SLC2 6A2, and ADH1C. 261. A gene transcript biomarker panel as described in claim 260 is provided, comprising a marker.

[0084] In a still further aspect of the invention, one or more of one or more genes selected from Table 8 A gene transcript biomarker panel is provided that includes gene transcript biomarker(s) of can be.

[0085] In a still further aspect of the invention, S100 calcium binding protein 8, S100 Calcium-binding protein A12, cadherin-related family member 1, S100 cal Calcium-binding protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis Cis-inducing factor mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced Transmembrane protein 2, calpain 13, RNA polymerase II elongation factor, prokaryotic cell membrane protein 2 Nephricin 2, aquaporin 9, interleukin 1 alpha, IgG receptor IIa F c fragment, TIMP metallopeptidase inhibitor 1, transcobalamin 1, and creatine one or more gene transcript biomarkers of one or more genes selected from the group consisting of phosphodiesterase B (phosphodiesterase B), ... A gene transcript biomarker panel is provided, comprising a plurality of gene transcripts.

[0086] In a still further aspect of the invention, one or more of one or more genes selected from Table 9 A gene transcript biomarker panel is provided that includes gene transcript biomarker(s) of can be.

[0087] In a still further aspect of the invention, a multicoil domain-containing TNF receptor superunit is Family member 17, complement factor B, containing the F-box and WD-repeat regions, enzyme A, lysosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3 , interferon alpha and interferon beta receptor subunit 2, phosphatase inhibitors Foseline aminotransferase 1, sortin nexin 25, heat shock protein F Family A (Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC1 1 homolog C, signal peptidase complex subunit, DNA damage-regulated autophagy modifier Protein 1, cytoplasmic polyadenylation element-binding protein 4, phosphoenolpyruvate carboxylate kinase 1, elongation factor of RNA polymerase II2, cathepsin H, and calpain 1 one or more gene transcript biomarker(s) of one or more genes selected from A gene transcript biomarker panel is provided, comprising:

[0088] In a still further aspect of the invention, a patient having or suspected of having ulcerative colitis is A method of treating ulcerative colitis in a patient is provided. The method comprises obtaining a first sample from the patient. and analyzing the first sample for CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, O TOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1 , REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2 , TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A 3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B- AS1, TMEM236, CD177P1, SLC17A4, and ZG16 and administering an anti-IL-23p19 antibody to the patient. administering the antibody to the patient, obtaining a second sample from the patient, and analyzing the second sample to detect CXCL8. , AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, RE G1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1 C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-4 0, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC1019 28405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SL Detecting at least one biomarker selected from C17A4, and ZG16. and an expression level of at least one biomarker detected in the first sample. A change in the expression level of at least one biomarker detected in the second sample from the The expression indicates a response to anti-IL-23p19 antibodies.

[0089] In another aspect, the present disclosure provides a method for treating ulcerative colitis by administering an anti-IL-23p19 antibody to a subject. As candidate patients for this study, we have identified patients who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF R ) The present invention relates to a method for identifying a patient suspected of having a HIV-infected virus, the method comprising obtaining a sample from the patient. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF R ) at least one biomer Based on biomarker analysis, patients were assigned to receive anti-IL-23p19 therapy. and identifying the patient as a candidate patient for receiving antibody treatment.

[0090] In another aspect, the present disclosure provides a method for treating or preventing ulcerative colitis in a patient with or suspected of having ulcerative colitis, the method comprising administering to said patient an anti-tumor necrosis factor (ATF) inhibitor. Child (anti-TNF) therapy resistance (anti-TNF R Patients with or suspected of having anti-IL-1 The present invention relates to a method of treating a patient with an anti-TNF-23p19 antibody. R Whether it is and whether the patient is anti-TNF R and treating the patient with an anti-IL-23p19 antibody if This includes:

[0091] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for treating symptoms associated with ulcerative colitis, the method comprising: and CXCL8, AQP9, IL1B, S100A9, TREM1, MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6, CD177P1, SLC17A4, and ZG16. Analyzing the sample for biomarkers and administering an anti-IL-23p19 antibody to the patient. obtaining a second sample from the patient; and detecting CXCL8, AQP9, IL1B, S10 0A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUO XA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA 2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, D MBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, RE G1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HM GCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, U GT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDK from N2B-AS1, TMEM236, CD177P1, SLC17A4, and ZG16 analyzing the second sample for at least one selected biomarker. nothing.

[0092] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing ulcerative colitis in a patient, the method comprising: (a) obtaining from the patient a sample of ulcerative colitis; In the obtained samples, CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A1 4, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, A QP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P , S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, N OS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD 1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM 6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TM At least one selected from EM236, CD177P1, SLC17A4, and ZG16 To determine the expression levels of one biomarker and (b) CXCL8, AQP9, IL-1 1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUO X2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4BP A, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, R EG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TN IP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, AB CG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS 4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PC K1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and a reference expression level of at least one biomarker selected from ZG16 and at least (c) comparing the determined expression level of one biomarker in the patient. If the biomarker expression level is increased compared to the reference expression level, or if the patient If the expression level of the biomarker in the ulcer is decreased compared to the reference expression level, and providing a diagnosis of idiopathic colitis.

[0093] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing ulcerative colitis, the method comprising: (a) using an analyzer unit , CXCL8, AQP9, IL1B, S100A9, T in samples obtained from patients. REM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, S LC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OT OP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, I DO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3 , TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-A At least one gene, including S1, TMEM236, CD177P1, SLC17A4, and ZG16 (b) determining the expression level of at least one biomarker; and Using this method, CXCL8, AQP9, IL1B, S100A9, TREM1, and MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6, at least one biomarker including CD177P1, SLC17A4, and ZG16 The reference expression level of the mosquito and the determined expression level(s) of at least one biomarker ) and (c) determining whether the biomarker expression level is increased relative to the reference expression level. or if the biomarker expression level is decreased compared to the reference expression level. and if so, providing a diagnosis of ulcerative colitis.

[0094] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis, the patient receiving anti-I The present invention relates to a method for determining whether a patient has been cured in response to L-23p19 antibody treatment. are CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, and MMP 1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, AB CA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26 A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, I GKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10 , CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, S LC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD1 For at least one biomarker, including 77P1, SLC17A4, and ZG16 and analyzing a sample obtained from the patient before the patient receives anti-IL-23p19 antibody treatment. Toto, CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MM P1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, A BCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC2 6A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP1 0, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A , LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD For at least one biomarker, including 177P1, SLC17A4, and ZG16 and analyzing samples obtained from patients after they have received anti-IL-23p19 antibody treatment. and that patients had at least one biomarker after receiving anti-IL-23p19 antibody treatment. If changes in the expression level of ulcerative colitis are detected, the patient may have ulcerative colitis. Determining that the suspected patient has been cured in response to anti-IL-23p19 antibody treatment; , including.

[0095] In another aspect, the present disclosure relates to a biomarker panel. The biomarker panel comprises CX CL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MM P7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12 , REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, A DH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2 D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXC L1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC1 01928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16 A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1 , SLC17A4, and ZG16.

[0096] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. A method of treating bowel frequency, the method comprising obtaining a first sample from a patient; The samples were analyzed to determine S100 calcium-binding protein 8, S100 calcium-binding protein Protein A12, cadherin-related family member 1, S100 calcium-binding protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial Doria-related 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN oncogenic gene, Src family tyrosine kinase, interferon-induced transmembrane protein 2 , calpain 13, RNA polymerase II2 elongation factor, prokinephycin 2, aqua Porin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TIMP meta thrombin time-dependent steroid hormone 1, transcobalamin 1, and creatine kinase B, and and detecting a biomarker selected from these combinations, and administering an anti-IL-23p19 antibody. administering the antibody to the patient; obtaining a second sample from the patient; and analyzing the second sample to determine S S100 calcium-binding protein 8, S100 calcium-binding protein A12, cadherin Phospho-associated family member 1, S100 calcium-binding protein A9, Triple s pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial-associated 3, Ig Fc fragment of G receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src phagocytosis Myri tyrosine kinase, interferon-induced transmembrane protein 2, calpain 13, RNA polymerase II2 elongation factor, prokinephrine 2, aquaporin 9, interleukin 1 Leukin-1 alpha, Fc fragment of IgG receptor IIa, TIMP metallopeptidase inhibitor Substance 1, transcobalamin 1, and creatine kinase B, and combinations thereof. and detecting at least one selected biomarker in the first sample. The expression level of at least one biomarker detected in the second sample Changes in expression levels of a single biomarker indicate response to anti-IL-23p19 antibodies .

[0097] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. A method for diagnosing bowel frequency, the method comprising: (a) detecting in a sample obtained from a patient , S100 calcium-binding protein 8, S100 calcium-binding protein A12, Adherin-related family member 1, S100 calcium-binding protein A9, Trip les pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane protein 2, calpain 1 3, RNA polymerase II2 elongation factor, prokinephrine 2, aquaporin 9, and insulin tialleukin-1 alpha, Fc fragment of IgG receptor IIa, TIMP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B, and combinations thereof (b) determining the expression levels of biomarkers selected from the S100 calcium binding assay; Syncytial protein 8, S100 calcium-binding protein A12, cadherin-related family Member 1, S100 calcium-binding protein A9, Triples pseudokinase 2, blood Platelet-activating factor, apoptosis-inducing factor mitochondrial-associated 3, IgG receptor IIb F c fragment, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase enzyme, interferon-induced transmembrane protein 2, calpain 13, RNA polymerase Elongation factor II2, prokinephrine 2, aquaporin 9, interleukin 1 alpha , Fc fragment of IgG receptor IIa, TIMP metallopeptidase inhibitor 1, transcosmos Biomers selected from the group consisting of creatine kinase B, creatine kinase B, and combinations thereof. comparing the determined expression level of the biomarker with a reference expression level of the mosquito; c) If the patient's biomarker expression level changes compared to the baseline expression level, bowel movements and providing a frequency diagnosis.

[0098] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. A method of treating bowel urgency, the method comprising obtaining a first sample from a patient; The samples were analyzed to identify coiled-coil domain-containing 175, a TNF receptor superfamily member. 17, complement factor B, containing F-box and WD-repeat regions; 7, lipase A, lysosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interferon a Receptor subunit 2 of interferon and interferon beta, phosphoserine aminotransferase Spherase 1, sortin nexin 25, heat shock protein family A (Hsp7 0) Member 13, Claudin 2, Lymphocyte antigen 96, SEC11 homolog C, Signal Peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation acetylation element-binding protein 4, phosphoenolpyruvate carboxykinase 1, RNA Polymerase II2 elongation factor, cathepsin H, calpain 13, and their combinations and administering an anti-IL-23p19 antibody to a patient. obtaining a second sample from the patient; and analyzing the second sample to identify a region containing a multi-coil region. 175, TNF receptor superfamily member 17, complement factor B, F-box and and WD-repeat region-containing 7, lipase A, lysosomal acid type, centrosomal protein 128, bakki Human IAP repeat-containing 3, interferon alpha, and interferon beta receptor subunit 2, phosphoserine aminotransferase 1, sortin nexin 25, heat shock protein family A (Hsp70) member 13, claudin 2 , lymphocyte antigen 96, SEC11 homolog C, signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation element-binding protein 4, phosphatase phenolpyruvate carboxykinase 1, RNA polymerase II elongation factor, and detecting a biomarker selected from the group consisting of tetracycline H, calpain 13, and a combination thereof. This includes:

[0099] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. A method for diagnosing bowel urgency, the method comprising: (a) detecting multiple nucleotides in a sample obtained from a patient; Heavy coil domain-containing 175, TNF receptor superfamily member 17, complement factor B, F-box and WD-repeat domain-containing 7, lipase A, lysosomal acid type, centrosomal protein Protein 128, baculovirus IAP repeat-containing 3, interferon alpha and interferon Ferron beta receptor subunit 2, phosphoserine aminotransferase 1, Rutinexin 25, heat shock protein family A (Hsp70) member 13, Claudin 2, lymphocyte antigen 96, SEC11 homolog C, signal peptidase complex Subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation element-binding protein Protein 4, phosphoenolpyruvate carboxykinase 1, RNA polymerase II2 elongation factor, cathepsin H, calpain 13, and combinations thereof. (b) determining the expression levels of markers containing coiled coil domains, TNF receptors, and Superfamily member 17, complement factor B, containing F-box and WD-repeat regions , lipase A, lysosomal acid type, centrosomal protein 128, baculovirus IAP repeats Contains 3, interferon alpha and interferon beta receptor subunit 2 , phosphoserine aminotransferase 1, sortin nexin 25, heat shock protein Protein family A (Hsp70) member 13, claudin 2, lymphocyte antigen 96, S EC11 homolog C, signal peptidase complex subunit, DNA damage-regulated autophagy Modification factor 1, cytoplasmic polyadenylation element-binding protein 4, phosphoenolpyruvate carboxykinase 1, RNA polymerase II2 elongation factor, cathepsin H, calpain 13, and combinations thereof, and a reference expression level of a biomarker selected from the group consisting of: (c) comparing the determined expression levels of the biomarkers in the patient. and providing a diagnosis of bowel urgency if the level is altered compared to a reference expression level. and,

[0100] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. A method for diagnosing bowel frequency, the method comprising: (a) measuring a patient's bowel movement frequency using an analyzer unit; In the samples obtained from Binding protein A12, cadherin-related family member 1, S100 calcium binding Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis inducer Mitochondrial-associated factor 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane kinase Protein 2, calpain 13, elongation factor for RNA polymerase II2, prokinephysin 2, aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, T IMP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B, and combinations thereof; and determining the expression level of a biomarker selected from the group consisting of ( b) using a computing device to identify S100 calcium-binding protein 8, S 100 Calcium-binding protein A12, cadherin-related family member 1, S10 Calcium-binding protein A9, Triples pseudokinase 2, platelet-activating factor, Apoptosis-inducing factor mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony stimulating factor Stimulatory factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interface Ron-induced transmembrane protein 2, calpain 13, elongation factor of RNA polymerase II2, Prokinephysin 2, aquaporin 9, interleukin 1 alpha, IgG receptor II Fc fragment of a, TIMP metallopeptidase inhibitor 1, transcobalamin 1, and Reference expression levels of biomarkers selected from the group consisting of creatine kinase B, and combinations thereof. (c) comparing the determined expression level(s) of the biomarker(s) with the determined expression level(s) of the biomarker(s); A change in marker expression levels compared to baseline expression levels provides a diagnosis of bowel frequency. This includes providing.

[0101] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. A method for diagnosing bowel urgency, the method comprising: (a) measuring a patient's bowel urgency using an analyzer unit; In samples obtained from the TNF receptor superfamily, the multicoiled region-containing 175 member 17, complement factor B, containing the F-box and WD-repeat regions; lipase A, lipase B; Sosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, inter Interferon alpha and interferon beta receptor subunit 2, phosphoserine Aminotransferase 1, sortin nexin 25, heat shock protein family A (Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C , signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cell Protein polyadenylation element-binding protein 4, phosphoenolpyruvate carboxykinase 1, RNA polymerase II2 elongation factor, cathepsin H, calpain 13, and (b) determining the expression level of a biomarker selected from a combination of Using a fusion device, multiple coil domain-containing 175, TNF receptor superfamily Lee member 17, complement factor B, F-box and WD-repeat region-containing 7, lipase A, Lysosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interleukin-1 Interferon alpha and interferon beta receptor subunit 2, phosphoserine Aminotransferase 1, sortin nexin 25, heat shock protein family A(Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cell Vacuolar polyadenylation element-binding protein 4, phosphoenolpyruvate carboxykinase RNA polymerase 1, elongation factor of RNA polymerase II2, cathepsin H, calpain 13, and The reference expression level of the biomarker selected from the combination of the above and the determined expression level of the biomarker (c) comparing the biomarker expression levels with the baseline expression level(s); and providing a diagnosis of bowel urgency if there is a change compared to the current level.

[0102] In another aspect, the present disclosure provides a method for the treatment of S100 calcium binding protein 8, S100 calcium Binding protein A12, cadherin-related family member 1, S100 calcium binding Protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis inducer Mitochondrial-associated factor 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane kinase Protein 2, calpain 13, elongation factor for RNA polymerase II2, prokinephysin 2, aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, T IMP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B.

[0103] In another aspect, the present disclosure provides multi-coil domain-containing 175 TNF receptors of the TNF receptor superfamily. member 17, complement factor B, containing the F-box and WD-repeat regions; lipase A, lipase B; Sosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, inter Interferon alpha and interferon beta receptor subunit 2, phosphoserine Aminotransferase 1, sortin nexin 25, heat shock protein family A (Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 homolog C , signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cell Protein polyadenylation element-binding protein 4, phosphoenolpyruvate carboxykinase 1, a small molecule containing the elongation factor of RNA polymerase II2, cathepsin H, and calpain 13 The present invention relates to a biomarker panel that includes at least one biomarker. [Brief explanation of the drawings]

[0104] This patent or application contains at least one drawing executed in color. Copies of this patent or this patent application publication, including color drawing(s), are available upon request and payment of the necessary fee. The Patent Office will provide the necessary information in accordance with the Patent Office's instructions.

[0105] The present disclosure will be better understood and will be more fully understood from the following detailed description, which, when considered in conjunction with the following detailed description, will be more fully understood from the following detailed description, which will be provided to illustrate, by way of example, the invention as defined by the appended claims. In this detailed description, reference will be made to the following drawings: . [Figure 1A] Figure 1 shows differentially expressed genes after mirikizumab treatment. Overlap of differentially expressed genes between baseline and week 12 in the mirikizumab-treated group (log2 fold change > 0.5 and FDR < 0.05). No genes in the placebo group showed differential expression based on these fold change and FDR thresholds. [Figure 1B]Differentially expressed genes after mirikizumab treatment are shown. Differentially expressed genes in the 200 mg mirikizumab group before (FIG. 1B) and after (FIG. 1C) normalization to placebo are shown as blue circles if decreased and orange circles if increased. The 20 most increased and decreased genes are labeled. [Figure 1C] Differentially expressed genes after mirikizumab treatment are shown. Differentially expressed genes in the 200 mg mirikizumab group before (FIG. 1B) and after (FIG. 1C) normalization to placebo are shown as blue circles if decreased and orange circles if increased. The 20 most increased and decreased genes are labeled. [Figure 1D] Figure 1 shows differentially expressed genes after mirikizumab treatment. After normalization to placebo, the most differentially expressed genes in the 200 mg mirikizumab group were sorted by gene network defined by the MetaCore database. [Figure 2A] Correlation between IL-23 pathway transcripts and change in disease activity score is shown. Pearson's correlation coefficient for differential expression of mirikizumab-regulated genes at week 12 with changes in corrected Mayo score (green), RHI (red), and UCEIS (gray) over the same time period. Genes identified as upregulated by IL-23 by the MetaCore database are labeled. [Figure 2B] Correlation between IL-23 pathway transcripts and changes in disease activity scores is shown. Heat map of Pearson correlation coefficients (Rho) for the differential expression of each gene identified above. The fold change value for each gene in the 200 mg mirikizumab dose group after normalization with the change in the placebo group is shown on the vertical axis. [Figure 3]Correlation between changes in mirikizumab-regulated genes and changes in disease activity scores is shown. Pearson correlation coefficients for differential expression of mirikizumab-regulated genes at week 12 with changes in the corrected Mayo score (green), RHI (red), and UCEIS (gray) over the same time period. Genes with a ≥ 2-fold differential expression in the 200 mg mirikizumab dose group are labeled after normalization by the change in the placebo group. All labeled genes that positively correlated with change in disease activity score decreased between baseline and week 12, and those that negatively correlated with change in disease activity score increased in expression over the period. [Figure 4A] The mirikizumab-regulated genes most highly correlated with change in disease score are shown. The Pearson correlation coefficient for the differential expression of each gene between baseline and week 12 with the change in corrected Mayo score (Figure 4A) and RHI (Figure 4B) over the same time period. The 20 most differentially regulated genes are labeled, and pathway analysis is summarized in Table 3. [Figure 4B] The mirikizumab-regulated genes most highly correlated with change in disease score are shown. The Pearson correlation coefficient for the differential expression of each gene between baseline and week 12 with the change in corrected Mayo score (Figure 4A) and RHI (Figure 4B) over the same time period. The 20 most differentially regulated genes are labeled, and pathway analysis is summarized in Table 3. [Figure 5A] Mirikizumab-regulated genes associated with anti-TNFα resistance and response are shown. The change in expression of each gene in the 200 mg mirikizumab dose group between baseline and week 12 was normalized to the change in expression in the placebo group over the same time period. Differentially expressed genes (log2 fold change ≧0.5 and FDR ≦0.05) are indicated by blue circles if decreased and orange circles if increased. Genes associated with resistance (FIG. 5A) and response (FIG. 5B) to anti-TNFα treatment are labeled. [Figure 5B]Mirikizumab-regulated genes associated with anti-TNFα resistance and response are shown. The change in expression of each gene in the 200 mg mirikizumab dose group between baseline and week 12 was normalized to the change in expression in the placebo group over the same time period. Differentially expressed genes (log2 fold change ≧0.5 and FDR ≦0.05) are indicated by blue circles if decreased and orange circles if increased. Genes associated with resistance (FIG. 5A) and response (FIG. 5B) to anti-TNFα treatment are labeled. [Figure 6] 1 is a heat map showing differential gene expression profiles between clinical responders at weeks 12 and 52 relative to mirikizumab and placebo ("PBO") responders. [Figure 7] Venn diagram of differentially and similarly expressed genes present only in mirikizumab responders, only in PBO responders, and present in both groups. [Figure 8] The top 10 mirikizumab-specific differentially expressed and similarly expressed genes (DEG-SEG genes) are shown. [Figure 9A] 1 shows differential gene expression from baseline ("BL") at Week 12 and Week 52 in mirikizumab responders. [Figure 9B] 9B and 9D show differential gene expression from baseline ("BL") in mirikizumab responders at weeks 12 and 52. Arrows in Figures 9B and 9D indicate the direction of change in gene expression. [Figure 9C] 1 shows differential gene expression from baseline ("BL") at Week 12 and Week 52 in placebo ("PBO") responders. [Figure 9D] 9B and 9D show differential gene expression from baseline ("BL") in placebo ("PBO") responders at weeks 12 and 52. Arrows in Figures 9B and 9D indicate the direction of change in gene expression. [Figure 10]A-D show correlations between clusters of genes and disease activity indices in patients treated with mirikizumab. A shows clusters of genes in mirikizumab ("Miri") responders with RHI PCC at week 12. B shows clusters of genes in mirikizumab ("Miri") responders with RHI PCC at week 52. C shows clusters of genes in mirikizumab ("Miri") responders with Mayo PCC index at week 12. D shows clusters of genes in mirikizumab ("Miri") responders with Mayo PCC index at week 52. PCC = Pearson correlation coefficient, grey NS = not significant, blue p-value, red p-value and PCC. [Figure 11] A and B are graphs showing patient-reported stool frequency (SF) (A) and bowel urgency (BU) (B) at baseline and week 12 of mirikizumab induction. [Figure 12] Graphs showing Kendall's tau (τ) versus clinical metrics including the Robarts Histopathology Index (RHI), Geboes score, and Modified Mayo Score (MMS) for stool frequency and bowel urgency. [Figure 13] Graph showing tau (τ) distribution for the top 20 genes associated with SF. [Figure 14] Graph showing expression of selected biomarkers (S100A8, MMP3, AQP9, and CDHR1) in relation to MMS-SF score (Modified Mayo Score - Bowel Frequency). [Figure 15] Graph showing tau (τ) distribution for the top 20 genes associated with SF. [Figure 16] Graph showing the expression of selected biomarkers (CCDC175, TNFRSF17, CFB, FBXW7) in relation to bowel urgency score. MMS-SF score = Modified Mayo Score - Stool Frequency. [Figure 17]1 is a Venn diagram showing genes associated with bowel frequency alone (145), genes associated with bowel urgency alone (198), and genes associated with both bowel frequency and bowel urgency (122). DETAILED DESCRIPTION OF THE INVENTION

[0106] Unless otherwise defined, all technical and scientific terms used herein are within the meaning of the present disclosure. has the same meaning as commonly understood by a person skilled in the art to which it pertains. Any methods and materials similar or equivalent to those described in can be used in the practice or testing of this disclosure. However, preferred methods and materials are described below.

