Abstract: The present invention relates to a patient-specific tumor treatment targeting individual expression patterns of tumor antigens, in particular shared tumor antigens, and individual tumor mutations. In one aspect, the present invention relates to a method for preventing or treating cancer in a patient comprising the steps of: (i) inducing a first immune response against one or more tumor antigens in the patient, and (ii) inducing a second immune response against one or more tumor antigens in the patient wherein the second immune response is specific for cancer specific somatic mutations present in cancer cells of the patient.

Abstract: The present invention relates to stabilization of RNA, in particular mRNA, and an increase in mRNA translation. The present invention particularly relates to a modification of RNA, in particular in vitro-transcribed RNA, resulting in increased transcript stability and/or translation efficiency. According to the invention, it was demonstrated that certain sequences in the 3?-untranslated region (UTR) of an RNA molecule improve stability and translation efficiency.

Abstract: The present invention relates to methods and compositions for stimulating an immune response. In particular, the present invention relates to immunostimulatory RNA molecules comprising sequences derived from an Influenza A virus nucleoprotein-encoding RNA molecule that act as adjuvants and/or immunostimulatory agents to enhance host immune responses.

Abstract: The present invention relates to novel binding agents and their use in medicine. In particular, the invention relates to binding agents such as bispecific antibodies binding human PD-L1 and binding human CD137. The invention furthermore relates to uses of the antibodies of the invention and to methods, nucleic acid constructs and host cells for producing antibodies of the invention.

Abstract: Multispecific antibodies binding to human CD40 and human CD137, methods for preparing such multispecific antibodies, and methods of using such multispecific antibodies for therapeutic or other purposes.

Abstract: The present disclosure relates to methods for preparing RNA lipoplex particles for delivery of RNA to target tissues after parenteral administration, in particular after intravenous administration, and compositions comprising such RNA lipoplex particles. The present disclosure also relates to methods which allow preparing RNA lipoplex particles in an industrial GMP-compliant manner. Furthermore, the present disclosure relates to methods and compositions for storing RNA lipoplex particles without substantial loss of the product quality and, in particular, without substantial loss of RNA activity.

Abstract: The present invention relates to compositions comprising polyplex formulations for delivery of RNA to a target organ or a target cell after parenteral administration, in particular after intramuscular administration. More precisely, the present invention relates to formulations for administration of RNA such as self-replicating RNA, in particular by intramuscular injection. In more detail, the formulations comprise polyplex particles from single stranded RNA and a polyalkyleneimine. The RNA may encode a protein of interest, such as a pharmaceutically active protein. Furthermore, the present invention relates to pharmaceutical products, comprising said RNA polyplex formulations for parenteral application to humans or to animals. The present invention relates as well to manufacturing of such pharmaceutical products, comprising, optionally, steps of sterile filtration, freezing and dehydration.

Abstract: The present invention relates to fusion molecules of antigens, the nucleic acids coding therefor and the use of such fusion molecules and nucleic acids. In particular, said invention relates to fusion molecules, comprising an antigen and the trans-membrane region and cytoplasmic region of a MHC molecule and/or the cytoplasmic region of a MHC or a SNARE molecule.

Abstract: The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.

Abstract: The present invention relates to methods for predicting T cell epitopes. In particular, the present invention relates to methods for predicting whether modifications in peptides or polypeptides such as tumor-associated neoantigens are immunogenic or not. The methods of the invention are useful, in particular, for the provision of vaccines which are specific for a patient's tumor and, thus, in the context of personalized cancer vaccines.

Abstract: The present disclosure provides methods, uses, and kits for treating cancer in an individual. The methods comprise administering to the individual a PD-1 axis binding antagonist (such as an anti-PD-1 or anti-PD-L1 antibody) and an RNA vaccine (e.g., a personalized cancer vaccine that comprises one or more polynucleotides encoding one or more neoepitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from the individual). Further provided herein are RNA molecules (e.g., a personalized RNA cancer vaccine that comprises one or more polynucleotides encoding one or more neoepitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from the individual), as well as DNA molecules and methods useful for production or use of RNA vaccines.

Abstract: Multispecific antibodies binding to human CD40 and human CD137, methods for preparing such multispecific antibodies, and methods of using such multispecific antibodies for therapeutic or other purposes.

Abstract: Multispecific antibodies binding to human CD40 and human CD137, methods for preparing such multispecific antibodies, and methods of using such multispecific antibodies for therapeutic or other purposes.

Abstract: The present invention provides molecules that mimic antigenic determinants of the CD3 (cluster of differentiation 3) T-cell co-receptor epsilon chain (CD3?). These molecules compete with CD3? for binding to a CD3? binding domain. e.g. a CD3? binding domain of an antibody, and are capable of detecting antibodies against CD3?. The mimotopes of the invention may be used to generate or inhibit immune responses in animals and preferably humans. Additionally, they may serve as tools for anti-CD3? antibody purification and the detection of anti-CD3? antibodies in biological samples.

Abstract: The present invention relates to novel binding agents and their use in medicine. In particular, the invention relates to binding agents such as bispecific antibodies binding human PD-L1 and binding human CD137. The invention furthermore relates to uses of the antibodies of the invention and to methods, nucleic acid constructs and host cells for producing antibodies of the invention.

Abstract: 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.

Abstract: The present invention provides molecules that mimic antigenic determinants of the integral transmembrane protein claudin 18.2 (CLDN18.2). These molecules compete with CLDN18.2 for binding to a CLDN18.2 binding domain, e.g. a CLDN18.2 binding domain of an antibody, and are capable of detecting antibodies against CLDN18.2. The mimotopes of the invention may be used to generate or inhibit immune responses in animals and preferably humans. Furthermore, they can be used for purposes of detecting agents comprising a CLDN18.2 binding domain in biological samples as well as for purifying agents comprising a CLDN18.2 binding domain.

Abstract: The present invention relates to particles comprising protamine, RNA and at least one endosome destabilizing agent, to methods of their production and to pharmaceutical compositions or kits containing the particles. It further relates to particles comprising protamine and RNA for use in methods of treatment or prevention of diseases and to kits comprising such particles together with at least one endosome destabilizing agent.

Abstract: 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.