Biontech Se

Ganymed Pharmaceuticals Ag

Biontech Ag

Johannes Gutenberg-Universität Mainz

Tron—translationale Onkologie An Der Universitátsmedizin Der Johannes Gutenberg—universitÄt Mainz Gemeinnützige Gmbh

Astellas Pharma Gmbh

Tron—translationale Onkologie An Der Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Ggmbh

Biontech Rna Pharmaceuticals Gmbh

Tron-translationale Onkologie an Der Universitatsmedizin Der Johannes Gutenberg-universitat Mainz

Genmab A+s

Universitãt Stuttgart

Other

Sanofi

Ludwig Institute for Cancer Research Limited

Uniwersytet Warszawski

Ugur Sahin

Paul Parren

Lloyd J Old

Ozlem Tureci

Michael Koslowski

Özlem Türeci

Sebastian Kreiter

Dirk Usener

Korden Walter

Mustafa Diken

Friederike Gieseke

Rita Mitnacht-Kraus

Stefan Woll

Maria Kreuzberg

Gerd Helftenbein

Isil Altintas

Tim Beissert

Petra Simon

Stefan Jacobs

Harald-Gerhard Geppert

Alexander Muik

Heinrich Haas

Gunda Brandenburg

Bernd Hubner

Rik Rademaker

Fabrice Le Gall

Roland Kontermann

Janine Schuurman

Edward Norbert Van Den Brink

Stefan Stevanovic

Yao-tseng Chen

David Satijn

Volker Schlüter

Tana Omokoko

Stefan Fritz

Andreas Kuhn

Michael Erdeljan

Christiane Regina Stadler

Kerstin Walzer

Christoph Uherek

Phillippe Thiel

Markus Fiedler

Anja Kristina Schröder

Christian Bender

Marco Alexander Poleganov

Kirsten Vormbrock

Thorsten Klamp

Claudia Paret

Martin Löwer

Philippe Thiel

Yves Hüsemann

Annette Vogel

Kerstin Reuter

Jens Schumacher

Karolina Anna Mroz

Hans-Ulrich Schmoldt

Hossam Hefesha

Michael Weichel

Stefanie Hubich

Magdalena Jadwiga Utsch

Cornelia Adriana Maria Heinz

Holger Hoff

Christoph Hartmann

Sandra Schneider

Matin Daneschdar

Stefan Wöll

Kathleen Hobohm

Jan Diekmann

Cornelia Heinz

Klaus Pfizenmaier

Katalin Kariko

Britta Vallazza

Kena Anne Swanson

Thomas Michael Hiller

Mario Perkovic

John Christopher Castle

Thorsten Litzenberger

Sylvia Luxen

Sebastian Boegel

Silke Holtkamp

Aran Frank Labrijn

Ralf-Holger Voss

Sebastian Hörner

Karsten Schnatbaum

Esther Cornelia Wilhelmina Breij

Michael Pfreundschuh

Ali O Gure

Joost J Neijssen

Ulf Reimer

Dennis Verzijl

Esther C W Breij

Meike Hutt

Martin Siegemund

Oliver Seifert

Kristel Kemper

David P E Satijn

Jacek Jemielity

Joanna Kowalska

Matthias Grimmler

The present invention relates to RNA therapy and, in particular, decreasing immunogenicity of RNA. Specifically, the present invention provides methods for decreasing immunogenicity of RNA, said methods comprising modifying the nucleotide sequence of the RNA by reducing the uridine (U) content, wherein said reduction of the U content comprises an elimination of U nucleosides from the nucleotide sequence of the RNA and/or a substitution of U nucleosides by nucleosides other than U in the nucleotide sequence of the RNA. Using RNA having decreased immunogenicity allows administration of RNA as a drug to a subject, e.g. in order to obtain expression of a pharmaceutically active peptide or protein, without eliciting an immune response which would interfere with therapeutic effectiveness of the RNA or induce adverse effects in the subject.

Method for reducing immunogenicity of RNA

The present invention relates to binding agents binding to receptors of the TNF superfamily, in particular binding agents binding to at least two different receptors of the TNF superfamily, as well as to their use in medicine. The present invention further relates to nucleic acid molecules encoding such binding agents, to cells comprising such nucleic acid molecules and to pharmaceutical compositions and kits.

Binding agents that bind OX40 (CD134) and method of use thereof to treat disease

The present invention relates to antibodies capable of binding to human OX40 and to variants thereof comprising a modified Fc region comprising at least one mutation that enhances the Fc-Fc interaction of the antibody and at least one mutation that reduces the Fc effector functions of the antibody. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.