[0107] UC is a form of colitis, an inflammatory disease of the intestine, usually the colon, that includes characteristic ulcers. Symptoms of active disease include diarrhea, usually bloody, and usually range from mild discomfort to severe dizziness. It is accompanied by abdominal pain of varying severity, ranging from severe cramping with severe pain.

[0108] Mayo score, modified Mayo score (MMS), and ulcerative colitis disease activity index ( There are several methods for assessing disease severity, including the UCDAI. The Mayo score is a composite measure consisting of four subscores: (i) Bowel Frequency (SF): The SF subscore is a patient-reported measure. is a 4-point scale that measures the number of bowel movements in a 24-hour period compared with the patient's usual number of bowel movements over the same period. A bowel movement is when the patient has had a bowel movement, or when blood only, blood and mucus, This is defined as going to the toilet when either passing only mucus or passing only mucus. The total number of stools passed within the period is recorded by the patient. SF is typically recorded at the start of the study or during the observation period. The normal SF for the patient is , SF reported when the patient was in remission or if the patient never achieved remission is a SF reported before the first onset of signs and symptoms of UC.

[0109] [Table 1] (ii) Rectal bleeding: The RB subscore is a patient-reported measure. The most significant amount of blood passed rectally on any given day is reported on a 4-point scale.

[0110] [Table 2] (iii) Endoscopic Subscore (ES): ES is the physician-reported It is a measure of the worst appearance of the mucosa during flexible sigmoidoscopy or colonoscopy, divided into four groups. Consistent with current clinical practice, frailty is measured using an ES of 1. Excluded.

[0111] [Table 3] (iv) Physician's Global Assessment (PGA): PGA is a This is a nurse-reported measure that summarizes the patient's assessment of UC disease activity on a 4-point scale. do.

[0112] [Table 4]

[0113] Each subscore is scored on a 4-point scale ranging from 0 to 3, with a maximum Mayo score of 1. The score is 12.

[0114] The MMS is a modification made to the original Mayo Index reference (Schro Eder et al., New Eng J Med,317(26):1625-1629,19 1987), which includes three of the four subscores of the Mayo score. Physician global assessment is not included. The MMS assesses three subscores, each on a scale of 0 to 3, with a maximum total score. The score is 9. Mayo score is 6-12 or MMS is 4-9, and each ES is 2 or more. Patients are defined as having moderately to severely active ulcerative colitis.

[0115] As used herein, a "subject in need" is a person who has a particular disease, disorder, or condition. Refers to subjects who have, are suspected of having, are susceptible to, or are at risk of having a disease. In particular, the present disclosure provides methods for treating ulcerative colitis and screening for biomarkers. The method of administering the drug to a patient who has, is suspected of having, or is likely to suffer from ulcerative colitis is It is used in a subset of subjects who are at high risk of developing pancreatic and ulcerative colitis. Such subjects include subjects with ulcerative colitis and subjects suspected of having ulcerative colitis. These subjects may include elephants, subjects susceptible to ulcerative colitis, and subjects at risk for ulcerative colitis. Subjects may be at risk for a range of conditions, including, but not limited to, family history, age, environment, and / or lifestyle ulcerative colitis, suspected of having ulcerative colitis, or predisposed to ulcerative colitis, and In other embodiments, the patient has or is at risk of having ulcerative colitis. Subjects suspected of, susceptible to, and at risk for ulcerative colitis The subject may be a subject who has or is suspected of having resistance to anti-TNF therapy. Anti-TNF treatment for ulcerative colitis may be difficult due to family history, age, environment, and / or lifestyle. may be or is suspected to be resistant to the device.

[0116] Based on the above, some embodiments of the disclosed method may involve the identification of specific sub-objects. A set or subclass (i.e., in addressing one or more specific conditions described herein) (a subset or subclass of objects that "need" the assistance of are not intended to be included in any subset or subclass of subjects in need of the treatments described herein. There is no.

[0117] As used herein, "susceptible to" and "at risk" refer to a person who is at risk for a particular disease. , having little resistance to a disorder or condition (having a genetic predisposition, disease, Having a family history of the disorder or condition and / or having symptoms of the disease, disorder or condition (including

[0118] As used herein, the term "biomarker" refers to a biological sample or a biological sample containing Any molecule or molecules found in a biological sample that can be used to characterize a given subject For example, a biomarker refers to a group of molecules whose presence, absence, or relative abundance can be detected by a particular characteristics of certain cell or tissue types or states, and / or specific pathological states or The characteristics of the condition and / or the severity of the pathological condition, the likelihood of progression or regression of the pathological condition A molecule or group of molecules that indicates the likelihood that a pathological condition will respond to a particular treatment. As another example, biomarkers may be used to identify cell types or microorganisms (bacteria, mycobacteria, The present invention may be a bacterial, fungal, viral, or other bacterial or viral molecule or group of molecules thereof. The biomarkers provided herein are useful for detecting and / or confirming the presence of ulcerative colitis. The biomarkers provided herein can be diagnostic biomarkers that can be used to It is a monitoring biomarker that can be analyzed serially to assess the status of ulcerative colitis. The biomarkers provided herein may also be used to assess response to anti-IL-23p19 antibody treatment. The present invention relates to a pharmacodynamic biomarker that can be used to determine the response of a patient to a drug. The biomarkers provided herein also indicate a favorable or negative effect from anti-IL-23p19 antibody treatment. to predict or identify individuals or populations more likely to experience adverse effects The biomarkers provided herein may also be predictive biomarkers that may be used for In addition, to demonstrate the possibility, presence, or degree of toxicity to anti-IL-23p19 antibodies, May be a safety biomarker measured before and / or after administration of L-23p19 antibody The biomarkers provided herein may also be used to identify progression and / or recurrence of ulcerative colitis. The biomarkers provided herein can be prognostic biomarkers for ulcer disease. may indicate the likelihood that an individual who has not been diagnosed with ulcerative colitis will develop ulcerative colitis, The biomarkers provided herein may be prevalence / risk biomarkers. It is also a surrogate biomarker that explains clinical outcomes after anti-IL-23p19 antibody treatment. It is possible.

[0119] As used herein, the term "gene transcript biomarker" refers to a specific gene Gene expression products corresponding to the gene, e.g., RNA transcripts expressed by a particular gene Gene transcript biomarkers are used in the same way as described above for more general biomarkers. The gene transcript biomarkers provided herein may be used to identify and characterize ulcerative colitis. It may be a diagnostic biomarker that can be used to detect and / or confirm the presence of The gene transcript biomarkers provided in this document are useful in assessing ulcerative colitis status. The genetic information provided herein may be used as a monitoring biomarker that can be analyzed continuously. Gene transcript biomarkers may also be useful in determining patient response to anti-IL-23p19 antibody treatment. The genes provided herein may be pharmacodynamic biomarkers that can be used to determine the level of a particular gene. Transcript biomarkers may also be useful in detecting favorable or adverse effects from anti-IL-23p19 antibody treatment. used to predict or identify individuals or populations more likely to experience adverse effects The gene transcript biomarkers provided herein may be predictive biomarkers that may be useful in determining the progression of a disease. also to indicate the possibility, presence, or degree of toxicity to anti-IL-23p19 antibodies. A safety biomarker measured before and / or after administration of an anti-IL-23p19 antibody. The gene transcript biomarkers provided herein may also be used to predict the progression and progression of ulcerative colitis. and / or may be a prognostic biomarker for identifying recurrence. Child transcript biomarkers also have been shown to predict the risk of developing ulcerative colitis in individuals who have not been diagnosed with ulcerative colitis. May be a prevalence / risk biomarker that may indicate the likelihood of developing enteritis The gene transcript biomarkers provided herein also demonstrate efficacy in patients receiving anti-IL-23p19 antibody treatment. They may be surrogate biomarkers that explain subsequent clinical outcomes. The terms "transcript biomarker" and "transcript biomarker" are used interchangeably herein.

[0120] As used herein, "expression of a biomarker (or gene transcript biomarker)" refers to a "Level" refers to the level of gene production from a gene encoding a biomarker, as is well known to those skilled in the art. The gene product is, for example, RNA (ribonucleic acid). c acid, ribonucleic acid) and protein. Expression levels can be measured, for example, by Northern blotting, amplification, polymerase chain reaction, microarray analysis, tag-based techniques (e.g., Serial analysis of gene expression and whole transcriptome shotgun sequencing or RNA-Seq Next-generation sequencing (e.g., eq), Western blotting, enzyme-linked immunosorbent assay (ELISA), Immunosorbent Assay (ELISA), and combinations thereof, are well known to those skilled in the art. It can be quantitatively measured by known methods.

[0121] As used herein, a "reference expression level" of a biomarker or gene transcript refers to a , expression levels of established biomarkers for subjects without ulcerative colitis, determined by medical and / or research professionals using established methods described in the expression levels of biomarkers in normal / healthy subjects without ulcerative colitis as determined by and / or refers to the known expression level of a biomarker obtained from the literature. The reference expression levels are also used in subjects without ulcerative colitis, normal / healthy subjects without ulcerative colitis, and The expression levels of the biomarkers in healthy subjects and in subjects with ulcer disease at the time the sample was obtained from the subject. Biomarker Expression for Subjects Without Ulcerative Colitis but Later Develop Ulcerative Colitis The expression level of a biomarker established for any combination of subjects, such as a marker level, is referred to as the expression level of the biomarker. The reference expression level of a biomarker may also be a baseline obtained from a subject to which the method is applied. Therefore, intra-subject changes from visit to visit can be used to assess the expression levels of ulcerative colitis. For example, the expression levels of multiple biomarkers may indicate an increased or decreased risk of enteritis. It may be obtained from multiple samples obtained from the same subject, but between multiple expression levels in each sample. Thus, in some embodiments, the same subject may be used to identify differences in The two or more samples obtained are analyzed for the expression level(s) of blood biomarkers and blood biomarkers. Reference expression levels may also be used to estimate the "placebo response" of a target gene. As used herein, "plain" may refer to the expression level of a biomarker in a "subject." A "sebo-responder" is a person who has been diagnosed by a medical professional and / or using the established methods described herein. Patients with ulcerative colitis as determined by a research expert who show clinical improvement but do not have anti-IL-23 Subjects who have not received the p19 antibody. Without being bound by theory, placebo Responders are those who have received a diagnosis and / or counseling and / or medical follow-up for ulcerative colitis. In response, placebo responders were thought to show improvement due to lifestyle changes made by placebo responders. can be done.

[0122] Examples of anti-IL-23p19 antibodies that may be used in the methods, treatments and uses of the present invention include: These include selkumaab, tildrakizumab, risankizumab, mirikizumab, and brazikumab. It can be obtained.

[0123] Guselkumab, CAS Registry Number 1350289-85-8, binds to the p19 domain of human IL-23. It is a fully human IgG1 lambda monoclonal antibody that binds to the IgG1 subunit. A method for making it is described in US Pat. No. 7,935,344.

[0124] Tildrakizumab, CAS Registry Number 1326244-10-3, is a pAffinity antibody of human IL-23. It is a humanized IgG1 kappa (κ) monoclonal antibody that targets the 19 subunit. The antibody and methods for making it are described in US Pat. No. 8,293,883.

[0125] Risankizumab, CAS Registry Number 1612838-76-2, binds to the p1 domain of human IL-23. It is a humanized IgG1 kappa (κ) monoclonal antibody that targets the 9 subunit. The body and methods for making it are described in US Pat. No. 8,778,346.

[0126] Mirikizumab (also referred to herein as "Miri"), CAS Registry Number 18842 01-71-1 is a humanized IgG4-antibody that targets the p19 subunit of human IL-23. It is a kappa (κ) monoclonal antibody. The antibody and method for producing it are described in U.S. Pat. No. 9,449,463. Mirikizumab is suitable for use in many aspects of the present invention. It is particularly suitable for use.

[0127] Suitable anti-IL-23p19 antibody-inducing doses include about 50 mg to about 600 mg. A suitable dose is an induction dose of 300 mg of anti-IL-23p19 antibody. The induction dose of antibody 19 is preferably administered intravenously. Suitably, it is 50 mg to 600 mg. Preferably, an induction dose of 300 mg is administered to the patient every four weeks for 12 weeks. After the dose(s), a dose in the range of about 150 mg to about 400 mg, preferably 200 mg of the antibody This may be followed by at least one maintenance dose of an IL-23p19 antibody. is a maintenance dose of 200 mg of an anti-IL-23p19 antibody. Preferably, Patients will receive a maintenance dose of 0.00 mg every 4 weeks or every 12 weeks. During the induction period: Administering at least one induction dose of an anti-IL-23p19 antibody to a patient in need thereof The desired therapeutic effect may be clinical remission, clinical improvement, or a combination thereof. End of induction period: bed reaction, endoscopic remission, endoscopic cure, and / or symptomatic remission. If the patient achieves the desired therapeutic effect during the induction period, the patient may then At least one maintenance dose is administered to maintain at least one of the outcomes. The therapeutic effect(s) are clinical remission, clinical response, endoscopic remission, endoscopic cure, and / or symptomatic remission. There is no minimum or maximum duration of the induction period, but typical Typically, the duration is 4, 8, or 12 weeks, and the end of the induction period is typically The end-of-induction evaluation is performed 4 or 8 weeks after the last induction dose is administered. To distinguish from the initial induction dose if the patient does not achieve a clinical response at the end of the initial induction period The administration of the induction dose may be extended, which is called an "extended induction dose." If a clinical response is achieved at the end of the study period, clinical remission, endoscopic remission, endoscopic cure, and and / or to maintain a clinical response, such as symptomatic remission, or other desired therapeutic effect(s). At least one maintenance dose of an anti-IL-23p19 antibody is administered. The first maintenance dose is It is administered 4 to 12 weeks after the patient receives the final extended induction dose. The interval corresponds to the variation in the period between the administration of the last extended induction dose and the end-of-extension induction assessment. The maintenance dose(s) may be administered at 4-week, 8-week, or 12-week intervals (multiple times) after the initial maintenance dose. The maintenance dose(s) may be administered by subcutaneous injection. If loss of response occurs during the maintenance period, one, two, or three extra doses of anti-IL-1 The 23p19 antibody is administered to the patient 4 to 12 weeks after the last boost dose is administered. If the patient achieves a clinical response, one or more additional maintenance doses of anti-IL-23p19 antibody may be administered. , was administered to the patient, and loss of response was assessed by (a) bowel frequency (SF) score and rectal bleeding (RB) score. (b) a ≥2-point increase from baseline in the combined score; Eight days with confirmation of negative Clostridium difficile testing A combination of SF and RB scores of >4 on two consecutive visits separated by at least 4, and c) Clinical response was defined as an endoscopic subscore (ES) of 2 or 3 and no significant rectal bleeding (RB) ) subscore decrease of 1 trillion or RB subscore of either 0 or 1, A reduction of more than 2 points in the modified Mayo score (MMS) subscore of the patient and a baseline is defined as achieving a greater than 30-35% reduction from baseline.

[0128] The methods disclosed herein can further include obtaining three or more samples from the patient. Biomarker expression levels change, remain changed over time, or are maintained over time For analysis of samples to determine patient, reference subject, and placebo responses, etc. It is particularly preferred to obtain multiple samples from a subject.

[0129] Suitable samples include whole blood, plasma, serum, tissue biopsies, fecal samples, and combinations thereof. Particularly suitable tissue biopsies include colonic tissue biopsies or rectal tissue biopsies. Colonic tissue biopsies consist of the terminal ileum, ascending colon, descending colon, and sigmoid colon. The colon tissue biopsy may be derived from a tissue selected from the group consisting of: a non-inflamed colon area; The biopsy may be taken from the edge of an ulcer or from the edge of an erosion. The mucosa may be spaced apart or spaced apart throughout the affected mucosa, or a combination thereof. That's fine.

[0130] For embodiments in which the patient is administered an anti-IL-23p19 antibody, the first sample contains an anti-IL-23p19 antibody. the second sample is taken before or at the same time as administration of an anti-IL-23p1 antibody; At least 2 weeks, at least 4 weeks, or at least 8 weeks after the first administration of the antibody; At least 12 weeks later, at least 16 weeks later, at least 20 weeks later, at least 24 weeks later After weeks, after at least 28 weeks, after at least 30 weeks, after at least 32 weeks, After 36 weeks, at least 40 weeks, at least 44 weeks, at least 48 weeks Alternatively, the sample may be collected after 52 weeks or at least 52 weeks after administration of an anti-IL-23p19 antibody. Approximately 4 weeks after administration of anti-IL-23p19 antibody, approximately 12 weeks after administration of anti-IL-23p19 antibody The sample may be obtained about 52 weeks after administration of anti-IL-2 Samples may be obtained 52 weeks after administration of the 3p19 antibody. Samples may also be obtained daily, weekly, monthly, and yearly. may be obtained at other intervals, including

[0131] Expression (and expression levels) can be determined by microarray analysis. Other suitable methods for detecting the presence of nucleotides include amplification (polymerase chain reaction), Northern blot analysis, and the like. Immunology, including immunoblotting, Southern blotting, in situ hybridization, and Western blotting enzyme-linked immunosorbent assay (ELISA), enzyme-linked fluorescent assay (Enzyme-Linked Immunosorbent Assay (ELISA)) Enzymed Fluorescence Assay (ELFA), immunoprecipitation, immunohistochemistry, and combinations of these Examples include:

[0132] The methods disclosed herein further comprise analyzing the tissue sample using histopathology. The tissue samples may be processed to obtain H&E staining, Romanowsky staining, and even unstained tissue samples. The tissue sample may also be stained for brightfield observation using the method described above. Staining can be performed using antibodies that specifically bind to the mosquito. The antibodies may contain a label, such as a fluorescent label. Although tissues can be seen, they can also be studied by exposing tissue samples to ultraviolet light. The antibody is either directly labeled with a fluorescent label or is conjugated to a fluorescent label that specifically binds to the biomarker antibody. The tissue sample can be labeled to detect a single biomarker using a second antibody. To determine the subcellular location of tissue mRNA, Interval transcriptomics can also be used to analyze tissue samples.

[0133] In one aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis, comprising: The present invention relates to a method for treating ulcerative colitis, the method comprising obtaining a first sample from a patient; One sample was analyzed and CXCL8, AQP9, IL1B, S100A9, TREM1, M MP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14 , VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQ P8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NO S2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1 , GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6 , NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TME At least one selected from M236, CD177P1, SLC17A4, and ZG16 detecting a biomarker and administering an anti-IL-23p19 antibody to the patient. obtaining a second sample from the patient and analyzing the second sample to detect CXCL8, AQP9, I L1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DU OX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4B PA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, T NIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, A BCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, M S4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, P CK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A4, and and detecting at least one biomarker selected from ZG16 and ZG17; A second sample from the expression level of at least one biomarker detected in the first sample. The change in the expression level of at least one biomarker detected in the sample is indicative of anti-IL- Indicating response to 23p19 antibodies. Particularly preferred biomarkers are CXCL8, AQP9 , IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C 4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, and In one embodiment, the biomarker comprises at least one of the following combinations: anti-IL-1, anti-IL-2, anti-IL-3, anti-IL-4, anti-IL-5, anti-IL-6, anti-IL-1, anti-IL-2, anti-IL-3 ...1, anti-IL-2, anti-IL-1, anti-IL-2, anti-IL-1, anti- -23p19 antibody treatment increased GUCA2B, OTOP2, AQP8, SLC26 A2, ADH1C, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC1 01928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16 A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1 , SLC17A4, ZG16, and combinations thereof. Biomarkers decreased after anti-IL-23p19 antibody treatment, including CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, D UOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4 BPA, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, P I3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTG S2, and one of these combinations.

[0134] In one embodiment, the expression detected in the second sample from the expression detected in the first sample is The observed changes in expression indicate that anti-IL-23p19 antibody administration should be continued. The change in expression is the change in expression in the second (or subsequent) sample compared to the expression in the first sample. The change in expression can also be an increase in expression in a second (or a third) sample compared to expression in a first sample. or a subsequent sample. The changes in expression levels in the sample(s) obtained from the ulcerative colitis) The expression levels in patients with ulcerative colitis who had not received anti-IL-23p19 antibodies were also measured. in sample(s) obtained from patients with or suspected of having ulcerative colitis The expression levels may be further compared to one of the

[0135] In another embodiment, the expression level detected in the first sample is If changes in expression levels are detected, anti-IL-23p19 antibody administration should be discontinued. The change in expression level is the change in the expression level in the second ( The change in expression level can also be an increase in the expression level in a first (or subsequent) sample. The expression level in the second (or subsequent) sample may be decreased compared to the expression level in the first sample. Expression in sample(s) obtained from patients administered anti-IL-23p19 antibodies The changes in levels are measured in healthy subjects (those not suspected of having ulcerative colitis or those with ulcerative colitis). and anti-IL-23p expression levels in sample(s) obtained from subjects with IL-23p 19 Patients with ulcerative colitis or suspected of having ulcerative colitis who have not received antibody therapy The expression level in the patient sample(s) is further compared to one of the expression levels in the patient sample(s). It is possible.

