Protein biomarker and uses thereof

Inventors

Schneider, Matthias • BLUM, Sabine • MENDELL-HARARY, Renee Jeanne • Freeman, Daniel J. • BECKMAN, Robert Allen • Jin, Xiaoping • YONESAKA, Kimio • Nakagawa, Kazuhiko

Assignees

Daiichi Sankyo Europe GmbH • Daiichi Sankyo Co Ltd • Kindai University • Amgen Inc

Abstract

The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at a protein level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at a protein level is assessed as low. The invention is also directed to methods of performing an ELISA, including sequential steps of contacting a solid surface with a plurality of solutions each comprising in turn a capture antibody, a blocking agent, a sample suspected of containing an analyte, a detection antibody and an enzyme conjugate, in which the solid surface is subjected to a wash process after each sequential step.

Core Innovation

A method of treating a human subject with a locally advanced or metastatic non-small cell lung cancer (NSCLC) is provided that is characterized as having a high heregulin (HRG) expression at a protein level. The method comprises obtaining a tumor sample from the human subject, determining the HRG expression at the protein level in the tumor sample, selecting the subject for treatment when the tumor sample has a high HRG expression at the protein level, and administering an anti-HER3 antibody.

The disclosed approach uses protein-level HRG expression as the basis for selecting therapy, and HRG is the only gene for which gene expression at the protein level is assessed for the purposes of selecting treatment for the subject. The disclosed selection framework is directed to using HRG protein expression to identify subjects likely to receive anti-HER3 antibody therapy in locally advanced or metastatic NSCLC.

The disclosed framework is further described as measuring HRG expression at the protein level using immunoassay and tissue-based approaches, including ELISA or immunohistochemistry, and as using an explicit high HRG expression threshold in relation to the protein level. The method can further specify subject selection based on EGFR mutation status and can include selecting and administering an anti-HER3 antibody from a named set of anti-HER3 antibody options.

Claims Coverage

The provided claim set includes one independent claim and multiple dependent refinements. The independent claim centers on HRG protein-level assessment as the sole protein-level gene measurement to select anti-HER3 antibody treatment for locally advanced or metastatic NSCLC.

Overall, the claim coverage is directed to a treatment-selection method where only protein-level HRG expression in a tumor sample is assessed to select subjects for administering an anti-HER3 antibody for locally advanced or metastatic NSCLC.

Stated Advantages

Documented Applications