Abstract: The present invention relates to a buffer system comprising a dicarboxylic acid or tricarboxylic acid or a salt thereof for synthesizing RNA molecules as well as a method of RNA in vitro transcription using this buffer system. The present invention also provides the use of this buffer system in RNA in vitro transcription and in the reduction or prevention of precipitates during RNA in vitro transcription.

Abstract: The present invention relates to the field of RNA analysis. In particular, the invention concerns the use of one or more nucleic acid molecules for the analysis of an RNA molecule. In particular, the method is suitable for use in quality control during or following production of RNA. Furthermore, the present invention provides methods for analyzing a mixture of RNA molecules or an RNA population.

Abstract: The present invention is concerned with linear double stranded DNA, which is coupled to a single support or a tag at the 3? end of its non-coding strand and methods for producing said linear double stranded DNA. The present invention further relates to the use of said linear double stranded DNA in an RNA in vitro transcription reaction and also to a method for producing RNA in vitro. The present invention also relates to a bioreactor for RNA in vitro transcription.

Abstract: The present invention is concerned with methods for analyzing RNA molecules. The provided methods involve conjugates for RNA cleavage comprising a chemical moiety with RNA cleaving activity and an oligonucleotide. The oligonucleotide is designed based on a target sequence present in an RNA molecule, and the cleavage of the RNA molecule is inter alia carried out at conditions allowing the hybridization of the oligonucleotide to the target 5 sequence. Thereby, the method is easily applicable to RNA molecules of any sequence. The method further involves the analysis of the RNA fragments obtained after cleavage to obtain information on the physical properties of the RNA molecule.

Abstract: The present invention is inter alia directed to syringes suitable for compositions comprising RNA, preferably RNA formulated in lipid-based carriers. In particular, kit or kit of parts comprising said suitable syringes are provided. The invention also relates to pre-filled syringes containing pharmaceutical compositions comprising RNA, preferably RNA formulated in lipid-based carriers. Also provided are methods of treating or preventing disorders or diseases, and first and second medical uses. Further the invention is directed to different analytic methods for determining the suitability of syringes for compositions comprising RNA and for detecting RNA agglomerations. Moreover, uses of suitable syringes e.g. for reducing or preventing RNA agglomeration, are described.

Abstract: The present invention relates to a bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing. Further, the use of a bioreactor for RNA in vitro transcription as described herein is part of the present invention. The present invention relates to an RNA in vitro transcription reactor designed to be operable in an automated manner under GMP-compliant conditions. In particular, said RNA in vitro transcription reactor allows repetitive use of DNA template for various RNA in vitro transcription reactions. Further, the invention relates to an apparatus for RNA manufacturing comprising (a) a module for template DNA synthesis, (b) a module for transcribing DNA into RNA comprising said RNA in vitro transcription reactor, and, optionally, (c) a module for RNA formulation.

Abstract: The present invention relates to a method for quality control analysis of an RNA sample comprising n different RNA molecule species using reverse transcription and a polymerase chain reaction (PCR) based assay, dPCR, preferably ddPCR, thereby determining at least one quality parameter. Moreover, the RNA molecules in the RNA sample may be in complexed form. In particular, the method is suitable for use in quality control during or following production of RNA samples for pharmaceutical use.

Abstract: The present invention relates to a device for preparing a DNA product by means of Capillary Polymerase Chain Reaction (PCR); a manufacturing device for a pharmaceutical product; a manufacturing module for a pharmaceutical product; a method for preparing a DNA product by means of Capillary Polymerase Chain Reaction; the use of the device for preparing a DNA product by means of Polymerase Chain Reaction; and the use of the device for a production of a pharmaceutical product. The device for preparing a DNA product by means of Capillary Polymerase Chain Reaction comprises a tube for guiding a PCR liquid, a first compartment, and at least second compartment. The tube is wound at least from the first compartment to the second compartment and from the second compartment to the first compartment, wherein the tube wound from compartment to compartment forms a helical stack of tube windings.