[0136] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0137] In another aspect, the present disclosure provides a method for treating ulcerative colitis by administering an anti-IL-23p19 antibody to a subject. As candidate patients for this study, we have identified patients who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF R ) The present invention relates to a method for identifying a patient suspected of having a HIV-infected virus, the method comprising obtaining a sample from the patient. and at least one biomarker of anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR). Based on biomarker analysis, patients were assigned to receive anti-IL-23p19 therapy. and identifying the patient as a candidate patient for receiving antibody treatment.

[0138] Suitable biomarkers for anti-tumor necrosis factor (anti-TNF) therapy resistance include OSMR and FC. GR3, CXCL6, interleukin-11, interleukin-24, interleukin These include Kin-13RA2, FAP, TWIST1, and WNT2.

[0139] The method comprises analyzing a sample obtained from a patient for CXCL8, AQP9, IL1B, S100A9, and , TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2 , SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT 1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A , IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS 2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2 A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B - AS1, TMEM236, CD177P1, SLC17A4, and ZG16 The method may further include analyzing for at least one biomarker that is detected in the blood.

[0140] The method comprises administering to the patient an anti-IL-23p19 antibody as described herein. It may further include.

[0141] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0142] In another aspect, the present disclosure provides a method for treating or preventing ulcerative colitis in a patient with or suspected of having ulcerative colitis, the method comprising administering to said patient an anti-tumor necrosis factor (ATF) inhibitor. Child (anti-TNF) therapy resistance (anti-TNF R Patients with or suspected of having anti-IL-1 The present invention relates to a method of treating a patient with an anti-TNF-23p19 antibody. R Whether it is and whether the patient is anti-TNF R and treating the patient with an anti-IL-23p19 antibody if This includes:

[0143] Samples obtained from patients were analyzed for OSMR, FCGR3, CXCL6, and interleukin-1. 1, interleukin-24, interleukin-13RA2, FAP, TWIST1, and anti-TNF, including WNT2 R Analyze transcripts.

[0144] The method involves the detection of CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12 , MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN 1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, S LC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100 A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, M MP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUC A2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXP E4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236 , CD177P1, SLC17A4, and ZG16. Regarding markers, before and after administration of anti-IL-23p19 antibody It may further include subsequently analyzing the obtained sample.

[0145] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0146] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for treating symptoms associated with ulcerative colitis, the method comprising: and CXCL8, AQP9, IL1B, S100A9, TREM1, MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6, CD177P1, SLC17A4, and ZG16. Analyzing the sample for biomarkers and administering an anti-IL-23p19 antibody to the patient. obtaining a second sample from the patient; and detecting CXCL8, AQP9, IL1B, S10 0A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUO XA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA 2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, D MBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, RE G1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HM GCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, U GT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDK from N2B-AS1, TMEM236, CD177P1, SLC17A4, and ZG16 analyzing the second sample for at least one selected biomarker. nothing.

[0147] Symptoms of ulcerative colitis include abdominal pain / discomfort, bloody stools, pus in the stool, fever, weight loss, and rectal At least one of the following symptoms may occur: bleeding, frequent diarrhea, recurrent diarrhea, fatigue, loss of appetite, and tenesmus (urgency) Contains at least one species.

[0148] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0149] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing ulcerative colitis, the method comprising: (a) a sample obtained from a patient; In CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1 , ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SL C26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A 8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MM P10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA 2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE 4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, At least one biotin selected from CD177P1, SLC17A4, and ZG16 Determining the expression levels of makers and (b) CXCL8, AQP9, IL1B, and S10 0A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUO XA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA 2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, D MBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, RE G1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HM GCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, U GT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDK from N2B-AS1, TMEM236, CD177P1, SLC17A4, and ZG16 A reference expression level of at least one selected biomarker and a reference expression level of at least one selected biomarker. (c) comparing the determined expression levels of the biomarkers in the patient. If the expression level is increased compared to the reference expression level, or if ... A decrease in the marker expression level compared to the reference expression level is diagnostic of ulcerative colitis. and providing a decision.

[0150] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0151] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing ulcerative colitis, the method comprising: (a) using an analyzer unit , CXCL8, AQP9, IL1B, S100A9, T in samples obtained from patients. REM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, S LC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OT OP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, I DO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3 , TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-A At least one gene, including S1, TMEM236, CD177P1, SLC17A4, and ZG16 (b) determining the expression level of at least one biomarker; and Using this method, CXCL8, AQP9, IL1B, S100A9, TREM1, and MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6, at least one biomarker including CD177P1, SLC17A4, and ZG16 The reference expression level of the mosquito and the determined expression level(s) of at least one biomarker ) and (c) determining whether the biomarker expression level is increased relative to the reference expression level. or if the biomarker expression level is decreased compared to the reference expression level. and if so, providing a diagnosis of ulcerative colitis.

[0152] The method includes using a computing device to calculate the results of the comparison with the reference biomarkers. and further comprising establishing an aid for diagnosing ulcerative colitis in a subject based on the It can be seen.

[0153] The method includes using a computing device to identify at least one biomarker from a sample. and comparing one determined amount(s) with at least one reference amount(s) of the biomarker. ), which comparison is performed automatically.

[0154] The method uses an analyzer unit to measure CXCL8, AQP9, IL1B, S100, A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOX A2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2 B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DM BT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG 1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMG CS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UG T2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN 2B-AS1, TMEM236, CD177P1, SLC17A4, and ZG16 The method may further include measuring binding of the ligand to at least one biomarker.

[0155] The method includes using a computing device to calculate the measured amount of binding of the ligand. It may further include calculating.

[0156] The method uses an analyzer unit to calculate the calculated amount of measured binding of the ligand. Based on CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1 , ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SL C26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A 8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MM P10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA 2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE 4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, of at least one biomarker including CD177P1, SLC17A4, and ZG16 It may further include determining the amount.

[0157] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis, the patient receiving anti-I The present invention relates to a method for determining whether a patient has been cured in response to L-23p19 antibody treatment. are CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, and MMP 1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, AB CA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26 A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, I GKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10 , CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, S LC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD1 For at least one biomarker, including 77P1, SLC17A4, and ZG16 and analyzing a sample obtained from the patient before the patient receives anti-IL-23p19 antibody treatment. Toto, CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MM P1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, A BCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC2 6A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP1 0, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A , LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD For at least one biomarker, including 177P1, SLC17A4, and ZG16 and analyzing samples obtained from patients after they have received anti-IL-23p19 antibody treatment. and that patients had at least one biomarker after receiving anti-IL-23p19 antibody treatment. If changes in the expression level of ulcerative colitis are detected, the patient may have ulcerative colitis. Determining that the suspected patient has been cured in response to anti-IL-23p19 antibody treatment; , including.

[0158] The method involves the detection of CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12 , MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN 1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, S LC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100 A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, M MP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUC A2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXP E4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236 at least one biomarker including CD177P1, SLC17A4, and ZG16 Regarding the treatment of IL-23p19 antibody, patients with ulcerative colitis or those without IL-23p19 antibody treatment were included. The method may further include analyzing a sample obtained from a patient suspected of having the disease.

[0159] The method involves the identification of GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C. The method may further comprise analyzing at least one biomarker including anti-IL-23p1 GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C after antibody treatment The expression level of at least one of the following is measured in patients administered an anti-IL-23p19 antibody: GUCA2A, OTOP2, AQP8, and SLC26A2 before anti-IL-23p19 antibody treatment , and the expression level of at least one of ADH1C is increased.

[0160] The method involves the determination of GUCA2A, O in patients who have not received an anti-IL-23p19 antibody. At least one biomarker containing TOP2, AQP8, SLC26A2, and ADH1C The expression levels of these proteins were analyzed, and the results were compared with those of patients who had not received anti-IL-23p19 antibodies. The expression level of at least one biomarker in the mice treated with anti-IL-23p19 antibody was measured. GUCA2A, OTOP2, AQP8, SLC26A2, and AD in patients receiving H1C and an anti-IL-23p19 antibody. Biomarker expression levels in patients receiving treatment are assessed using anti-IL-23p19 antibody treatment. If the expression level of the biomarker is increased compared to that in patients not receiving the and determining that the patient administered the anti-IL-23p19 antibody treatment is cured. It may include.

[0161] In another aspect, the present disclosure relates to a biomarker panel. The biomarker panel comprises CX CL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MM P7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12 , REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, A DH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2 D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXC L1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC1 01928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16 A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1 , SLC17A4, and ZG16.

[0162] In one aspect, the biomarker panel comprises GUCA2A, OTOP2, AQP8, SLC2 6A2, and ADH1C.

[0163] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for treating bowel frequency, the method comprising obtaining a first sample from a patient; analyzing the sample to detect a biomarker selected from Table 8; and administering the antibody to the patient; obtaining a second sample from the patient; and analyzing the second sample. and analyzing the first sample to detect a biomarker selected from Table 8. and determining whether the expression level of at least one biomarker detected in the second sample is higher than the expression level of the at least one biomarker detected in the first sample. The change in the expression level of at least one biomarker was determined by the anti-IL-23p19 antibody. The response to

[0164] Particularly preferred biomarkers selected from Table 8 include S100 calcium binding protein. Protein 8, S100 calcium-binding protein A12, cadherin-related family member 1, S100 calcium-binding protein A9, Triples pseudokinase 2, platelet activation mitochondrial-associated apoptosis-inducing factor 3, Fc fragment of IgG receptor IIb, Colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, I Interferon-induced transmembrane protein 2, calpain 13, and RNA polymerase II2 Elongation factor, prokinephycin 2, aquaporin 9, interleukin 1 alpha, IgG Fc fragment of receptor IIa, TIMP metallopeptidase inhibitor 1, transcobalamin 1, and creatine kinase B.

[0165] The method comprises administering to the patient an anti-IL-23p19 antibody as described herein. and

[0166] The method may further include analyzing the tissue sample.

[0167] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0168] In another aspect, the present disclosure provides a method for treating bowel movements in a patient having or suspected of having ulcerative colitis. 1. A method for diagnosing the frequency of a genotype selected from Table 8 in a sample obtained from a patient, comprising: (a) detecting a genotype selected from Table 8 in a sample obtained from the patient; (b) determining the expression levels of selected biomarkers; and comparing the expression level to a reference expression level of a biomarker selected from Table 8; and c) If the biomarker expression level in the patient is altered compared to the reference expression level and providing a diagnosis of bowel frequency in that case.

[0169] Particularly preferred biomarkers selected from Table 8 include S100 calcium binding protein. Protein 8, S100 calcium-binding protein A12, cadherin-related family member 1, S100 calcium-binding protein A9, Triples pseudokinase 2, platelet activation mitochondrial-associated apoptosis-inducing factor 3, Fc fragment of IgG receptor IIb, Colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, I Interferon-induced transmembrane protein 2, calpain 13, and RNA polymerase II2 Elongation factor, prokinephycin 2, aquaporin 9, interleukin 1 alpha, IgG Fc fragment of receptor IIa, TIMP metallopeptidase inhibitor 1, transcobalamin 1, creatine kinase B, and combinations thereof.

[0170] The method may further include analyzing the tissue sample.

[0171] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0172] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for treating bowel urgency, the method comprising obtaining a first sample from a patient; analyzing the sample to detect a biomarker selected from Table 9; and administering the antibody to the patient; obtaining a second sample from the patient; and analyzing the second sample. and analyzing the first sample to detect a biomarker selected from Table 9. The expression levels of the biomarkers detected in the first sample are compared with the expression levels of the biomarkers detected in the second sample. Changes in the expression levels of the target gene indicate a response to anti-IL-23p19 antibodies.

[0173] Particularly preferred biomarkers to select from Table 9 include multicoil region-containing 175, TNF receptor superfamily member 17, complement factor B, F-box and WD-antibody Subdomain-containing 7, lipase A, lysosomal acid type, centrosomal protein 128, baculoyl IAP repeat-containing 3, receptor for interferon alpha and interferon beta Subunit 2, phosphoserine aminotransferase 1, sortin nexin 25, heat shock Hsp70 family A (Hsp70) member 13, claudin 2, lymphocytes antigen 96, SEC11 homolog C, signal peptidase complex subunit, DNA damage Regulatory autophagy modifier 1, cytoplasmic polyadenylation element binding protein 4, phosphoenol Pyruvate carboxykinase 1, elongation factor for RNA polymerase II2, cathepsin H , calpain 13, and combinations thereof.

[0174] The method comprises administering to the patient an anti-IL-23p19 antibody as described herein. and

[0175] The method may further include analyzing the tissue sample.

[0176] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0177] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing bowel urgency, the method comprising: (a) detecting in a sample obtained from a patient: (b) determining the expression level of a biomarker selected from Table 9; and The determined expression level is compared to a reference expression level of a biomarker selected from Table 9. and (c) the biomarker expression level in the patient changes compared to the reference expression level. and if so, providing a diagnosis of bowel urgency.

[0178] Particularly preferred biomarkers to select from Table 9 include multicoil region-containing 175, TNF receptor superfamily member 17, complement factor B, F-box and WD-antibody Subdomain-containing 7, lipase A, lysosomal acid type, centrosomal protein 128, baculoyl IAP repeat-containing 3, receptor for interferon alpha and interferon beta Subunit 2, phosphoserine aminotransferase 1, sortin nexin 25, heat shock Hsp70 family A (Hsp70) member 13, claudin 2, lymphocytes antigen 96, SEC11 homolog C, signal peptidase complex subunit, DNA damage Regulatory autophagy modifier 1, cytoplasmic polyadenylation element binding protein 4, phosphoenol Pyruvate carboxykinase 1, elongation factor for RNA polymerase II2, cathepsin H , calpain 13, and combinations thereof.

[0179] The method may further include analyzing the tissue sample.

[0180] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0181] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing bowel frequency, the method comprising: (a) detecting a patient's bowel frequency using an analyzer unit; determining the expression level of a biomarker selected from Table 8 in a sample obtained from the subject; and (b) using a computing device, determining expression of the biomarker. Comparing the level(s) to a reference expression level of a biomarker selected from Table 8 and (c) if the biomarker expression level is altered compared to the reference expression level, and providing a bowel frequency diagnosis.

[0182] Particularly preferred biomarkers selected from Table 8 include S100 calcium binding protein. Protein 8, S100 calcium-binding protein A12, cadherin-related family member 1, S100 calcium-binding protein A9, Triples pseudokinase 2, platelet activation mitochondrial-associated apoptosis-inducing factor 3, Fc fragment of IgG receptor IIb, Colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, I Interferon-induced transmembrane protein 2, calpain 13, and RNA polymerase II2 Elongation factor, prokinephycin 2, aquaporin 9, interleukin 1 alpha, IgG Fc fragment of receptor IIa, TIMP metallopeptidase inhibitor 1, transcobalamin 1, creatine kinase B, and combinations thereof.

[0183] The method may further include analyzing the tissue sample.

[0184] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0185] In another aspect, the present disclosure provides a method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis. The present invention relates to a method for diagnosing bowel urgency, the method comprising: (a) measuring a patient's bowel urgency using an analyzer unit; determining the expression level of a biomarker selected from Table 9 in a sample obtained from the subject; and (b) using a computing device, determining expression of the biomarker. Comparing the level(s) to a reference expression level of a biomarker selected from Table 9 and (c) if the biomarker expression level is altered compared to the reference expression level, and providing a diagnosis of bowel urgency.

[0186] Particularly preferred biomarkers to select from Table 9 include multicoil region-containing 175, TNF receptor superfamily member 17, complement factor B, F-box and WD-antibody Subdomain-containing 7, lipase A, lysosomal acid type, centrosomal protein 128, baculoyl IAP repeat-containing 3, receptor for interferon alpha and interferon beta Subunit 2, phosphoserine aminotransferase 1, sortin nexin 25, heat shock Hsp70 family A (Hsp70) member 13, claudin 2, lymphocytes antigen 96, SEC11 homolog C, signal peptidase complex subunit, DNA damage Regulatory autophagy modifier 1, cytoplasmic polyadenylation element binding protein 4, phosphoenol Pyruvate carboxykinase 1, elongation factor for RNA polymerase II2, cathepsin H , calpain 13, and combinations thereof.

[0187] The method may further include analyzing the tissue sample.

[0188] This method is based on the Modified Mayo Score (MMS), Total Mayo Score, and Mayo Endoscopic Subscore. Core, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes score, R Clinical metrics, including the Obarts Histopathology Index (RHI), and combinations of these, were analyzed. The method may further include:

[0189] In another aspect, the present disclosure provides a biomarker comprising at least one biomarker selected from Table 8. The present invention relates to a biomarker panel. Markers include S100 calcium-binding protein 8, S100 calcium-binding protein Protein A12, cadherin-related family member 1, S100 calcium-binding protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial Doria-related 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN oncogenic gene, Src family tyrosine kinase, interferon-induced transmembrane protein 2 , calpain 13, RNA polymerase II2 elongation factor, prokinephycin 2, aqua Porin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa, TIMP meta These include glutathione-3, thrombin-1, transcobalamin-1, and creatine kinase B. can be.

[0190] In another aspect, the present disclosure provides a biomarker comprising at least one biomarker selected from Table 9. The present invention relates to a biomarker panel. Markers include coiled coil domain-containing 175, a member of the TNF receptor superfamily, and 17, complement factor B, containing F-box and WD-repeat regions; 7, lipase A, lysosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, interferon a Receptor subunit 2 of interferon and interferon beta, phosphoserine aminotransferase Spherase 1, sortin nexin 25, heat shock protein family A (Hsp7 0) Member 13, Claudin 2, Lymphocyte antigen 96, SEC11 homolog C, Signal Peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation acetylation element-binding protein 4, phosphoenolpyruvate carboxykinase 1, RNA These include polymerase II2 elongation factor, cathepsin H, and calpain 13. [Example]

[0191] Materials and Methods Study design and participants 14 countries (Australia, Belgium, Canada, Czech Republic, Denmark, George Hungary, Japan, Lithuania, Moldova, the Netherlands, Poland, the United Kingdom, and the United States This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial at 75 sites in the US. , registered from January 2016 to September 2017.

[0192] The study was conducted at the International Conference on Harmonisation of Good Clinical Practice (ICPC). All informed consent forms and The protocol was approved by the appropriate ethical review committee before the start of the study. provided written informed consent before receiving study medication.

[0193] Procedures and Results Endoscopic findings were scored by one of two blinded central readers. Two biopsy samples obtained during endoscopy at baseline and study week 12 were used to assess the Histological disease activity was assessed by a central reader. All biopsies were taken from a small area of ​​the anal verge. The specimens were collected at a minimum of 30 cm.

[0194] If a discrete lesion is present, biopsies are obtained preferentially at the edge of the ulcer, or If not present, the specimen was taken from the edge of the sore. Macroscopic disease is present but no distinct lesions are present. If no gross disease is present, biopsies are obtained at intervals throughout the affected mucosa. Biopsies were obtained from the entire body.

[0195] histopathology Two endoscopic biopsy specimens for histopathological evaluation were taken from a small area of ​​the anal verge at each endoscopy. The most affected area was obtained from at least 30 cm. One of two blinded pathologists The Geboes score and the Roberts Histopathology Index (RHI) were used to assess the Samples were assessed for histological disease activity. The Geboes score was divided into seven categories ( or grade), each of which is classified as "structural (structural change)" (Grade 0 ), "chronic inflammatory infiltrate" (grade 1), "lamina propria eosinophils" (grade 2A), "lamina propria "Neutrophils" (Grade 2B), "Neutrophils in the epithelium" (Grade 3), "Crypt destruction" (Gray Histological findings, including "surface epithelial damage" (grade 5) and "surface epithelial damage" (grade 6), should be recorded. The score includes subscores that indicate the degree of abnormality seen for that histological feature, with a subscore of 0 being Scores indicate normal appearance, with higher subscores indicating increasing abnormal appearance. Four Geboes score categories ("chronic inflammatory infiltrate," "lamina propria neutrophils," "epithelial Using the weighted results from the "Neutrophil count" and "Surface epithelial damage" criteria, a score of 0 (disease activity) was calculated. The RHI derives a continuous score ranging from 0 (no disease activity) to 33 (severe disease activity). It was developed as a response tool to detect therapeutic effects in early drug development.

[0196] The endpoints in this example were endoscopic improvement (endoscopic subscore of 0 or 1) and organization. Histological remission (neutrophils in the lamina propria, neutrophils in the epithelium, and erosion or ulceration) (defined as a Geboes histological subscore of 0 for any parameter) Mucosal healing was determined by the presence of both histological remission and endoscopic improvement. There is no consensus on what constitutes lamina propria eosinophils, and there is a lack of reproducibility and Given the limited prognostic data and limited clinical data, achieving a successful reduction in eosinophils is unlikely to result in histologic remission. The Robarts Histopathology Index (RHI) score was not included in the primary definition. It was determined at the same time as the BOES score.

[0197] RNA Extraction and Gene Array Methodology Gene expression was measured on GeneChip HT A2.0 arrays using Affymetrix 553 colon tissue biopsies from I6T-MC-AMAC using the WT protocol Biopsies from the same subject for each time point were pooled together for a total of 277 These were subjected to quality control (QC) checkpoints. The samples were subjected to thorough analysis (e.g., RNA sample quality / quantity, and amplification) and then proceeded to HTA2.0 processing.

[0198] RNA sample preparation and quality control Colon tissue samples were collected in two tubes per subject per time point. Colon samples from 20 subjects were collected to ensure sufficient mass was available for analysis. A sampling pilot was performed by pooling biopsies. RNA extraction was performed according to the BioA The QC metrics for the BA system included: 28S / 18S ratio (0.75~3.0), RNA Integrity Number ( The RIBOGREEN® fluorescent dye assay was performed. RNA concentrations were measured using a 1000 kJ / ml ELISA kit. Samples with concentrations below 5 ng / μl were excluded from subsequent processing. The samples were then analyzed using an Agilent 2100 bioanalyzer. All samples were of sufficient mass for the assay and were HT Proceeded to A2 processing.

[0199] RNA samples that passed CGL QC metrics were aliquoted into 96-well plates (10 0 ng input). Two samples were removed after one patient discontinued and were taken from week 12. Four biopsies were not collected from subjects who left the study after the week 0 biopsy was collected and were not included in the allele. Data sets for week 0 of 224 and week 12 of 220 that passed QC left behind.

