Unlock instant, AI-driven research and patent intelligence for your innovation.

Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists

A biomarker, integrin technology, applied in the field of biomarkers for evaluating the use of β7 integrin antagonists in the treatment of gastrointestinal inflammatory disorders, which can solve the problems of patients not achieving steroid-free remission and mucosal healing

Active Publication Date: 2015-12-09
F HOFFMANN LA ROCHE & CO AG
View PDF58 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

No currently available therapy achieves sustained remission in more than 20%-30% of IBD patients with chronic disease (Hanauer et al., Lancet 359:1541-49 (2002); Sandborn et al., NEnglJMed353:1912-25 (2005))
Furthermore, sustained steroid-free remission and mucosal healing (clinical outcomes associated with true disease modification) are not achieved in the majority of patients

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists
  • Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists
  • Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0256] A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of rhuMabβ7 (etrolizumab) in Patients with Moderate-to-Severe Ulcerative Colitis

[0257] Clinical Study Description

[0258] Description of rhuMAbβ7 (etrolizumab)

[0259] rhuMAbβ7 (etrolizumab) is a humanized monoclonal antibody based on human IgG1 subclass IIIV H , κ subtype-IV L Consensus sequence, and specificity against the β7 subunit of integrin heterodimers. see Figure 1A and B. It has been shown to bind α4β7 with high affinity (K of about 116 pM d ) and αEβ7 (K about 1800pM d ).

[0260] This recombinant antibody has two heavy chains (446 residues) and two light chains (214 residues) covalently linked by interchain and intrachain disulfide bonds typical of IgGl antibodies. For the studies described here, it was produced in Chinese Hamster Ovary (CHO) cells. The molecular weight of the intact aglycosylated rhuMAbβ7 molecule is approximately 144 kDa. Each...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Methods of assessing or monitoring the effect, efficacy, responsiveness to treatment, and / or determining a dose or dosing regimen of therapeutic agents, such as integrin beta7 antagonists, for the treatment of gastrointestinal inflammatory disorders are provided. In certain aspects, methods of using integrin beta7 subunit-containing receptor occupancy by the integrin beta7 antagonist on colonic lymphocytes as an indicator ("biomarker") of the effect, efficacy, or responsiveness to treatment, and / or as a means to determine dosing or dosing regimens of therapeutic agents such as beta7 integrin antagonists for the treatment of gastrointestinal inflammatory disorders are provided. In certain aspects, methods of assessing the effect, efficacy, or responsiveness to beta7 integrin antagonist treatment by measuring gene expression levels of one or more integrin receptor ligands, lymphocyte genes, cytokine genes, or the number of alphaE-positive cells in intestinal crypt epithelium are provided.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to Provisional US Application No. 61 / 914,619, filed December 11, 2013, and Provisional US Application No. 61 / 805,860, filed March 27, 2013, both of which are hereby incorporated by reference in their entireties. [0003] sequence listing [0004] This application contains a Sequence Listing that has been submitted via EFS-Web, which is hereby incorporated by reference in its entirety. This ASCII copy, created on March 17, 2014, is named P5599R1WO_PCTSequenceListing.txt and is 20,255 bytes in size. technical field [0005] Methods of assessing or monitoring effect, efficacy, responsiveness to treatment and / or determining dosage or dosing regimen of a therapeutic agent, such as an integrin beta7 antagonist, for the treatment of a gastrointestinal inflammatory disorder (e.g., inflammatory bowel disease) are provided . In certain aspects, occupancy of receptors containing integrin β7 subun...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/00G01N33/53
CPCG01N33/6893C12Q1/6883C12Q2600/106C12Q2600/158G01N2333/70546G01N2800/065G01N2800/52C07K16/2839G01N33/53
Inventor L·迪尔M·凯伊尔M·T·唐X·魏M·B·威廉姆斯
Owner F HOFFMANN LA ROCHE & CO AG