# US 2018/0022800 A1 · Biomarker

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- Number: US 2018/0022800 A1
- Document ID: US20180022800A1
- Status: Published application
- Kind: A1
- Application number: 15/547,154
- Filed: 2016-01-28
- Published: 2018-01-25
- Earliest claimed: 2015-01-29
- Assignees: Isis Innovation Limited
- Applicants: Isis Innovation Limited
- Inventors: Nathaniel Richard West; Benjamin Michael Joseph Owens; Ahmed Nabil Hegazy; Fiona Margaret Powrie
- Web page: https://patentgrep.com/patent/US20180022800A1

## CPC

- C07K 16/248: {IL-6}
- A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K 38/1793: {for cytokines; for lymphokines; for interferons}
- A61K 38/204: {IL-6}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/241: {Tumor Necrosis Factors}
- G01N 33/6869: {Interleukin}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- G01N 2333/5412: IL-6
- G01N 2800/065: Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to methods of treating chronic intestinal inflammation and/or inflammatory bowel disease by administering an antagonist of oncostatin-M (OSM) and/or OSM receptor-β (OSMR). The invention also relates to methods for diagnosing or prognosing chronic intestinal inflammation and/or inflammatory bowel disease in an individual and for predicting whether or not an individual will respond to an anti-TNFα therapy. The methods comprise measuring OSM and/or OSMR in the individual.

## Claims

### Claim 1

A method of treating or preventing chronic intestinal inflammation and/or inflammatory bowel disease (IBD) in an individual, the method comprising administering to the individual an antagonist of oncostatin-M (OSM) and/or OSM receptor-β (OSMR), and thereby treating or preventing chronic intestinal inflammation and/or IBD in the individual.

### Claim 2 (depends on 1)

The method of claim 1, in which the antagonist inhibits Th17 CD4+ T cells or development of the Th17 pathway.

### Claim 3

A method of diagnosing or prognosing chronic intestinal inflammation and/or IBD in an individual, which method comprises measuring OSM and/or OSMR in the individual, and thereby diagnosing or prognosing the chronic intestinal inflammation and/or IBD in the individual.

### Claim 4 (depends on 3)

The method of claim 3, which comprises measuring OSM and OSMR in the individual, comparing the OSM and OSMR levels with reference OSM and OSMR levels or the OSM and OSMR levels of a reference sample, and determining the OSM index (OSMi).

### Claim 5 (depends on 3)

The method of claim 3, which is a method of predicting whether or not an individual in remission from chronic intestinal inflammation and/or IBD will have a recurrence.

### Claim 6 (depends on 3, 4, 5)

The method of any one of claims 3 to 5, in which an elevated level of OSM, OSMR, and/or OSMi, as compared with or calculated using a reference sample or reference level(s), indicates a positive diagnosis, a negative prognosis and/or that the individual will have a recurrence.

### Claim 7 (depends on 3, 4, 5)

The method of any one of claims 3 to 5, in which a reduced level of OSM, OSMR, and/or OSMi, as compared with or calculated using a reference sample or reference level(s), indicates a negative diagnosis, a positive prognosis and/or that the individual will not have a recurrence.

### Claim 8 (depends on 1, 3, 4, 5, 6)

The method of treating or preventing chronic intestinal inflammation and/or IBD according to claim 1, in which the individual has been diagnosed or prognosed in accordance with the method of any one of claims 3 to 6.

### Claim 9 (depends on 3, 4, 5, 6)

A method of treating or preventing chronic intestinal inflammation and/or IBD in an individual, the method comprising (a) diagnosing or prognosing chronic intestinal inflammation and/or IBD in the individual in accordance with the method of any one of claims 3 to 6; and (b) administering to the individual an agent useful in the treatment of chronic intestinal inflammation and/or IBD.

### Claim 10 (depends on 9)

The method of claim 9, in which the agent is an antagonist of OSM and/or OSMR.

### Claim 11 (depends on 1, 8, 9)

The method of any one of claims 1, 8 and 9, in which the antagonist is an antagonist of OSM or OSMR activity or expression.

### Claim 12 (depends on 11)

The method of claim 11, in which the antagonist is an anti-OSM or anti-OSMR antibody, or an OSM or OSMR fusion protein.

### Claim 13

Products containing:
(i) means for determining the level of OSM and/or OSMR in an individual having or suspected of having or being at risk of developing chronic intestinal inflammation and/or IBD; and
(ii) an agent for treatment or prevention of chronic intestinal inflammation and/or IBD.

### Claim 14

A method for predicting whether or not an individual will respond to an anti-tumour necrosis factor α (TNFα) therapy, which method comprises measuring OSM and/or OSMR in the individual, and thereby predicting whether or not the individual will respond to the anti-TNFα therapy.

### Claim 15 (depends on 14)

The method of claim 14, in which the anti-TNFα therapy is treatment with an anti-TNFα antibody.

### Claim 16 (depends on 15)

The method of claim 15, in which the anti-TNFα antibody is infliximab, adalimumab, certolizumab or golimumab.

### Claim 17 (depends on 14, 15, 16)

The method of any one of claims 14 to 16, in which a reduced level of OSM, OSMR, and/or OSMi, as compared with or calculated using a reference sample or reference level(s), indicates that the individual will respond to the anti-TNFα therapy.