[0200] gene chip array Probe-level data from the HTA2 platform were back-converted using standard RMA methods. Preprocessed with ground correction and quantile normalization, and analyzed using Affymetrix NETAFFX ( Probe set defined by the NA35 / GRCh37 human reference genome release The data were then aggregated to the exon level, where highly correlated exon-based profiles were identified as follows: The probes were aggregated to the level of "exon groups," which are data-defined clusters of probe sets. Calculate the correlation matrix between the expression sets and the distance metric between pairs of probe sets, The correlation coefficient was defined as 1 minus the pairwise correlation. The Rhclust function was used to generate a hierarchical cluster. Perform dendrogram generation and form exon groups by cutting the dendrogram at a distance of 0.8. Once exon groups were defined, aggregate expression for the samples was analyzed using two-way ANOVA. The probe and sample effects were obtained from the sample effects in the VA model. by the rlm function in the R MASS package applied to probe-level data The estimates were made using robust regression implemented.

[0201] Differential expression statistical analysis The set of exons generated from the above procedure was filtered according to two criteria: 1) The SD of log2(expression) is less than 0.286 (corresponding to a CV of approximately 20%). 1) the exon group, and 2) the mean log2 (expression) of the negative control (normal gene -> 75th percentile of median log2 expression for intronic probe sets If a gene contained multiple exons, the probe set The feature with the highest number of entries is selected to represent the expression of genes as a whole and to obtain the highest average expression. The link was broken by features with levels. In all models, Benjamin The NI-Hochberg method was used to compare the mean and mean values ​​across treatment groups and across all tested experiments. Apply multiplicity correction to the resulting p-values ​​to account for the number of comparisons made across groups. did.

[0202] Mixed Effect Repeated Measurements Model (MRMM) , and fit each filtered exon group separately to age, sex, batch, and base. BMI at baseline, prior biologic therapy, and modified Mayo score at baseline Calculate fold change between week 0 and week 12 time points using (MMS) as a covariate Crossed timepoint contrast model The differential expression of each exon group in the treatment group was compared with its differential expression in the placebo group. The fold change was greater than 0.5 log2 units (approximately 1.41× change) and and exons with a False Discovery Rate (FDR) adjusted q value of less than 0.05 Groups were classified as differentially expressed.

[0203] Correlation statistical analysis Exon clustering was performed using age, sex, and array chip batch as covariates. The relationship between differential expression of immunocytes and changes in clinical metrics between weeks 0 and 12 was examined. Clinical metrics included MMS, total Mayo score, and intra-Mayo score. Endoscopic subscore, Ulcerative Colitis Endoscopic Severity Index (UCEIS) total score, Geboes The included test results include the score, and the Roberts Histopathology Index (RHI). fecal calprotectin and peripheral blood titers of IL-17A, IL-22, and CRP there were. This study is registered with ClinicalTrials.gov, number NCT02589665. It was recorded.

[0204] result Patients, study details and biological samples Between December 2015 and September 2017, 358 patients were screened for eligibility. Of these, 224 patients had a baseline life expectancy of 18.2 years. 220 underwent a 12-week biopsy. Of these 220 patients, 63 Over % had received prior biologic therapy, and 47.3% had baseline corticosteroid use. Baseline disease characteristics were well balanced across treatment groups. The data were similar between treatment groups, with similar disease activity (modified Mayo score) and mucosal inflammation (Mayo score). yaw endoscopy subscore), and histology (Geboes index and RHI) (Table 1).

[0205] [Table 5]

[0206] Mirikizumab-mediated changes in transcripts in ulcerative colitis The 200 mg mirikizumab treatment group had a 12-month survival rate compared with placebo in all three treatment groups. In addition to showing maximal efficacy at week 12, there was no differential effect between baseline and week 12. The number of expressed genes in colon biopsies was also the highest (Figure 1A). To better distinguish the effects of standard treatment from those of standard treatment, changes in gene expression were compared to placebo. In the 200 mg mirikizumab group both without (Fig. 1B) and with (Fig. 1C) standardization , assessed between baseline and week 12. Normalization to placebo was differentially A reduction in the number of transcripts identified provided a higher degree of confidence.

[0207] Transitions with greatest change at week 12 after normalizing for change in the placebo group The transcripts are shown in Table 2. The most significant increases in expression were AQP8, ABCG2, HMGCS2, and S In epithelial cells found in healthy colonic mucosa, including LC26A3 and GUCA2A It is found in genes that code for proteins that are common in the epithelial lining and bursa These strongly upregulated transcripts may reflect the restoration of colonic integrity in healthy colonic mucosa. These findings represent both structural components and important functional proteins that are important for function in these patients. The most upregulated transcript was AQP8. (aquaporin-8), which mediates water recovery from fecal contents in the apical colon This gene encodes an important water transporter on the surface of the kidney, which is important for patients who experience frequent, watery diarrhea. Similarly, efflux transporters such as ABCG2 may have beneficial effects on UC patients. and, when normalized, provides improved mucosal function in UC patients. Conversely, the greatest decrease in expression was observed in tissue remodeling (MMP3, MMP10), oxidative stress (D UOX2, DUOXA2, NOS2), and chemotaxis (CXCL1, CXCL2, CXCL 3) Genes associated with IBD activity by their function in It is suspected.

[0208] Correlation between IL-23 pathway transcripts and disease activity score Changes in the expression levels of genes upregulated by IL-23 receptor activation were observed in MET Defined by ACORE™ (Clarivet, PA, USA) , correlated with changes in disease activity metrics MMS, UCEIS, and RHI at week 12. (Figure 2A). The most highly correlated genes were TGFB1, IL1B, and IL6. Among these, IL1B was also observed in placebo-controlled 200 mg Mirikizumab. In the mab group, it was one of the genes whose expression decreased most between baseline and week 12. Upregulated by IL-23 / IL-23R engagement and changes in disease activity metrics All genes significantly correlated with were positively correlated, and the extent of gene expression changes was improved. IL2 correlated with disease activity metrics but did not pass the significance threshold of FDR ≤ 0.05 Figure 2B shows the placebo-adjusted differential expression of each gene between baseline and week 12. The heatmap shows the current Pearson correlation coefficient (Rho), the modified Mayo score, RHI, and UCEIS over the same period, vertically, by the fold change of these genes. Mirikizumab-regulated genes are more likely to be associated with histopathological disease than with endoscopy (UCEIS). The more sensitive the transcripts of these genes, the stronger the correlation with disease indices (MMS, RHI). The present inventors have demonstrated that IL1B is highly correlated with disease activity and that We found that both the α-glucanase gene and the α-glucanase gene have high differential expression compared to other genes.

[0209] Correlation between mirikizumab-altered transcripts and disease activity scores Changes in individual transcripts correlate with disease activity as defined by MMS, Geboes, or RHI. This correlated with the changes in serotonin levels, reflecting the strongest changes in mirikizumab treatment-induced regulation (Table 2). Several transcripts associated with changes in disease activity were identified, and all transcripts positively correlated with disease. All transcripts are uniformly and consistently downregulated by mirikizumab. All transcripts related to Qi and negativity are upregulated by mirikizumab treatment. Izumob-regulated transcript changes showed a profile of disease attenuation, 12 days after initiation of treatment This is consistent with observations suggesting preliminary evidence of molecular healing as early as weeks.

[0210] Pathway analysis of the top mirikizumab-regulated genes most highly correlated with changes in disease scores The most highly regulated transcripts identified in Figure 3 (strict cutoff of r value) The two disease indices selected were RHI and MM. S, but these are the highest-logarithmic correlations 10 Provides q-value As shown in Figure 4 and Table 2, these transcripts changed with changes in disease activity. Common functions include cell adhesion and extracellular matrix (ECM) remodeling This provides insight into the pathways of fibrosis, followed by features seen in profibrotic pathways and tissue repair. there was.

[0211] Mirikizumab-induced changes in gene expression and correlation with systemic biomarkers L-1β, IL-6, S100A8 and S100A9 transcripts and systemic biomarkers IL-17, IL-22, C-reactive protein (CRP) and feces The correlation between fecal calprotectin (fCLP) and α-glucan was determined (Table 2 Changes in colonic expression of S100A8 / 9, IL-1β, and IL-6 were observed in fCLP and It correlated strongly with serum IL-17A levels and less strongly with serum CRP levels. Circulating levels of IL-22 were significantly correlated with S100A9 and IL-1β. These correlations were significantly correlated with changes in IL-6, but not with S100A8 or IL-6. The available biomarkers, such as fCAL, IL-1β, and IL-6, are This correlated with several changes in protein-encoding transcripts, suggesting the involvement of p19 in the colonic mucosa. It was shown to reflect

[0212] [Table 6]

[0213] Mirikizumab-regulated core TNF resistance transcripts Smilie et al. showed that inflammation-related fibroblasts, monocytes, and dendritic cells respond to anti-TNFα therapy. Using a meta-analysis of bulk expression data from 60 responders and 57 non-responders to showed high relative expression of genes that are part of the drug resistance signature identified by In contrast to the drug-resistant phenotype, anti-TNFα sensitivity genes in colonic tissues , was most enriched in epithelial cells. R A message that reflects the important drivers of The transcripts included in the analysis are shown. The number of regulated transcripts (Fig. 5B) was significantly higher than that of TNF R Less than what was seen in the cluster This result suggests that p19-IL23, compared with antibodies targeting TNFα, This is consistent with a different mechanism of action for protein-targeting mirikizumab. Bu is TNF R The genes that were predominant in the transcript cluster were regulated. The results of these studies showed that mirikizumab treatment reduced TNF R may act to reduce transcripts associated with , and TNF R This provides a phenotype in colon tissue that differs from that seen in patients. This indicates that there may be cases where this is the case.

[0214] Strong changes in transcript expression levels were observed in the 200 mg mirikizumab group. The changes provide a window into the changes induced by mirikizumab treatment. Genes upregulated by mab showed a trend towards healthy mucosa and were upregulated The increased transcripts represent improved barrier integrity and they provide functional transporters in the colon. For example, an increase in the water transporter aquaporin 8 may limit the water content in feces. Increases in the anion transporters SLC26A2 and SLC16A9 were associated with mirikizumab treatment. , resulting in mucosa capable of retaining functional transporters as early as 12 weeks after the start of treatment. Reaffirm that there may be cases where mirikizumab-related Therefore, some of the most reliably downregulated genes were identified in the UC mucosal biopsies. Previous studies have shown it to be increased in UC.

[0215] S100A8 and A9 transcripts contribute to the calprotectin protein from the colonic mucosa Mirikizumab treatment resulted in dose-dependent changes in fCLP. These changes were reported previously. Consistent with this finding, a statistically significant correlation was observed between S1 S100A8 and S100A9 transcripts were downregulated in the colon with mirikizumab treatment in patients This was observed along with a decrease in the levels of fCLP in the most highly mirikizumab-regulated The genes involved are those involved in inflammatory signals (IL1β, CXCL1, CXCL2, and CXCL3). Decrease in transcripts mediating matrix destruction in the colonic mucosa (matrix metalloproteinases These molecular changes reflect the attenuation of ATP (10) and ATP (3) and the increase of anion and water transporters. indicates the onset of mucosal healing.

[0216] The IL23 pathway is involved in the genetic predisposition to UC, and the IL23R gene (rs1048 A meta-analysis of the association between 10 polymorphisms in the genotype (excluding 9629) and UC risk confirmed Analysis of IL23-regulated transcripts overlaid on transcript changes correlated with disease activity showed consistent downregulation of IL23 pathway genes. Analysis of UC patients revealed inflammation-associated fibrosis. Blast cells, monocytes, and tissue-resident antigen-presenting cells are primarily deficient from anti-TNF therapy and secondary The authors demonstrate high relative expression of genes enriched in biopsy samples from patients with secondary disease. In contrast, the anti-TNFα sensitivity genes in colonic tissue originate from epithelial cells. Such TNF R In a meta-analysis of transcripts enriched in the colonic mucosa, Several transcripts appeared to be regulated by liquizumab, as shown in Table 2. These transcripts are potentially expressed in cell types identified by previous studies. The key is the change in OSMR expression, which is downregulated by mirikizumab. Colonic mucosa is TNF R previously hypothesized to represent potential alternative disease pathways. Compared with anti-TNF responsive patients, R Significantly in the mucosa of UC patients OSM, a gene showing increased expression, is expressed in inflammation-associated mononuclear cells and antigen-presenting cells. Its receptor, OSMR, was enriched in inflammation-associated fibroblasts. Mirikizumab downregulated OSMR in the colonic mucosa within 12 weeks of mirikizumab treatment. This finding suggests that TNF R This indicates the suppression of activation of this pathway seen in patients with These patients may have better outcomes. Many genes involved in this process are regulated by mirikizumab.

[0217] The changes observed within 12 weeks of mirikizumab treatment were similar to those observed with vedolizumab ( However, the transcriptome was different from that observed after VDZ treatment. Vedolizumab analyses of changes in serotonin levels were not normalized to those in the placebo group. It is believed to provide a more rigorous method, which is related to the edge with a q=0.05 threshold. Therefore, placebo-adjusted 20 The gene expression changes observed in the 0 mg mirikizumab group were related to spontaneous mucosal healing. This is more likely to be related to mirikizumab treatment rather than related to the control group. Top 10 transcripts modified by VDZ and top 10 identified in the examples There was little commonality between the transcripts of VDZ and the Comparison is to healthy controls rather than diseased baseline patients enrolled in the VDZ trial Notably, the change in expression at week 12 compared to week 0 was The changes in expression at 52 weeks after treatment with VDZ were: There was some overlap with the changes at week 12 with mirikizumab. The majority of the induced changes were concentrated within signaling pathways derived from the Th17 pathway. However, the changes induced by VDZ are due to chemotaxis, and VDZ targets α4β7 integrin. This was consistent with the mechanism of action of DZ and the resulting chemotactic signal.

[0218] Example 2 method: Clinical response (9-point Mayo subscore [rectal bleeding, bowel frequency, endoscopy]) was assessed at week 12. ≥2-point and ≥35% reduction in RB subscore from baseline [BL] mirikizumab treatment achieved a reduction of ≥1 or RB subscore of 0 or 1 Patients were randomly assigned to receive mirikizumab 200 mg subcutaneously every 4 weeks or every 12 weeks until week 52. Patients who achieved a clinical response were given placebo (PBO) at induction. Patients who received PBO continued on PBO in the maintenance period. Colon biopsies were taken from the anal verge for at least 30 minutes. cm most affected area (Mirikizumab N=31, PBO N=7) at week 0, Data were obtained at weeks 12 and 52 using the Bayesian Limma R package. The transcript changes from baseline to week 12 in the PBO and mirikizumab arms were The results were classified into differentially expressed genes (DEGs). Among these DEGs, similarly expressed genes (Similarly E-expressed Genes) were identified. es, SEG) were evaluated as those whose expression levels at week 12 were maintained up to week 52. Identified.

[0219] result: Analysis of transcript changes at week 52 in responders at week 12 who maintained disease remission The DEG-SEG profile in responders was identified (see Figure 6). One cluster of genes upregulated in the in vivo study included CXCL8, AQP9, IL1B, and S These included 100A9, TREM1, MMP12, MMP1, MMP7, and TCN1. The second cluster of genes upregulated in the baseline included DUOX2, DUOXA2, and S These included LC6A14, VNN1, ABCA12, REG1B, and C4BPA. The cluster of regulated genes was GUCA2B, OTOP2, AQP8, SLC26A2, and ADH1C. Of these genes, 63 (70.8%) were milikisma 5 (5.6%) were present only in PBO responders, 21 (23.6%) were present only in PBO responders, and ) were present in both groups (see Figure 7). The magnitude of transcript changes was significantly higher in patients with MM compared to PBO responders. In the kizumab responder group, the increase was greater at week 12 and more consistent through week 52 The table in Figure 8 shows the top 10 mirikizumab-specific DEG-SEG genes. Another cluster of DEG-SEGs correlated with the dynamic index (Robarts histopathology index [R HI] and modified Mayo, both r>0.5) persisted in mirikizumab-treated patients. The effect was shown to be sustained in placebo patients, but not in patients on placebo. Week 12 after mirikizumab treatment Noticeably, two clusters of genes that were upregulated at baseline were transformed into downregulated ones. and clusters of genes that were downregulated at baseline became upregulated. As shown in Figure 9A, the cluster of genes remained unchanged from week 12 to week 52. From week 12 to week 52, the expression trended downward (Figure 9 (See arrow direction). Placebo responders (“PBO”, in the absence of mirikizumab treatment) Two of the genes were upregulated at baseline in patients who showed spontaneous improvement under the The cluster of downregulated genes changed to downregulated ones (Fig. 9C), whereas the cluster of downregulated genes at baseline As shown in Figure 9D, the cluster of genes in PBO remained unchanged. The changes in biomarkers remained constant (indicated by horizontal arrows). Figure 1 As shown in Figures 10A-10D, the cluster of mirikizumab-responsive genes correlated with disease activity. These results showed that mirikizumab treatment significantly improved the baseline The expression of two clusters of up-regulated genes in the line was changed to a down-regulated state. and the expression of the cluster of down-regulated genes at baseline was increased to that of the up-regulated The first gene cluster observed in placebo responders was The changes in the first and second gene clusters were similar to those observed in the placebo group due to lifestyle changes. This likely reflects the response of these gene clusters to changes. In addition, two clusters contained markers related to inflammation. A cluster of genes that were downregulated in the line changed to become upregulated. In contrast, the cluster of genes that were downregulated at baseline was downregulated in the placebo group. At 52 weeks after mirikizumab treatment, genes upregulated at baseline remained Two clusters of offspring remained downregulated, with genes downregulated at baseline These results suggest that mirikizumab may be effective during induction. The induced changes in gene expression were observed up to 52 weeks (the end point of data collection). These results also demonstrate that the mirikizumab-treated The responders were significantly different in terms of both fold change and significance from the transcripts in the PBO responder group. This demonstrates that the two genes have differentially expressed transcripts that are distinct from one another.

[0220] In this sample of PBO and mirikizumab responders at week 12, mirikizumab responders were broader, larger, and more sustained in size at week 52 compared with PBO responders Qualitative description of the transcripts revealed changes in the PBO responders compared with the spontaneous healing that occurred in the PBO responders. These results demonstrated distinct molecular healing pathways associated with mirikizumab treatment. A cluster of transcripts associated with mirikizumab-mediated healing in ulcerative colitis was identified and provides molecular clues for its role. The most upregulated proteins showed consistency across targets, endoscopic indices, and clinical indices. were associated with water and ion transport, indicating an epithelial origin.

[0221] Example 3 In this example, patients with moderate to severe active UC (NCT02589665) Reflecting colonic mucosal gene expression and disease activity during the 12-week induction period of the Phase 2 study Mirikizumab-induced upregulation of colonic transporter transcripts was investigated. Controlled bowel frequency in a phase 2 study of patients with moderate to severe ulcerative colitis has been improved.

[0222] method: Patients were randomized 1:1:1:1 to receive intravenous placebo, with the possibility of exposure-based dose escalation. 50 mg or 200 mg mirikizumab with serotonin receptor agonist activity, or 600 mg fixed mirikizumab Mab was administered every 4 weeks for 12 weeks. SF was reported daily by the patient. and four levels representing increased SF above their normal or healthy baseline (BL). The SF frequency ranking scale was converted to an ordinal scale [0-3] (0 = normal bowel frequency for the subject). 1 = 1-2 more bowel movements than normal, 2 = 3-4 more bowel movements than normal, 3 = (Five or more bowel movements above normal). Colon biopsy of patients (PBO N=58, 50 mg miliary Liquizumab N=52, 200mg mirikizumab N=51, 600mg mirikizumab N (=54) were collected at BL and 12 weeks and analyzed using an Affymetrix HTA2. Gene expression was measured using a low-energy array workflow. Expression or SF values ​​were pooled and associations were determined based on the non-parametric Kendall's tau (τ). Pathway analysis (hallmark and reactome) of related genes was performed, and overrepresentation analysis was performed. The p-values ​​for enrichment were determined by the hypergeometric distribution test and the Benjamini- Adjustments were made for multiple testing by the Hochberg procedure. Data from the 200 mg treatment group Using the data, a paired t-test comparing expression levels at BL and week 12 was performed. Differential gene expression after liquizumab treatment was determined. Higher expression resulted in higher SF. If so, a "positive" correlation to gene expression was considered.

[0223] A total of 267 genes had SF(tau(τ)>0.3 and qval<0.001, Table 8 Of these, 212 were positively associated (high expression correlates with high SF). 55 were negatively associated (high expression was associated with low SF), and 55 were negatively associated (high expression was associated with low SF). The 212 transcripts identified were uniformly and consistently downregulated with mirikizumab treatment, whereas the 212 transcripts identified with SF were downregulated with mirikizumab treatment. Fifty-five negatively associated transcripts were consistently upregulated with mirikizumab treatment ( Table 3 , Figure 17). The biological pathways include inflammatory response, extracellular matrix dysregulation, neutrophil loss, and cytokine production. In-cell signaling pathways were mentioned, particularly the TNF and IL6 pathways (Table 4).

[0224] [Table 7]

[0225] [Table 8]

[0226] The top 20 genes associated with SF are listed in Table 5. Figure 13 shows the top 20 genes associated with SF. Figure 14 shows the tau (τ) distribution for the top 20 genes. The expression of S100A8, MMP3, AQP9, and CDHR1 is shown.

[0227] [Table 9]

[0228] This example identifies colonic transcripts associated with stool frequency, a clinical disease activity measure, Treatment with mirikizumab upregulated genes associated with normalization of SF, resulting in a significant improvement in UC patients. It was demonstrated to downregulate genes associated with inflammation in intestinal tissue samples.

[0229] Example 4 In this example, colon tissue transcripts and markers at baseline (BL) and week 12 (W) were analyzed. We investigated the association between patient-reported bowel urgency (BU) and mutations in genes associated with BU. The effect of liquizumab induction treatment was evaluated.

