Artificial RNA, Composition, Vaccine, Kit or Parts Kit and Use
Artificial RNA encoding RSV antigenic peptides, formulated with polymeric carriers or lipid nanoparticles, addresses the lack of effective RSV vaccines by inducing strong immune responses with minimal side effects, suitable for diverse demographics.
Patent Information
- Authority / Receiving Office
- BR · BR
- Patent Type
- Applications
- Current Assignee / Owner
- CUREVAC SE
- Filing Date
- 2019-04-17
- Publication Date
- 2026-07-07
AI Technical Summary
Current vaccines and treatments for Respiratory Syncytial Virus (RSV) infections are inadequate, with no licensed vaccine available and existing treatments being either ineffective or risky, and there is a need for a safe and effective vaccine that can induce strong immune responses without adverse side effects, particularly for infants, newborns, pregnant women, the elderly, and immunocompromised patients.
Development of artificial RNA comprising heterologous untranslated regions (UTRs) and coding regions for RSV-derived antigenic peptides or proteins, formulated with polymeric carriers or lipid nanoparticles, designed to enhance translation, induce specific immune responses, and be suitable for intramuscular administration.
The artificial RNA induces robust adaptive immune responses, including B-cell memory and cellular T-cell responses, with rapid onset of immunity and minimal systemic side effects, suitable for various at-risk populations.
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Description
Artificial RNA, Composition, Vaccine, Kit or Parts Kit and Use DIVIDED FROM BR 11 2020 020933 3 Introduction
[0001] The present invention is directed to artificial RNA suitable for use in the treatment or prophylaxis of a Respiratory Syncytial Virus (RSV) infection or a disorder related to such infection. In particular, the artificial RNA of the invention comprises at least one heterologous untranslated region (UTR), preferably a 3' and / or a 5' UTR, and a coding region encoding at least one RSV-derived antigenic peptide or protein, in particular, at least one RSV protein fusion (F)-derived antigenic peptide or protein. The artificial RNA is preferably characterized by increased expression efficacies of coding regions operatively linked to said UTR elements. The present invention is also directed to compositions and vaccines comprising said artificial RNA in association with a polymeric carrier, a polycationic protein or peptide, or a lipid nanoparticle (LNP).Additionally, the invention relates to a kit, particularly a kit of parts comprising the artificial RNA or composition or vaccine. The invention is further directed to a method of treating or preventing a disorder or disease, and the first and second medical uses of the artificial RNA, composition or vaccine.
[0002] Respiratory syncytial virus (RSV) is an enveloped, non-segmented, negative-strand RNA virus in the family Paramyxoviridae, genus Pneumovirus. It is the most common cause of respiratory syncytial virus (RSV). Petition 870260029351, dated 03 / 28 / 2026, p. 65 / 555 2 / 372 is common for bronchiolitis and pneumonia among children in their first year of life. RSV also causes repeated infections, including severe lower respiratory tract disease, which can occur at any age, especially among the elderly or individuals with compromised cardiac, pulmonary, or immune systems. Currently, passive immunization is used to prevent serious illnesses caused by RSV infection, especially in infants with prematurity, bronchopulmonary dysplasia, or congenital heart disease.
[0003] The recommended treatment for RSV bronchiolitis consists primarily of respiratory support and hydration. No specific antiviral therapy is recommended. The neutralizing monoclonal antibody Palivizumab is used for prophylaxis in infants at higher risk of severe infection, but it is very expensive and impractical for universal use. Currently, there is no licensed / approved RSV vaccine, and the development of a safe and effective RSV vaccine is a global public health priority.
[0004] In a vaccine trial in the 1960s, infants and young children were immunized with either a formalin-inactivated whole-virion RSV preparation (FIRSV) or an equivalent paramyxovirus preparation (FIPIV). Five percent of individuals who were immunized with FI-PIV and then naturally infected with RSV during the next RSV season were hospitalized; 80 percent of individuals who were immunized with FI-RSV and then infected with RSV were hospitalized, and two children died. This improvement from an RSV infection due to vaccination is a Petition 870260029351, dated 03 / 28 / 2026, page 66 / 555 3 / 372 specific problem for the development of vaccines against RSV infections.
[0005] Therefore, respiratory syncytial virus (RSV) infections are the largest remaining unmet infant vaccine need in developed countries and a major unmet infant vaccine need worldwide. More than 40 years of effort have yet to result in a licensed RSV vaccine for humans.
[0006] Despite the humanized monoclonal antibody Palivizumab mentioned above, live attenuated vaccine viruses have been developed that elicit a strong immune response, but are not recommended for use in specific target groups (infants, children, the elderly, and immunocompromised patients). Furthermore, DNA vectors expressing RSV F protein carrying B-cell epitopes have been used to induce the production of neutralizing antibodies. In this context, documents WO2008 / 077527 and WO96 / 040945 disclose vectors comprising DNA sequences encoding RSV F protein for use as vaccines. However, the use of DNA as a vaccine can be dangerous due to unwanted insertion into the genome, possibly leading to disruption of functional genes and cancer or the formation of anti-DNA antibodies.
[0007] Document WO2015 / 024668 discloses RNA sequences encoding antigenic RSV peptides or proteins selected from fusion protein F, glycoprotein G, short hydrophobic protein SH, matrix protein M, nucleoprotein N, large polymerase L, protein M2-1, protein M2-2, phosphoprotein Petition 870260029351, dated 03 / 28 / 2026, page 67 / 555 4 / 372 P, the non-structural protein NS1, the non-structural protein NS2, and an antigenic composition comprising RNA complexed with protamine suitable for intradermal administration.
[0008] Document WO2017 / 070622 discloses a vaccine comprising RNA encoding antigenic peptides or proteins of RSV selected from F-glycoprotein and G-glycoprotein, wherein the RNA is formulated into lipid nanoparticles.
[0009] In addition to some of the approaches mentioned above, there remains an unmet medical need for an effective vaccine for prophylaxis or treatment of RSV infections.
[0010] Consequently, the objective of the underlying invention is to provide innovative artificial RNA encoding RSV antigenic peptides or proteins and compositions / vaccines comprising said RNA for use as a vaccine for prophylaxis or treatment of RSV infections, particularly in infants, newborns, pregnant women, the elderly, and immunocompromised patients.
[0011] Additionally, it would be desirable for the RNA-based composition or vaccine to have some of the following advantageous features: Enhanced translation of RNA constructs at the injection site (e.g., muscle) - Highly efficient induction of RSV antigen-specific immune responses against the encoded antigenic peptide or protein in a very low dosage regimen. - Suitability for maternal immunization Petition 870260029351, dated 03 / 28 / 2026, page 68 / 555 5 / 372 - Suitable for vaccinating babies and / or newborns - Suitable for intramuscular administration - Induction of a functional humoral immune response specific to RSV - RSV-specific B-cell memory induction Faster onset of immune protection against RSV Longevity of immune responses induced against RSV - Induction of broad cellular T cell responses against RSV - Induction of a pro-inflammatory environment (local and transient) - No induction of systemic cytokine or chemokine response after vaccine administration. - Good tolerability, no side effects, non-toxic. No improvement in an RSV infection due to vaccination. - Advantageous stability characteristics of the vaccine - Speed, adaptability, simplicity, and scalability of RSV vaccine production.
[0012] The objectives highlighted above are resolved by the matter claimed. Definitions
[0013] For clarity and readability, the following definitions are provided. Any feature of the technique mentioned in these definitions can be read in each and every embodiment of the invention. Additional definitions and explanations may be specifically provided in the context of those embodiments.
[0014] Percentages in the context of numbers should be Petition 870260029351, dated 03 / 28 / 2026, page 69 / 555 6 / 372 understood as relative to the total number of the respective items. In other cases, and unless the context indicates otherwise, percentages should be understood as percentages by weight (% by weight).
[0015] Adaptive immune response: The term “adaptive immune response” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to an antigen-specific response of the immune system (the adaptive immune system). Antigen specificity allows the generation of responses that are adapted to specific pathogens or pathogen-infected cells. The ability to mount these adapted responses is usually maintained in the body by “memory cells” (B cells). In the context of the invention, the antigen is provided by the artificial RNA coding sequence that encodes at least one antigenic peptide or protein.
[0016] Antigen: The term “antigen” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a substance that can be recognized by the immune system, preferably the adaptive immune system, and has the capacity to trigger an antigen-specific immune response, for example, through the formation of antigen-specific antibodies and / or T cells as part of an adaptive immune response. Typically, an antigen may be or may comprise a peptide or protein that can be presented by MHC to T cells. Furthermore, fragments, variants and derivatives of peptides or proteins derived Petition 870260029351, dated 03 / 28 / 2026, page 70 / 555 7 / 372 of, for example, RSV F protein comprising at least one epitope are understood as antigens in the context of the invention. In the context of the present invention, an antigen may be the translation product of an artificial RNA provided as specified herein.
[0017] Antigenic peptide or protein: The term “antigenic peptide or protein” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a peptide, protein (or polyprotein) derived from a protein / polyprotein (antigenic) that can stimulate the body’s adaptive immune system to provide an adaptive immune response. Therefore, an “antigenic peptide or protein” comprises at least one epitope (as defined herein) or antigen (as defined herein) of the protein from which it is derived (for example, in the context of the invention, RSV peptide or protein, preferably RSV F protein or variants thereof).
[0018] Artificial nucleic acid: The term “artificial nucleic acid” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to an artificial nucleic acid that does not occur naturally. An artificial nucleic acid may be a DNA molecule, an RNA molecule, or a hybrid molecule comprising portions of both DNA and RNA. Typically, artificial nucleic acids may be designed and / or generated through genetic manipulation methods to match a desired artificial nucleotide sequence (sequence). Petition 870260029351, dated 03 / 28 / 2026, p. 71 / 555 8 / 372 heterologous). In this context, an artificial sequence is usually a sequence that may not occur naturally, that is, it differs from the wild-type sequence in at least one nucleotide. The term “wild-type” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a sequence that occurs in nature. Additionally, the term “artificial nucleic acid” is not restricted to meaning “a single molecule,” but is typically understood to comprise a set of essentially identical molecules.
[0019] Artificial RNA: The term “artificial RNA” as used in this document is intended to refer to RNA that does not occur naturally. In other words, artificial RNA can be understood as a non-natural nucleic acid molecule. Such RNA molecules may be non-natural due to their individual sequence (which does not occur naturally, for example, a coding sequence modified by G / C content, UTRs) and / or due to other modifications, for example, structural modifications of nucleotides that do not occur naturally. Typically, artificial RNA can be designed and / or generated through genetic manipulation methods to match a desired artificial nucleotide sequence (heterologous sequence). In this context, an artificial RNA sequence is usually a sequence that may not occur naturally, that is, it differs from the wild-type sequence by at least one nucleotide.The term "artificial RNA" is not limited to meaning "a single molecule," but is typically understood to encompass a set of... Petition 870260029351, dated 03 / 28 / 2026, page 72 / 555 9 / 372 essentially identical molecules. Consequently, the same may refer to a plurality of essentially identical RNA molecules contained in an aliquot or sample. In the context of the invention, the RNA of the invention is an artificial RNA as defined herein.
[0020] Cationic: Unless a different meaning is clear from the specific context, the term cationic means that the respective structure carries a positive charge, either permanently or not permanently, but in response to certain conditions, such as pH. Thus, the term cationic covers both permanently cationic and cationizable.
[0021] Capable of cationization: The term capable of cationization as used in this document means that a compound, group, or atom is positively charged at a lower pH and uncharged at a higher pH of its environment. Furthermore, in non-aqueous environments where no pH value can be determined, a compound, group, or atom capable of cationization is positively charged at a high hydrogen ion concentration and uncharged at a low hydrogen ion concentration or activity. This depends on the individual properties of the cationization or polycationization compound, in particular, the pKa of the respective cationization group or atom at which the pH or hydrogen ion concentration is charged or uncharged. In dilute aqueous environments, the fraction of cationization compounds, groups, or atoms that carry a positive charge can be estimated using the so-called Henderson-Hasselbalch equation, which is well Petition 870260029351, dated 03 / 28 / 2026, p. 73 / 555 10 / 372 known by a person skilled in the art. For example, in some embodiments, if a compound or fraction is capable of cationization, it is preferable that it be positively charged at a pH value of about 1 to 9, preferably 4 to 9, 5 to 8, or even 6 to 8, more preferably at a pH value of or below 9, or below 8, or below 7, most preferably at physiological pH values, for example, about 7.3 to 7.4, that is, under physiological conditions, particularly under physiological salt conditions of the cell in vivo. In other embodiments, it is preferable that the compound or fraction capable of cationization be predominantly neutral at physiological pH values, for example, about 7.0-7.4, but become positively charged at lower pH values. In some embodiments, the preferred pKa range for the compound or fraction capable of cationization is about 5 to about 7.
[0022] Coding sequence / coding region: The term “coding sequence” or “coding region” and the corresponding abbreviation “cds” as used herein will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a sequence of nucleotide triplets that can be translated into a peptide or protein. A coding sequence in the context of the present invention is preferably an RNA sequence consisting of several nucleotides that can be divided into three, beginning with a start codon and preferably ending with a stop codon.
[0023] Composition: In the context of the invention, a Petition 870260029351, dated 03 / 28 / 2026, page 74 / 555 11 / 372 composition refers to any type of composition in which the specified ingredients (e.g., artificial RNA of the invention in association with LNP) may optionally be incorporated with any additional constituents, usually with at least one pharmaceutically acceptable carrier or excipient. Thus, the composition may be a dry composition, such as a powder or granules, or a solid unit, such as a lyophilized form or a tablet. Alternatively, the composition may be in liquid form, and each constituent may be independently incorporated in dissolved or dispersed form (e.g., suspended or emulsified).
[0024] Compound: As used in this document, a compound means a chemical substance that is a material consisting of molecules that have essentially the same structure and chemical properties. For a small molecular compound, the molecules are typically identical with respect to their atomic composition and structural configuration. For a macromolecular or polymeric compound, the molecules of a compound are highly similar, but not all are necessarily identical. For example, a segment of a polymer that is designed to consist of 50 monomeric units may also contain individual molecules with, for example, 48 or 53 monomeric units.
