Biomarkers useful in the treatment of il-23a related diseases

Abstract

This invention generally relates to biomarkers useful in the treatment of IL-23 related diseases, in particular inflammatory diseases such as psoriasis. The invention also relates to methods of using the biomarkers disclosed herein, for example in therapies utilizing IL-23 antagonists.

1 - 23 . (canceled) 
     
     
         24 . A method of determining whether a potential therapeutic agent is efficacious in the treatment of psoriasis comprising:
 a) obtaining a first biological sample from a psoriasis patient prior to being treated with the potential therapeutic agent;   b) treating the psoriasis patient with the potential therapeutic agent;   c) obtaining a second biological sample from the psoriasis patient after being treated with the potential therapeutic agent;   d) measuring in said first and second sample the levels of expression of one or more biomarkers; and   e) comparing the biomarker levels in the second sample to the levels in the first sample, wherein lower biomarker levels in the second sample than in the first sample indicate that the potential therapeutic agent is efficacious, and further wherein the one or more biomarkers are genes associated with the IL-23/IL-17 axis, keratinocyte and epithelial cell differentiation, tissue inflammation and the IFNα pathway.   
     
     
         25 . The method according to  claim 24 , wherein lower biomarker levels in the second sample than in the first sample correlate with improvement in clinical efficacy measures. 
     
     
         26 . The method according to  claim 24 , further comprising continuing the treatment of the patient if biomarker levels in the second sample is lower than the levels in the first sample. 
     
     
         27 . A method of treating psoriasis in a subject comprising:
 a) determining whether to initiate treatment of the subject, modify the treatment dose, modify the dosing interval, or discontinue treatment, based on the method of any of the preceding claims; and   b) modifying the treatment regimen based on the determination.   
     
     
         28 . A method of monitoring patient response to a psoriasis treatment comprising:
 a) obtaining a first biological sample from the patient;   b) measuring the level of one or more biomarkers in said first biological sample, wherein said one or more biomarkers are genes/proteins associated with the IL-23/IL-17 axis, keratinocyte and epithelial cell differentiation, tissue inflammation and the IFNα pathway;   c) administering a treatment compound to the patient;   d) obtaining a second biological sample from the patient;   e) measuring the level of said one or more biomarkers in said second biological sample; and   f) comparing the levels of the one or more biomarkers obtained from first and second biological samples;   wherein a decreased level of the one or more biomarkers in the second biological sample indicates an effective response.   
     
     
         29 . A method for monitoring patient compliance with a drug treatment protocol for psoriasis comprising:
 a) obtaining a biological sample from said patient;   b) measuring the level of one or more biomarkers, wherein the one or more biomarkers are genes/proteins associated with the IL-23/IL-17 axis, keratinocyte and epithelial cell differentiation, tissue inflammation and the IFNα pathway; and   c) determining if the level is decreased in the patient sample compared to the level in a control untreated sample;   wherein a decreased level indicates patient compliance with said drug treatment protocol.   
     
     
         30 . The method of  claim 27 , wherein the level of the one or more biomarkers in the second biological sample is decreased by at least about 50% 55%, 60%, 65%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% or more as compared to the level in the first biological sample. 
     
     
         31 . The method of  claim 27 , wherein the biological sample is a skin biopsy, blood, plasma or serum sample. 
     
     
         32 . The method of  claim 27 , wherein the IL-23A antagonist is an anti-IL-23A antibody or an antigen binding fragment thereof. 
     
     
         33 . The method of  claim 27 , wherein the levels of biomarkers are determined by RNA sequencing or ELISA. 
     
     
         34 . An ELISA kit comprising one or more antibodies or antigen binding fragments thereof that specifically bind to one or more biomarkers selected from the the group consisting of S-100 proteins, neutrophil gelatinase lipocalin and β-defensin 2. 
     
     
         35 . The ELISA kit of  claim 34 , further comprising instructions for use of the kit in monitoring psoriasis.