Method of treating tendinopathy by using interleukin-17 (il-17) antagonist

A tendon, post-treatment technique for the treatment of tendinopathy with interleukin-17 (IL-17) antagonists that addresses weak evidence of long-term efficacy, no efficacy, and controversial benefits

Pending Publication Date: 2020-06-26
NOVARTIS AG +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Autologous platelet-rich plasma (PRP) injections are currently used, however evidence for their long-term efficacy is weak, so the benefit of PRP for tendinopathy remains controversial, with several trials showing no efficacy compared to saline (Krogh TP et al. 2013) Am J Sports Med 41:625-35; de Vos RJ et al (2010) JAMA; 303:144-9)

Method used

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  • Method of treating tendinopathy by using interleukin-17 (il-17) antagonist
  • Method of treating tendinopathy by using interleukin-17 (il-17) antagonist
  • Method of treating tendinopathy by using interleukin-17 (il-17) antagonist

Examples

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example 1

[0212] Example 1 - In tendinopathy, IgG 1 Tissue exposure and effects of anti-IL-17 monoclonal antibodies

[0213] In an in vivo rat disease model, tendinopathy of the rotator cuff tendon was induced by unilateral surgical partial tenotomy of the supraspinatus tendon along the coronal plane. IgG administered subcutaneously or intravenously one week before or one day before surgical induction of tendinopathy 1 Anti-IL-17 monoclonal antibody (CJM112) (15 mg / kg) or vehicle, followed by weekly subcutaneous or intravenous administration for three weeks. Four weeks after the surgical induction of tendinopathy and one week after the last dose of antibody, antibody exposure in rotator cuff tendon tissue, and its pharmacological effects on tendinopathy inflammation and on gait imbalance were assessed. Following tissue homogenization and protein extraction, terminal trough exposure levels of antibodies in rotator cuff tendon tissue, skeletal muscle, and skin were assessed by enzyme-li...

example 2-I

[0217] Ex vivo and in vitro examples of tendon bundle inflammation induced by example 2-IL17

[0218] In an isolated rat tail tendon fascicle model, a model of nonload-induced tendon degeneration, RNASeq analysis revealed hallmarks of intrinsic tendon fascicle inflammation. Unloaded tracts showed >10-fold upregulation of multiple cytokines, chemokines and MMPs including IL6, CXCL1, CCL2, CCL20, CSF1-3, MMP2, 3 and 9. IL-17RA and IL-17RC were found to be highly expressed in tendon bundles, indicating that this tissue is sensitive to IL-17. Computational analysis of signaling pathways from in-house databases identified five pathway hits specific for IL-17 or TH17 cell-specific signatures. Addition of recombinant IL-17A (1.67 nM) to unloaded tendon bundles induced a further increase in the expression of cytokines, chemokines and MMPs (IL-6, CXCL-1, PTGS-2, MMP-3). Simultaneously, and in accordance with tendon degeneration, the tendon marker genes scleraxis and tenomodulin were ...

example 3- 1

[0220]Example 3 - a randomized, double-blind, placebo-controlled, parallel group, phase II, 24-week study investigating patients who were treated with oral NSAID / acetaminophen, physical therapy, or corticosteroid injections Efficacy, safety and tolerability of AIN457 in patients with refractory active overuse tendinopathy

[0221] "Enthesitis" is the term used to describe inflammation of the attachment points of tendons, ligaments, or joint capsules. It is indicated for diseases associated with spondyloarthritis (SpA) including AS and PsA. Enthesitis can be inflammatory or mechanically induced; both can share common features (McGonagle D and Benjamin M (2009) Reports on Rheumatic Diseases Series 6.4:1-6).

[0222] As seen in studies with secukinumab, neutralization of IL-17 has been demonstrated to have efficacy in inflammatory enthesitis of PsA and AS. In study CAIN457F2312, enthesitis was assessed in a subgroup of patients with disease activity at baseline. In this patien...

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Abstract

The present disclosure relates to methods for treating tendinopathy, e.g., rotator cuff tendinopathy, by using IL-17 antagonists, e.g., secukinumab. Also disclosed herein are uses of IL-17 antagonists, e.g., IL-17 antibodies, such as secukinumab, for treating tendinopathy patients, as well as medicaments, dosing regimens, pharmaceutical formulations, dosage forms, and kits for use in the discloseduses and methods.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 580,715, filed November 2, 2017, which is hereby incorporated by reference in its entirety. technical field [0003] The present disclosure relates to the use of IL-17 antagonists (e.g. IL-17 antibodies or antigen-binding fragments thereof such as secukinumab or ixekizumab; or IL-17) in patients with tendinopathy Receptor antibodies or antigen-binding fragments thereof, such as brodalumab, for treating tendinopathy and inducing regeneration of tendon tissue, and methods for promoting tendon repair. Background technique [0004] Overuse tendinopathy is a complex multifaceted tendon disorder that is clinically diagnosed after activity-related pain onset, decreased function, and sometimes local swelling of the tendon (Riley G( 2005) Expert Rev Mol Med [Expert Review in Molecular Medicine]; 7:1-25; Riley G (2008) Nat Clin Pract Rheumatol [Natur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P19/04C07K16/24
CPCC07K16/244C07K2317/76A61P19/04A61K2039/505C07K2317/92C07K2317/94
Inventor I·麦金内斯N·米拉F·科尔宾格G·布鲁因M·希克L·明德霍尔姆E·韦伯S·卡特
Owner NOVARTIS AG
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