Medimmune Limited

Amgen Inc.

Abbott Laboratories Corporation

Katie Streicher

Koustubh Ranade

Meina Liang

Yen-Wah Lee

Robert W Georgantas, Iii

Lydia Greenlees

Partha S Chowdhury

Jing Li

Reena Varkey

Brandon Higgs

Raffaella Faggioni

Yihong Yao

Ethan Grant

William Rees

Chris Morehouse

Jingjing Chen

Robert A Gasser, Jr

Inna Vainshtein

Melissa Parker

Susan E Brophy

Michael A Bowen

Bruce J Dille

Gerard Davis

Nicolette Jeanblanc

Jonathan Jacobs

Robert W Georgantas

Michael Bowen

Robert W Georgantas Iii

The present invention relates to the use of the Chemokine (C&#x2014;C motif) ligand 20 (CCL20) as a biomarker to stratify or identify populations of patients suffering from interleukin-23 (IL23)-mediated diseases (e.g., Crohn's disease) responsive to treatment with an, anti-IL23 antagonist (including, e.g., anti-IL23 antibodies). Levels of CCL20 above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent, (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent. CCL20 can be used in combination with other IL23 pathway biomarkers such as IL22 and/or lipocalin-2 (LCN2).

CCL20 as a predictor of clinical response to IL23-antagonists

The present invention relates to the use of components of the IL23 pathway as biomarkers, e.g., IL22, LCN2 and combinations thereof, to stratify or identify populations of patients suffering from IL23-mediated diseases (e.g., Crohn's disease) responsive to treatment with an anti-IL23 antagonist (including, e.g., anti-IL23 antibodies or antigen-binding fragments thereof). Levels of IL23 pathway biomarkers above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent (e.g., an ant-IL23 antibody), (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent.

Prediction of clinical response to IL23-antagonists using IL23 pathway biomarkers

This disclosure provides a robust, sensitive, and specific assay for the detection and measurement of periostin levels in samples obtained from human patients having, or suspected of having an IL-13-mediated disease or disorder. The disclosure further provides novel antiperiostin monoclonal antibodies that recognize at least isoforms 1, 2, 3, 4, 7, and 8 of human periostin, and assay kits comprising one or more of these antibodies.

Methods of using antibodies to determine periostin levels in a sample

Disclosed herein is a method for producing a recombinant polypeptide in a mammalian cell culture in which the mammalian cells have a modified microRNA activity level. In one embodiment, a microRNA activity level is increased. In another embodiment, a microRNA activity level is decreased. In a more particular embodiment, the mammalian cells have a reduced miRNA-let-7a activity level.

Recombinant polypeptide production

Monoclonal antibodies which bind human periostin

Growing community of inventors

Gaithersburg, MD, United States of America

Katie Streicher