[0025] Derived from: The term derived from as used throughout this descriptive report in the context of a nucleic acid, i.e., for a nucleic acid derived from (another) nucleic acid, means that the nucleic acid, which is derived from (another) nucleic acid, Petition 870260029351, dated 03 / 28 / 2026, p. 75 / 555 12 / 372 shares at least 50%, preferably at least 55%, preferably at least 60%, preferably at least 65%, preferably at least 70%, more preferably at least 75%, more preferably at least 80%, 81%, 82%, 83%, 84%, more preferably at least 85%, 86%, 87%, 88%, 89%, even more preferably at least 90%, 91%, 92%, 93%, 94%, even more preferably at least 95%, 96%, 97%, and particularly preferably at least 98%, 99% sequence identity with the nucleic acid from which it is derived. The expert is aware that sequence identity is typically calculated for the same types of nucleic acids, that is, for DNA sequences or for RNA sequences.Thus, it is understood that if a DNA is “derived from” an RNA or if an RNA is “derived from” a DNA, in a first step, the RNA sequence is converted into the corresponding DNA sequence (in particular, by replacing uracils (U) with thymidines (T) along the sequence) or vice versa, the DNA sequence is converted into the corresponding RNA sequence (in particular, by replacing thymidines (T) with uracils (U) along the sequence). Subsequently, the sequence identity of the DNA sequences or the sequence identity of the RNA sequences is determined. Preferably, a nucleic acid “derived from” a nucleic acid also refers to the nucleic acid that is modified compared to the nucleic acid from which it is derived, for example, in order to further increase RNA stability and / or prolong and / or increase protein production. It is evident that such modifications are preferential, which do not impair the... Petition 870260029351, dated 03 / 28 / 2026, page 76 / 555 13 / 372 RNA stability, for example, compared to the nucleic acid from which it is derived. In the context of amino acid sequences (e.g., antigenic peptides or proteins), the term "derived from" means that the amino acid sequence that is derived from (another) amino acid sequence (e.g., RSV protein F) shares at least 50%, preferably at least 55%, preferably at least 60%, preferably at least 65%, preferably at least 70%, more preferably at least 75%, more preferably at least 80%, 81%, 82%, 83%, 84%, more preferably at least 85%, 86%, 87%, 88%, 89%, even more preferably at least 90%, 91%, 92%, 93%, 94%, even more preferably at least 95%, 96 97%, and particularly, preferably, at least 98%, 99% sequence identity with the amino acid sequence from which it is derived.
[0026] Thus, it is understood that if an antigenic peptide or protein is “derived from” an RSV fusion protein (F), the antigenic peptide or protein that is “derived from” said RSV F protein may represent a variant or fragment of the RSV F protein, for example, F0 (full-length precursor), F-del, F0_DSCav1, F_DSCav1_mut1, F_DSCav1_mut2, F_DSCav1_mut3, F-del_DSCav1, Fdel_DSCav1_mut1, F-del_DSCav1_mut2, F-del_DSCav1_mut3 (as specified herein). Furthermore, the antigenic peptide or protein that is “derived from” said RSV F proteins (e.g., F0, F-del, F0_DSCav1, F_DSCav1_mut1, F_DSCav1_mut2, F_DSCav1_mut3, F-del_DSCav1, F-del_DSCav1_mut1, F-del_DSCav1_mut2, F-del_DSCav1_mut3) Petition 870260029351, dated 03 / 28 / 2026, page 77 / 555 14 / 372 may differ in amino acid sequence, sharing a certain percentage of identity as defined above. Additional suitable examples of RSV F proteins from which an antigenic peptide or protein can be derived are provided in Table 1.
[0027] Epitope: The term epitope (also referred to as antigen determinant in the art) as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to T cell epitopes and B cell epitopes. T cell epitopes or parts of antigenic peptides or proteins may comprise fragments that preferably have a length of about 6 to about 20 or even more amino acids, for example, fragments as processed and presented by MHC class I molecules that preferably have a length of about 8 to about 10 amino acids, for example, 8, 9 or 10, (or even 11 or 12 amino acids), or fragments as processed and presented by MHC class II molecules that preferably have a length of about 13 to about 20 or even more amino acids, wherein these fragments may be selected from any part of the amino acid sequence.These fragments are typically recognized by T cells in the form of a complex consisting of the peptide fragment and an MHC molecule; that is, the fragments are typically recognized in their native form. B cell epitopes are typically located on the outer surface of (native) protein or peptide antigens that preferably have 5 to 15 amino acids, with a greater preference for those with 5 to 12. Petition 870260029351, dated 03 / 28 / 2026, page 78 / 555 15 / 372 amino acids, even more preferably those having 6 to 9 amino acids that can be recognized by antibodies, i.e., in their native form. Such protein or peptide epitopes may be further selected from any of the variants mentioned in this document of such proteins or peptides. In this context, antigenic determinants may be conformational or discontinuous epitopes that are composed of segments of the proteins or peptides as defined in this document that are discontinuous in the amino acid sequence of the proteins or peptides as defined in this document, but are put together in the three-dimensional structure, or continuous or linear epitopes that are composed of a single polypeptide chain. In the context of the present invention, an epitope may be the translation product of an artificial RNA provided as specified in this document.
[0028] Fragment: The term fragment as used throughout this descriptive report in the context of a nucleic acid sequence or an amino acid sequence can typically be a shorter portion of a full-length sequence of, for example, a nucleic acid sequence or an amino acid sequence. Consequently, a fragment typically consists of a sequence that is identical to the corresponding stretch contained in the full-length sequence. A preferred fragment of a sequence in the context of the present invention consists of a continuous stretch of entities, such as nucleotides or amino acids, corresponding to a continuous stretch of entities in the molecule from which the Petition 870260029351, dated 03 / 28 / 2026, p. 79 / 555 16 / 372 fragment is derived representing at least 5%, 10%, preferably at least 30%, more preferably at least 40%, more preferably at least 50%, still more preferably at least 60%, still more preferably at least 70%, and most preferably at least 80% of the total molecule (i.e., total length) from which the fragment is derived (e.g., RSV F protein). The term fragment as used throughout this descriptive report in the context of proteins or peptides may typically comprise a sequence of a protein or peptide as defined herein that refers to its amino acid sequence (or its encoded nucleic acid molecule), N-terminus and / or C-terminus truncated compared to the amino acid sequence of the original (native) protein (or its encoded nucleic acid molecule).Thus, such truncation may occur at the amino acid level or, correspondingly, at the nucleic acid level. A sequence identity with respect to such a fragment as defined herein may therefore preferably refer to the whole protein or peptide as defined herein or to the whole nucleic acid molecule (coding) of such protein or peptide. In the context of antigens, such a fragment may have a length of about 6 to about 20 or even more amino acids, for example, fragments as processed and presented by MHC class I molecules, preferably having a length of about 8 to about 10 amino acids, for example, 8, 9 or 10, (or even 6, 7, or 12 amino acids), or fragments as processed and. Petition 870260029351, dated 03 / 28 / 2026, p. 80 / 555 17 / 372 presented by MHC class II molecules, preferably having a length of about 13 or more amino acids, for example, 13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids, wherein these fragments can be selected from any part of the amino acid sequence. These fragments are typically recognized by T cells in the form of a complex consisting of the peptide fragment and an MHC molecule, that is, the fragments are typically recognized in their native form. Protein or peptide fragments (e.g., in the context of antigens) may comprise at least one epitope of those proteins or peptides. Additionally, domains of a protein, such as the extracellular domain, the intracellular domain, or the transmembrane domain, and shortened or truncated versions of a protein may also be understood as comprising a protein fragment.
[0029] Heterologous: The term heterologous or “heterologous sequence” as used throughout this descriptive report in the context of a nucleic acid sequence or an amino acid sequence refers to a sequence (e.g., DNA, RNA, amino acid) that will be recognized and understood by the element of common skill in the art, and is intended to refer to a sequence that is derived from another gene, another allele, or another species. Two sequences are typically understood to be heterologous if they are not derivable from the same gene or the same allele. Petition 870260029351, dated 03 / 28 / 2026, p. 81 / 555 18 / 372 nucleic acid molecule, such as, for example, in the same RNA or the same protein.
[0030] Humoral immune response: The term “humoral immunity” or “humoral immune response” will be recognized and understood by the element of common skill in the technique, and is, for example, intended to refer to B cell-mediated antibody production and, optionally, to accessory processes that accompany antibody production. A humoral immune response can be typically characterized, for example, by Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation, and memory cell generation. Humoral immunity can also typically refer to the effector functions of antibodies that include pathogen and toxin neutralization, classical complement activation, and opsonin promotion of phagocytosis and pathogen elimination.
[0031] Identity (of a sequence): The term “identity” as used throughout this descriptive report in the context of a nucleic acid sequence or an amino acid sequence will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to the percentage to which two sequences are identical. To determine the percentage to which two sequences are identical, for example, nucleic acid sequences or amino acid sequences as defined herein, preferably the amino acid sequences encoded by the artificial nucleic acid sequence as defined herein or the sequences themselves. Petition 870260029351, dated 03 / 28 / 2026, p. 82 / 555 19 / 372 amino acids, the sequences can be aligned in order to be subsequently compared with each other. Therefore, for example, a position in a first sequence can be compared to the corresponding position in the second sequence. If a position in the first sequence is occupied by the same component (residue) as is the case in a position in the second sequence, the two sequences are identical at that position. If this is not the case, the sequences differ at that position. If insertions occur in the second sequence compared to the first sequence, gaps can be inserted in the first sequence to allow for further alignment. If deletions occur in the second sequence compared to the first sequence, gaps can be inserted in the second sequence to allow for further alignment.Therefore, the percentage to which two sequences are identical is a function of the number of identical positions divided by the total number of positions, including those positions that are only occupied in one sequence. The percentage to which two sequences are identical can be determined using a mathematical algorithm. A preferred, but not limiting, example of a mathematical algorithm that can be used is the algorithm integrated into the BLAST program. Sequences that are identical to the sequences of the present invention to a certain extent can be identified by this program.
[0032] Immunogen, immunogenic: The term immunogen or immunogenic will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a compound that has the ability to stimulate / induce an immune response. Preferably, a Petition 870260029351, dated 03 / 28 / 2026, page 83 / 555 20 / 372 An immunogen is a peptide, polypeptide, or protein. An immunogen within the meaning of the present invention is the translation product of a supplied artificial nucleic acid, preferably RNA, comprising at least one coding sequence encoding at least one peptide, RSV-derived antigenic protein as defined herein. Typically, an immunogen elicits an adaptive immune response.
[0033] Immune response: The term “immune response” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a specific reaction of the adaptive immune system to a particular antigen (referred to as a specific or adaptive immune response) or to a non-specific reaction of the innate immune system (referred to as a non-specific or immune response) or a combination thereof.
[0034] Immune system: The term “immune system” will be recognized and understood by the common skill element in the technique, and is, for example, intended to refer to a system of the organism that can protect organisms from infection. If the pathogen overcomes a physical barrier of an organism and enters that organism, the innate immune system provides an immediate, but non-specific, response. If pathogens evade this innate response, vertebrates possess a second layer of protection, the adaptive immune system. Here, the immune system adapts its response during an infection to enhance its recognition of the pathogen. Then, this enhanced response is retained after the pathogen has been eliminated, in the form of immunological memory, and allows Petition 870260029351, dated 03 / 28 / 2026, page 84 / 555 21 / 372 that the adaptive immune system mounts faster and stronger attacks each time this pathogen is encountered. Accordingly, the immune system comprises the innate or adaptive immune system. Each of these two parts typically contains the so-called humoral and cellular components.
[0035] Innate immune system: The term “innate immune system” (also known as non-specific or non-specific immune system) will be recognized and understood by the element of common skill in the technique, and is, for example, intended to refer to a system that typically comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. This means that the cells of the innate system can recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, they do not confer lasting or protective immunity to the host.The innate immune system can be activated, for example, by Toll-like receptor (TLR) ligands or other auxiliary substances, such as lipopolysaccharides, TNF alpha, CD40 ligand, or cytokines, monokines, lymphokines, interleukins or chemokines, IL-1 to IL-33, IFN alpha, IFN beta, IFN gamma, GM-CSF, G-CSF, M-CSF, LT beta, TNF alpha, growth factors, and hGH, a human Toll-like receptor ligand (e.g., TLR1 to TLR10), a murine Toll-like receptor ligand (e.g., TLR1 to TLR13), a NOD-type receptor ligand, a RIG-I-type receptor ligand, an immunostimulatory nucleic acid, an immunostimulatory RNA (isRNA), a. Petition 870260029351, dated 03 / 28 / 2026, p. 85 / 555 22 / 372 CpG-DNA, an antibacterial agent or an antiviral agent.
[0036] Lipidoid compound: A lipidoid compound, also simply called a lipidoid, is a lipid-like compound, that is, an amphiphilic compound with physical properties similar to a lipid. In the context of the present invention, the term lipid is considered to encompass lipidoid compounds.
[0037] Monovalent vaccine, monovalent composition: The term “monovalent vaccine,” “monovalent composition,” “univalent vaccine,” or “univalent composition” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a composition or a vaccine comprising only one antigen of a virus. Consequently, said vaccine or composition comprises only one type of RNA encoding a single antigen for a single organism. The term “monovalent vaccine” includes immunization against a single valence. In the context of the invention, a monovalent vaccine or composition against RSV would comprise an artificial RNA encoding a single antigenic peptide or protein derived from a specific RSV (e.g., RSV F).
[0038] Nucleic acid: The term “nucleic acid” or “nucleic acid molecule” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a molecule comprising, preferably, consisting of nucleic acid components. The term nucleic acid molecule preferably refers to DNA or RNA molecules. It is preferably used as a synonym for the term polynucleotide. Preferably, a nucleic acid or nucleic acid molecule Petition 870260029351, dated 03 / 28 / 2026, page 86 / 555 23 / 372 nucleic acid is a polymer comprising or consisting of nucleotide monomers that are covalently linked together by phosphodiester bonds of a sugar / phosphate backbone. The term “nucleic acid molecule” also encompasses modified nucleic acid molecules, such as base-modified, sugar-modified, or backbone-modified DNA or RNA molecules as defined herein.
[0039] Nucleic acid sequence / RNA sequence / amino acid sequence: The term “nucleic acid sequence”, “RNA sequence” or “amino acid sequence” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to the particular and individual order of the succession of their nucleotides or amino acids respectively.
[0040] Permanently cationic: The term “permanently cationic” as used in this document will be recognized and understood by the element of common skill in the art, and means, for example, that the respective compound or group or atom is positively charged at any pH value or hydrogen ion activity of its environment. Typically, the positive charge results from the presence of a quaternary nitrogen atom. When a compound carries a plurality of such positive charges, it may be called permanently polycationic, which is a subcategory of permanently cationic.
