Anti-TNF and anti-IL17 combination therapy biomarkers for inflammatory disease

A combined therapy and technology for inflammatory diseases, applied in allergic diseases, biological tests, bone diseases, etc., can solve the problem that the treatment plan is not completely effective

Inactive Publication Date: 2015-12-23
ABBVIE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In many cases, current treatment options are not fully effective

Method used

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  • Anti-TNF and anti-IL17 combination therapy biomarkers for inflammatory disease
  • Anti-TNF and anti-IL17 combination therapy biomarkers for inflammatory disease
  • Anti-TNF and anti-IL17 combination therapy biomarkers for inflammatory disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0164] Example 1 - Efficacy of Anti-TNF and Anti-IL17 Alone and Combined in a Mouse Collagen-Induced Arthritis Model

[0165] In this example, the efficacy of anti-TNF or anti-IL17 or a combination thereof was evaluated in a collagen-induced arthritis model in mice, and the results are shown in image 3middle. Male DBA / 1J mice were injected i.d. at the base of the tail with 100 μl of an emulsion containing 100 μg type II bovine collagen dissolved in 0.1 N acetic acid and 100 μl of complete Freund's adjuvant containing 100 μg Mycobacterium Tuberculois H37Ra. Mice were boosted i.p. with 1.0 mg zymosanA in 200 μL phosphate buffered saline (PBS) 21 days later. Disease onset occurred within 3 days of the boost. Mice were monitored for arthritis daily for the first week and three times weekly thereafter. Each paw was scored by the following criteria: 0=normal; 1=swelling at one site (foot or ankle); 2=swollen foot and ankle; 3=stiffness of the joint. Scores were summed for all f...

Embodiment 2

[0166] Example 2: Comparison of bone protection of anti-TNF and anti-IL17 alone and in combination in a mouse collagen-induced arthritis model

[0167] In this example, the higher efficacy of combined blockade of TNF and IL17 to prevent bone loss was demonstrated and shown in Figure 4 middle. Arthritis was induced in DBS / 1J mice as described in Example 1. At the end of the study, three weeks after the onset of arthritic signs, the level of bone loss was assessed. The protective efficacy against bone loss is measured in animals that have received the therapeutic treatment regimen. Hind paws were removed in the middle of the tibia / fibula and stored in 10% neutral buffered formalin. The paw was imaged using a Scanco μCT40 (ScancoMedical AG) at 55 kVp and 145 μA using high-resolution settings (1000 projections / 180° at 2048 × 2048 pixel reconstruction) and Isotropic Voxels with an integration time of 180 μs to obtain a 18 μm × 18 μm × 18 μm Final isotropic voxel size. A cylin...

Embodiment 3

[0168] Example 3: Interaction of TNF and IL-17 in CIA and RA

[0169] In this example, gene expression profiling was used as a tool to study biomarkers reflecting the synergy of anti-TNF and anti-IL17 treatments. In this case, the 8C11 antibody was used as the anti-TNF treatment, and the rat anti-mouse anti-IL17 antibody MAB421 was used as the anti-IL17 treatment unless otherwise indicated. Using methods known in the art, characterize responses to disease-associated RNAs and identify cohorts that are sensitive to combined anti-TNF and anti-IL17 therapy but significantly less sensitive to anti-TNF or anti-IL17 monotherapy. CXCL1 and CXCL5 were identified as biomarkers because they are stable over time in readily available biological fluids that require minimal preparation or manipulation in the clinical setting. Using the collagen-induced arthritis (CIA) model in mice, measurements of CXCL1 and CXCL5 biomarkers in whole paw homogenates indicated that changes in RNA levels are ...

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Abstract

The invention provides methods for predicting the efficacy of anti-TNF and anti-IL17 combination therapies in the treatment of a subject suffering from inflammatory disease by determining the level CXCL1 and / or CXCL5 markers in a sample derived from the subject.

Description

[0001] related application [0002] This application claims priority to US Provisional Application No. 61 / 754,917, filed January 21, 2013. The entire content of the aforementioned application is expressly incorporated herein by reference. Background technique [0003] Anti-cytokine therapy has become the standard of care for treating the symptoms and arresting the progression of inflammatory diseases. However, despite a variety of treatment options, many patients still do not achieve a substantial reduction in disease activity. In principle, increasing the level of immunosuppression by combining agents seems a plausible strategy for obtaining improved efficacy. But attempts to combine anticytokine therapy for this purpose have been plagued by unacceptable safety and tolerability issues (Genovese et al., Arthritis & Rheumatism, 50(5):1412-1419, 2004). Nevertheless, it remains a problem to find the right combination therapy for the treatment of inflammatory diseases that can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N33/50
CPCA61P19/02A61P29/00A61P37/00G01N33/6863G01N2333/522G01N2333/525G01N2333/54G01N2800/52A61K39/3955C12Q1/6883
Inventor J·W·沃斯C·A·卡夫
Owner ABBVIE INC
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