Hoffmann-la Roche Inc.

Roche Innovation Center Copenhagen A/s

F. Hoffmann-la Roche Ag

Sabine Sewing

Annie Moisan

Marcel Gubler

Adrian B Roth

Henrik Frydenlund Hansen

Troels Koch

Marius Hoener

Lykke Pedersen

Christoph Rosenbohm

Jacob Ravn

Peter Hagedorn

Søren Ottosen

Erik Daa Funder

Susanne Raab

Nanna Albaek

Susanne Kammler

Souphalone Luangsay

Celine Risterucci

Brian Leonard

Daniel Turley

Johanna Marie Walther

Franziska Boess

Natascha Hruschka

Erich Koller

Cristina Bertinetti-Lapatki

Susanne Mohr

Tobias Nilsson

Søren V Rasmussen

Steffen Schmidt

Adrian Roth

The present disclosure provides antisense oligonucleotides targeting Regulator of telomere elongation helicase 1 (RTEL1). The disclosure also provides, enhanced antisense oligonucleotides targeting RTEL1 for use in treating and/or preventing a hepatitis B virus (HBV) infection. Also disclosed are pharmaceutical compositions and their use.

Enhanced oligonucleotides for inhibiting RTEL1 expression

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.

In vitro nephrotoxicity screening assay

The invention relates to methods for predicting the in vivo toxicity of oligonucleotides, such as antisense oligonucleotides using in vitro cell based assays based on gymnotically administering oligonucleotides to primary mammalian hepatocytes and subsequently measuring the levels of toxicity biomarkers such as the release of LDH into the cell culture media and/or intracellular ATP.

In vitro toxicity screening assay

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

The present invention relates to a pharmaceutical combination for the treatment of schizophrenia and acute manic episodes associated with bipolar disorders, which comprises a compound which is active on a trace amine-associated receptor 1 (TAAR1 agonist) and an antipsychotic drug. This combination can reduce metabolic side effects which appear if using an antipsychotic drug alone.

Pharmaceutical combination

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Basel, Switzerland

Sabine Sewing