[0041] Pharmaceutically effective quantity: The term “pharmaceutically effective quantity” or “effective quantity” will be recognized and understood by the element of Petition 870260029351, dated 03 / 28 / 2026, page 87 / 555 24 / 372 common skill in the art, and is, for example, intended to refer to an amount of a compound (e.g., the artificial RNA of the invention) that is sufficient to induce a pharmaceutical effect, such as, in the context of the invention, an immune response (e.g., against an antigenic peptide, protein, polyprotein as defined herein).
[0042] Polyvalent / Multivalent Vaccine, Polyvalent / Multivalent Composition: The term “polyvalent vaccine”, “polyvalent composition”, “multivalent vaccine” or “multivalent composition” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a composition or a vaccine comprising antigens from more than one strain of a virus, or comprising different antigens from the same virus or any combination thereof. The terms describe that said vaccine or composition has more than one valence. In the context of the invention, a polyvalent RSV vaccine would comprise a vaccine comprising an artificial RNA encoding antigenic peptides or proteins derived from several different RSV strains or comprising artificial RNA encoding different antigens from the same RSV strain or a combination thereof.In the preferred embodiment, a polyvalent RSV vaccine or composition comprises more than one, preferably 2, 3, 4 or even more different artificial RNA species, each encoding at least one different RSV antigenic peptide or protein (e.g., RSV F and RSV M or RSV F and RSV N). Methods for producing polyvalent mRNA vaccines are disclosed in PCT application PCT / EP2016 / 082487. Petition 870260029351, dated 03 / 28 / 2026, page 88 / 555 25 / 372 or in the published patent application WO2017 / 1090134A1.
[0043] “Stabilized nucleic acid molecule or “stabilized RNA”: The term “stabilized nucleic acid molecule or “stabilized RNA” refers to a nucleic acid molecule, preferably an RNA molecule, that is modified so that it is more stable with respect to disintegration or degradation, for example, by environmental factors or enzymatic digestion, such as by exo- or endonuclease degradation, than the nucleic acid molecule without modification. Preferably, a stabilized nucleic acid molecule, for example, stabilized RNA, in the context of the present invention is stabilized in a cell, such as a prokaryotic or eukaryotic cell, preferably in a mammalian cell, such as a human cell. The stabilizing effect can also be exerted outside of cells, for example, in a buffer solution, etc., for example, in a manufacturing process for a pharmaceutical composition comprising the stabilized nucleic acid molecule.
[0044] T-cell responses: The term “cellular immunity” or “cellular immune response” or “cellular T-cell responses” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to the activation of macrophages, natural killer (NK) cells, antigen-specific cytotoxic T lymphocytes, and the release of various cytokines in response to an antigen. More generally, cellular immunity is not based on antibodies, but on the activation of cells of the immune system. Typically, a cellular immune response can be Petition 870260029351, dated 03 / 28 / 2026, page 89 / 555 26 / 372 characterized, for example, by activation of antigen-specific cytotoxic T lymphocytes that have the capacity to induce apoptosis in cells, for example, in specific immune cells such as dendritic cells or other cells, displaying epitopes of foreign antigens on their surface. In the context of the invention, the antigen is provided by artificial RNA encoding at least one antigenic peptide or protein derived from RSV, suitably inducing T cell responses. The artificial RNA, the composition, the vaccine of the invention advantageously elicit cellular T cell responses against RSV F antigens.
[0045] Variant (of a sequence): The term variant as used throughout this descriptive report in the context of a nucleic acid sequence will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a variant of nucleic acid sequences that forms the basis of a nucleic acid sequence. For example, a variant nucleic acid sequence may exhibit one or more nucleotide deletions, insertions, additions, and / or substitutions compared to the nucleic acid sequence from which the variant is derived. Preferably, a variant of a nucleic acid sequence is at least 40%, preferably at least 50%, more preferably at least 60%, more preferably at least 70%, still more preferably at least 80%, still more preferably at least 90%, most preferably at least 95% identical to the nucleic acid sequence from which the variant is derived.Preferably, the variant is a functional variant. A variant of one. Petition 870260029351, dated 03 / 28 / 2026, page 90 / 555 27 / 372 nucleic acid sequence may have at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% nucleotide identity in a stretch of 10, 20, 30, 50, 75, or 100 nucleotides of such nucleic acid sequence.
[0046] The term variant as used throughout this descriptive report in the context of proteins or peptides will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to a protein or peptide variant that has an amino acid sequence that differs from the original sequence in one or more mutations, such as one or more substituted, inserted and / or deleted amino acids. Preferably, these fragments and / or variants have the same biological function or specific activity compared to the full-length native protein, for example, its specific antigenic property. Protein or peptide variants as defined in the context of the present invention may comprise conservative amino acid substitution(s) compared to their native sequence, i.e., physiologically unmutated.These amino acid sequences, as well as their coding nucleotide sequences, in particular, are contained within the term variants as defined in this document. Substitutions in which amino acids originating from the same class are exchanged are called conservative substitutions. In particular, these are amino acids that have aliphatic side chains, positively or negatively charged side chains, aromatic groups in the side chains, or amino acids whose side chains can insert themselves into hydrogen bonds. Petition 870260029351, dated 03 / 28 / 2026, p. 91 / 555 28 / 372 for example, side chains that have a hydroxyl function. This means that, for example, an amino acid with a polar side chain is replaced by another amino acid with a similar polar side chain, or, for example, an amino acid characterized by a hydrophobic side chain is replaced by another amino acid with a hydrophobic side chain (e.g., serine (threonine) by threonine (serine) or leucine (isoleucine) by isoleucine (leucine)). Insertions or substitutions are possible, in particular, at those sequence positions that do not cause any modification to the three-dimensional structure or do not affect the linkage region. Modifications to the three-dimensional structure by insertion (or insertions) or deletion (or deletions) can be easily determined, for example, using CD spectra (circular dichroism spectra).A variant of a protein or peptide may have at least 70%, 75%, 80%, 85%, 90%, 98%, or 99% amino acid identity in a stretch of 10, 20, 30, 50, 75, or 100 amino acids of such protein or peptide. Preferably, a variant of a protein comprises a functional variant of the protein, meaning that the variant exerts the same effect or functionality as the protein from which it is derived.
[0047] Untranslated region of 3', UTR element of 3', 3' UTR: The term 3' untranslated region or 3' UTR element will be recognized or understood by the common skill element in the art, and is, for example, intended to refer to a part of a nucleic acid molecule that is located 3' (i.e., downstream) from a coding sequence and that is typically not Petition 870260029351, dated 03 / 28 / 2026, page 92 / 555 29 / 372 translated into protein. Usually, a 3' UTR is the part of an mRNA that is located between the coding sequence (cds) and the poly(A) sequence of the mRNA. In the context of the invention, the term 3' UTR may also include elements that are not encoded in the DNA template from which an artificial RNA is transcribed, but which are added after transcription during maturation, for example, a poly(A) sequence.
[0048] 5' Untranslated Region, 5' UTR Element, 5' UTR: The term “5' untranslated region (5' UTR)” will be recognized and understood by the common skill element in the art, and is, for example, intended to refer to a part of a nucleic acid molecule that is located 5' (i.e., “upstream”) of a coding sequence and that is not translated into protein. A 5' UTR is understood to be a particular section of messenger RNA (mRNA) that is located 5' from the coding sequence or mRNA. Typically, the 5' UTR begins with the transcriptional start site and ends one nucleotide before the start codon of the coding sequence. Preferably, 5' UTRs have a length of more than 20, 30, 40, or 50 nucleotides. The 5' UTR may include elements for controlling gene expression, also called regulatory elements. Such regulatory elements may be, for example, ribosomal binding sites.A 5' UTR can be post-transcriptionally modified, for example, by adding a 5' termination.
[0049] 5'-terminal oligopyrimidine tract (TOP), TOP-UTR: The term “5'-terminal oligopyrimidine tract Petition 870260029351, dated 03 / 28 / 2026, page 93 / 555 30 / 372 The term "5' (TOP)" should be understood as a pyrimidine nucleotide stretch located in the 5'-terminal region of a nucleic acid molecule, such as the 5'-terminal region of certain mRNA molecules or the 5'-terminal region of a functional entity, for example, the transcript of certain genes. The sequence begins with a cytidine that usually corresponds to the transcriptional start site, and is followed by a stretch of usually about 3 to 30 pyrimidine nucleotides. For example, the TOP may comprise 3-30 or even more nucleotides. The pyrimidine stretch, and thus the 5' TOP, terminates in a 5'-to-the-first purine nucleotide located downstream of the TOP. Messenger RNA containing a 5'-terminal oligopyrimidine tract is often called TOP mRNA. Consequently, genes that provide such messenger RNAs are called TOP genes.The term “TOP motif” or “5’ TOP motif” should be understood as a nucleic acid sequence that corresponds to a 5’ TOP as defined above. Thus, a TOP motif in the context of the present invention is preferably a stretch of pyrimidine nucleotides having a length of 3–30 nucleotides. Preferably, the TOP motif consists of at least 3 pyrimidine nucleotides, preferably at least 4 pyrimidine nucleotides, preferably at least 5 pyrimidine nucleotides, more preferably at least 6 nucleotides, most preferably at least 7 nucleotides, most preferably at least 8 pyrimidine nucleotides, wherein the stretch of pyrimidine nucleotides preferably begins at its . Petition 870260029351, dated 03 / 28 / 2026, page 94 / 555 31 / 372 5' with a cytosine nucleotide. In TOP genes and TOP mRNAs, the TOP motif preferably begins at its 5' end with the transcriptional start site and terminates at a nucleotide 5' from the first purine residue in said gene or mRNA. A TOP motif within the meaning of the present invention is preferably located at the 5' end of a sequence representing a 5' UTR or at the 5' end of a sequence encoding a 5' UTR. Thus, preferably, a stretch of 3 or more pyrimidine nucleotides is termed a “TOP motif” within the meaning of the present invention if that stretch is located at the 5' end of a respective sequence, such as the artificial nucleic acid, the 5' UTR element of the artificial nucleic acid, or the nucleic acid sequence that is derived from the 5' UTR of a TOP gene as described herein.In other words, a stretch of 3 or more pyrimidine nucleotides that is not located at the 5' end of a 5' UTR or a 5' UTR element, but elsewhere within a 5' UTR or a 5' UTR element, is preferably not called a "TOP motif". In some embodiments, the nucleic acid sequence of the 5' UTR element that is derived from a 5' UTR of a TOP gene terminates at its 3' end with a nucleotide located at position 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 downstream of the start codon (e.g., A(U / T)G) of the gene or RNA from which it is derived. Thus, the 5' UTR element does not comprise any part of the protein-coding sequence. Thus, preferably, the only protein-coding part of at least one sequence of... Petition 870260029351, dated 03 / 28 / 2026, page 95 / 555 32 / 372 nucleic acid, particularly the RNA sequence, is provided by the coding sequence. Brief description of the invention
[0050] The present invention is based on the inventor's surprising finding that at least one peptide or protein derived from a Respiratory Syncytial Virus (RSV) F protein encoded by the artificial RNA of the invention can be efficiently expressed in a mammalian cell. Even more unexpectedly, the inventors have shown that the artificial RNA of the invention can induce specific and protective functional immune responses in, for example, cotton mice (see, for example, Examples 2, 3). Through various optimizations in the RSV F antigen design, immune responses could be further enhanced. Furthermore, the expression of the RSV F antigen encoded by the artificial nucleic RNA could be increased by selecting suitable heterologous 5' untranslated regions (UTRs) and suitable heterologous 3' untranslated regions (UTRs) (see, for example, Example 4). Advantageously, said artificial RNA of the invention comprising advantageous 3' / 5' UTR combinations induces very efficient antigen-specific immune responses against the encoded RSV F. Additionally, the artificial RNA of the invention comprised in lipid nanoparticles (LNPs) very efficiently induces antigen-specific immune responses against RSV F at very low dosage and dose regimens (see, for example, Example 3). Furthermore, for example, Examples 8 and 12 provide compositions / vaccines comprising an artificial RNA. Petition 870260029351, dated 03 / 28 / 2026, page 96 / 555 33 / 372 additionally encoding an additional antigen wherein said artificial RNA encoding an additional antigen adequately elicits or enhances T cell responses and results in a Th1-polarized immune response, which is considered to be an important prerequisite for a potential RSV vaccine (Th2-polarized responses have been associated with respiratory disease (RD) in animal models). Additionally, the compositions are suitable for inducing T cell responses. Consequently, the artificial RNA and the composition / vaccine comprising said artificial RNA of the invention are suitable for eliciting an immune response against RSV F in a mammalian individual. Artificial RNA and the composition / vaccine comprising said RNA. Artificial RNA is therefore suitable for use as a vaccine, for example, as a human vaccine, for example, as a vaccine for pregnant women or babies.
[0051] In a first aspect, the present invention provides an artificial nucleic acid, preferably an artificial RNA comprising at least one 5' untranslated region (UTR) and / or at least one 3' untranslated region (UTR), and at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR encoding at least one antigenic peptide or protein derived from RSV F protein or a fragment or variant thereof.
[0052] In preferred embodiments, the artificial RNA comprises at least one nucleic acid sequence derived from a 3' UTR of a gene selected from an ALB7 gene, an alpha-globin gene, a PSMB3, CASP1, COX6B1, GNAS, NDUFA1 and RPS9, from a homolog, a Petition 870260029351, dated 03 / 28 / 2026, page 97 / 555 34 / 372 fragment or variant of any of these genes.
[0053] In preferred embodiments, the artificial RNA comprises at least one nucleic acid sequence derived from a 5' UTR of a gene selected from an RPL32, an HSD17B4, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2 gene, or from a homolog, fragment or variant of any of these genes.