Abstract: The present invention is concerned with linear double stranded DNA, which is coupled to a single support or a tag at the 3? end of its non-coding strand and methods for producing said linear double stranded DNA. The present invention further relates to the use of said linear double stranded DNA in an RNA in vitro transcription reaction and also to a method for producing RNA in vitro. The present invention also relates to a bioreactor for RNA in vitro transcription.

Abstract: The present invention relates to a bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing. Further, the use of a bioreactor for RNA in vitro transcription as described herein is part of the present invention. The present invention relates to an RNA in vitro transcription reactor designed to be operable in an automated manner under GMP-compliant conditions. In particular, said RNA in vitro transcription reactor allows repetitive use of DNA template for various RNA in vitro transcription reactions. Further, the invention relates to an apparatus for RNA manufacturing comprising (a) a module for template DNA synthesis, (b) a module for transcribing DNA into RNA comprising said RNA in vitro transcription reactor, and, optionally, (c) a module for RNA formulation.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-freeze drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry 10 powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The present invention relates to a method for quality control analysis of an RNA sample comprising n different RNA molecule species using reverse transcription and a polymerase chain reaction (PCR) based assay, dPCR, preferably ddPCR, thereby determining at least one quality parameter. Moreover, the RNA molecules in the RNA sample may be in complexed form. In particular, the method is suitable for use in quality control during or following production of RNA samples for pharmaceutical use.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-freeze drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The invention is inter alia directed to a pharmaceutical composition or vaccine for multidose administration comprising lipid-based carriers encapsulating an RNA, wherein the composition comprises at least one antimicrobial preservative selected from an aromatic alcohol, a sugar alcohol, thiomersal, or a combination thereof. The present invention is also directed to a kit or kit of parts for preparing and/or administering the pharmaceutical composition or vaccine for multidose administration. Also provided are methods of treating or preventing a disorders or a diseases, and first and second medical uses of the pharmaceutical composition or vaccine. Further provided is the use of aromatic alcohols, sugar alcohols, and/or thiomersal for preserving and/or preparing a composition or vaccine comprising lipid-based carriers encapsulating an RNA.

Abstract: The present invention relates to a manufacturing device for a pharmaceutical product, a manufacturing module for a pharmaceutical product, a manufacturing system for a pharmaceutical product, a method for producing a pharmaceutical product, a method for producing a DNA template, a method for producing an RNA, a method for producing a formulated RNA and uses of the manufacturing device, module or system. The manufacturing device for a pharmaceutical product comprises a housing, a process chamber, a technical chamber, a separation element, and a control unit. The housing is closed relative to the environment outside the housing. The housing encompasses the process chamber and the technical chamber. The process chamber is separated from the technical chamber by the separation element. The control unit is configured to control a gas flow through the process chamber. The control unit is configured to control the gas flow to provide in the process chamber a positive pressure relative to the environment.

Abstract: The present invention relates to a method for synthesizing an RNA molecule of a given sequence, comprising the step of determining the fraction (1) for each of the four nucleotides G, A, C and U in said RNA molecule, and the step of synthesizing said RNA molecule by in vitro transcription in a sequence-optimized reaction mix, wherein said sequence-optimized reaction mix comprises the four ribonucleoside triphosphates GTP, ATP, CTP and UTP, wherein the fraction (2) of each of the four ribonucleoside triphosphates in the sequence-optimized reaction mix corresponds to the fraction (1) of the respective nucleotide in said RNA molecule, a buffer, a DNA template, and an RNA polymerase.

Abstract: The present invention is directed to a method for modifying the retention time of RNA on a chromatographic column. The present invention also concerns a method for purifying RNA from a mixture of at least two RNA species. Furthermore, the present invention relates to a method for co-purifying at least two RNA species from a mixture of at least two RNA species. In particular, the present invention provides a method for harmonizing the numbers of A and/or U nucleotides in at least two RNA species. The present invention is also directed to RNA obtainable by said methods, a composition comprising said RNA or a vaccine comprising said RNA and methods for producing such RNA and compositions. Further, the invention concerns a kit, particularly a kit of parts, comprising the RNA, composition or vaccine. The invention is further directed to a method of treating or preventing a disorder or a disease, first and second medical uses of the RNA, composition and vaccine.