Hoffmann-la Roche Inc.

Roche Innovation Center Copenhagen A/s

F. Hoffmann-la Roche Ag

Marcel Gubler

Annie Moisan

Sabine Sewing

Adrian B Roth

Matthias Heinrich Nettekoven

Bernd Kuhn

Werner Neidhart

Luca Claudio Gobbi

Wolfgang Haap

Paul Hebeisen

Henrik Frydenlund Hansen

Eric Argirios Kitas

Hans Peter Wessel

Troels Koch

Peter Hagedorn

Jacob Ravn

Christoph Rosenbohm

Nanna Albaek

Rudolf E Minder

Brigitte Schott

Adrian Roth

The invention relates to methods for predicting the in vivo nephrotoxicity of a nucleic acid molecule, in particular a nucleic acid molecule such as a siRNA or an antisense oligonucleotide using an in vitro cell based assay measuring the levels of EGFR as toxicity biomarker, potentially in combination with other biomarkers like ATP and KIM-1.

In vitro nephrotoxicity screening assay

The invention relates to methods for predicting the in vivo nephrotoxicity of a drug substance, in particular a nucleic acid molecule such as a siRNA or an antisense oligonucleotide using an in vitro cell based assay measuring the levels of extracellular EGF as toxicity biomarker, potentially in combination with other biomarkers like ATP and KIM-1.

The invention relates to a method of identifying stereodefined phosphorothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

Chiral library screen

Compounds of formula as well as pharmaceutically acceptable salts and esters thereof, wherein Rto Rhave the significance given in the application and which can be used in the form of pharmaceutical compositions.

FBPase inhibitors for diabetes

This invention relates to compounds of the formula wherein B, X, Y, Z, Rand Rare as defined in the description, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by ACC&#x3b2; inhibitors.

Benzodioxepine derivatives

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Arlesheim, Switzerland

Marcel Gubler