[0054] Suitably, the artificial RNA of the invention comprises at least one coding sequence encoding at least one antigenic peptide or protein derived from an RSV F protein operatively linked to a 3' UTR and a 5' UTR selected from a-1 (HSD17B4 / PSMB3), a-2 (Ndufa4 / PSMB3), a-3 (SLC7A3 / PSMB3), a4 (NOSIP / PSMB3), a-5 (MP68 / PSMB3), b-1 (UBQLN2 / RPS9), b-2 (ASAH1 / RPS9), b-3 (HSD17B4 / RPS9), b-4 (HSD17B4 / CASP1), b-5 (NOSIP / COX6B1), c-1 (NDUFA4 / RPS9), c-2 (NOSIP / NDUFA1), c-3 (NDUFA4 / COX6B1), c-4 (NDUFA4 / NDUFA1), c-5 (ATP5A1 / PSMB3), d-1 (Rpl31 / PSMB3), d-2 (ATP5A1 / CASP1), d-3 (SLC7A3 / GNAS), d-4 (HSD17B4 / NDUFA1), d-5 (Slc7a3 / Ndufa1), e-1 (TUBB4B / RPS9), e-2 (RPL31 / RPS9) (HSD17B4 / GNAS), f-5 (MP68 / COX6B1), g-1 (MP68 / NDUFA1), g-2 (NDUFA4 / CASP1), g-3 (NDUFA4 / GNAS), g-4 (NOSIP / CASP1), g-5 (RPL31 / CASP1),h-1 (RPL31 / COX6B1), h-2 (RPL31 / GNAS), h3 (RPL31 / NDUFA1), h-4 (Slc7a3 / CASP1), h-5 (SLC7A3 / COX6B1), i-1 (SLC7A3 / RPS9), i-2 (RPL32 / ALB7) or i-3 (agglobin gene), where a-1 (HSD17B4 / PSMB3), a-4 (NDUFA4 / PSMB3), c-1 (NDUFA4 / RPS9), e-4 (NOSIP / RPS9), g-2 (NDUFA4 / CASP1), Petition 870260029351, dated 03 / 28 / 2026, page 98 / 555 35 / 372 i-2 (RPL32 / ALB7) or i-3 (alpha-globin) is particularly preferred.
[0055] At least one antigenic peptide or protein derived from RSV F protein may be a full-length F protein (called F0, aa 1-574) or an F protein with a deleted C-terminus (called “F-del, aa 1-553), or a fragment or variant thereof.
[0056] At least one antigenic peptide or protein may additionally comprise a mutation that stabilizes the antigen in the pre-conformation / prefusion conformation state, preferably a DSCav1 mutation (S155C, S290C, S190F and V207L) or a fragment or variant, or a functional variant thereof (called DSCavl, for example, F0_DSCav1 or F-del_DSCav1).
[0057] At least one antigenic peptide or protein may be a fusion protein comprising the two subunits, F1 and F2 of mature F in a single chain, connected via a linker (GS) to improve protein stability (F(1-103)-GS-F(145-574); F(1-103)GS-F(145-553)).
[0058] The protein comprising the two mature F subunits in a single chain (called F1-linked F2), for example, (F(1-103)-GS-F(145-574); F(1-103)-GS-F(145553) may additionally comprise a DSCav1 mutation called mut0 in this document).
[0059] The protein comprising the two mature F subunits in a single chain (called F1-linked F2) may, in addition to the DSCav1 mutation, comprise at least one additional mutation that promotes interprotomer disulfide bonds, wherein the mutations may be Petition 870260029351, dated 03 / 28 / 2026, p. 99 / 555 36 / 372 selected from (S46G, A149C, S215P, Y458C, K465Q; (referred to as mut1 in this document), (S46G, E92D, A149C, S215P, Y458C, K465Q; referred to as mut2 in this document), or (S46G, N67I, E92D, A149C, S215P, Y458C, K465Q; referred to as mut3” in this document), (A149C, Y458C; referred to as mut4” in this document), (N183GC, N428C; referred to as “mut5” in this document), (Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q; referred to as mut6” in this document), (Q98C, Q361C, L95M, I221M, R429K; referred to as mut7” in this document), or (N183GC, N428C, S46G, N67I, E92D, S215P, K465Q; referred to as “mut8” in this document) or a fragment or variant, or a functional variant thereof.
[0060] At least one antigenic peptide or protein derived from the RSV F protein encoded by the artificial RNA of the invention may be selected from F0, F-del, F0_DSCav1, F_DSCav1_mut1, F_DSCav1_mut2, F_DSCav1_mut3, F_DSCav1_mut4, F_DSCav1_mut5, F_DSCav1_mut6, F_DSCav1_mut7, F_DSCav1_mut8, F_DSCav1_mut0, F-del_DSCav1, F-del_DSCav1_mut1, F-del_DSCav1_mut2, F-del_DSCav1_mut3, Fdel_DSCav1_mut4, F-del_DSCav1_mut5, F-del_DSCav1_mut6, Fdel_DSCav1_mut7, F-del_DSCav1_mut8, F-del_DSCav1_mut0 are preferred.
[0061] At least one sequence may encode at least one of the amino acid sequences that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID NOs: 68, 483, 898, 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, Petition 870260029351, dated 03 / 28 / 2026, p. 100 / 555 37 / 372 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 8279-9683, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999, 18368, 18737, 19106, 19475 or a fragment or variant of any of the sequences.
[0062] Preferably, the artificial RNA may comprise a coding sequence that is identical or at least 70%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID Nos: 69-77, 484-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596, 4958-4965 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 21363-21384, 11727-11734, 12096-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679-14686, 15048-15055, 15417-15424, 15786-15793 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376 18738-18745, 19107-19114, 19476-19483, 21389-21410 or a fragment or variant of any of these sequences.
[0063] Artificial RNA may comprise a codon-modified coding sequence selected from a C-maximized coding sequence, a CAI-maximized coding sequence, a coding sequence adapted using a human codon, a G / C-modified coding sequence, and a G / C-optimized coding sequence, or any combination thereof.
[0064] Artificial RNA can be mRNA, viral RNA, Self-replicating RNA, a circular RNA or replicon RNA. In Petition 870260029351, dated 03 / 28 / 2026, page 101 / 555 38 / 372 preferred modes, artificial RNA is mRNA.
[0065] The artificial RNA, preferably mRNA, may further comprise at least one selected from a termination structure, a poly(A) sequence, a poly(C) sequence, a histone stem-loop and / or a 3' terminal sequence element.
[0066] The artificial RNA of the invention preferably comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 78-482, 11735-12094, 21415-21417, 21561-21563, 21489, 21490, 21635, 21636 or a fragment or variant of any of these SEQ ID Nos (F0 encoding): 493-897, 1210412463, 21418-21420, 21564-21566, 21491, 21492, 21637, 21638 or a fragment or variant of any of these SEQ ID Nos (F-del encoding): 907-1266, 12473-12832, 2142121423, 21567-21569, 21493-21495, 21639-21641 or a fragment or variant of any of these SEQ ID Nos (F0_DSCav1 encoding): 1276-1635, 8278, 12842-13201, 21424-21426, 21570-21572, 21496-21498, 21642-21644 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1 encoding): 1645-2004, 13949-14308, 21433-21435, 21579-21581, 21505-21507, 21651-21653 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut1 encoding): 2014-2373, 14318-14677, 21436-21438, 21582-21584, 21508-21510, 21654-21656 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut1 encoding): 2383-2742, 14687-15046, Petition 870260029351, dated 03 / 28 / 2026, page 102 / 555 39 / 372 21439-21441, 21585-21587, 21511-21513, 21657-21659 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut2 encoding): 2752-3111, 15056-15415, 21442-21444, 21588-21590, 21514-21516, 21660-21662 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut2 encoding): 3121-3480, 15425-15784, 21445-21447, 21591-21593, 21517-21519, 21663-21665 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut3 encoding): 3490-3849, 15794-16153, 21448-21450, 21594-21596, 21520-21522, 21666-21668 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut3 encoding): 3859-4218, 13211-13570, 21427-21429, 21573-21575, 21499-21501, 21645-21647 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut0 encoding): 4228-4587, 13580-13939, 21430-21432, 21576-21578, 21502-21504,21648-21650 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut0 encoding): 4597-4956, 16163-16522, 21451-21453, 21597-21599, 21523-21525, 21669-21671 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut4 encoding): 4966-5325, 16532-16891, 21454-21456, 21600-21602, 21526-21528, 21672-21674 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut4 encoding): 5335-5694, 16901-17260, 21457-21459, 21603-21605, 21529-21531, 21675-21677 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut5 encoding): 5704-6063, 17270-17629, 21460-21462, 21606-21608, 21532-21534, 21678-21680 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut5 encoding): 6073-6432, 17639-17998, Petition 870260029351, dated 03 / 28 / 2026, page 103 / 555 40 / 372 21463-21465, 21609-21611, 21535-21537, 21681-21683 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut6 encoding): 6442-6801, 18008-18367, 21466-21468, 21612-21614, 21538-21540, 21684-21686 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut6 encoding): 6811-7170, 18377-18736, 21469-21471, 21615-21617, 21541-21543, 21687-21689 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut7 encoding): 7180-7539, 18746-19105, 21472-21474, 21618-21620, 21544-21546, 21690-21692 or a fragment or variant of any of these SEQ ID Nos (Fdel_DSCav1_mut7 encoding): 7549-7908, 19115-19474, 21475-21477, 21621-21623, 21547-21549, 21693-21695 or a fragment or variant of any of these SEQ ID Nos (F_DSCav1_mut8 encoding): 7918-8277, 19484-19843, 21478-21480, 21624-21626, 21550-21552, 21696-21698 or a fragment or variant of any of these (Fdel_DSCav1_mut8 encoding).
[0067] In a second aspect, the present invention provides a composition comprising the artificial RNA of the first aspect.
[0068] In preferred embodiments, the composition comprising the artificial RNA of the first aspect comprises at least one artificial RNA comprising at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein selected from matrix protein M, nucleoprotein N, protein M2-1 and / or phosphoprotein P or combinations thereof.
[0069] Matrix protein M, nucleoprotein N, protein Petition 870260029351, dated 03 / 28 / 2026, page 104 / 555 41 / 372 M2-1, M2-2 protein, and / or P-phosphoprotein are suitable T-cell antigens and can promote efficient T-cell responses from the composition or vaccine when administered to an individual.
[0070] The artificial RNA may comprise a coding sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of these SEQ ID NOs: 9685-9692, 10135-10142, 10638-10645, 1118411191, 21385-21388, 19845-19852, 20214-20221, 20583-20590, 20952-20959, 21411-21414 or a fragment or variant of any of these sequences.
[0071] Appropriately, said additional artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from SEQ ID NOs: 9693-10052, 1014310502, 10646-11005, 11192-11551, 19853-20212, 20222-20581, 20591-20950, 20960-21319, 21481-21488, 21627-21634, 21553-21560, 21699-21706 or a fragment or variant of any of these sequences.
[0072] Appropriately, the composition may comprise the artificial RNA of the invention complexed with, encapsulated in, or associated with one or more lipids, thereby forming lipid nanoparticles.
[0073] The composition may preferably comprise the artificial RNA of the invention complexed with one or more lipids, thereby forming lipid nanoparticles (LNPs), wherein the LNP consists essentially of Petition 870260029351, dated 03 / 28 / 2026, page 105 / 555 42 / 372 (i) at least one cationic lipid as defined herein, preferably a lipid of formula (III), more preferably lipid III-3; (ii) a neutral lipid as defined herein, preferably 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); (iii) a steroid or steroid analogue as defined in this document, preferably cholesterol; and (iv) a PEG lipid as defined in this document, for example, PEG-DMG or PEG-cDMA, preferably a PEGylated lipid of formula (IVa); wherein (i) to (iv) are in a molar ratio of approximately 20-60% cationic lipid: 5-25% neutral lipid: 25-55% sterol; 0.5-15% PEG lipid.
[0074] The present invention also relates to an RSV vaccine comprising said artificial RNA or said composition.
[0075] The present invention is also directed to the use of artificial RNA, composition and vaccine in the treatment or prophylaxis of an RSV infection.
[0076] In particular, the present invention is directed to the use of artificial RNA, composition and vaccine in the treatment or prophylaxis of an RSV infection or a disorder related to such infection.
[0077] The invention also relates to a method of treating or preventing a disorder or disease in an individual, first and second medical uses of artificial RNA, compositions and vaccines. Additionally, the invention is directed to a kit, particularly to a kit of parts comprising artificial RNA, compositions and Petition 870260029351, dated 03 / 28 / 2026, p. 106 / 555 43 / 372 vaccines. Detailed description of the invention
[0078] This application is filed together with a sequence listing in an electronic format that forms part of the description of this application (WIPO Standard ST.25). The information contained in the electronic format of the sequence listing filed with this application is incorporated in its entirety by reference herein. When reference is made to a “SEQ ID NO”, the corresponding nucleic acid sequence or amino acid sequence (aa) in the sequence listing that has the respective identifier is referenced. For many sequences, the sequence listing also provides additional detailed information, for example, regarding certain structural features, sequence optimizations, GenBank identifiers, or additional detailed information regarding their coding capability. In particular, such information is provided under the numerical identifier. <223> in the WIPO ST.25 pattern sequence listing.Consequently, information provided under said numerical identifier <223> are explicitly included in their entirety in this document and should be understood as an integral part of the description of the underlying invention. Artificial nucleic acid:
[0079] In a first aspect, the invention relates to an artificial nucleic acid comprising a) at least one untranslated 5' heterologous region (UTR of 5') and / or at least one untranslated 3' heterologous region (UTR of 3'); and Petition 870260029351, dated 03 / 28 / 2026, p. 107 / 555 44 / 372 (b) at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR that encodes at least one antigenic peptide or protein derived from a Respiratory Syncytial Virus (RSV) or a fragment or variant thereof.
[0080] In a preferred embodiment of the first aspect, the invention relates to an artificial RNA, preferably an RNA suitable for vaccination, comprising a) at least one untranslated 5' heterologous region (UTR of 5') and / or at least one untranslated 3' heterologous region (UTR of 3'); and (b) at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR that encodes at least one antigenic peptide or protein derived from an RSV fusion protein (F) or a fragment or variant thereof.
[0081] In general, the RNA of the invention may consist of a protein-coding region and 5' and / or 3' untranslated regions (UTRs). The 3' UTR is variable in sequence and size; it extends between the stop codon and the poly(A) tail. Importantly, the 3' UTR sequence harbors several regulatory motifs that determine RNA turnover, stability, and localization, and thus governs many aspects of post-transcriptional regulation. In the medical application of RNA (e.g., immunotherapy applications, vaccination), the regulation of RNA translation into protein is of paramount importance for therapeutic safety and efficacy. The present inventors have surprisingly found that Petition 870260029351, dated 03 / 28 / 2026, page 108 / 555 45 / 372 Certain combinations of 3' and / or 5' UTRs act together to synergistically enhance the expression of operatively linked nucleic acid sequences encoding RSV antigenic peptides or proteins. Artificial RNA molecules harboring the inventive UTR combinations advantageously enable the rapid and transient expression of high quantities of RSV F-derived antigenic peptides or proteins. Consequently, the artificial RNA provided in this document is particularly useful and suitable for various in vivo applications, including RSV vaccination.