[0230] Patients were randomized 1:1:1:1 to receive intravenous placebo (N=63), exposure-based 50 mg (N=63) or 200 mg (N=62) of milikir with the possibility of dose escalation irikizumab or 600 mg (N=61) fixed mirikizumab every 4 weeks for 12 weeks. Patient colon biopsies were collected at BL and week 12 (placebo N=5 8, 50mg miri N=52, 200mg N=51, 600mg N=54). Gene expression was analyzed using the Affymetrix HTA2.0 microarray workflow. Differential gene expression was measured by a paired analysis comparing expression values ​​at week 12 and BL. Determined by T-test. BU was reported by patients daily as yes / no. The proportion of days of BL and BU at week 12 was ranked on a 4-point scale for the 3 days before the visit. Calculated by degree (0 = no urgency for all of the past three days, 3 = urgency for all of the past three days). Gene expression and BU values ​​at BL and week 12 were pooled and non-parametric. Associations were identified based on sex and Kendall's tau (τ). Pathway analysis of correlated genes was performed using MS Using overrepresentation analysis on hallmark and reactome gene sets from igDB The p-values ​​for enrichment were determined by the hypergeometric distribution test and the Benjamini-H Adjustment was made for multiple testing by the BH method. Higher expression was associated with more A "positive" correlation to gene expression was considered if it resulted in many BUs.

[0231] A total of 249 patients reported BU scores at BL and week 12. The presence of BU was , 320 genes (tau (τ) > 0.225 and qval < 0.001) were associated with Pathway analysis identified pathways significantly associated with BU (Table 6). 320 correlations Of the transcripts identified, 296 were positively associated (higher gene expression) with BU frequency, and 24 were Negatively associated (lower gene expression) (see Figure 17). Mirikizumab (200m Treatment with BU resulted in a statistically significant decrease in 296 transcripts positively associated with BU, and a significant decrease in B This resulted in an increase in 24 transcripts that were negatively correlated with U.

[0232] [Table 10]

[0233] The top 20 genes associated with BU are listed in Table 7.

[0234] FIG. 15 shows the tau (τ) distribution for the top 20 genes associated with SF.

[0235] Figure 16 shows the relationship between MMS-SF scores and S100A8, MMP3, AQP9, and C Expression of DHR1 is shown.

[0236] [Table 11]

[0237] This example demonstrates that mucositis and urgency correlate with bowel urgency and are consistently modulated by mirikizumab. We identified colonic transcripts associated with inflammatory bowel disease and healing.

[0238] [Table 12-1]

[0239] [Table 12-2]

[0240] [Table 12-3]

[0241] [Table 12-4]

[0242] [Table 12-5]

[0243] [Table 13-1]

[0244] [Table 13-2]

[0245] [Table 13-3]

[0246] [Table 13-4]

[0247] [Table 13-5]

[0248] [Table 13-6]

[0249] The results provided in the Examples demonstrate that transcriptional changes following mirikizumab treatment correlate with disease activity. The changes mediated by mirikizumab were consistent with TNF-α. R mucous membrane and transcripts enriched in this p19-mediated pathway in such patients. This provided an opportunity to intervene using mirikizumab. The effect was strong at week 12 and maintained through week 52 in patients with ulcerative colitis. Administration of IL-23p19 antibody normalizes genes related to both bowel frequency and bowel urgency did.

[0250] In view of the above, it is believed that the several advantages of the present disclosure are achieved and other advantageous results are attained. It will be appreciated that variations in the above method may be made without departing from the scope of the present disclosure. All matter contained in the above description and shown in the accompanying drawings is provided by way of example only, as such matter may be modified in various ways. It is intended that the terms and conditions of this document should be interpreted in a general and not restrictive sense. It is illustrated.

[0251] When introducing elements of the present disclosure or its various versions, embodiments or aspects, the articles "a," ​​"an," "the," and "said" mean that there is one or more elements. "comprising," "including," and The term "having" is intended to be inclusive and includes the listed elements. This means that there may be additional elements other than the element.

[0252] Numbered Embodiments 1. To treat ulcerative colitis in patients with or suspected of having ulcerative colitis 10. A method for detecting a marker for a marker comprising: obtaining a first sample from a patient; and analyzing the first sample to determine: CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA 12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2 , ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGK V2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, C XCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LO C101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC 16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177 At least one biomarker selected from P1, SLC17A4, and ZG16 is detected. administering an anti-IL-23p19 antibody to the patient; and collecting a second sample from the patient. and analyzing a second sample to determine the levels of CXCL8, AQP9, IL1B, S100A9 , TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2 , SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT 1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A , IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS 2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2 A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B - AS1, TMEM236, CD177P1, SLC17A4, and ZG16 and detecting at least one biomarker detected in the first sample. The expression level of at least one biomarker detected in the second sample. A change in the expression level of at least one biomarker indicates a response to anti-IL-23p19 antibody. This shows the response. 2. In another aspect, the present disclosure provides a method for treating ulcerative colitis by administering anti-IL-23p19 antibody treatment to a subject. Patients with anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF) are candidates for this treatment. R ) For a method of identifying a patient who is or is suspected of having a HIV-infected virus, the method comprises obtaining a sample from the patient. and at least one biomarker of anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR). Based on the analysis of biomarkers, patients were assigned to receive anti-IL-23p1 and identifying the patient as a candidate patient for receiving antibody treatment. 3. Patients with or suspected to have ulcerative colitis and resistance to anti-TNF treatment 1. A method of treating a patient suspected of having IL-23p19 with an anti-IL-23p19 antibody, the method comprising: The method is to determine whether the patient is receiving TNF R and determining whether the patient has TNF R If so, the patient and treating the subject with an anti-IL-23p19 antibody. 4. Ulcerative colitis-related diseases in patients with or suspected of having ulcerative colitis 1. A method for treating a condition characterized by the presence of CXCL1, the method comprising obtaining a first sample from a patient; 8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7 , TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, R EG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH 1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D- 40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1 , PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101 928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9 , ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, S Testing was performed for at least one biomarker selected from LC17A4 and ZG16. administering an anti-IL-23p19 antibody to the patient; and collecting a second sample from the patient. Obtaining samples of CXCL8, AQP9, IL1B, S100A9, TREM1, M MP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14 , VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQ P8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NO S2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1 , GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6 , NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TME At least one selected from M236, CD177P1, SLC17A4, and ZG16 and analyzing the second sample for the biomarkers. 5. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis 1. A method for detecting CXCL8 in a sample obtained from a patient, the method comprising: (a) detecting CXCL8 in a sample obtained from the patient; AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, T CN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG 1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C , MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40 , PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, P TGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC10192 8405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, A DH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC The expression level of at least one biomarker selected from the group consisting of 17A4, 17A5, and ZG16 was determined. (b) CXCL8, AQP9, IL1B, S100A9, TREM1, M MP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14 , VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQ P8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NO S2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1 , GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6 , NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TME At least one selected from M236, CD177P1, SLC17A4, and ZG16 a reference expression level of a biomarker and a determined expression level of at least one biomarker; (c) comparing the biomarker expression level in the patient with the reference expression level. If the biomarker expression level in the patient is increased compared to the reference level, or if the biomarker expression level in the patient is increased compared to the reference level, and providing a diagnosis of ulcerative colitis when the expression level of the antibody is decreased compared to a control expression level. include. 6. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis The method comprises: (a) analyzing a sample obtained from a patient using an analyzer unit; In CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1 , ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SL C26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A 8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MM P10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA 2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE 4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, of at least one biomarker including CD177P1, SLC17A4, and ZG16 (b) determining the expression level of CXCL using a computing device. 8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7 , TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, R EG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH 1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D- 40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1 , PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101 928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9 , ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, S a reference expression level of at least one biomarker, including LC17A4 and ZG16; and comparing the determined expression level(s) of at least one biomarker with (c) if the biomarker expression level is increased compared to the reference expression level; or ulcerative colitis if the biomarker expression level is decreased compared to the reference expression level and providing a diagnosis of 7. Patients with or suspected to have ulcerative colitis who have not received anti-IL-23p19 antibody therapy a method for determining whether a patient is cured in response to a treatment, the method comprising: P9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN 1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B , C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, M MP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, P I3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTG S2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC1019284 05, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH 1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17 A4, and ZG16, and at least one biomarker, Analyzing a sample obtained from the patient prior to receiving p19 antibody treatment and determining whether CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PT GS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928 405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, AD H1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC1 For at least one biomarker, including 7A4, and ZG16, the patient is anti-IL-2 Analyzing samples obtained from patients after receiving 3p19 antibody treatment and determining whether the patients have anti-IL-1 -Expression level of at least one biomarker after receiving 23p19 antibody treatment If changes in the IL-14 expression level are detected, patients with or suspected of having ulcerative colitis should be screened for anti-IL-1. and determining that the patient is cured in response to the L-23p19 antibody treatment. 8.CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MM P1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, A BCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC2 6A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP1 0, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A , LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD Contains at least one biomarker including 177P1, SLC17A4, and ZG16 , biomarker panel. 9. To treat bowel frequency in patients with or suspected of having ulcerative colitis The method includes obtaining a first sample from a patient and analyzing the first sample to determine a marker in accordance with Table 8. and detecting a biomarker selected from the group consisting of: administering the antibody to the patient, obtaining a second sample from the patient, and analyzing the second sample. and detecting a biomarker selected from Table 8 and combinations thereof; A second sample from the expression level of at least one biomarker detected in the first sample. The change in the expression level of at least one biomarker detected in the sample is indicative of anti-IL- Response to 23p19 antibody is shown. 10. To assess bowel frequency in patients with or suspected of having ulcerative colitis The method of claim 1, further comprising: (a) detecting a nucleotide sequence selected from Table 8 in a sample obtained from the patient; (b) determining the expression levels of the biomarkers and combinations thereof; The determined expression level is compared to a reference expression level of a biomarker selected from Table 8. and (c) the biomarker expression level in the patient changes compared to the reference expression level. and if so, providing a diagnosis of bowel frequency. 11. Treating bowel urgency in patients with or suspected of having ulcerative colitis 1. A method, the method comprising obtaining a first sample from a patient and analyzing the first sample to obtain a 9 and combinations thereof, and detecting a biomarker selected from anti-IL-23p1 Administering the antibody to a patient, obtaining a second sample from the patient, and analyzing the second sample. and detecting a biomarker selected from Table 9 and combinations thereof; a second sample from the expression level of at least one biomarker detected in the first sample; The change in the expression level of at least one biomarker detected in the sample is due to anti-IL-1 Response to -23p19 antibody is shown. 12. Diagnose bowel urgency in patients with or suspected of having ulcerative colitis A method, the method comprising: (a) detecting expression of a biomarker selected from Table 9 and combinations thereof; (b) determining the expression level of a biomarker selected from Table 9. (c) comparing the expression levels of the biomarkers and combinations thereof in the patient with reference expression levels of the biomarkers and combinations thereof; If the biomarker expression level in the patient is altered compared to the reference expression level, bowel urgency is considered. and providing a diagnosis of 13. Assess bowel frequency in patients with or suspected of having ulcerative colitis A method, the method comprising: (a) using an analyzer unit to analyze a sample obtained from a patient; and determining the expression levels of biomarkers selected from Table 8 and combinations thereof in the and (b) using a computing device to analyze the determined expression levels of the biomarkers. The level(s) may be compared to the reference expression levels of biomarkers selected from Table 8 and combinations thereof. (c) determining whether the biomarker expression level changes relative to the reference expression level; and if so, providing a diagnosis of bowel frequency. 14. Diagnose bowel urgency in patients with or suspected of having ulcerative colitis A method, the method comprising: (a) using an analyzer unit to analyze a sample obtained from a patient; and determining the expression levels of biomarkers selected from Table 9 and combinations thereof in the and (b) using a computing device to analyze the determined expression levels of the biomarkers. The level(s) may be compared to the reference expression levels of biomarkers selected from Table 9 and combinations thereof. (c) determining whether the biomarker expression level changes relative to the reference expression level; and if so, providing a diagnosis of bowel urgency. 15. A biomarker panel comprising at least one biomarker selected from Table 8. . 16. A biomarker panel comprising at least one biomarker selected from Table 9. .

Claims

1. Methods for treating ulcerative colitis in patients with or suspected of having ulcerative colitis It is a law, obtaining a first sample from the patient; and analyzing the first sample to detect CXCL8, AQP, 9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1 , DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MM P3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI 3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS 2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC10192840 5, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1 C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A 4, and one or more gene transcript biomarkers of one or more genes selected from ZG16. detecting the mosquito(s); administering an anti-IL-23p19 antibody to said patient; obtaining a second sample from the patient; and analyzing the second sample to detect CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PT GS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928 405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, AD H1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC1 7A4, and ZG16. detecting the marker(s); Expression of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from a level A change in the expression level of the marker(s) indicates a response to the anti-IL-23p19 antibody. ,method.

2. 10. The method of claim 1, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating colitis, comprising: obtaining a first sample from the patient; and analyzing the first sample to detect CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2 and ADH1C detecting one or more gene transcript biomarker(s) for one or more genes selected from To put out and administering an anti-IL-23p19 antibody to said patient; obtaining a second sample from the patient; and analyzing the second sample to detect CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2 and ADH1C detecting one or more gene transcript biomarker(s) for one or more genes selected from and of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from expression levels; A change in the expression level of the marker(s) indicates a response to the anti-IL-23p19 antibody. Show, how.

3. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers of the genes according to claim 1 or claim 2 are detecting said expression levels of at least two of the following:

4. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers of the genes according to claim 1 or claim 2 are detecting said expression levels of at least three of the following:

5. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers of the genes according to claim 1 or claim 2 are detecting said expression levels of at least four of the following:

6. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers (multiple) of the genes according to claim 1 or claim 2 are detecting the expression levels of at least five of the genes (including the nucleotides of the nucleotide sequence of interest, ... and the nucleotide sequence of interest)

7. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers (multiple) of the genes according to claim 1 or claim 2 are detecting the expression levels of at least six of the nucleotides (nucleotides) present in the nucleotide sequence.

8. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers (multiple) of the genes according to claim 1 or claim 2 are detecting the expression levels of at least seven of the nucleotides (nucleotides) of interest (possibly nucleotides).

9. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers (multiple) of the genes according to claim 1 or claim 2 are detecting the expression levels of at least eight of the nucleotides (nucleotides) present in the nucleotide sequence.

10. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers (multiple) of the genes according to claim 1 or claim 2 are detecting the expression levels of at least nine of the nucleotides (nucleotides) present in the nucleotide sequence.

11. In a patient having or suspected of having ulcerative colitis according to claim 1 or claim 2 1. A method of treating ulcerative colitis in a patient suffering from ulcerative colitis, comprising administering the anti-IL-23p19 antibody to a patient in need thereof prior to administration of the anti-IL-23p19 antibody and Subsequently, the gene transcript biomarkers (multiple) of the genes according to claim 1 or claim 2 are detecting the expression levels of at least 10 of the nucleotides (nucleotides) present in the target gene (e.g., nucleotides present in the target gene ...

12. the expression of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from the current a change in the expression of IL-23p19 indicates that administration of the anti-IL-23p19 antibody should be continued.

12. A method for treating or suspected of having ulcerative colitis according to claim 1, 10. A method for treating ulcerative colitis in a patient.

13. After administration of the anti-IL-23p19 antibody, one or more gene transcript biomarkers (multiple and wherein the one or more gene transcript biomarker(s) is / are increased, and the one or more gene transcript biomarker(s) is / are increased, OTOP2, AQP8, SLC26A2, ADH1C, ABCG2, HMGCS2, TM IGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, T RPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1 , TMEM236, CD177P1, SLC17A4 and ZG16. To treat ulcerative colitis in patients with or suspected of having ulcerative colitis as described in How to do it.

14. One or more gene transcript biomarker(s) are / are detected by the anti-IL-23p19 antibody treatment. and wherein the one or more gene transcript biomarker(s) are / are decreased after administration of the one or more gene transcript biomarkers, such as CXCL8, AQ P9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN 1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B , C4BPA, REG3A, DMBT1, REG1P, S100A8, IGKV2D-4 0, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1 and and PTGS2 in a patient with or suspected of having ulcerative colitis according to claim 12. A method of treating ulcerative colitis in a patient.

15. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression The method of claim 1, wherein the colloidal phase is determined by a method of profiling. A method of treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

16. 16. The method of claim 15, wherein the method of gene expression profiling is a PCR-based method. To treat ulcerative colitis in patients with or suspected of having ulcerative colitis as described in How to do it.

17. 16. The method of claim 15, wherein the method of gene expression profiling is immunohistochemistry. Methods of treating ulcerative colitis in patients having or suspected of having ulcerative colitis - Patent Application 20070122999 。

18. 16. The method of claim 15, wherein the gene expression profiling method is a proteomics technique. To treat ulcerative colitis in patients with or suspected of having ulcerative colitis as described in How to do it.

19. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more Normalized to the expression levels of reference genes or their expression products, claims 15 to 18 ulcers in patients with or suspected of having ulcerative colitis according to any one of How to treat genital colitis.

20. 20. The method of claim 1, wherein the sample is derived from a colon tissue biopsy or a rectal tissue biopsy. Ulcerative colitis in a patient having or suspected of having ulcerative colitis according to any one of claims 1 to 4. How to treat.

21. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon.

21. The subject having or having ulcerative colitis according to claim 20, wherein the subject is from a tissue selected from the group consisting of:

10. A method for treating ulcerative colitis in a patient suspected of having ulcerative colitis.

22. 22. The method of claim 20 or claim 21, wherein the colon tissue biopsy is from a non-inflamed area of ​​the colon. Methods of treating ulcerative colitis in patients having or suspected of having ulcerative colitis - Patent Application 20070122999 。

23. 22. The method of claim 20 or claim 21, wherein the colon tissue biopsy is from an inflamed colon region. A method of treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

24. The first sample is taken prior to or concurrently with administration of the anti-IL-23p19 antibody. and said second sample is taken at least two weeks after said first administration of said anti-IL-23p19 antibody. after at least 4 weeks, after at least 8 weeks, after at least 12 weeks, after at least 1 After 6 weeks, after at least 20 weeks, after at least 24 weeks, after at least 28 weeks, At least 30 weeks later, at least 32 weeks later, at least 36 weeks later, at least 40 weeks later at least 44 weeks, at least 48 weeks, or at least 52 weeks after the 24. A method for treating or suspected of having ulcerative colitis according to any one of claims 1 to 23.

10. A method for treating ulcerative colitis in a patient.

25. The anti-IL-23p19 antibody is selected from the group consisting of mirikizumab, guselkumab, risankizumab, tilukizumab, and the like. The ulcerative colitis according to any one of claims 1 to 24, which is drakizumab or brazikumab. A method of treating ulcerative colitis in a patient having or suspected of having colitis.

26. 26. The ulcerative colitis treatment of claim 25, wherein the anti-IL-23p19 antibody is mirikizumab.

1. A method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

27. 27. The method of claim 26, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating colitis, comprising: a) administering three induction doses of mirikizumab to the patient by intravenous infusion at four-week intervals; administering a dose of mirikizumab to a patient in need thereof, wherein each induction dose comprises 300 mg of mirikizumab; b) administering a maintenance dose of mirikizumab to said patient by subcutaneous injection every 4 or 12 weeks; administering the first maintenance dose within 2 to 8 days after the last induction dose was administered; and administering a maintenance dose of 200 mg mirikizumab two weeks later, each maintenance dose containing 200 mg mirikizumab. A method comprising:

28. the first maintenance dose is administered 4 to 6 weeks after the final induction dose is administered; 28. The method of claim 27, wherein the patient has or is suspected of having ulcerative colitis. How to treat enteritis.

29. Subsequent maintenance dose(s) of mirikizumab are administered 4 weeks after the first maintenance dose.

29. A method for treating or suspected of having ulcerative colitis according to claim 27 or claim 28, wherein the method is administered at intervals 10. A method for treating ulcerative colitis in a patient suspected of having ulcerative colitis.

30. Subsequent maintenance dose(s) of mirikizumab are administered 12 weeks after the administration of said first maintenance dose.

29. The method of claim 27 or claim 28, wherein the method is administered at intervals of 10 minutes or more.

10. A method for treating ulcerative colitis in a patient suspected of having ulcerative colitis.

31. 26. The ulcerative colitis treatment of claim 25, wherein the anti-IL-23p19 antibody is guselkumab.

1. A method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

32. 32. The method of claim 31, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating colitis, comprising: a) Three induction doses of guselkumab will be administered to the patient by intravenous infusion at 4-week intervals. wherein each induction dose contains 100-500 mg of guselkumab. And, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or administering to said patient by subcutaneous injection at 12 week intervals, said initial maintenance dose is administered 2 to 8 weeks after the final induction dose is administered. Hmm, a method.

33. 33. The method of claim 32, wherein each induction dose comprises 200 mg of guselkumab. A method of treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

34. 33. The method of claim 32, wherein each induction dose comprises 400 mg of guselkumab. A method of treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

35. The ulcerative colitis of claim 25, wherein the anti-IL-23p19 antibody is risankizumab. A method of treating ulcerative colitis in a patient having or suspected of having colitis.

36. 26. The ulcerative colitis of claim 25, wherein the anti-IL-23p19 antibody is tildrakizumab. A method of treating ulcerative colitis in a patient having or suspected of having colitis.

37. 26. The ulcerative colitis treatment of claim 25, wherein the anti-IL-23p19 antibody is brazikumab.

1. A method for treating ulcerative colitis in a patient having or suspected of having ulcerative colitis.

38. Ulcerative colitis-related symptoms in patients with or suspected of having ulcerative colitis 1. A method of treating a condition comprising: obtaining a first sample from the patient; and analyzing the first sample to detect CXCL8, AQP, 9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN1 , DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MM P3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI 3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS 2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC10192840 5, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1 C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC17A 4, and one or more gene transcript biomarkers of one or more genes selected from ZG16. detecting the mosquito(s); administering an anti-IL-23p19 antibody to said patient; obtaining a second sample from the patient; and analyzing the second sample to detect CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PT GS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928 405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, AD H1C, PCK1, CDKN2B-AS1, TMEM236, CD177P1, SLC1 7A4, and ZG16. detecting the marker(s); Expression of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from a level A change in the expression level of the marker(s) indicates a response to the anti-IL-23p19 antibody. ,method.

39. If the symptoms are abdominal pain / discomfort, bloody stool, pus in stool, fever, weight loss, rectal bleeding, frequent One or more of the following symptoms are present: persistent diarrhea, recurrent diarrhea, fatigue, loss of appetite, and tenesmus (urgency) 39. The method of claim 38, wherein the patient has or is suspected of having ulcerative colitis. A method for treating symptoms associated with colitis.