Antibodies capable of binding to OX40, variants thereof and uses thereof

The present invention relates to the treatment of cancer, in particular breast cancer, particularly triple-negative breast cancer. More particularly, the invention concerns methods for cancer treatment involving a specific set of tumor antigens.

Tumor antigens for determining cancer therapy

The present invention provides a binding agent that binds to EpCAM and to CD137 which is useful to treat or prevent a tumor or cancer, or to prevent progression of a tumor or cancer.

Binding agents binding to EpCAM and CD137

It was the object of the present invention to provide RNA with increased stability and translation efficiency and means for obtaining such RNA. It should be possible to obtain increased grades of expression by using said RNA in gene therapy approaches.

Modification of RNA, producing an increased transcript stability and translation efficiency

Methods for effecting the de-differentiation of somatic cells to cells having stem cell characteristics, in particular pluripotency, include the steps of introducing RNA encoding factors inducing the de-differentiation of somatic cells into the somatic cells and culturing the somatic cells allowing the cells to de-differentiate.

Use of RNA for reprogramming somatic cells

The present invention relates to systems and methods suitable for high-level protein production. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA replicon that can be replicated by the replicase in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associated with undesired virus-particle formation. The present invention is suitable for efficiently and safely producing a protein of interest in a target organism. Respective methods of protein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention.

Trans-replicating RNA

The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin and comprises an open reading frame encoding a reprogramming factor. Such RNA replicons are useful for expressing a reprogramming factor in a cell, in particular a somatic cell. Cells engineered to express such reprogramming factors are useful in cell transplantation therapies.

RNA replicon for reprogramming somatic cells

The present invention relates to 5'-cap compounds, in particular the stabilization of RNA by such 5′-cap compounds, and provides compositions, such as pharmaceutical compositions, and cells comprising an RNA which is modified with such a 5′-cap compound, as well as methods for producing a peptide or protein of interest using the compositions or cells according to the present invention. Furthermore, the present invention provides the RNA, compositions, or cells for use in therapy, in particular for use in a method of treating a disease or disorder by protein replacement therapy, genome engineering, genetic reprogramming, and immunotherapy; a method for increasing the stability of RNA in cells; a method for increasing the expression of RNA in cells; and a method for providing an RNA with a 5′-cap structure.

5'-cap-trinucleotide- or higher oligonucleotide compounds and their use in stabilizing RNA, expressing proteins in therapy

The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin. The RNA replicon comprises sequence elements required for replication by the replicase, but these sequence elements do not encode any protein or fragment thereof, such as an alphavirus non-structural protein or fragment thereof. Thus, in the RNA replicon according to the invention, sequence elements required for replication by the replicase and protein-coding region(s) are uncoupled. According to the present invention the uncoupling is achieved by the removal of at least one initiation codon compared to a native alphavirus genomic RNA. In particular, the RNA replicon comprises a 5' replication recognition sequence, wherein the 5′ replication recognition sequence is characterized in that it comprises the removal of at least one initiation codon compared to a native alphavirus 5′ replication recognition sequence. The replicase of alphavirus origin may be encoded by an open reading frame on the RNA replicon or on a separate RNA molecule. The present invention enables efficient and safe expression of a protein of interest in a cell or organism, but is not associated with undesired production of fragments of alphavirus non-structural protein. Methods of protein production in vitro and in vivo, as well as medical uses, are provided herein.

RNA replicon for versatile and efficient gene expression

The present invention relates to methods for predicting whether peptides or polypeptides comprising disease specific amino acid modifications, in particular tumor-associated neo-antigens, comprise epitopes, in particular tumor-associated neo-epitopes, which are useful for immunotherapy such as for vaccination. The methods of the invention may be used, in particular, for the provision of vaccines which are specific for a patient's tumor and, thus, in the context of personalized cancer vaccines.

Methods for predicting the usefulness of disease specific amino acid modifications for immunotherapy

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

Coronavirus vaccine

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-COV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-COV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to a method for stimulating, priming and/or expanding in vivo T cells genetically modified to express a chimeric antigen receptor (CAR) targeted to an antigen, comprising contacting the T cells with the antigen or a variant thereof in vivo. In one embodiment, the antigen or variant thereof is provided by administering a nucleic acid encoding the antigen or variant thereof.

Enhancing the effect of CAR-engineered T cells by means of nucleic acid vaccination

Growing community of inventors

Mainz, Germany

Ugur Sahin