[0082] Suitably, the artificial RNA may comprise at least one heterologous 5' UTR and / or at least one heterologous 3' UTR. In this context, a UTR of the invention comprises or consists of a nucleic acid sequence derived from a 5' UTR or a 3' UTR of any naturally occurring gene or a fragment, homolog, or variant thereof. Preferably, a 5' UTR or a 3' UTR of the invention is heterologous to at least one coding sequence encoding at least one F-derived antigenic peptide or protein of RSV. Suitable heterologous 5' UTRs or heterologous 3' UTRs are derived from naturally occurring genes (that are not derived from RSV). In other embodiments, synthetically engineered 5' UTRs or 3' UTRs may be used in the context of the present invention.
[0083] In preferred embodiments, at least one artificial RNA comprises at least one heterologous 3' UTR.
[0084] Preferably, at least one heterologous 3' UTR comprises or consists of a sequence of Petition 870260029351, dated 03 / 28 / 2026, page 109 / 555 46 / 372 nucleic acids derived from a 3' UTR of a chordate gene, preferably a vertebrate gene, more preferably a mammalian gene, most preferably a human gene, or from a variant of a 3' UTR of a chordate gene, preferably a vertebrate gene, more preferably a mammalian gene, most preferably a human gene.
[0085] Preferably, the artificial RNA of the present invention comprises a 3' UTR that can be derived from a gene that refers to an RNA with an improved lifespan (which provides a stable RNA), for example, a 3' UTR as defined and described below.
[0086] Preferably, at least one heterologous 3' UTR comprises a nucleic acid sequence derived from a 3' UTR of a gene that preferably encodes a stable mRNA, or from a homolog, fragment or variant of said gene.
[0087] In preferred embodiments of the first aspect, the artificial RNA of the invention comprises at least one heterologous 3' UTR, wherein the at least one heterologous 3' UTR comprises a nucleic acid sequence derived from a 3' UTR of a gene selected from PSMB3, ALB7, alpha-globin (called muag), CASP1, COX6B1, GNAS, NDUFA1 and RPS9, or from a homolog, fragment or variant of any of these genes.
[0088] 3' UTR derived from ALB7: In preferred embodiments, the 3' UTR comprises or consists of a nucleic acid sequence that is derived from the 3' UTR of a vertebrate albumin gene or a variant thereof, preferably from the 3' UTR of an albumin gene. Petition 870260029351, dated 03 / 28 / 2026, p. 110 / 555 47 / 372 of mammal or a variant thereof, more preferably of the 3' UTR of a human albumin gene or a variant thereof, even more preferably of The 3' UTR of the human albumin gene according to GenBank Accession Number NM_000477.5, or a homolog, fragment or variant thereof. Consequently, the artificial RNA of the invention may comprise a 3' UTR derived from an ALB7 gene, wherein said 3' UTR derived from an ALB7 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, % or 99% identical to SEQ ID NO: 35 or 36 or a fragment or variant thereof.
[0089] 3' UTR derived from Alpha-globin gene: In preferred embodiments, the 3' UTR comprises or consists of a nucleic acid sequence that is derived from the 3' UTR of a vertebrate alpha-globin gene (called muag) or a variant thereof, preferably from the 3' UTR of a mammalian alpha-globin gene or a variant thereof, more preferably from the 3' UTR of a human alpha-globin gene or a variant thereof, even more preferably from the 3' UTR of the human alpha-globin gene. Consequently, the RNA of the invention may comprise a 3' UTR derived from an alpha-globin gene, wherein said 3' UTR derived from an alpha-globin gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37 or a fragment or variant thereof. Petition 870260029351, dated 03 / 28 / 2026, p. 111 / 555 48 / 372
[0090] 3' UTR derived from PSMB3: The artificial RNA of the invention may comprise a 3' UTR that is derived from a 3' UTR of a gene encoding a proteasome beta subunit protein type 3 (PSMB3) or a homolog, variant, fragment or derivative thereof. Such 3' UTRs preferably comprise or consist of nucleic acid sequences derived from the 3' UTR of a proteasome beta subunit gene type 3 (PSMB3), preferably from a vertebrate, more preferably from a mammal, most preferably from a human proteasome beta subunit gene type 3 (PSMB3) or a homolog, variant, fragment or derivative thereof. The said gene may preferably encode a type 3 proteasome subunit protein beta (PSMB3) corresponding to a human type 3 proteasome subunit protein beta (PSMB3) (UniProt reference number P49720, entry version no. 183 of August 30, 2017).Consequently, the artificial RNA of the invention may comprise a 3' UTR derived from a PSMB3 gene, wherein said 3' UTR derived from a PSMB3 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 23 or 24 or a fragment or variant thereof.
[0091] 3' UTR derived from CASP1: The artificial RNA of the invention may comprise a 3' UTR that is derived from a 3' UTR of a gene encoding a Caspase 1 (CASP1) protein or a homolog, variant, fragment or derivative thereof. Such 3' UTRs preferably comprise or Petition 870260029351, dated 03 / 28 / 2026, p. 112 / 555 49 / 372 consist of a nucleic acid sequence derived from the 3' UTR of a Caspase-1 (CASP1) gene, preferably from a vertebrate, more preferably a mammal, most preferably a human Caspase-1 (CASP1) gene or a homolog, variant, fragment or derivative thereof. Consequently, the RNA of the invention may comprise a 3' UTR derived from a CASP1 gene, wherein said 3' UTR derived from a CASP1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98% or 99% identical to the SEQ ID NO: 25 or 26 or a fragment or variant thereof.
[0092] 3' UTR derived from COX6B1: The artificial RNA of the invention may comprise a 3' UTR that is derived from a 3' UTR of a COX6B1 gene encoding a cytochrome c oxidase 6B1 (COX6B1) subunit protein or a homolog, variant, fragment or derivative thereof. Such 3' UTRs preferably comprise or consist of a nucleic acid sequence that is derived from the 3' UTR of a cytochrome c oxidase 6B1 (COX6B1) subunit gene, preferably from a vertebrate, more preferably from a mammal, most preferably from a human cytochrome c oxidase 6B1 (COX6B1) subunit gene or a homolog, variant, fragment or derivative thereof. The said gene may preferably encode a cytochrome c oxidase 6B1 (COX6B1) subunit protein corresponding to a human cytochrome c oxidase 6B1 (COX6B1) subunit protein (UniProt reference number P14854, entry version no. 166 of August 30, 2017). Consequently, the artificial RNA of the invention may Petition 870260029351, dated 03 / 28 / 2026, p. 113 / 555 50 / 372 comprising a 3' UTR derived from a COX6B1 gene, wherein said 3' UTR derived from a COX6B1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 27 or 28 or a fragment or variant thereof.
[0093] 3' UTR derived from GNAS: The artificial RNA of the invention may comprise a 3' UTR that is derived from a 3' UTR of a GNAS gene encoding a short isoform of guanine G nucleotide-binding protein(s) alpha subunit protein(s) or a homolog, variant, fragment or derivative thereof. Such 3' UTRs preferably comprise or consist of a nucleic acid sequence that is derived from the 3' UTR of a gene of short isoforms (GNAS) of guanine G nucleotide-binding protein(s) alpha subunit (or proteins), preferably from a vertebrate, more preferably from a mammalian gene of short isoforms of guanine nucleotide-binding protein(s) alpha subunit (GNAS) or a homolog, variant, fragment or derivative thereof.The said gene may preferably encode a short isoform protein of the Guanine Nucleotide-binding G(s) protein subunit (GNAS) corresponding to a short isoform protein of the Guanine Nucleotide-binding G(s) protein subunit (GNAS) (UniProt reference number P63092, entry version no. 153 of August 30, 2017). Consequently, the artificial RNA of the invention may comprise a 3' UTR derived from a GNAS gene, wherein said 3' UTR is derived... Petition 870260029351, dated 03 / 28 / 2026, p. 114 / 555 51 / 372 of a GNAS gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 29 or a fragment or variant thereof.
[0094] 3' UTR derived from NDUFA1: The artificial RNA of the invention may comprise a 3' UTR that is derived from a 3' UTR of a gene encoding a protein of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1) or a homolog, variant, fragment or derivative thereof. Such 3' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 3' UTR of a gene of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 (NDUFA1), preferably from a vertebrate, more preferably a gene of alpha subcomplex subunit 1 of NADH dehydrogenase [ubiquinone] 1 mammalian (NDUFA1) gene or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a protein subunit 1 of the NADH dehydrogenase subcomplex alpha. [ubiquinone] 1 (NDUFA1) corresponding to a protein of subunit 1 of the alpha subcomplex of NADH dehydrogenase [ubiquinone] 1 (NDUFA1) human (UniProt reference number O15239, entry version no. 152 of August 30, 2017). Consequently, the artificial RNA of the invention may comprise a 3' UTR derived from an NDUFA1 gene, wherein said 3' UTR derived from an NDUFA1 gene comprises or consists of a nucleic acid sequence that is identical to or at least 70%, 80%, 85%, 86%, 87%, 88%, %, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% Petition 870260029351, dated 03 / 28 / 2026, p. 115 / 555 52 / 372 or 99% identical to SEQ ID NO: 31 or 32 or a fragment or variant thereof.
[0095] 3' UTR derived from RPS9: The artificial RNA of the invention may comprise a 3' UTR that is derived from a 3' UTR of a gene encoding a 40S ribosomal protein S9 (RPS9) or a homolog, variant, fragment or derivative thereof. Such 3' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 3' UTR of a 40S ribosomal protein S9 (RPS9) gene, preferably from a vertebrate, more preferably from a mammal, most preferably from a human 40S ribosomal protein S9 (RPS9) gene, or a homolog, variant, fragment or derivative thereof. The said gene may preferably encode a 40S ribosomal protein S9 (RPS9) protein corresponding to a human 40S ribosomal protein S9 (RPS9) protein (UniProt reference number P46781, entry version no. 179 of August 30, 2017).Consequently, the artificial RNA of the invention may comprise a 3' UTR derived from an RPS9 gene, wherein said 3' UTR derived from an RPS9 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 33 or 34 or a fragment or variant thereof.
[0096] Additional 3' UTRs: In the embodiments, the artificial RNA as defined herein comprises a 3' UTR as described in WO2 016 / 107 877. In this context, the disclosure of WO2016 / 107877 Petition 870260029351, dated 03 / 28 / 2026, p. 116 / 555 Section 53 / 372 relating to 3' UTR sequences is incorporated by reference thereto. Particularly suitable 3' UTRs are SEQ ID Nos: 1 to 24 and SEQ ID Nos: 49 to 318 of patent application WO2016 / 107877 or fragments or variants of these sequences. Consequently, the 3' UTRs of the artificial RNA of the present invention may comprise or consist of a corresponding RNA sequence of nucleic acid sequence according to SEQ ID Nos: 1 to 24 and SEQ ID Nos: 49 to 318 of the patent application. WO2016 / 107877. In other embodiments, the artificial RNA as defined herein comprises a 3' UTR as described in WO2017 / 036580. In this context, the disclosure in WO2017 / 036580 relating to 3' UTR sequences is incorporated by reference hereto. Particularly suitable 3' UTRs are SEQ ID Nos. 152 to 204 of patent application WO2017 / 036580 or fragments or variants of these sequences. Consequently, the 3' UTR of the artificial RNA of the present invention may comprise or consist of a corresponding RNA sequence of the nucleic acid sequence according to SEQ ID Nos. 152 to 204 of patent application WO2017 / 036580.
[0097] According to preferred embodiments, the artificial RNA comprises at least one heterologous 5' UTR.
[0098] In embodiments, the at least one artificial nucleic acid as defined herein, in particular, the RNA as defined herein may comprise at least one heterologous 5' UTR.
[0099] Preferably, at least one 5' UTR comprises or consists of a nucleic acid sequence derived from the 5' UTR of a chordate gene, of Petition 870260029351, dated 03 / 28 / 2026, p. 117 / 555 54 / 372 preference, of a vertebrate gene, with more preference, of a mammalian gene, with maximum preference, of a human gene or of a 5' UTR variant of a chordate gene, preferably, a vertebrate gene, with more preference, a mammalian gene, with maximum preference, a human gene.
[0100] Preferably, the artificial RNA of the present invention comprises a 5' UTR that can be derived from a gene that refers to an RNA with an improved lifespan (which provides a stable RNA), for example, a 5' UTR as defined and described below.
[0101] Preferably, at least one heterologous 5' UTR comprises a nucleic acid sequence derived from a 5' UTR of a gene that preferably encodes a stable mRNA, or from a homolog, fragment or variant of said gene.
[0102] In preferred embodiments of the first aspect, the artificial RNA of the invention comprises at least one heterologous 5' UTR, wherein the at least one heterologous 5' UTR comprises a nucleic acid sequence derived from a 5' UTR of a gene selected from HSD17B4, RPL32, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2 or from a homolog, fragment or variant of any of these genes.
[0103] 5' UTR derived from RPL32: The artificial RNA of the invention may comprise a 5' UTR derived from a 5' UTR of a gene encoding a 60S L32 ribosomal protein or a homolog, variant, fragment or derivative thereof, wherein said 5' UTR preferably lacks the 5' TOP motif. Such 5' UTRs comprise or Petition 870260029351, dated 03 / 28 / 2026, page 118 / 555 55 / 372 preferably consist of a nucleic acid sequence derived from the 5' UTR of a 60S ribosomal protein gene L32 (RPL32), preferably from a vertebrate, more preferably a mammal, most preferably a human 60S ribosomal protein gene L32 (RPL32) or a homolog, variant, fragment or derivative thereof, wherein the 5' UTR preferably does not comprise the TOP 5' of said gene. Said gene may preferably encode a 60S L32 ribosomal protein (RPL32) corresponding to a 60S L32 ribosomal protein (RPL32) (UniProt reference number P62899, entry version no. 138 of August 30, 2017). Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from an RPL32 gene, wherein said 5' UTR derived from an RPL32 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 21 or a fragment or variant thereof.