40. A patient having or suspected of having ulcerative colitis according to claim 38 or claim 39.

1. A method for treating symptoms associated with ulcerative colitis in obtaining a first sample from the patient; and analyzing the first sample to detect CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2 and ADH1C detecting one or more gene transcript biomarker(s) for one or more genes selected from To put out and administering an anti-IL-23p19 antibody to said patient; obtaining a second sample from the patient; and analyzing the second sample to detect CXCL8, A QP9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TC N1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1 B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2 and ADH1C detecting one or more gene transcript biomarker(s) for one or more genes selected from and of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from expression levels; A change in the expression level of the marker(s) indicates a response to the anti-IL-23p19 antibody. Show, how.

41. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 before or simultaneously with the administration of an anti-IL-23p19 antibody, and after the administration of the anti-IL-23p19 antibody. 38 or 40. detecting both of said expression levels.

42. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40 is administered before or after administration of a p19 antibody. detecting the expression levels of at least three of the gene transcript biomarkers. ,method.

43. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40 is administered before or after administration of a p19 antibody. detecting the expression levels of at least four of the gene transcript biomarkers. ,method.

44. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40 is administered before or after administration of a p19 antibody. detecting the expression levels of at least five of the gene transcript biomarker(s); A method comprising:

45. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40, before or simultaneously with administration of a p19 antibody. Detecting the expression levels of at least six of the gene transcript biomarker(s). The method includes:

46. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40 is administered before or after administration of a p19 antibody. detecting the expression levels of at least seven of the gene transcript biomarker(s); A method comprising:

47. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40 is administered before or after administration of a p19 antibody. detecting the expression levels of at least eight of the gene transcript biomarker(s); A method comprising:

48. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40, before or simultaneously with administration of a p19 antibody. Detecting the expression levels of at least nine of the gene transcript biomarker(s). The method includes:

49. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 38 to 40.

1. A method of treating symptoms associated with ulcerative colitis in a patient having said anti-IL-23 The gene of claim 38 or claim 40 is administered before or after administration of a p19 antibody. Detecting the expression levels of at least 10 of the gene transcript biomarker(s). A method comprising:

50. the expression of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from the current a change in the expression of IL-23p19 indicates that administration of the anti-IL-23p19 antibody should be continued.

50. A method for treating or suspected of having ulcerative colitis according to any one of claims 38 to 49, 10. A method for treating symptoms associated with ulcerative colitis in a patient.

51. After administration of the anti-IL-23p19 antibody, one or more gene transcript biomarkers (multiple and wherein the one or more gene transcript biomarker(s) is / are increased, and the one or more gene transcript biomarker(s) is / are increased, OTOP2, AQP8, SLC26A2, ADH1C, ABCG2, HMGCS2, TM IGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, T RPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1 , TMEM236, CD177P1, SLC17A4 and ZG16. ulcerative colitis-associated ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat the symptoms.

52. One or more gene transcript biomarker(s) are / are detected by the anti-IL-23p19 antibody treatment. and wherein the one or more gene transcript biomarker(s) are / are decreased after administration of the one or more gene transcript biomarkers, such as CXCL8, AQ P9, IL1B, S100A9, TREM1, MMP12, MMP1, MMP7, TCN 1, DUOX2, DUOXA2, SLC6A14, VNN1, ABCA12, REG1B , C4BPA, REG3A, DMBT1, REG1P, S100A8, IGKV2D-4 0, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1 and and PTGS2. A method of treating symptoms associated with ulcerative colitis in a patient.

53. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression 53. The method of claim 38, wherein the method is determined by a method of profiling. Symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat.

54. 54. The method of claim 53, wherein the method of gene expression profiling is a PCR-based method. ulcerative colitis-associated ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat the symptoms.

55. 54. The method of claim 53, wherein the method of gene expression profiling is immunohistochemistry. Symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat.

56. 54. The method of claim 53, wherein the method of gene expression profiling is a proteomics technique. ulcerative colitis-associated ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat the symptoms.

57. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more Normalized to the expression level of a reference gene or its expression product, 56. In a patient having or suspected of having ulcerative colitis according to any one of claims 56 to 57, A method for treating symptoms associated with ulcerative colitis.

58. 58. The method according to any one of claims 38 to 57, wherein the sample is derived from a colon tissue biopsy or a rectal tissue biopsy. Ulcerative colitis in a patient having or suspected of having ulcerative colitis according to any one of claims 1 to 4 How to treat symptoms associated with inflammation.

59. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon.

59. The subject having or having ulcerative colitis according to claim 58, wherein the subject is from a tissue selected from the group consisting of:

10. A method for treating symptoms associated with ulcerative colitis in a patient suspected of having ulcerative colitis.

60. 61. The method of claim 59 or claim 60, wherein the colon tissue biopsy is from a non-inflamed area of ​​the colon. Symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat.

61. 61. The method of claim 59 or claim 60, wherein the colon tissue biopsy is from an inflamed colon region. Symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis How to treat.

62. The first sample is taken prior to or concurrently with administration of the anti-IL-23p19 antibody. and said second sample is taken at least two weeks after said first administration of said anti-IL-23p19 antibody. after at least 4 weeks, after at least 8 weeks, after at least 12 weeks, after at least 1 After 6 weeks, after at least 20 weeks, after at least 24 weeks, after at least 28 weeks, At least 30 weeks later, at least 32 weeks later, at least 36 weeks later, at least 40 weeks later at least 44 weeks, at least 48 weeks, or at least 52 weeks after the 62. A method for treating or suspected of having ulcerative colitis according to any one of claims 38 to 61.

10. A method for treating symptoms associated with ulcerative colitis in a patient.

63. The anti-IL-23p19 antibody is selected from the group consisting of mirikizumab, guselkumab, risankizumab, tilukizumab, and the like. The ulcerative colitis relieving agent according to any one of claims 38 to 62, which is drakizumab or brazikumab. Treating symptoms associated with ulcerative colitis in patients with or suspected of having colitis How to do it.

64. 64. The ulcerative colitis treatment of claim 63, wherein the anti-IL-23p19 antibody is mirikizumab. Treating symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis method.

65. 65. The method of claim 64, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating symptoms associated with colitis, comprising: a) administering three induction doses of mirikizumab to the patient by intravenous infusion at four-week intervals; administering a dose of mirikizumab to a patient in need thereof, wherein each induction dose comprises 300 mg of mirikizumab; b) administering a maintenance dose of mirikizumab to said patient by subcutaneous injection every 4 or 12 weeks; administering the first maintenance dose within 2 to 8 days after the last induction dose was administered; and administering a maintenance dose of 200 mg mirikizumab two weeks later, each maintenance dose containing 200 mg mirikizumab. A method comprising:

66. the first maintenance dose is administered 4 to 6 weeks after the final induction dose is administered; 66. The method of claim 65, wherein the patient has or is suspected of having ulcerative colitis. A method for treating symptoms associated with enteritis.

67. Subsequent maintenance dose(s) of mirikizumab are administered 4 weeks after the first maintenance dose.

67. A method for treating or suspected of having ulcerative colitis according to claim 65 or claim 66, wherein the method is administered at intervals 10. A method for treating symptoms associated with ulcerative colitis in a patient suspected of having ulcerative colitis.

68. Subsequent maintenance dose(s) of mirikizumab are administered 12 weeks after the administration of said first maintenance dose.

67. The method of claim 65 or claim 66, wherein the method is administered at intervals of 10 minutes or less.

10. A method for treating symptoms associated with ulcerative colitis in a patient suspected of having ulcerative colitis.

69. 64. The ulcerative colitis treatment of claim 63, wherein the anti-IL-23p19 antibody is guselkumab. Treating symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis method.

70. 70. The method of claim 69, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating symptoms associated with colitis, comprising: a) Three induction doses of guselkumab will be administered to the patient by intravenous infusion at 4-week intervals. wherein each induction dose contains 100-500 mg of guselkumab. And, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or administering to said patient by subcutaneous injection at 12 week intervals, said initial maintenance dose is administered 2 to 8 weeks after the final induction dose is administered. Hmm, a method.

71. 71. The method of claim 70, wherein each induction dose comprises 200 mg of guselkumab. Methods of treating symptoms associated with ulcerative colitis in patients having or suspected of having ulcerative colitis - Patent Application 20070122999 。

72. 71. The method of claim 70, wherein each induction dose comprises 400 mg of guselkumab. Methods of treating symptoms associated with ulcerative colitis in patients having or suspected of having ulcerative colitis - Patent Application 20070122999 。

73. 64. The method of claim 63, wherein the anti-IL-23p19 antibody is risankizumab. To treat symptoms associated with ulcerative colitis in patients with or suspected of having colitis. How to do it.

74. 64. The method of claim 63, wherein the anti-IL-23p19 antibody is risankizumab. To treat symptoms associated with ulcerative colitis in patients with or suspected of having colitis. How to do it.

75. 64. The ulcerative colitis treatment of claim 63, wherein the anti-IL-23p19 antibody is brazikumab. Treating symptoms associated with ulcerative colitis in patients with or suspected of having ulcerative colitis method.

76. As a candidate patient for anti-IL-23p19 antibody treatment for ulcerative colitis, Tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Patients with or suspected of having A method for identifying obtaining a sample from said patient; OSMR, FCGR3, CXCL6, interleukin-11, interleukin- 24, interleukin-13RA2, FAP, TWIST1, and WNT2. One or more genes that are involved in the resistance to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) Ｒ ) analyzing the sample for gene transcript biomarker(s); Based on the analysis of the gene transcript biomarkers, the patient is treated with anti-IL-23p1 and identifying the patient as a candidate patient for receiving antibody treatment.

77. 77. A method for receiving anti-IL-23p19 antibody treatment for ulcerative colitis according to claim 76. Candidate patients have or have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method for identifying a patient suspected of having CXCL8, AQP9, IL1B, S10 0A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUO XA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA 2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, D MBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, RE G1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HM GCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, U GT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDK Selected from N2B-AS1, TMEM236, CD177P1, SLC17A4 and ZG16 For one or more gene transcript biomarker(s) of one or more selected genes, The method further comprising analyzing the sample or another sample obtained from the patient.

78. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression 78. The ulcerative colitis of claim 76 or claim 77, as determined by a method of profiling. Anti-tumor necrosis factor (anti-IL-23p19) as a candidate patient for anti-IL-23p19 antibody treatment for colitis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Identify patients with or suspected of having How to do it.

79. 79. A method for receiving anti-IL-23p19 antibody treatment for ulcerative colitis according to claim 78. Candidate patients include those with anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) have or have 10. A method for identifying a patient suspected of having a genetic disorder, comprising: ,The method is a PCR-based method.

80. 79. The method of claim 78, wherein the method of gene expression profiling is immunohistochemistry. As a candidate patient for anti-IL-23p19 antibody treatment for ulcerative colitis, Tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Patients with or suspected of having How to identify.

81. 79. The method of claim 78, wherein the method of gene expression profiling is a proteomics technique. As a candidate patient for receiving anti-IL-23p19 antibody treatment for ulcerative colitis as described , anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-tumor necrosis factor (anti-TNF) Ｒ ) or suspected of having Methods for identifying patients.

82. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more Normalized to the expression level of a reference gene or its expression product.

81. A method for treating ulcerative colitis comprising administering to a subject a subject of the present invention an anti-IL-23p19 antibody treatment for ulcerative colitis according to any one of claims 81 to 81. Candidate patients for this study include those with anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF) Ｒ ) A method for identifying a patient suspected of having

83. 84. The method according to any one of claims 76 to 83, wherein the sample is derived from a colon tissue biopsy or a rectal tissue biopsy. A candidate for receiving anti-IL-23p19 antibody treatment for ulcerative colitis according to any one of claims 1 to 4. Patients were those with anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) having or having Methods for identifying patients suspected of having HIV.

84. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon. The anti-IL-1 antibody for ulcerative colitis according to claim 83, which is derived from a tissue selected from the group consisting of: Candidates for 23p19 antibody treatment include those resistant to anti-tumor necrosis factor (anti-TNF) therapy. (anti-TNF) Ｒ 2. A method for identifying patients having or suspected of having a pulmonary edema.

85. 85. The method of claim 83 or claim 84, wherein the colon tissue biopsy is from a non-inflamed area of ​​the colon. As a candidate patient for anti-IL-23p19 antibody treatment for ulcerative colitis, Tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Patients with or suspected of having How to identify.

86. 85. The method of claim 83 or claim 84, wherein the colon tissue biopsy is from an inflamed colon region. As a candidate patient for anti-IL-23p19 antibody treatment for ulcerative colitis, Necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Patients with or suspected of having How to determine.

87. The anti-IL-23p19 antibody is selected from the group consisting of mirikizumab, guselkumab, risankizumab, tilukizumab, and the like. The ulcer according to any one of claims 76 to 86, which is drakizumab or brazikumab. As a candidate patient for anti-IL-23p19 antibody treatment for chronic colitis, Death factor (anti-TNF) therapy resistance (anti-TNF Ｒ Identify patients with or suspected of having How to do it.

88. Patients with or suspected of having ulcerative colitis and who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) Ｒ Patients with or suspected of having IL-23p19 are treated with an anti-IL-23p19 antibody. A method of placing A sample is obtained from the patient, and OSMR, FCGR3, CXCL6, interleukin- 11. Interleukin-24, interleukin-13RA2, FAP, TWIST1 and one or more anti-tumor necrosis factor (anti-TNF) genes of one or more genes selected from WNT2. ) therapy resistance (anti-TNF Ｒ ) analyzing the sample for gene transcript biomarker(s); By analyzing the patient, it is possible to determine whether the patient has anti-TNF Ｒ determining whether The patient is anti-TNF Ｒ and treating the patient with an anti-IL-23p19 antibody. A method comprising:

89. The anti-IL-23p19 antibody of claim 88 is used to treat or prevent ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or have 89. A method of treating a patient suspected of having a gene encoding the gene of claim 88, comprising administering to said patient a gene encoding the gene of claim 88. detecting said expression levels of at least two of said gene transcript biomarkers. 。

90. The anti-IL-23p19 antibody of claim 88 is used to treat or prevent ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 89. A method of treating a patient suspected of having a gene encoding the gene of claim 88, comprising administering to said patient a gene encoding the gene of claim 88. detecting said expression levels of at least three of the gene transcript biomarkers. 。

91. The anti-IL-23p19 antibody of claim 88 is used to treat or prevent ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 89. A method of treating a patient suspected of having a gene encoding the gene of claim 88, comprising administering to said patient a gene encoding the gene of claim 88. detecting said expression levels of at least four of the gene transcript biomarkers. 。

92. The anti-IL-23p19 antibody of claim 88 is used to treat or prevent ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or have 89. A method of treating a patient suspected of having a gene encoding the gene of claim 88, comprising administering to said patient a gene encoding the gene of claim 88. detecting the expression levels of at least five of the gene transcript biomarker(s); Including, a method.

93. A patient suffering from or suspected of suffering from ulcerative colitis according to any one of claims 88 to 93. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or suspected to have 1. A method for treating a patient suffering from an allergic reaction to CXCL8, AQP9, IL1B, S100A9, T REM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, S LC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA2B, OT OP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, I DO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3 , TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-A S1, TMEM236, CD177P1, SLC17A4, and ZG16 Anti-IL-1 for one or more gene transcript biomarker(s) of one or more genes Analyze samples obtained before and after anti-IL-23p19 antibody administration. It further includes: Detected in the sample obtained prior to administration of the anti-IL-23p19 antibody the anti-IL-23p from the expression levels of the one or more gene transcript biomarkers; The one or more gene transcripts detected in the sample obtained after administration of antibody 19. A change in the expression level of the immunological marker(s) is Ｒ The anti-IL- A method showing a response to a 23p19 antibody.

94. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or have 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then at least one of the gene transcript biomarkers of the gene of claim 93. detecting two of said expression levels.

95. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then at least one of the gene transcript biomarkers of the gene of claim 93. detecting three of said expression levels.

96. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then at least one of the gene transcript biomarkers of the gene of claim 93. detecting four of said expression levels.

97. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or have 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then the gene transcript biomarker(s) of the gene of claim 93. detecting at least five of said expression levels.

98. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then the gene transcript biomarker(s) of the gene of claim 93. detecting at least six of said expression levels.

99. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then the gene transcript biomarker(s) of the gene of claim 93. detecting at least seven of said expression levels.

100. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or have 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then the gene transcript biomarker(s) of the gene of claim 93. detecting at least eight of said expression levels.

101. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then the gene transcript biomarker(s) of the gene of claim 93. detecting at least nine of said expression levels.

102. The anti-IL-23p19 antibody of claim 93 is used to treat or treat patients with ulcerative colitis. suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNFR) 1. A method of treating a patient suspected of having an IL-23p19 antibody, comprising administering to said patient an IL-23p19 antibody prior to administration of the IL-23p19 antibody. and then the gene transcript biomarker(s) of the gene of claim 93. detecting at least 10 of said expression levels.

103. Detected in the sample taken prior to administration of the anti-IL-23p19 antibody the expression of the one or more gene transcript biomarkers, The one or more gene transcript biomarkers detected in the sample taken after administration of the The change in expression of the marker is Ｒ Administration of the anti-IL-23p19 antibody to a patient The anti-IL-2 antibody according to any one of claims 93 to 102, which indicates that 3p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor Child (anti-TNF) therapy resistance (anti-TNF) Ｒ Treat patients with or suspected of having method.

104. After administration of the anti-IL-23p19 antibody, one or more gene transcript biomarkers (multiple and wherein the one or more gene transcript biomarker(s) is / are increased, and the one or more gene transcript biomarker(s) is / are increased, OTOP2, AQP8, SLC26A2, ADH1C, ABCG2, HMGCS2, TM IGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, T RPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1 , TMEM236, CD177P1, SLC17A4 and ZG16. The anti-IL-23p19 antibody described in and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or suspected to have How to treat patients who are

105. The anti-IL-23p19 antibody according to claim 103 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or 1. A method of treating a patient suspected of having a steroid drug, comprising: (a) is decreased after treatment with the anti-IL-23p19 antibody, and transcription of the one or more genes is decreased after treatment with the anti-IL-23p19 antibody, The biomarker(s) are CXCL8, AQP9, IL1B, S100A9, TRE M1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC 6A14, VNN1, ABCA12, REG1B, C4BPA, REG3A, DMBT1 , REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1 and PTGS2.

106. The anti-IL-23p19 antibody according to any one of claims 88 to 105 is used to treat ulcerative colitis. Patients with or suspected of having colitis and who are resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) NF Ｒ 20. A method of treating a patient having or suspected of having one or more of the following: The expression levels of gene transcript biomarker(s) are used in gene expression profiling. determined by the method of,method.

107. The anti-IL-23p19 antibody according to claim 106 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or 10. A method of treating a patient suspected of having a disease comprising: The method is a PCR-based method.

108. The anti-IL-23p19 antibody according to claim 106 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or 10. A method of treating a patient suspected of having a disease comprising: The method is immunohistochemistry.

109. The anti-IL-23p19 antibody according to claim 106 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or 10. A method of treating a patient suspected of having a disease comprising: The method is a proteomics technique.

110. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more 106. The method of claim 105, wherein the expression level is normalized to the expression level of a reference gene or its expression product. The anti-IL-23p19 antibody according to any one of claims 1 to 109 is used to treat a patient with ulcerative colitis. or suspected to have anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) 2. A method of treating a patient having or suspected of having:

111. 111. The method according to any one of claims 88 to 110, wherein the sample is derived from a colon tissue biopsy or a rectal tissue biopsy. The anti-IL-23p19 antibody according to any one of claims 1 to 4 is used to treat a patient with or suspected of having ulcerative colitis. and are suspected to be resistant to anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF Ｒ ) have or have How to treat patients suspected of having this condition.

112. the colon tissue biopsy is selected from the group consisting of the terminal ileum, the ascending colon, the descending colon, and the sigmoid colon.

112. The method of claim 111, wherein the anti-IL-23p19 antibody derived from a selected tissue is used to treat tumors. Patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor (anti-TNF) therapy resistance ( anti-TNF Ｒ 2. A method of treating a patient having or suspected of having cerebrospinal fluid (CEF)

113. 113. The method of claim 111 or 112, wherein the colon tissue biopsy is from a non-inflamed colon area. The anti-IL-23p19 antibody described above was used to treat patients with or suspected of having ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or suspected of having How to treat patients.

114. 113. The method of claim 111 or 112, wherein the colon tissue biopsy is from an inflamed colon area. and administering the anti-IL-23p19 antibody of Anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Patients with or suspected of having How to treat a person.

115. The sample collected after administration of the anti-IL-23p19 antibody is At least 2 weeks, at least 4 weeks, at least 8 weeks after the first administration of antibody after, at least 12 weeks after, at least 16 weeks after, at least 20 weeks after, at least After 24 weeks, at least 28 weeks, at least 30 weeks, at least 32 weeks, At least 36 weeks later, at least 40 weeks later, at least 44 weeks later, at least 48 weeks later 115. The method of claim 93, wherein the cells are harvested after 52 weeks or at least 52 weeks. The anti-IL-23p19 antibody described above was used to treat patients with or suspected of having ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or suspected of having How to treat patients.

116. The anti-IL-23p19 antibody is selected from the group consisting of mirikizumab, guselkumab, risankizumab, tilukizumab, and the like. The antibody according to any one of claims 88 to 115, which is drakizumab or brazikumab. IL-23p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor Tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Patients with or suspected of having How to treat.

117. The anti-IL-23p19 antibody of claim 116 is mirikizumab. 23p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Treating patients with or suspected of having How to do it.

118. The anti-IL-23p19 antibody according to claim 117 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or 1. A method of treating a patient suspected of having a) administering three induction doses of mirikizumab to the patient by intravenous infusion at four-week intervals; administering a dose of mirikizumab to a patient in need thereof, wherein each induction dose comprises 300 mg of mirikizumab; b) administering a maintenance dose of mirikizumab to said patient by subcutaneous injection every 4 or 12 weeks; administering the first maintenance dose within 2 to 8 days after the last induction dose was administered; and administering a maintenance dose of 200 mg mirikizumab two weeks later, each maintenance dose containing 200 mg mirikizumab. A method comprising:

119. the first maintenance dose is administered 4 to 6 weeks after the final induction dose is administered; The anti-IL-23p19 antibody of claim 118 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or have How to treat a patient suspected of having rheumatoid arthritis.