### Claim 18 (depends on 17)

The method of claim 17, further comprising selecting or recommending anti-TNFα therapy for treatment of the individual.

### Claim 19 (depends on 18)

The method of claim 18, in which the anti-TNFα therapy is selected or recommended as a first-line method of treatment for the individual.

### Claim 20 (depends on 18)

The method of claim 18 or claim 18, further comprising administering anti-TNFα therapy to the individual.

### Claim 21 (depends on 13, 14, 15)

The method of any one of claims 13 to 15, in which an elevated level of OSM, OSMR, and/or OSMi, as compared with or calculated using a reference sample or reference level(s), indicates that the individual will not respond to the anti-TNFα therapy.

### Claim 22 (depends on 20)

The method of claim 20, further comprising selecting or recommending a therapeutic treatment other than anti-TNFα therapy for treatment of the individual.

### Claim 23 (depends on 21)

The method of claim 21, further comprising administering the therapeutic treatment other than anti-TNFα therapy to the individual.

### Claim 24 (depends on 22)

The method of claim 22, in which the therapeutic treatment other than anti-TNFα therapy is administration of an anti-inflammatory agent.

### Claim 25 (depends on 23)

The method of claim 23, in which the anti-inflammatory agent is a corticosteroid.

### Claim 26 (depends on 13, 14, 15, 16, 17, 18)

A method of treating or preventing a TNFα-mediated disease or condition in an individual, the method comprising administering a TNFα antagonist to the individual, and thereby treating or preventing the TNFα-mediated disease or condition, in which method the individual has been predicted to respond to the TNFα antagonist in accordance with the method of any one of claims 13 to 18.

### Claim 27

An assay for measuring the level of OMS and/or OMSR in an individual having or suspected of having or being at risk of developing a TNFα-mediated disease, chronic intestinal inflammation and/or IBD, comprising contacting a biological sample from the individual with an agent that binds to OSM or OSMR, measuring complex formation between the agent and OSM or OSMR, optionally calculating the OSMi, comparing the measured value or the OSMi value with a reference value, and thereby predicting whether or not the individual having a TNFα-mediated disease will respond to an anti-TNFα therapy, or diagnosing or prognosing the chronic intestinal inflammation and/or IBD in the individual.

### Claim 28

A system comprising
(a) a measuring module for quantifying the level of OSM and/or OSMR in a biological sample from an individual having a TNFα-mediated disease, chronic intestinal inflammation and/or IBD;
(b) a storage module configured to store data output from the measuring module and reference and/or control data;
(c) a computation module configured to compute the value of the data output from the measuring module and the reference or control data; and
(d) an output module configured to display a prediction of whether or not the individual with a TNFα-mediated disease will respond to an anti-TNFα therapy or a recommended therapy for treatment of the individual, or a diagnosis or prognosis for the individual having chronic intestinal inflammation and/or IBD, based on the value of the output data.

### Claim 29 (depends on 2, 3, 4, 5, 6, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)

The method of any one of claims 2 to 6 and 13 to 24, in which the method is carried out on a biological sample from the individual.

### Claim 30 (depends on 26, 27, 28)

The assay of claim 26, the system of claim 27, or the method of claim 28, in which the biological sample is a blood sample, a serum sample, a stool sample, an intestinal biopsy, or a surgical resection sample.

### Claim 31 (depends on 29)

The assay, system or method of claim 29, in which the biological sample is a serum sample.

### Claim 32 (depends on 2, 3, 4, 5, 6, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 28, 29, 30)

A test kit for use in a method according to any one of claims 2 to 6, 13 to 24 and 28 to 30, which test kit comprises means for determining the level of OSM and/or OSMR in the individual and instructions for use in the method.

### Claim 33 (depends on 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

The method, assay, system or test kit of any one of claims 13 to 31, in which the individual has chronic intestinal inflammation, an autoimmune disease or an inflammatory disease.

### Claim 34 (depends on 32)

The method, assay, system or test kit of claim 32 in which the autoimmune disease or inflammatory disease is IBD.

### Claim 35 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 26, 27, 28, 29, 30, 31, 33)

The method, products, assay, system or test kit of any one of claims 1 to 12, 26 to 31 and 33, in which the IBD is associated with colorectal cancer.

### Claim 36 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 26, 27, 28, 29, 30, 31, 33, 34)

The method, products, assay, system or test kit of any one of claims 1 to 12, 26 to 31, 33 and 34, in which the IBD is Crohn's disease (CD) or ulcerative colitis (UC).

### Claim 37 (depends on 35)

The method, products, assay, system or test kit of claim 35, in which the CD is colonic CD or ileal CD.

### Claim 38

The method, products, assay, system or test kit of any one of the preceding claims, in which the individual is a mammal.

### Claim 39 (depends on 37)

The method, products, assay, system or test kit of claim 37, in which the mammal is a human.

### Claim 40

A method of determining the likelihood that an individual with chronic intestinal inflammation and/or IBD will need surgery, which method comprises measuring OSM and/or OSMR in the individual, and thereby determining the likelihood that the individual will need surgery.