[0104] 5' UTR derived from HSD17B4: The artificial RNA of the invention may comprise a 5' UTR derived from a 5' UTR of a gene encoding a 17-beta-hydroxysteroid dehydrogenase 4 or a homolog, variant, fragment or derivative thereof, preferably lacking the 5' TOP motif. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a 17-beta-hydroxysteroid dehydrogenase 4 (also called a type 2 multifunctional peroxisomal enzyme gene), preferably from a vertebrate, more preferably from a Petition 870260029351, dated 03 / 28 / 2026, page 119 / 555 56 / 372 mammalian, preferably, of a human 17-beta-hydroxysteroid dehydrogenase 4 (HSD17B4) gene or a homolog, variant, fragment or derivative thereof, wherein, preferably, the 5' UTR does not comprise the 5' TOP of said gene. Said gene may preferably encode a 17-beta-hydroxysteroid dehydrogenase 4 protein corresponding to human 17-beta-hydroxysteroid dehydrogenase 4 (UniProt reference number Q9BPX1, entry version no. 139 of August 30, 2017) or a homolog, variant, fragment or derivative thereof. Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from an HSD17B4 gene, wherein said 5' UTR derived from an HSD17B4 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98% or 99% identical to, the SEQ ID NO: 1 or 2 or a fragment or a variant thereof.
[0105] 5' UTR derived from ASAH1: The artificial RNA of the invention may comprise a 5' UTR derived from a 5' UTR of a gene encoding acid ceramidase (ASAH1) or a homolog, variant, fragment or derivative thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of an acid ceramidase (ASAH1) gene, preferably from a vertebrate, more preferably from a mammal, most preferably from a human acid ceramidase (ASAH1) gene or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode an acid ceramidase (ASAH1) protein corresponding to human acid ceramidase (ASAH1) (UniProt reference number Q13510, version Petition 870260029351, dated 03 / 28 / 2026, page 120 / 555 57 / 372 of entry no. 177 of 7 June 2017) or a homologue, variant, fragment or derivative thereof. Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from an ASAH1 gene, wherein said 5' UTR derived from an ASAH1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, %, 96%, 97%, 98% or 99% identical to SEQ ID NO: 3 or 4 or a fragment or variant thereof.
[0106] 5' UTR derived from ATP5A1: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding mitochondrial ATP synthase alpha subunit (ATP5A1) or a homolog, variant, fragment or derivative thereof, wherein said 5' UTR preferably lacks the 5' TOP motif. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a mitochondrial ATP synthase alpha subunit gene (ATP5A1), preferably from a vertebrate, more preferably from a mammal, and most preferably from a human mitochondrial ATP synthase alpha subunit gene (ATP5A1) or a homolog, variant, fragment or derivative thereof, wherein the 5' UTR preferably does not comprise the 5' TOP of said gene.The said gene may preferably encode a mitochondrial ATP synthase alpha subunit protein corresponding to the alpha subunit of human mitochondrial acidic ATP synthase (UniProt reference number P25705, entry version 208 of August 30, 2017) or a homolog, variant, fragment or derivative thereof. Consequently, the artificial RNA of the invention may... Petition 870260029351, dated 03 / 28 / 2026, p. 121 / 555 58 / 372 comprising a 5' UTR derived from an ATP5A1 gene, wherein said 5' UTR derived from an ATP5A1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 5 or 6 or a fragment or variant thereof.
[0107] 5' UTR derived from MP68: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of an MP68 gene or a homolog, fragment or variant thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a vertebrate 6.8 kDa mitochondrial proteolipid gene (MP68), more preferably from a mammalian 6.8 kDa mitochondrial proteolipid gene (MP68), or a homolog, variant, fragment or derivative thereof. The said gene may preferably encode a 6.8 kDa mitochondrial proteolipid protein (MP68) corresponding to a human 6.8 kDa mitochondrial proteolipid protein (MP68) (UniProt reference number P56378, entry version no. 127 of February 15, 2017).Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from an MP68 gene, wherein said 5' UTR derived from an MP68 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 7 or 8 or a fragment or variant thereof.
[0108] 5' UTR derived from NDUFA4: The artificial RNA of Petition 870260029351, dated 03 / 28 / 2026, p. 122 / 555 59 / 372 The invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding a cytochrome c oxidase (NDUFA4) subunit or a homolog, fragment, or variant thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a cytochrome c oxidase (NDUFA4) gene, preferably from a vertebrate, more preferably from a mammalian cytochrome c oxidase (NDUFA4) gene, or a homolog, variant, fragment, or derivative thereof. The said gene may preferably encode a cytochrome c oxidase subunit protein (NDUFA4) corresponding to a human cytochrome c oxidase subunit protein (NDUFA4) (UniProt reference number 000483, entry version no. 149 of August 30, 2017). Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from an NDUFA4 gene, wherein said 5' UTR derived from an NDUFA4 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 9 or 10 or a fragment or variant thereof.
[0109] 5' UTR derived from NOSIP: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding a nitric oxide synthase (NOSIP) interacting protein or a homolog, variant, fragment or derivative thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a nitric oxide synthase (NOSIP) interacting protein gene. Petition 870260029351, dated 03 / 28 / 2026, page 123 / 555 60 / 372 gene, preferably from a vertebrate, more preferably from a mammal, most preferably from a nitric oxide synthase (NOSIP) interacting protein gene or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a nitric oxide synthase (NOSIP) interacting protein corresponding to a human nitric oxide synthase (NOSIP) interacting protein (UniProt reference number Q9Y314, entry version no. 130 of 7 June 2017). Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from a gene GNAS, wherein said 5' UTR derived from a GNAS gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, % or 99% identical to SEQ ID NO: 11 or 12 or a fragment or variant thereof.
[0110] 5' UTR derived from RPL31: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding a 60S L31 ribosomal protein or a homolog, variant, fragment or derivative thereof, wherein said 5' UTR preferably lacks the 5' TOP motif. Such a 5' UTR preferably comprises or consists of a nucleic acid sequence derived from the 5' UTR of a 60S L31 ribosomal protein (RPL31) gene, preferably from a vertebrate, more preferably a mammal, most preferably a mammalian 60S L31 ribosomal protein (RPL31) gene or a homolog, variant, fragment or derivative thereof, wherein the 5' UTR does not comprise, Petition 870260029351, dated 03 / 28 / 2026, page 124 / 555 61 / 372 preferably, the TOP 5' of said gene. Said gene may preferably encode a 60S L31 ribosomal protein (RPL31) corresponding to a 60S L31 ribosomal protein (RPL31) (UniProt reference number P62899, entry version no. 138 of August 30, 2017). Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from an RPL31 gene, wherein said 5' UTR derived from an RPL31 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13 or a fragment or variant thereof.
[0111] 5' UTR derived from SLC7A3: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding a cationic amino acid transporter protein 3 (solute carrier family member 7, SLC7A3) or a homolog, variant, fragment or derivative thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a cationic amino acid transporter gene 3 (SLC7A3), preferably from a vertebrate, more preferably from a mammalian cationic amino acid transporter gene 3 (SLC7A3) or a homolog, variant, fragment or derivative thereof. The said gene may preferably encode a cationic amino acid transporter protein 3 (SLC7A3) corresponding to a human cationic transporter protein 3 (SLC7A3) (UniProt reference number Q8WY07, entry version no. 139 of August 30, 2017).Consequently, the artificial RNA of the invention may... Petition 870260029351, dated 03 / 28 / 2026, p. 125 / 555 62 / 372 comprising a 5' UTR derived from an SLC7A3 gene, wherein said 5' UTR derived from an SLC7A3 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 15 or 16 or a fragment or variant thereof.
[0112] 5' UTR derived from TUBB4B: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding a beta-4B tubulin chain protein (TUBB4B) or a homolog, variant, fragment or derivative thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a beta-4B tubulin chain gene (TUBB4B), preferably from a vertebrate, more preferably from a mammal, and most preferably from a human beta-4B tubulin chain gene (TUBB4B) or a homolog, variant, fragment or derivative thereof. The said gene may preferably encode a beta-4B tubulin chain protein (TUBB4B) corresponding to the human beta-4B tubulin chain protein (TUBB4B) (UniProt reference number Q8WY07, entry version no. 142 of August 30, 2017).Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from a TUBB4B gene, wherein said 5' UTR derived from a TUBB4B gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 17 or 18 or a fragment thereof. Petition 870260029351, dated 03 / 28 / 2026, p. 126 / 555 63 / 372 a variant of it.
[0113] 5' UTR derived from UBQLN2: The artificial RNA of the invention may comprise a 5' UTR that is derived from a 5' UTR of a gene encoding a ubiquilin 2 (UBQLN2) protein or a homolog, variant, fragment or derivative thereof. Such 5' UTRs preferably comprise or consist of a nucleic acid sequence derived from the 5' UTR of a ubiquilin 2 (UBQLN2) gene, preferably from a vertebrate, more preferably from a mammalian ubiquilin 2 (UBQLN2) gene or a homolog, variant, fragment or derivative thereof. Said gene may preferably encode a ubiquilin 2 (UBQLN2) protein corresponding to UniProt reference number Q9UHD9, entry version 151 of August 30, 2017.Consequently, the artificial RNA of the invention may comprise a 5' UTR derived from a UBQLN2 gene, wherein said 5' UTR derived from a UBQLN2 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 19 or 20 or a fragment or variant thereof.
[0114] Additional 5' UTRs: In the embodiments, the artificial RNA as defined herein comprises a 5' UTR as described in WO2 013 / 1437 00. In this context, the disclosure of WO2013 / 143700 relating to 5' UTR sequences is incorporated by reference hereto. Particularly preferred 5' UTRs are nucleic acid sequences derived from SEQ ID NOs: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and Petition 870260029351, dated 03 / 28 / 2026, p. 127 / 555 64 / 372 SEQ ID NO: 1422 of patent application WO2 013 / 14 3700 or fragments or variants of these sequences. In this context, it is preferable that the 5' UTR of the artificial RNA according to the present invention comprises or consists of a corresponding RNA sequence of the nucleic acid sequence according to SEQ ID NOs: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of patent application WO2013 / 143700. In other embodiments, the artificial RNA of the invention comprises a 5' UTR as described in document WO2016 / 107877. In this context, the disclosure of document WO2016 / 107877 relating to 5' UTR sequences is incorporated by reference hereto. Particularly preferred 5' UTRs are nucleic acid sequences according to SEQ ID NOs: 25 to 30 and SEQ ID Nos. 319 to 382 of patent application WO2016 / 107877 or fragments or variants of these sequences. In this context, it is particularly preferred that the 5' UTR of the artificial RNA comprises or consists of a corresponding RNA sequence of the nucleic acid sequence according to SEQ ID Nos. 25 to 30 and SEQ ID Nos. 319 to 382 of patent application WO2016 / 107877. In other embodiments, the artificial RNA of the invention comprises a 5' UTR as described in document WO2017 / 036580. In this context, the disclosure of document WO2017 / 036580 relating to 5' UTR sequences is incorporated by reference hereto. Particularly preferred 5' UTRs are nucleic acid sequences according to SEQ ID Nos. 1 to 151 of patent application WO2017 / 036580, or fragments or variants of these sequences. In this context, it is particularly preferred that the 5' UTR of the artificial RNA comprise... Petition 870260029351, dated 03 / 28 / 2026, p. 128 / 555 65 / 372 or consist of a corresponding RNA sequence of nucleic acid sequence according to SEQ ID Nos: 1 to 151 of patent application WO2017 / 036580.
[0115] The inventors observed that certain combinations of at least one heterologous 5' UTR and / or at least one heterologous 3' UTR are advantageously enhancing the translation of at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR that encodes at least one antigenic peptide or protein derived from an RSV F protein in the target tissue (e.g., muscle, dermis).
[0116] Consequently, it is preferred that at least one 5' heterologous UTR as defined herein and at least one 3' heterologous UTR as defined herein act synergistically to increase the production (i.e., translation) of antigenic peptide or protein from the artificial RNA of the invention. These advantageous combinations of 5' and 3' UTRs are specified below. Each of the abbreviations introduced below, namely, a-1, a-2, a-3, a-4, a-5, b-1, b-2, b-3, b-4, b-5, c-1, c-2, c-3, c-4, c-5, d-1, d-2, d-3, d-4, d-5, e-1, e-2, e-3, e-4, e-5, e-6, f-1, f-2, f-3, f-4, f-5, g-1, g-2, g-3, g-4, g-5, h-1, h-2, h-3, h-4, h-5, i-1, i-2, i-3, is used throughout the descriptive report of the present invention and represents an advantageous combination of 5' and / or 3' UTRs of the invention.
[0117] Consequently, in preferred embodiments of the first aspect, the artificial RNA of the invention comprises Petition 870260029351, dated 03 / 28 / 2026, p. 129 / 555 66 / 372 a-1. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-2. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-3. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-4.at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or at least one 5' UTR derived from a 5' UTR of an MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof. Petition 870260029351, dated 03 / 28 / 2026, p. 130 / 555 67 / 372 same and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-1. at least one 5' UTR derived from a 5' UTR of a UBQLN2 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-2. at least one 5' UTR derived from a 5' UTR of an ASAH1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-3.at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-4. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from an RNA sequence. Petition 870260029351, dated 03 / 28 / 2026, p. 131 / 555 68 / 372 corresponding, homologous, fragment or variant thereof; or b-5. at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or c-1. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or c-2.at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-3. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or. Petition 870260029351, dated 03 / 28 / 2026, p. 132 / 555 69 / 372 c-4. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-5. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-1. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-2.at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-3. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from an RNA sequence. Petition 870260029351, dated 03 / 28 / 2026, p. 133 / 555 70 / 372 corresponding, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or d-4. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or d-5. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-1.at least one 5' UTR derived from a 5' UTR of a TUBB4B gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-2. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a UTR of. Petition 870260029351, dated 03 / 28 / 2026, p. 134 / 555 71 / 372 3' of an RPS9 gene, or a corresponding RNA sequence, homolog, fragment or variant thereof; or e-3. at least one 5' UTR derived from a 5' UTR of an MP68 gene, or a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or a corresponding RNA sequence, homolog, fragment or variant thereof; or e-4. at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or a corresponding RNA sequence, homolog, fragment or variant thereof; or e-5.at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-6. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof. Petition 870260029351, dated 03 / 28 / 2026, p. 135 / 555 72 / 372 same; or f-1. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-2. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-3. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-4.at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-5. at least one 5' UTR derived from a 5' UTR of. Petition 870260029351, dated 03 / 28 / 2026, p. 136 / 555 73 / 372 an MP68 gene, or a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or a corresponding RNA sequence, homolog, fragment or variant thereof; or g-1. at least one 5' UTR derived from a UTR of 5' of an MP68 gene, or of a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or of a corresponding RNA sequence, homolog, fragment or variant thereof; or g-2. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or of a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or of a corresponding RNA sequence, homolog, fragment or variant thereof; or g-3. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-4.at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment, or variant thereof. Petition 870260029351, dated 03 / 28 / 2026, p. 137 / 555 74 / 372 same and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-5. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-1. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-2.at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-3. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from an RNA sequence. Petition 870260029351, dated 03 / 28 / 2026, p. 138 / 555 75 / 372 corresponding, homologous, fragment or variant thereof; or h-4. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or h-5. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or i-1.at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof. eu-2. at least one 5' UTR derived from a 5' UTR of an RPL32 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an ALB7 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof. Petition 870260029351, dated 03 / 28 / 2026, p. 139 / 555 76 / 372 i-3. at least one 3' UTR derived from a 3' UTR of an alpha-globin gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof.