120. Subsequent maintenance dose(s) of mirikizumab are administered 4 weeks after the first maintenance dose. The anti-IL-23p19 antibody of claim 118 or claim 119 is administered at intervals. Patients with or suspected of having ulcerative colitis and receiving anti-tumor necrosis factor (anti-TNF) therapy (anti-TNF) Ｒ 2. A method of treating a patient having or suspected of having cerebrospinal fluid (CEF)

121. Subsequent maintenance dose(s) of mirikizumab are administered 12 weeks after the administration of said first maintenance dose. The anti-IL-23p19 antibody of claim 118 or claim 119 is administered at intervals of 10 minutes. ulcerative colitis and anti-tumor necrosis factor (anti-TNF) Therapy resistance (anti-TNF Ｒ 2. A method of treating a patient having or suspected of having cerebrospinal fluid (CEF)

122. The anti-IL-23p19 antibody of claim 116 is guselkumab. 23p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Treating patients with or suspected of having How to do it.

123. The anti-IL-23p19 antibody according to claim 122 is used to treat or treat patients with ulcerative colitis. and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ ) or 1. A method of treating a patient suspected of having a) Three induction doses of guselkumab will be administered to the patient by intravenous infusion at 4-week intervals. wherein each induction dose contains 100-500 mg of guselkumab. And, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or administering to said patient by subcutaneous injection at 12 week intervals, said initial maintenance dose is administered 2 to 8 weeks after the final induction dose is administered. Hmm, a method.

124. The anti-IL-23 antibody of claim 123, wherein each induction dose contains 200 mg of guselkumab. p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF) Ｒ How to treat patients with or suspected of having Law.

125. The anti-IL-23 antibody of claim 123, wherein each induction dose comprises 400 mg of guselkumab. p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF) Ｒ How to treat patients with or suspected of having Law.

126. The anti-IL-23p19 antibody of claim 116 is risankizumab. -23p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor cataracts Death factor (anti-TNF) therapy resistance (anti-TNF Ｒ Treat patients with or suspected of having How to do it.

127. The anti-IL-23p19 antibody of claim 116 is tildrakizumab. The L-23p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor Necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Treat patients with or suspected of having How to treat.

128. The anti-IL-23p19 antibody of claim 116 is brazikumab. 23p19 antibody is used to treat patients with or suspected of having ulcerative colitis and anti-tumor necrosis factor (anti-TNF) therapy resistance (anti-TNF Ｒ Treating patients with or suspected of having How to do it.

129. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis A method for (a) detecting CXCL8, AQP9, IL1B, S10 in a sample obtained from the patient; 0A9, TREM1, MMP12, MMP1, MMP7, TCN1, DUOX2, DUO XA2, SLC6A14, VNN1, ABCA12, REG1B, C4BPA, GUCA 2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, D MBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, RE G1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HM GCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, U GT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDK from N2B-AS1, TMEM236, CD177P1, SLC17A4, and ZG16 Expression levels of one or more gene transcript biomarker(s) of one or more selected genes. determining a bell; (b) determining the determined expression levels of the one or more gene transcript biomarker(s); CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MM P1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, A BCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC2 6A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP1 0, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A , LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD one or more gene transcript biomarkers selected from 177P1, SLC17A4, and ZG16 comparing the expression level of the marker(s) to a reference expression level; (c) determining whether the biomarker expression level in the patient is greater than or equal to the reference expression level; or if the biomarker expression level in the patient is increased relative to the reference expression level and if the level is decreased compared to the current level, providing a diagnosis of ulcerative colitis. ,method.

130. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least two of the transcript biomarkers. Law.

131. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least three of the transcript biomarkers. Law.

132. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least four of the transcript biomarkers. Law.

133. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least five of the transcript biomarkers. Law.

134. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least six of the transcript biomarkers. Law.

135. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least seven of the transcript biomarkers. Law.

136. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least eight of the transcript biomarkers. Law.

137. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least nine of the transcript biomarkers. Law.

138. 130. The method of claim 129, wherein the patient has or is suspected of having ulcerative colitis.

130. A method for diagnosing idiopathic colitis, comprising the step of: detecting the expression levels of at least 10 of the transcript biomarkers. Law.

139. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression 139. The method of claim 129, wherein the method is determined by a profiling method. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis as described above How to do this.

140. 140. An ulcer in a patient having or suspected of having ulcerative colitis according to claim 139.

1. A method for diagnosing inflammatory bowel disease, comprising: The method is a CR-based method.

141. 140. An ulcer in a patient having or suspected of having ulcerative colitis according to claim 139.

20. A method for diagnosing immunological colitis, wherein the method of gene expression profiling comprises: immunohistochemistry, method.

142. 140. An ulcer in a patient having or suspected of having ulcerative colitis according to claim 139.

1. A method for diagnosing idiopathic colitis, wherein the method of gene expression profiling comprises The method is a proteomics technique.

143. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more Normalized to the expression level of a reference gene or its expression product.

42. In a patient having or suspected of having ulcerative colitis according to any one of claims 42. A method for diagnosing ulcerative colitis.

144. Claims 129-143, wherein the sample is from a colon tissue biopsy or a rectal tissue biopsy ulcers in patients with or suspected of having ulcerative colitis according to any one of Method for diagnosing idiopathic colitis.

145. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon.

145. The method of claim 144, wherein the subject has or has ulcerative colitis and the subject is from a tissue selected from the group consisting of: SUMMARY OF THE INVENTION A method for diagnosing ulcerative colitis in a patient suspected of having ulcerative colitis.

146. 146. The method of claim 144 or 145, wherein the colon tissue biopsy is from a non-inflamed colon area. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis as described above How to do this.

147. 146. The method of claim 144 or claim 145, wherein the colon tissue biopsy is from an inflamed colon area. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis How to do this.

148. 130. One or more gene transcript biomarkers of one or more genes according to claim 129. determining the expression level of one or more and determining the expression level(s) of the gene transcript biomarker(s).

130. A comparison of the expression levels of one or more gene transcript biomarkers of paragraph 129 to a reference expression level. Claims 129-147, wherein the comparing is performed using a computing device ulcers in patients with or suspected of having ulcerative colitis according to any one of Method for diagnosing idiopathic colitis.

149. The computing device determines a result of the comparison with the reference biomarker.

149. The method of claim 148, wherein the method provides assistance in diagnosing ulcerative colitis in said subject. To diagnose ulcerative colitis in patients with or suspected of having ulcerative colitis as described How to do this.

150. The analyzer unit is used to calculate the amount of ligand binding based on the calculated amount of ligand binding. CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP 1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, AB CA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26 A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, I GKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10 , CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, S LC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD1 77P1, SLC17A4, and ZG16.

10. The method of claim 1, further comprising determining the amount of one or more gene transcript biomarkers. 48 or 149 in a patient having or suspected of having ulcerative colitis. A method for diagnosing ulcerative colitis.

151. Patients with or suspected of having ulcerative colitis are treated with anti-IL-23p19 antibodies.

1. A method for determining whether a subject has responded to a treatment and is cured, comprising: (a) (i) CXCL8, AQP9, IL1B, S100A9, TREM1, MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6. One or more genes selected from CD177P1, SLC17A4, and ZG16 For one or more gene transcript biomarker(s), the patient is analyzing a sample obtained from said patient prior to receiving the treatment; (b) (i) CXCL8, AQP9, IL1B, S100A9, TREM1, MMP1 2, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VN N1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S10 0A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GU CA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, NX PE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM23 6. One or more genes selected from CD177P1, SLC17A4, and ZG16 For one or more gene transcript biomarker(s), the patient is analyzing a sample obtained from said patient after receiving the treatment; (c) (i) after the patient has received the anti-IL-23p19 antibody treatment, If a change in the expression level of the gene transcript biomarker(s) is detected, The patient having or suspected of having ulcerative colitis responds to the anti-IL-23p19 antibody treatment. and determining that the patient is cured. or (a) (ii) CXCL8, AQP9, IL1B, S100A9, TREM1, MMP 12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, V NN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8 , SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S1 00A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2 , MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, G UCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, N XPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM2 36, CD177P1, SLC17A4, and ZG16 the anti-IL-23p19 antibody for one or more gene transcript biomarker(s) of Samples obtained from patients with or suspected of having ulcerative colitis who had not received any systemic treatment were used. To analyze and (b) (ii) CXCL8, AQP9, IL1B, S100A9, TREM1, MMP 12, MMP1, MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, V NN1, ABCA12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8 , SLC26A2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S1 00A8, IGKV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2 , MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, G UCA2A, LOC101928405, MS4A12, UGT2A3, TRPM6, N XPE4, SLC16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM2 36, CD177P1, SLC17A4, and ZG16 and wherein the patient is anti-IL-23p19 with respect to one or more gene transcript biomarker(s). analyzing a sample obtained from the patient after receiving the antibody treatment; (c)(ii) one or more gene transcription factors after the patient receives anti-IL-23p19 antibody treatment A change in expression level of the biological biomarker(s) indicates a response to anti-IL-23p19 antibody treatment. Expression levels of one or more gene transcript biomarker(s) in patients who did not receive If the antibody is detected as anti-I, the patient may have or be suspected of having ulcerative colitis. determining that the patient is cured in response to L-23p19 antibody treatment.

152. A patient having or suspected of having ulcerative colitis is treated with the anti-IL- 1. A method for determining whether a patient has been cured in response to treatment with a 23p19 antibody, comprising: (a) (i) GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C For one or more gene transcript biomarker(s) of one or more genes selected from and analyzing a sample obtained from the patient before the patient receives anti-IL-23p19 antibody treatment. To analyze and (b) (i) GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C For one or more gene transcript biomarker(s) of one or more genes selected from and analyzing a sample obtained from the patient after the patient has received anti-IL-23p19 antibody treatment. To analyze and (c) (i) after the patient has received the anti-IL-23p19 antibody treatment, If the expression level of the gene transcript biomarker(s) is increased, ulcerative colitis is diagnosed. the patient having or suspected of having colitis responds to the anti-IL-23p19 antibody treatment. and determining that the patient is cured, or (a)(ii) GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1 C. One or more gene transcript biomarker(s) of one or more genes selected from Patients with ulcerative colitis who did not receive anti-IL-23p19 antibody treatment analyzing a sample obtained from a patient suspected of having (b)(ii) GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1 C. One or more gene transcript biomarker(s) of one or more genes selected from In this regard, a sample obtained from a patient after the patient received anti-IL-23p19 antibody treatment was To analyze and (c) (ii) one of the above in the patient who has not received anti-IL-23p19 antibody treatment. and comparing the expression levels of the above gene transcript biomarker(s) to determine whether the patient has an antibody. and (b) determining whether the one or more gene transcript biomarkers (or a combination thereof) are elevated after receiving IL-23p19 antibody treatment. If the expression level of one or more of the above-mentioned genes is increased, the patient is suspected of having or having ulcerative colitis. determining that the patient is cured in response to the anti-IL-23p19 antibody treatment; A method comprising:

153. The gene transcript biomarker of the gene of claim 151 or claim 152 and detecting the expression levels of at least two of the above. A patient suspected of having the anti-IL-23p19 antibody of claim 151 or claim 152 A method for determining whether a patient has been cured in response to antibody treatment.

154. The gene transcript biomarker of the gene of claim 151 or claim 152 and detecting the expression levels of at least three of the above. A patient suspected of having the anti-IL-23p19 antibody of claim 151 or claim 152 A method for determining whether a patient has been cured in response to antibody treatment.

155. The gene transcript biomarker of the gene of claim 151 or claim 152 and detecting the expression levels of at least four of the above. A patient suspected of having the anti-IL-23p19 antibody of claim 151 or claim 152 A method for determining whether a patient has been cured in response to antibody treatment.

156. The gene transcript biomarker of the gene of claim 151 or claim 152 and detecting the expression levels of at least five of the above. A patient suspected of having the anti-IL-23p19 antibody of claim 151 or claim 152 A method for determining whether a patient has been cured in response to antibody treatment.

157. At least one of the gene transcript biomarkers of the gene of claim 151 The method comprises detecting the expression levels of the five of the above-mentioned markers in a subject having or suspected of having ulcerative colitis. and the patient is cured in response to treatment with the anti-IL-23p19 antibody of claim 151. How to determine whether or not

158. 152. The gene transcript biomarker(s) of claim 151 . detecting at least six of the expression levels of the ulcerative colitis. and a patient suspected of having the disease responds to treatment with the anti-IL-23p19 antibody of claim 151. How to determine whether a patient is cured or not.

159. 152. The gene transcript biomarker(s) of claim 151 . detecting at least seven of the expression levels of the inflammatory cytokines, and a patient suspected of having the disease responds to treatment with the anti-IL-23p19 antibody of claim 151. How to determine whether a patient is cured or not.

160. 152. The gene transcript biomarker(s) of claim 151 . detecting at least eight of the expression levels of the inflammatory cytokines, and a patient suspected of having the disease responds to treatment with the anti-IL-23p19 antibody of claim 151. How to determine whether a patient is cured or not.

161. 152. The gene transcript biomarker(s) of claim 151 . Detecting the expression levels of at least nine of the above. and a patient suspected of having the disease responds to treatment with the anti-IL-23p19 antibody of claim 151. How to determine whether a patient is cured or not.

162. 152. The gene transcript biomarker(s) of claim 151 . Detecting the expression level of at least 10 of the above. and a patient suspected of having the disease responds to treatment with the anti-IL-23p19 antibody of claim 151. How to determine whether a patient is cured or not.

163. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression Patients with or suspected of having ulcerative colitis, as determined by profiling methods The patient is treated with an anti-IL-23p19 antibody according to any one of claims 151 to 162. A method for determining whether a patient has responded to treatment and is cured.

164. ulcerative colitis, wherein the gene expression profiling method is a PCR-based method; A patient having or suspected of having the disease is treated with the anti-IL-23p19 antibody of claim 163.

20. A method for determining whether a patient has been cured in response to treatment with the compound.

165. The method of gene expression profiling is immunohistochemistry. A method for treating a patient having or suspected of having IL-23p19 with the anti-IL-23p19 antibody of claim 163. A method for determining whether a patient is cured in response to a treatment.

166. ulcerative colitis, wherein the gene expression profiling method is a proteomics technique; A patient having or suspected of having the disease is treated with the anti-IL-23p19 antibody of claim 163.

20. A method for determining whether a patient has been cured in response to treatment with the compound.

167. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more ulcerative colitis, normalized to the expression levels of reference genes or their expression products. A patient having or suspected of having an antibody according to any one of claims 163 to 166. A method for determining whether a patient is cured in response to treatment with an IL-23p19 antibody.

168. The sample is derived from a colon tissue biopsy or a rectal tissue biopsy and is a sample of a patient with or without ulcerative colitis. A patient suspected of having the anti-IL-23p1 antibody of any one of claims 151 to 167 9. A method for determining whether a patient is cured in response to treatment with the antibody.

169. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon. A patient with or suspected of having ulcerative colitis claims a tissue selected from the group consisting of: Determine whether the patient is cured in response to treatment with the anti-IL-23p19 antibody of paragraph 168. How to do it.

170. having or having ulcerative colitis, wherein the colon tissue biopsy is from a non-inflamed colon area. A patient suspected of having IL-23p19 is treated with the anti-IL-23p19 antibody of claim 168 or claim 169. A method for determining whether a patient is cured in response to a treatment.

171. The colon tissue biopsy is from an inflamed colon area and is suspected of having or having ulcerative colitis. The patient is treated with the anti-IL-23p19 antibody of claim 168 or claim 169. A method for determining whether a patient is cured in response to a treatment.

172. The sample collected from the patient administered an anti-IL-23p19 antibody is at least two weeks, at least four weeks after said first administration of 23p19 antibody, After 8 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, At least 24 weeks later, at least 28 weeks later, at least 30 weeks later, at least 32 weeks later weeks later, at least 36 weeks later, at least 40 weeks later, at least 44 weeks later, Patients with or without ulcerative colitis were included, with the sample taken at 48 weeks or at least 52 weeks later. A patient suspected of having an IL-23p1 antibody according to any one of claims 151 to 171 9. A method for determining whether a patient has been cured in response to treatment with the antibody.

173. The anti-IL-23p19 antibody is selected from the group consisting of mirikizumab, guselkumab, risankizumab, tilukizumab, and the like. The antibody according to any one of claims 151 to 172, which is drakizumab or brazikumab. Patients with or suspected of having ulcerative colitis who respond to treatment with an IL-23p19 antibody A method for determining whether a patient is cured.

174. The anti-IL-23p19 antibody of claim 173 is mirikizumab. Patients with or suspected of having ulcerative colitis respond to treatment with 23p19 antibodies. How to determine if you are healing or not.

175. 175. A method for treating ulcerative colitis in response to treatment with the anti-IL-23p19 antibody of claim 174.

1. A method for determining whether a patient having or suspected of having a disease has been cured, comprising: a) administering three induction doses of mirikizumab to the patient by intravenous infusion at four-week intervals; administering a dose of mirikizumab to a patient in need thereof, wherein each induction dose comprises 300 mg of mirikizumab; b) administering a maintenance dose of mirikizumab to said patient by subcutaneous injection every 4 or 12 weeks; administering the first maintenance dose within 2 to 8 days after the last induction dose was administered; and administering a maintenance dose of 200 mg mirikizumab two weeks later, each maintenance dose containing 200 mg mirikizumab. A method comprising:

176. the first maintenance dose is administered 4 to 6 weeks after the final induction dose is administered; 176. A method for treating ulcerative colitis in response to treatment with the anti-IL-23p19 antibody of claim 175.

2. A method for determining whether a patient having or suspected of having a pulmonary embolism is cured.

177. subsequent maintenance dose(s) of mirikizumab administered 4 weeks after administration of said first maintenance dose; The anti-IL-23p19 antibody of claim 175 or claim 176 is administered at intervals. Whether patients with or suspected of having ulcerative colitis are cured in response to the treatment given How to determine.

178. subsequent maintenance dose(s) of mirikizumab administered 12 weeks after administration of said first maintenance dose; The anti-IL-23p19 antibody of claim 175 or claim 176, to determine whether patients with or suspected of having ulcerative colitis are cured in response to the treatment used. How to determine whether

179. The anti-IL-23p19 antibody of claim 173 is guselkumab. Patients with or suspected of having ulcerative colitis respond to treatment with 23p19 antibodies. How to determine if you are healing or not.

180. A patient with ulcerative colitis who responds to treatment with the anti-IL-23p19 antibody of claim 179.

1. A method for determining whether a patient having or suspected of having a disease has been cured, comprising: a) Three induction doses of guselkumab will be administered to the patient by intravenous infusion at 4-week intervals. wherein each induction dose contains 100-500 mg of guselkumab. And, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or administering to said patient by subcutaneous injection at 12 week intervals, said initial maintenance dose is administered 2 to 8 weeks after the final induction dose is administered. Hmm, a method.

181. The anti-IL-23 antibody of claim 180, wherein each induction dose comprises 200 mg of guselkumab. Patients with or suspected of having ulcerative colitis have been cured in response to treatment with p19 antibodies. How to determine whether

182. The anti-IL-23 antibody of claim 180, wherein each induction dose comprises 400 mg of guselkumab. Patients with or suspected of having ulcerative colitis have been cured in response to treatment with p19 antibodies. How to determine whether

183. The anti-IL-23p19 antibody of claim 173 is risankizumab. - Patients with or suspected of having ulcerative colitis who respond to treatment with 23p19 antibodies How to determine if you are cured or not.

184. The anti-IL-23p19 antibody of claim 173 is tildrakizumab. Patients with or suspected of having ulcerative colitis who are responsive to treatment with L-23p19 antibodies How to determine if a patient is cured.

185. The anti-IL-23p19 antibody of claim 173 is brazikumab. Patients with or suspected of having ulcerative colitis respond to treatment with 23p19 antibodies. How to determine if you are healing or not.

186. Methods for treating bowel frequency in patients with or suspected of having ulcerative colitis There was, obtaining a first sample from the patient; The first sample was analyzed to obtain the following table: Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 detecting one or more gene transcript biomarker(s) of a gene selected from And, administering an anti-IL-23p19 antibody to said patient; obtaining a second sample from the patient; The second sample is analyzed to detect one or more genes selected from the above. and detecting a child transcript biomarker(s); The one or more gene transcript biomarkers detected in the first sample the expression levels of the one or more genes detected in the second sample from the A change in the expression level of the transcript biomarker(s) is detected in response to the anti-IL-23p19 antibody. A method for indicating a response.

187. Defecation in a patient having or suspected of having ulcerative colitis according to claim 186.

1. A method of treating frequency, comprising: obtaining a first sample from the patient; The first sample is analyzed to detect S100 calcium binding protein 8, S100 calcium Calcium-binding protein A12, cadherin-related family member 1, S100 calcium Binding protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing Mitochondrial-associated factor 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor body, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane kinase Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinase Synthin 2, aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa , TIMP metallopeptidase inhibitor 1, transcobalamin 1, and creatinine and detecting one or more gene transcript biomarker(s) of a gene selected from the group consisting of phosphodiesterase B and phosphodiesterase B. And, administering an anti-IL-23p19 antibody to said patient; obtaining a second sample from the patient; The second sample is analyzed to detect S100 calcium binding protein 8, S100 calcium Calcium-binding protein A12, cadherin-related family member 1, S100 calcium Binding protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis-inducing Mitochondrial-associated factor 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor body, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane kinase Protein 2, calpain 13, elongation factor of RNA polymerase II2, prokinase Synthin 2, aquaporin 9, interleukin 1 alpha, Fc fragment of IgG receptor IIa , TIMP metallopeptidase inhibitor 1, transcobalamin 1, and creatinine one or more gene transcript biomarkers of one or more genes selected from the group consisting of: and detecting The one or more gene transcript biomarkers detected in the first sample the expression levels of the one or more genes detected in the second sample from the A change in the expression level of the transcript biomarker(s) is detected in response to the anti-IL-23p19 antibody. A method for indicating a response.

188. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least two of the markers.

189. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and subsequently, the gene transcript biomarkers of the genes according to claim 1 or claim 2. detecting said expression levels of at least three of said genes.

190. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least four of the markers.

191. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least five of the markers.

192. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least six of the markers.

193. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least seven of the markers.

194. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least eight of the markers.

195. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least nine of the markers.

196. Having or suspected of having ulcerative colitis according to claim 186 or claim 187 A method of treating bowel frequency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 186 or claim 187. detecting said expression levels of at least ten of the markers.

197. the expression of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from the current a change in the expression of IL-23p19 indicates that administration of the anti-IL-23p19 antibody should be continued. having or having ulcerative colitis according to any one of claims 186 to 196, A method for treating bowel frequency in patients suspected of having

198. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression The method according to any one of claims 186 to 197, wherein the method is determined by a profiling method. Methods for treating bowel frequency in patients with or suspected of having ulcerative colitis 。

199. 198. The method of gene expression profiling is a PCR-based method. Treating bowel frequency in patients with or suspected of having ulcerative colitis as described in method.