[0118] Suitably, the artificial RNA of the invention comprises at least one coding sequence encoding at least one antigenic peptide or protein derived from an RSV F protein operatively linked to a 3' UTR and a 5' UTR selected from a-1 (HSD17B4 / PSMB3), a-2 (Ndufa4 / PSMB3), a-3 (SLC7A3 / PSMB3), a4 (NOSIP / PSMB3), a-5 (MP68 / PSMB3), b-1 (UBQLN2 / RPS9), b-2 (ASAH1 / RPS9), b-3 (HSD17B4 / RPS9), b-4 (HSD17B4 / CASP1), b-5 (NOSIP / COX6B1), c-1 (NDUFA4 / RPS9), c-2 (NOSIP / NDUFA1), c-3 (NDUFA4 / COX6B1), c-4 (NDUFA4 / NDUFA1), c-5 (ATP5A1 / PSMB3), d-1 (Rpl31 / PSMB3), d-2 (ATP5A1 / CASP1), d-3 (SLC7A3 / GNAS), d-4 (HSD17B4 / NDUFA1), d-5 (Slc7a3 / Ndufa1), e-1 (TUBB4B / RPS9), e-2 (RPL31 / RPS9) (HSD17B4 / GNAS), f-5 (MP68 / COX6B1), g-1 (MP68 / NDUFA1), g-2 (NDUFA4 / CASP1), g-3 (NDUFA4 / GNAS), g-4 (NOSIP / CASP1), g-5 (RPL31 / CASP1), h-1 (RPL31 / COX6B1),h-2 (RPL31 / GNAS), h3 (RPL31 / NDUFA1), h-4 (Slc7a3 / CASP1), h-5 (SLC7A3 / COX6B1), i-1 (SLC7A3 / RPS9), i-2 (RPL32 / ALB7) or i-3 (agglobin gene).
[0119] In particularly preferred embodiments of the first aspect, the artificial RNA of the invention comprises UTR elements according to a-1 (HSD17B4 / PSMB3), a-4 (NDUFA4 / PSMB3), c-1 (NDUFA4 / RPS9), e-4
[0120] (NOSIP / RPS9), g-2 (NDUFA4 / CASP1), i-2 Petition 870260029351, dated 03 / 28 / 2026, p. 140 / 555 77 / 372 (RPL32 / ALB7) or i-3 (alpha-globin (muag)).
[0121] In a particularly preferred embodiment of the first aspect, the artificial RNA of the invention comprises UTR elements according to a-1 (HSD17B4 / PSMB3).
[0122] The invention relates to an artificial RNA, preferably an RNA suitable for vaccination, comprising at least one heterologous 5' UTR as defined above and / or at least one heterologous 3' UTR as defined above and at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR, wherein said coding sequence encodes at least one antigenic peptide or protein derived from a Respiratory Syncytial Virus (RSV) or a fragment or variant thereof.
[0123] As used in this document, the term Respiratory Syncytial Virus or the corresponding abbreviation RSV is not limited to a particular strain, variant, serotype or virus isolate, etc., comprising any Respiratory Syncytial Virus of any origin.
[0124] According to various embodiments, artificial RNA, preferably the artificial RNA coding sequence, comprises or consists of a nucleic acid sequence that is derived from viruses with NCBI Taxonomy ID (NCBI-ID) provided in List 1 below. List 1: RSV virus strains:
[0125] Human orthopneumovirus, HRSV (NCBI-ID 11250); Human respiratory syncytial virus A, HRSV-A, Respiratory syncytial virus group A (NCBI-ID 208893); Human respiratory syncytial virus A Long strain, Human respiratory syncytial virus (subgroup A / Long strain) (NCBI-ID Petition 870260029351, dated 03 / 28 / 2026, p. 141 / 555 78 / 372 11260); Human Respiratory Syncytial Virus A2, Human Respiratory Syncytial Virus (A2 strain), HRSVA (NCBI-ID 11259); Human Respiratory Syncytial Virus (RSB1734 strain), (NCBI-ID 11253); Human Respiratory Syncytial Virus (RSB5857 strain) (NCBI-ID 11254); Human Respiratory Syncytial Virus (RSB6190 strain), (NCBI-ID 11255); Human Respiratory Syncytial Virus (RSB6256 strain), (NCBI-ID 11256); Human Respiratory Syncytial Virus (cRSB642 strain), (NCBI-ID 11252); Human Respiratory Syncytial Virus (RSB6614 strain), (NCBI-ID 11257); Human respiratory syncytial virus B, HRSV-B, Human respiratory syncytial virus group B, (NCBI-ID 208895); Human respiratory syncytial virus 9320 (NCBI-ID 253182); Human respiratory syncytial virus B1 (NCBI-ID 79692); Human respiratory syncytial virus (subgroup B / strain 18537), (NCBI-ID 11251); Human respiratory syncytial virus (subgroup B / strain 8 / 60), (NCBI-ID 11258); Human respiratory syncytial virus S2, (NCBI-ID 410078);Human Respiratory Syncytial Virus (RSS-2) strain, (NCBI-ID 11261); Unclassified Human Respiratory Syncytial Virus, (NCBI-ID 410233); Human Respiratory Syncytial Virus (RSP112 / Sweden / 02-03) strain, (NCBI-ID 410237); Human Respiratory Syncytial Virus (RSP120 / Sweden / 02-03) strain, (NCBI-ID 410238); Human Respiratory Syncytial Virus (RSP121 / Sweden / 02-03) strain, (NCBI-ID 410239); Human Respiratory Syncytial Virus (RSP122 / Sweden / 02-03) strain, (NCBI-ID 410247); Human respiratory syncytial virus (RSP13 / Sweden / 02-03 strain), (NCBI-ID 410241); Human respiratory syncytial virus (RSP140 / Sweden / 02-03 strain), (NCBI-ID 410248); Human respiratory syncytial virus (RSP16 / Sweden / 02-03 strain), (NCBI-ID; Petition 870260029351, dated 03 / 28 / 2026, page 142 / 555 79 / 372 410242); Human respiratory syncytial virus (RSP171 / Sweden / 02-03 strain), (NCBI-ID 410246); Human respiratory syncytial virus (RSP183 / Sweden / 02-03 strain), (NCBI-ID 410249); Human respiratory syncytial virus (RSP191 / Sweden / 02-03 strain), (NCBI-ID 410240); Human respiratory syncytial virus (RSP199 / Sweden / 02-03 strain), (NCBI-ID 410250); Human respiratory syncytial virus (RSP212 / Sweden / 02-03 strain), (NCBI-ID 410251); Human respiratory syncytial virus (RSP41 / Sweden / 02-03 strain), (NCBI-ID 410234); Human respiratory syncytial virus (RSP45 / Sweden / 02-03 strain), (NCBI-ID 410235); Human respiratory syncytial virus (RSP56 / Sweden / 02-03 strain), (NCBI-ID 410243); Human respiratory syncytial virus (RSP58 / Sweden / 02-03 strain), (NCBI-ID 410236); Human respiratory syncytial virus (RSP67 / Sweden / 02-03 strain), (NCBI-ID 410244); Human respiratory syncytial virus (RSP94 / Sweden / 02-03 strain) (NCBI-ID 410245); Memphis-37 RSV isolate of Respiratory Syncytial Virus, (Memphis-37 strain) (NCBI-ID 12814).
[0126] In preferred embodiments of the invention, at least one antigenic peptide or protein is derived from a Memphis-37 RSV isolate of Respiratory Syncytial Virus (Memphis-37 strain) (NCBI-ID: 12814). Throughout the present invention, including the information contained in the ST25 sequence listing, the abbreviation HRSV(Memphis-37) is used for said particularly preferred RSV virus.
[0127] In preferred embodiments of the invention, at least one antigenic peptide or protein is derived from a human respiratory syncytial virus A2, human respiratory syncytial virus (strain A2) (NCBI-ID: 11259). Throughout the Petition 870260029351, dated 03 / 28 / 2026, page 143 / 555 80 / 372 present invention, including the information contained in the ST25 sequence listing, the abbreviation HRSV(A2) is used for said particularly preferred RSV virus.
[0128] It should be understood that the skilled individual may also use amino acid sequences and nucleic acid sequences derived from any RSV strains provided in Listing 1 to adapt the teaching of the present invention and obtain RNA constructs, compositions and vaccines according to the invention.
[0129] In several embodiments, at least one antigenic peptide or protein may be selected from fusion protein (F), glycoprotein G, hydrophobic short protein SH, matrix protein M, nucleoprotein N, large polymerase L, protein M2-1, protein M2-2, phosphoprotein P, nonstructural protein NS1, or nonstructural protein NS2 of Respiratory Syncytial Virus (RSV) or a fragment, variant, or derivative thereof.
[0130] In particularly preferred embodiments of the first aspect, at least one antigenic peptide or protein is derived from an RSV fusion protein (F). In this context, the amino acid sequence of at least one antigenic peptide or protein may be selected from any peptide or protein derived from an RSV F fusion protein and from a fragment, variant, or derivative thereof.
[0131] The RSV F protein is initially expressed (after infection of a host cell) as a single polypeptide precursor, designated full-length fusion F protein (referred to as F0 in this document). F0 forms a trimer in the endoplasmic reticulum and is Petition 870260029351, dated 03 / 28 / 2026, page 144 / 555 81 / 372 is processed by a cellular / host furin-type protease at two conserved sites, generating polypeptides F1, F2, and Pep27. The Pep27 polypeptide is excised and does not form part of the mature F protein. The F2 polypeptide originates from the N-terminal portion of the F0 precursor and binds to the F1 polypeptide via two disulfide bonds. The F1 polypeptide originates from the C-terminal portion of the F0 precursor and anchors the mature F protein to the membrane via a transmembrane domain that is linked to a cytoplasmic tail. Three F2-F1 heterodimer units (protomers) assemble to form a mature F protein. Initially, the mature F protein is in a metastable form (referred to as the pre-fusion conformation in this document). After activation, it undergoes a dramatic and irreversible conformational change (called post-fusion conformation) that fuses the viral and target cell membranes.
[0132] Consequently, the artificial RNA of the first aspect, preferably the artificial RNA suitable for vaccination, encodes at least one antigenic peptide or protein derived from an RSV F protein or a fragment or variant thereof.