200. 199. The method of claim 198, wherein said method of gene expression profiling is immunohistochemistry.

10. A method of treating bowel frequency in a patient having or suspected of having ulcerative colitis.

201. 198. The method of gene expression profiling is a proteomics technique. Treating bowel frequency in patients with or suspected of having ulcerative colitis as described in method.

202. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more Normalized to the expression level of a reference gene or its expression product. In a patient having or suspected of having ulcerative colitis according to any one of claims 01 to 01. How to treat bowel frequency.

203. Claims 186-202, wherein the sample is from a colon tissue biopsy or a rectal tissue biopsy. Defecation in a patient with or suspected of having ulcerative colitis according to any one of the preceding claims How to treat frequency.

204. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon.

204. The method of claim 203, wherein the subject has or has ulcerative colitis and the subject is from a tissue selected from the group consisting of:

10. A method for treating bowel frequency in a patient suspected of having gallbladder disease.

205. 205. The method of claim 203 or claim 204, wherein the colon tissue biopsy is from a non-inflamed colon area. Methods for treating bowel frequency in patients with or suspected of having ulcerative colitis 。

206. 205. The method of claim 203 or claim 204, wherein the colon tissue biopsy is from an inflamed colon region. Methods for treating bowel frequency in patients with or suspected of having ulcerative colitis 。

207. The first sample is taken prior to or concurrently with administration of the anti-IL-23p19 antibody. and said second sample is taken at least two weeks after said first administration of said anti-IL-23p19 antibody. after at least 4 weeks, after at least 8 weeks, after at least 12 weeks, after at least 1 After 6 weeks, after at least 20 weeks, after at least 24 weeks, after at least 28 weeks, At least 30 weeks later, at least 32 weeks later, at least 36 weeks later, at least 40 weeks later at least 44 weeks, at least 48 weeks, or at least 52 weeks after the 24. A method for treating or suspected of having ulcerative colitis according to any one of claims 1 to 23.

10. A method for treating bowel frequency in a patient suffering from urinary tract infection.

208. The anti-IL-23p19 antibody is mirikizumab, guselkumab, risankizumab, tilikizumab, The inhibitor according to any one of claims 186 to 207, which is drakizumab or brazikumab. A method for treating bowel frequency in a patient having or suspected of having ulcerative colitis.

209. The ulcerative colitis of claim 208, wherein the anti-IL-23p19 antibody is mirikizumab. A method of treating bowel frequency in a patient having or suspected of having enteritis.

210. Defecation in a patient with or suspected of having ulcerative colitis according to claim 209.

1. A method of treating frequency, comprising: a) administering three induction doses of mirikizumab to the patient by intravenous infusion at four-week intervals; administering a dose of mirikizumab to a patient in need thereof, wherein each induction dose comprises 300 mg of mirikizumab; b) administering a maintenance dose of mirikizumab to said patient by subcutaneous injection every 4 or 12 weeks; administering the first maintenance dose within 2 to 8 days after the last induction dose was administered; and administering a maintenance dose of 200 mg mirikizumab two weeks later, each maintenance dose containing 200 mg mirikizumab. A method comprising:

211. the first maintenance dose is administered 4 to 6 weeks after the final induction dose is administered; 211. The method of claim 210, wherein the frequency of bowel movements is increased in a patient having or suspected of having ulcerative colitis. How to treat the degree.

212. Subsequent maintenance dose(s) of mirikizumab are administered 4 weeks after the first maintenance dose.

212. A method for treating or with ulcerative colitis according to claim 210 or claim 211, wherein the method is administered at intervals 10. A method for treating bowel frequency in a patient suspected of having gallbladder disease.

213. Subsequent maintenance dose(s) of mirikizumab are administered 12 weeks after the administration of said first maintenance dose.

212. The method of claim 210 or 211, wherein the method is administered at intervals of 10 minutes or less to a patient with or without ulcerative colitis.

10. A method for treating bowel frequency in a patient suspected of having

214. The ulcerative colitis of claim 208, wherein the anti-IL-23p19 antibody is guselkumab. A method of treating bowel frequency in a patient having or suspected of having enteritis.

215. Defecation in a patient with or suspected of having ulcerative colitis according to claim 214.

1. A method of treating frequency, comprising: a) Three induction doses of guselkumab will be administered to the patient by intravenous infusion at 4-week intervals. wherein each induction dose contains 100-500 mg of guselkumab. And, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or administering to said patient by subcutaneous injection at 12 week intervals, said initial maintenance dose is administered 2 to 8 weeks after the final induction dose is administered. Hmm, a method.

216. The ulcerative colitis of claim 215, wherein each induction dose comprises 200 mg of guselkumab.

1. A method for treating bowel frequency in a patient having or suspected of having

217. The ulcerative colitis of claim 215, wherein each induction dose comprises 400 mg of guselkumab.

1. A method for treating bowel frequency in a patient having or suspected of having

218. The ulcerative colitis of claim 208, wherein the anti-IL-23p19 antibody is risankizumab. A method of treating bowel frequency in a patient having or suspected of having colitis.

219. The ulcer of claim 208, wherein the anti-IL-23p19 antibody is tildrakizumab.

10. A method for treating bowel frequency in a patient having or suspected of having idiopathic colitis.

220. The ulcerative colitis of claim 208, wherein the anti-IL-23p19 antibody is brazikumab. A method of treating bowel frequency in a patient having or suspected of having enteritis.

221. For diagnosing bowel frequency in patients with or suspected of having ulcerative colitis 1. A method comprising: (a) the following table: Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 one or more gene transcript biomarker(s) of one or more genes selected from determining the expression level; (b) determining the determined expression levels of the one or more gene transcript biomarker(s); The assay is performed by combining one or more gene transcript biomarkers ( and comparing the expression level of the gene to a reference expression level of the gene(s) of interest (e.g., one or more of the gene(s) of interest); (c) determining whether the biomarker expression level in the patient is greater than or equal to the reference expression level; and if so, providing a diagnosis of bowel frequency.

222. Defecation in a patient having or suspected of having ulcerative colitis according to claim 221. A method for diagnosing frequency, comprising: (a) analyzing the second sample for S100 calcium binding protein 8, S100 calcium binding protein 9, Calcium-binding protein A12, cadherin-related family member 1, S100 calcium Calcium-binding protein A9, Triples pseudokinase 2, platelet-activating factor, apoptosis Mitochondrial-associated factor 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 Receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon induction Transmembrane protein 2, calpain 13, RNA polymerase II2 elongation factor, prokinase Phycin 2, aquaporin 9, interleukin 1 alpha, IgG receptor IIa Fc fragments, TIMP metallopeptidase inhibitor 1, transcobalamin 1, and creatine one or more gene transcript biomarkers (multiple) of one or more genes selected from the group consisting of: determining the expression level of one or more of the genes; (b) S100 calcium-binding protein 8, S100 calcium-binding protein A1 2, Cadherin-related family member 1, S100 calcium-binding protein A9, T Riples pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial association SEQ ID NO: 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane protein 2, Kalpa In-13, RNA polymerase II2 elongation factor, prokinephrine 2, aquaporin 9 , interleukin 1 alpha, Fc fragment of IgG receptor IIa, TIMP metallopeptides 1 selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 39, 38, 39, a reference expression level of one or more gene transcript biomarker(s) of one or more genes; the determined expression levels of the one or more gene transcript biomarker(s); To compare and (c) determining whether the biomarker expression level in the patient is greater than or equal to the reference expression level; and if so, providing a diagnosis of bowel frequency.

223. Methods for treating bowel urgency in patients with or suspected of having ulcerative colitis There was, (a) obtaining a first sample from said patient; (b) analyzing said first sample to obtain the following table: Table 3-1 Table 3-2 Table 3-3 Table 3-4 Table 3-5 Table 3-6 detecting one or more gene transcript biomarkers of one or more genes selected from And, (c) administering an anti-IL-23p19 antibody to said patient; (d) obtaining a second sample from the patient; (e) analyzing the second sample for one or more genes from the table above; detecting the transcript biomarker(s); The one or more gene transcript biomarkers detected in the first sample the expression levels of the one or more genes detected in the second sample from the A change in the expression level of the transcript biomarker(s) is detected in response to the anti-IL-23p19 antibody. A method for indicating a response.

224. 224. The method of claim 223, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating pressure, comprising: (a) obtaining a first sample from said patient; (b) analyzing the first sample to identify multiple coiled-coil domain-containing 175, TNF receptor superfamily members; Family member 17, complement factor B, containing the F-box and WD-repeat regions, lipase ZeA, lysosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, Interferon alpha and interferon beta receptor subunit 2, phospho Serine aminotransferase 1, sortin nexin 25, heat shock protein phagocytosis MilliA (Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 Homology C, signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation element binding protein 4, phosphoenolpyruvate carboxylate kinase 1, elongation factor of RNA polymerase II2, cathepsin H, and calpain 13 detecting one or more gene transcript biomarker(s) for one or more genes selected from To put out and (c) administering an anti-IL-23p19 antibody to said patient; (d) obtaining a second sample from the patient; (e) analyzing the second sample to identify multiple coiled-coil domain-containing 175, TNF receptor superfamily members; Family member 17, complement factor B, containing the F-box and WD-repeat regions, lipase ZeA, lysosomal acid type, centrosomal protein 128, baculovirus IAP repeat-containing 3, Interferon alpha and interferon beta receptor subunit 2, phospho Serine aminotransferase 1, sortin nexin 25, heat shock protein phagocytosis MilliA (Hsp70) member 13, claudin 2, lymphocyte antigen 96, SEC11 Homology C, signal peptidase complex subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation element binding protein 4, phosphoenolpyruvate carboxylate kinase 1, elongation factor of RNA polymerase II2, cathepsin H, and calpain 13 from one or more gene transcript biomarker(s) of one or more genes selected from detecting one or more gene transcript biomarker(s) of one or more genes; , including The one or more gene transcript biomarkers detected in the first sample the expression levels of the one or more genes detected in the second sample from the A change in the expression level of the transcript biomarker(s) is detected in response to the anti-IL-23p19 antibody. A method for indicating a response.

225. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least two of the markers.

226. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least three of the markers.

227. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least four of the markers.

228. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least five of the markers.

229. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least six of the markers.

230. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least seven of the markers.

231. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least eight of the markers.

232. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least nine of the markers.

233. Having or suspected of having ulcerative colitis according to claim 223 or claim 224 A method of treating bowel urgency in a patient, comprising administering an anti-IL-23p19 antibody to a subject. and then the gene transcript biosynthesis of the gene of claim 223 or claim 224. detecting said expression levels of at least ten of the markers.

234. the expression of the one or more gene transcript biomarkers detected in the first sample. the one or more gene transcript biomarkers detected in the second sample from the current a change in the expression of IL-23p19 indicates that administration of the anti-IL-23p19 antibody should be continued. having or having ulcerative colitis according to any one of claims 223 to 233, A method for treating bowel urgency in a patient suspected of having

235. The expression levels of the one or more gene transcript biomarker(s) are used to determine gene expression The method according to any one of claims 223 to 234, wherein the method is determined by a profiling method. Methods for treating bowel urgency in patients with or suspected of having ulcerative colitis 。

236. 236. The method of claim 235, wherein the patient has or is suspected of having ulcerative colitis.

1. A method for treating pressure, wherein the method of gene expression profiling is PCR-based It is a method, a method.

237. 236. The method of claim 235, wherein the patient has or is suspected of having ulcerative colitis.

1. A method for treating pressure, comprising: That's the method.

238. 236. The method of claim 235, wherein the patient has or is suspected of having ulcerative colitis.

1. A method for treating pressure, wherein the method of gene expression profiling comprises proteomic analysis. A method that is a technology.

239. The expression levels of the one or more gene transcript biomarker(s) are determined by one or more Normalized to the expression level of a reference gene or its expression product.

38. In a patient having or suspected of having ulcerative colitis according to any one of claims 38. How to treat bowel urgency.

240. Claims 223-239, wherein the sample is from a colon tissue biopsy or a rectal tissue biopsy. Intestinal resection in a patient with or suspected of having ulcerative colitis according to any one of claims 1 to 5 How to treat pressure.

241. The colon tissue biopsy is from the group consisting of the terminal ileum, ascending colon, descending colon, and sigmoid colon.

241. The method of claim 240, wherein the subject has or has ulcerative colitis and the subject is from a tissue selected from the group consisting of:

10. A method for treating bowel urgency in a patient suspected of having bowel urgency.

242. 242. The method of claim 240 or 241, wherein the colon tissue biopsy is from a non-inflamed colon area. Methods for treating bowel urgency in patients with or suspected of having ulcerative colitis 。

243. 242. The method of claim 240 or claim 241, wherein the colon tissue biopsy is from an inflamed colon area.

10. A method for treating bowel urgency in a patient having or suspected of having ulcerative colitis.

244. The first sample is taken prior to or concurrently with administration of the anti-IL-23p19 antibody. and said second sample is taken at least two weeks after said first administration of said anti-IL-23p19 antibody. after at least 4 weeks, after at least 8 weeks, after at least 12 weeks, after at least 1 After 6 weeks, after at least 20 weeks, after at least 24 weeks, after at least 28 weeks, At least 30 weeks later, at least 32 weeks later, at least 36 weeks later, at least 40 weeks later at least 44 weeks, at least 48 weeks, or at least 52 weeks after the having or having ulcerative colitis according to any one of claims 223 to 243 A method for treating bowel urgency in a patient suspected of having

245. The anti-IL-23p19 antibody is selected from the group consisting of mirikizumab, guselkumab, risankizumab, tilukizumab, and the like. The compound according to any one of claims 223 to 244, which is drakizumab or brazikumab. A method for treating bowel urgency in a patient having or suspected of having ulcerative colitis.

246. The ulcerative colitis of claim 245, wherein the anti-IL-23p19 antibody is mirikizumab. A method of treating bowel urgency in a patient having or suspected of having enterocolitis.

247. 247. A method for treating ulcerative colitis in a patient with or suspected of having ulcerative colitis according to claim 246.

1. A method of treating pressure, comprising: a) administering three induction doses of mirikizumab to the patient by intravenous infusion at four-week intervals; administering a dose of mirikizumab to a patient in need thereof, wherein each induction dose comprises 300 mg of mirikizumab; b) administering a maintenance dose of mirikizumab to said patient by subcutaneous injection every 4 or 12 weeks; administering the first maintenance dose within 2 to 8 days after the last induction dose was administered; and administering a maintenance dose of 200 mg mirikizumab two weeks later, each maintenance dose containing 200 mg mirikizumab. A method comprising:

248. the first maintenance dose is administered 4 to 6 weeks after the final induction dose is administered; 248. Bowel urgency in a patient having or suspected of having ulcerative colitis according to claim 247. How to treat the feeling.

249. Subsequent maintenance dose(s) of mirikizumab are administered 4 weeks after the first maintenance dose.

249. A method for treating or with ulcerative colitis according to claim 247 or claim 248, wherein the method is administered at intervals 10. A method for treating bowel urgency in a patient suspected of having bowel urgency.

250. Subsequent maintenance dose(s) of mirikizumab are administered 12 weeks after the administration of said first maintenance dose.

249. The method of claim 247 or 248, wherein the method is administered at intervals of 10 minutes or less.

10. A method for treating bowel urgency in a patient suspected of having

251. The ulcerative colitis of claim 245, wherein the anti-IL-23p19 antibody is guselkumab. A method of treating bowel urgency in a patient having or suspected of having enterocolitis.

252. 215. The method of claim 214, wherein the patient has or is suspected of having ulcerative colitis.

1. A method of treating pressure, comprising: a) Three induction doses of guselkumab will be administered to the patient by intravenous infusion at 4-week intervals. wherein each induction dose contains 100-500 mg of guselkumab. And, b) Maintenance doses of guselkumab every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or administering to said patient by subcutaneous injection at 12 week intervals, said initial maintenance dose is administered 2 to 8 weeks after the final induction dose is administered. Hmm, a method.

253. The ulcerative colitis of claim 252, wherein each induction dose comprises 200 mg of guselkumab.

10. A method for treating bowel urgency in a patient having or suspected of having:

254. The ulcerative colitis of claim 252, wherein each induction dose comprises 400 mg of guselkumab.

10. A method for treating bowel urgency in a patient having or suspected of having:

255. The ulcerative colitis of claim 245, wherein the anti-IL-23p19 antibody is risankizumab. A method of treating bowel urgency in a patient having or suspected of having colitis.

256. The ulcer of claim 245, wherein the anti-IL-23p19 antibody is tildrakizumab.

10. A method for treating bowel urgency in a patient having or suspected of having idiopathic colitis.

257. The ulcerative colitis of claim 245, wherein the anti-IL-23p19 antibody is brazikumab. A method of treating bowel urgency in a patient having or suspected of having enterocolitis.

258. Method for diagnosing bowel urgency in patients with or suspected of having ulcerative colitis There was, (a) the following table: Table 4-1 Table 4-2 Table 4-3 Table 4-4 Table 4-5 Table 4-6 the expression level of one or more gene transcript biomarkers of one or more genes selected from and determining (b) determining the determined expression levels of the one or more gene transcript biomarker(s); The assay is performed by combining one or more gene transcript biomarkers ( and comparing the expression level of the gene to a reference expression level of the gene(s) of interest (e.g., one or more of the gene(s) of interest); (c) determining the expression level of said one or more gene transcript biomarker(s) in said patient; If the expression level(s) of the gene(s) is / are altered compared to said reference expression level, a diagnosis of bowel urgency is provided. and providing.

259. 258. A method for treating ulcerative colitis in a patient with or suspected of having ulcerative colitis, comprising:

1. A method for diagnosing compulsion, comprising: (a) Coil-multicoiled domain-containing 175, TNF receptor superfamily member 17, complement Body factor B, F-box and WD-repeat region-containing 7, lipase A, lysosomal acid type, central Protein 128, baculovirus IAP repeat-containing 3, interferon alpha and and interferon beta receptor subunit 2, phosphoserine aminotransferase ase 1, sortin nexin 25, heat shock protein family A (Hsp70) members Bar13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, signal peptide Subunit of the phospholipase complex, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation factor Protein-binding protein 4, phosphoenolpyruvate carboxykinase 1, RNA polymerase one or more genes selected from the group consisting of elongation factor of phosphodiesterase II2, cathepsin H, and calpain 13 determining the expression level of one or more gene transcript biomarker(s) of the gene; (b) Coil-multiplexed domain-containing 175, TNF receptor superfamily member 17, complement Body factor B, F-box and WD-repeat region-containing 7, lipase A, lysosomal acid type, central Protein 128, baculovirus IAP repeat-containing 3, interferon alpha and and interferon beta receptor subunit 2, phosphoserine aminotransferase ase 1, sortin nexin 25, heat shock protein family A (Hsp70) members Bar13, claudin 2, lymphocyte antigen 96, SEC11 homolog C, signal peptide Subunit of the phospholipase complex, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation factor Protein-binding protein 4, phosphoenolpyruvate carboxykinase 1, RNA polymerase one or more genes selected from the group consisting of elongation factor of phosphodiesterase II2, cathepsin H, and calpain 13 a reference expression level of one or more gene transcript biomarker(s) of a gene; and comparing the determined expression levels of the gene transcript biomarker(s) above with And, (c) determining the expression level of said one or more gene transcript biomarker(s) in said patient; If the expression level(s) of the gene(s) is / are altered compared to said reference expression level, a diagnosis of bowel urgency is provided. and providing.

260. CXCL8, AQP9, IL1B, S100A9, TREM1, MMP12, MMP1 , MMP7, TCN1, DUOX2, DUOXA2, SLC6A14, VNN1, ABC A12, REG1B, C4BPA, GUCA2B, OTOP2, AQP8, SLC26A 2, ADH1C, MMP3, REG3A, DMBT1, REG1P, S100A8, IG KV2D-40, PI3, TNIP3, REG1A, IDO1, NOS2, MMP10, CXCL1, PTGS2, ABCG2, HMGCS2, TMIGD1, GUCA2A, L OC101928405, MS4A12, UGT2A3, TRPM6, NXPE4, SL C16A9, ADH1C, PCK1, CDKN2B-AS1, TMEM236, CD17 one or more genes selected from 7P1, SLC17A4, and ZG16 A gene transcript biomarker panel including child transcript biomarkers.

261. GUCA2A, OTOP2, AQP8, SLC26A2, and ADH1C 261. The method of claim 260, comprising one or more gene transcript biomarkers of one or more genes Gene transcript biomarker panel.

262. The table below: Table 5-1 Table 5-2 Table 5-3 Table 5-4 Table 5-5 one or more gene transcript biomarker(s) of one or more genes selected from A gene transcript biomarker panel comprising:

263. S100 calcium-binding protein 8, S100 calcium-binding protein A12, Adherin-related family member 1, S100 calcium-binding protein A9, Trip les pseudokinase 2, platelet-activating factor, apoptosis-inducing factor mitochondrial-associated 3, Fc fragment of IgG receptor IIb, colony-stimulating factor 3 receptor, LYN proto-oncogene, Src family tyrosine kinase, interferon-induced transmembrane protein 2, calpain 1 3. RNA polymerase II2 elongation factor, prokinephrine 2, aquaporin 9, and insulin tRNA-1 alpha, Fc fragment of IgG receptor IIa, TIMP metallopeptidase one or more selected from inhibitor 1, transcobalamin 1, and creatine kinase B a gene transcript biomarker comprising one or more gene transcript biomarker(s) of a gene of Marker panel.

264. The table below: Table 6-1 Table 6-2 Table 6-3 Table 6-4 Table 6-5 Table 6-6 a genetic analysis of a gene comprising one or more gene transcript biomarkers of one or more genes selected from Child transcript biomarker panel.

265. Coiled coil-containing 175, TNF receptor superfamily member 17, complement factor B, F-box and WD-repeat region-containing 7, lipase A, lysosomal acid type, centrosomal protein Protein 128, baculovirus IAP repeat-containing 3, interferon alpha and interferon Terferon beta receptor subunit 2, phosphoserine aminotransferase 1 , sortin nexin 25, heat shock protein family A (Hsp70) member 1 3, Claudin 2, lymphocyte antigen 96, SEC11 homolog C, signal peptidase complex Coalescing subunit, DNA damage-regulated autophagy modifier 1, cytoplasmic polyadenylation element binding Protein 4, phosphoenolpyruvate carboxykinase 1, RNA polymerase I I2 elongation factor, cathepsin H, and calpain 13. A gene transcript biomarker panel comprising one or more gene transcript biomarker(s). Lu.

Images