[0133] In preferred embodiments, at least one antigenic peptide or protein derived from an RSV F protein may be derived from any of the following amino acid sequences (NCBI Protein Accession Numbers) provided in List 2 below. List 2: NCBI Protein Accession Numbers for RSV Fusion Proteins (F):
[0134] Protein Accession No., AJF44801.1, AJF44759.1, Petition 870260029351, dated 03 / 28 / 2026, p. 145 / 555 82 / 372 AJF44661.1, AAB38519.1, AVQ93568.1, AVQ93606.1, AVQ93588.1, AVQ93552.1, AVQ93470.1, AVQ93485.1, AVQ93554.1, AVQ93500.1, AVQ93408.1, AVQ93366.1, AVQ93457.1, AVQ93393.1, AOS49123.1, AHV81506.1, ANZ80034.1, AFX60234.1, AFX60215.1, AFX60220.1, AFX60173.1, AFX60150.1, AFX60135.1, AFV46413.1, AFP99061.1, AFX60138.1, AFM55442.1, AFM95385.1, AFM55288.1, AFM55211.1, AJF44602.1, AAB38518.1, AVQ93589.1, AVQ93601.1, AVQ93575.1, AVQ93556.1, AVQ93489.1, AVQ93533.1, AVQ93551.1, AVQ93426.1, AVQ93443.1, AVQ93402.1, AVQ93372.1, AVQ93362.1, AOS48496.1, AFX60128.1, AMN91253.1, AFX60231.1, AFX60214.1, AFX60213.1, AFX60169.1, AFX60148.1, AFV46420.1, AFV46414.1, AFM95400.1, AFP99060.1, AFM55420.1, AFM55354.1, AFM55266.1, AFI25262.1, 2207424A, AVQ93587.1 AVQ93597.1 AVQ93562.1 AVQ93468.1 AVQ93471.1 AVQ93542.1 AVQ93481.1 AVQ93547.1 AVQ93398.1 AVQ93429.1 AVQ93377.1 AVQ93455.1 AVQ93585.1 AMT78271.1 AFX60129.1 P03420.1, AFX60232.1 AFX60212.1 AFX60190.1 AFX60162.1 AFX60141.1 AFX60200.1 AFV46410.1 AFV46401.1 AFM95365.1 AFM55552.1 AFM55343.1 AFM55277.1 AFD34266.1 AAB38520.1, , AVQ93599.1, , AVQ93563.1, , AVQ93561.1, , AVQ93467.1, , AVQ93458.1, , AVQ93472.1, , AVQ93546.1, , AVQ93558.1, , AVQ93401.1, , AVQ93359.1, , AVQ93412.1, , AVQ93364.1, , ART28504.1, , AHX57174.1, , AEQ63389.1, AIO08046.1, , AFX60222.1, , AFX60208.1, , AFX60187.1, , AFX60156.1, , AFX60127.1, , AFV46419.1, , AFV46403.1, , AFP99064.1, , AFM55563.1, , AFM55365.1, , AFM55387.1, , AFM55255.1, , AFM55332.1, AAB38517.1, AVQ93571.1, AVQ93594.1, AVQ93607.1, AVQ93590.1, AVQ93494.1, AVQ93514.1, AVQ93512.1, AVQ93461.1, AVQ93361.1, AVQ93365.1, AVQ93391.1, AVQ93378.1, AVQ93404.1, AHW81390.1, ARB66328.1, NP_056863.1, AFX60219.1, AFX60202.1, AFX60201.1, AFX60151.1, AFX60137.1, AFV46417.1, AFV46409.1, AFM95376.1, AFM55530.1, AFP99059.1, AFM55299.1, AFM55222.1, AFD34264.1, Petition 870260029351, on 03 / 28 / 2026, page. 146 / 555 83 / 372 AFD34262 AEQ63641 4CCF_A, AEQ63586 AEO45869 AEO23054 AEC32085 ADZ95779 ADZ95775 AAX23994 AAQ97028 AAM44851 CAA26143 AAO72323 AGG39517 BBC54570 BBC54564 BBC54245 BBC54235 BBC54178 BBC54170 BBC54160 BBC54150 BBC54199 BBC54122 BBB35193 BBB35130 BBB35121 BBB35153 BBB35094 .1, AFD34265. .1, AEQ63487. AEQ63334.1, .1, AEO45919. 1. AEO45929. 1. AEO23052. .1, ADZ95784. .1, ADZ95780. .1, ACY68435. 1. AAQ97026. .1, AAC57027. .1, P11209.2 .1, 1512372A, AAB86664.1, AAO72324.1, AAB82446.1, .1 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, .1, AAM68154 .1, BBC54612. 1. BBC54579. 1. BBC54581. 1. BBC54243. 1. BBC54234. 1. BBC54202. .1, BBC54210. 1. BBC54163. 1. BBC54207. 1. BBC54220. 1. BBC54124. .1, BBB35199. .1, BBB35160. .1, BBB35138. .1, BBB35115. .1, BBB35183. 1, AFD34261 1, AEQ63520 AEO45949.1 1, AEO45909 1, AEO45850 1, AEO23051 1, ADZ95783 1, ADZ95777 1, ACO83302 1, AAR14266 1, AAQ97029, P13843.1 1, AFD34260.1, 1, AEQ63378.1, AEO45939.1, 1, AEO45889.1, 1, AEO45859.1, 1, AEC32087.1, 1, ADZ95782.1, 1, ADZ95778.1, 1, ABI35685.1, 1, AAQ97027.1, 1, AAQ97031.1, AAO72325.1, AFD34259.1, AEQ63367.1, AEQ63312.1, AEO45879.1, AEQ63444.1, ADZ95785.1, ADZ95781.1, ADZ95776.1, AFI25251.1, AAQ97030.1, AAM68160.1, AAM68157.1, , AAA47410. BBC54636.1 BBC54595.1 BBC54571.1 BBC54238.1 BBC54236.1 BBC54151.1 BBC54169.1 BBC54215.1 BBC54194.1 BBC54181.1 BBB35202.1 BBB35184.1 BBB35162.1 BBB35176.1 BBB35150.1 BBB35104.1 1, P12568.1, , BBC54627.1, , BBC54555.1, , BBC54553.1, , BBC54242.1, , BBC54244.1, , BBC54142.1, , BBC54213.1, , BBC54156.1, , BBC54149.1, , BBC54132.1, , BBB35201.1, , BBB35126.1, , BBB35181.1, , BBB35142.1, , BBB35097.1, , BBB35099.1, ARB07894.1, BBC54621.1, BBC54552.1, BBC54565.1, BBC54239.1, BBC54186.1, BBC54134.1, BBC54203.1, BBC54179.1, BBC54138.1, BBC54146.1, BBB35192.1, BBB35133.1, BBB35165.1, BBB35136.1, BBB35109.1, BBB35188.1, Petition 870260029351, dated 03 / 28 / 2026, page 147 / 555 84 / 372 AKA45871.1, AGG39457.1, AUH15164.1, AUC68555.1, AUC68291.1, AMA66580.1, AHY21331.1, ATV93506.1, BBA57890.1, ASK05520.1, ARQ15966.1, APW78867.1, APW78713.1, AOS48870.1, AGN28484.1, AOS48815.1, AOS48683.1, AOS48397.1, AOS48265.1, AHV81286.1, AOD40104.1, AJF44535.1, ANZ80331.1, ANZ80188.1, ANZ80056.1, ANZ79990.1, AMT79718.1, AMT79388.1, AMT79091.1, AMT78832.1, ASV65838.1, ARR29240.1, ATV81343.1, AUC68478.1, AUC68149.1, AIZ95750.1, AHY21165.1, ATV93509.1, BBA57901.1, ART28427.1, ARN61507.1, APW78900.1, APW78680.1, APW78614.1, AHX57240.1, AOS48738.1, AOS48551.1, AOS48375.1, AOS48254.1, AOD40888.1, AOD40082.1, ANZ80463.1, ANZ80320.1, ANZ80144.1, ANZ80012.1, ANZ79902.1, AMT79586.1, AMT79201.1, AMT79047.1, AMT78689.1, AGG39373.1, ARR29251.1, AUC68654.1, AUC68445.1, AUC68094.1, AIZ95541.1, AHY21143.1, AIZ95717.1, ASZ70099.1, ART28339.1, ARA15413.1, APW78878.1, APW78658.1, AMT78905.1, AHX57031.1, AOS49068.1, AOS48485.1, AOS48353.1, AOS48221.1, AOD40516.1, AOD39908.1, ANZ80408.1, ANZ80364.1, ANZ80133.1, ANZ80067.1, ANZ79759.1, AMT79553.1, AMT79190.1, AMT79014.1, AMT78645.1, AII22107.1, ARR29189.1, AUC68577.1, AUC68500.1, AMA67097.1, AIZ95519.1, AHY21132.1, ATV81354.1, ART28361.1, ART28297.1, AGG39394.1, APW78779.1, APW78647.1, AMT77402.1, AOS48980.1, AOS48727.1, AOS48518.1, AOS48287.1, ANZ79638.1, AOD40214.1, AJF44826.1, ANZ80397.1, ANZ80276.1, ANZ80111.1, ANZ79979.1, ANZ79715.1, AMT79542.1, AMT79157.1, AMT79003.1, AMT78513.1, AGG39400.1, ARR29207.1, AUC68566.1, AUC68522.1, AMA66866.1, AHY21419.1, AGG39478.1, ART28317.1, AQX36844.1, ART28328.1, APW78845.1, APW78702.1, APW78636.1, AOZ15479.1, AOS48848.1, AOS48716.1, AOS48441.1, AOS48320.1, ALC74025.1, AOD40125.1, AJF44506.1, ANZ80386.1, ANZ80221.1, ANZ80122.1, ANZ79935.1, ANZ79671.1, AMT79476.1, AMT79124.1, AMT78872.1, AMT78480.1, Petition 870260029351, dated 03 / 28 / 2026, page 148 / 555 85 / 372 AMT78447.1, AMT77963.1, AMN91385.1, CUS01880.1, AMA67350.1, AMA67130.1, AMA66998.1, AMA66844.1, AMA66569.1, AMA66448.1, AGG39469.1, AJZ70067.1, AJZ69913.1, AJZ69748.1, AJZ69660.1, AJO16077.1, AJF44835.1, AJF44643.1, AJF44555.1, AHA83913.1, AHA83705.1, AII30203.1, AHY21287.1, AHX57537.1, AIZ95893.1, AIZ95673.1, AEQ63542.2, AEQ63411.1, AHX56987.1, AHV81836.1, AMT78392.1, AMT77908.1, AMN91264.1, CUS01877.1, AMA67251.1, AMA67185.1, AMA66987.1, AMA66833.1, AMA66547.1, AMA66415.1, AJZ70144.1, AJZ70001.1, AJZ69880.1, AJZ69726.1, AJZ69715.1, AJO16055.1, AJF44790.1, AJF44628.1, AJF44526.1, AGN28715.1, AHA83630.1, AHY21463.1, AHY21276.1, AHX57471.1, AIZ95871.1, AIZ95596.1, AEQ63575.1, AHX57570.1, AHV82100.1, AHV81682.1, AMT78194.1, AMT77776.1, AMN91242.1, CUS01874.1, AMA67262.1, AMA67163.1, AMA66976.1, AMA66624.1, AMA66503.1, AMA66393.1, AJZ70166.1, AJZ69990.1, AJZ69847.1, AJZ69682.1, AJZ69627.1, AKE31881.1, AJF44737.1, AJF44624.1, AJF44517.1, AHA83902.1, AGG39505.1, AHY21397.1, AHY21254.1, AHX57427.1, AIZ95816.1, AIZ95585.1, AEQ63531.1, AHX57152.1, AHV82001.1, AHV81649.1, AMT78084.1, AMT77710.1, AHX57504.1, CUS01870.1, AMA67229.1, AMA67086.1, AMA66965.1, AMA66613.1, AMA66492.1, AMA66360.1, AJZ70155.1, AJZ69968.1, AJZ69869.1, AJZ69671.1, AJZ69616.1, AKE31882.1, AJF44716.1, AJF44613.1, AKA45882.1, AHA83837.1, AIY70242.1, AHY21320.1, AHY21199.1, AHX57042.1, AIZ95772.1, AIZ95552.1, AEQ63498.1, AHX57064.1, AHV81891.1, AHV81484.1, AMT78051.1, AMT77424.1, CUS01881.1, CUS01875.1, AMA67196.1, AMA67075.1, AMA66921.1, AMA66591.1, AMA66481.1, AGG39553.1, AJZ70133.1, AJZ69946.1, AJZ69770.1, AJZ69704.1, AJZ69638.1, AKE31878.1, AJF44725.1, AJF44566.1, AKA45849.1, AHA83826.1, AIY70198.1, AHY21298.1, AHY21176.1, AIZ95981.1, AIZ95629.1, AEQ63553.2, AEQ63422.1, AHX57009.1, AHV81880.1, AHV81462.1, Petition 870260029351, dated 03 / 28 / 2026, page 149 / 555 86 / 372 AHV81385.1, AHV81122.1, AHV80869.1, AGG39556.1, AGG39529.1, AGG39499.1, AGG39487.1, AGG39454.1, AGG39403.1, AHA84012.1, AHA84034.1, AHA83891.1, AGT75357.1, AGN28748.1, AGN28528.1, AGL96784.1, AAS93660.1, AHG54517.1, ASF87338.1, AEQ98756.1, AHV81363.1, AHV81089.1, AHV80836.1, AGG39550.1, AGG39526.1, AGG39496.1, AGG39475.1, AGG39442.1, AGG39397.1, AHJ60043.1, AHA84023.1, AHA83880.1, AGN92848.1, AGN28693.1, AGN28462.1, AAS93662.1, AAS93663.1, ASF87348.1, ASF87342.1, AEQ98757.1, AHV81330.1, AHV81012.1, AHV80803.1, AGG39547.1, AGG39523.1, AGG39493.1, AGG39472.1, AGG39439.1, AGG39391.1, BAO49770.1, AHA83990.1, AHA83782.1, AGN28792.1, AGN28638.1, AGN28440.1, AAS93657.1, AAS93664.1, ASF87341.1, ASF87352.1, AEQ98755.1, AHV81253.1, AHV80957.1, AGG39559.1, AGG39544.1, AGG39514.1, AGG39484.1, AGG39466.1, AGG39436.1, AGG39379.1, BAO49766.1, AHA83957.1, AHA83760.1, AGN28781.1, AGN28627.1, AGL96787.1, AAS93656.1, AAS93655.1, ASF87344.1, ASF87337.1, AEQ98752.1, AHV81154.1, AHV80880.1, AGG39562.1, AGG39541.1, AGG39502.1, AGG39490.1, AGG39463.1, AGG39415.1, AHL84194.1, BAO49767.1, AHA83924.1, AHA83694.1, AGN28759.1, AGN28539.1, AGL96786.1, AAS93659.1, CUS01869.1, ASF87351.1, ASF87336.1, AEQ98753.1, AEQ98747.1, ASF87325.1, ASF87326.1, 5W23 A, 5EA3 F, 5UDD A, 5EA8_F, AHG54458.1, AEN74947.1, AHG54485.1, AHG54477.1, AHG54451.1, AHG54463.1, AHG54445.1, AEO12131.1, AEN74945.1, AEN74944.1, ASF87335.1, AHG54515.1, AHA61605.1, AHV81660.1, AHG54441.1 or AIY60640.1.
[0135] In the context of the present invention, “RSV F protein”, “RSV fusion protein (F)”, “RSV F” or “F” can be understood in its broadest sense and refers to F0 (F polypeptide precursor), F1, F2 and Pep27 polypeptides, F2-F1 heterodimer or mature F protein. Petition 870260029351, dated 03 / 28 / 2026, page 150 / 555 87 / 372 (comprising three F2-F1 heterodimers) or fragments and variants of any of these. Consequently, the term “RSV fusion protein (F) derived peptide or protein” refers to a peptide, protein, fragment, or variant derived from, for example, F0 (F protein polypeptide precursor), F1, F2, and Pep27 polypeptides, F2-F1 heterodimer, or the mature F protein. Additionally, the term “RSV fusion protein (F) derived peptide or protein” refers to a peptide, protein, fragment, or variant derived from “RSV F protein” or “RSV fusion protein (F)” as defined above that may be genetically engineered to, for example, lack certain protein elements (e.g., cytoplasmic tail, furin cleavage site, Pep27) or, for example, comprise additional elements (e.g., linker elements, heterologous signal peptides, etc.). For example, the term “peptide or protein derived from an RSV fusion protein (F)” refers to the peptide, protein, fragment, or variant derived from F0, F-del, F0_DSCav1, F_DSCav1_mut1, F_DSCav1_mut2, F_DSCav1_mut3, F_DSCav1_mut4, F_DSCav1_mut5, F_DSCav1_mut6, F_DSCav1_mut7, F_DSCav1_mut8, F_DSCav1_mut0, F-del_DSCav1, F-del_DSCav1_mut1, Fdel_DSCav1_mut2, F-del_DSCav1_mut3, F-del_DSCav1_mut4, Fdel_DSCav1_mut5, F-del_DSCav1_mut6, F-del_DSCav1_mut7, Fdel_DSCav1_mut8, F-del_DSCav1_mut0 (for explanation of the constructs see Table 1). Particularly suitable F protein variants that can be encoded by the RNA of the first aspect are specified below and are provided in Table 1.
[0136] It should be noted that, when reference is made Petition 870260029351, dated 03 / 28 / 2026, page 151 / 555 88 / 372 to amino acid (aa) residues and their position in an F protein of RSV, any numbering used herein, unless otherwise stated, refers to the position of the respective aa residue in a corresponding F0 precursor protein of HRSV(A2) (SEQ ID NO: 68) or a corresponding F0 precursor protein of HRSV (Memphis-37) (SEQ ID NO: 8937 or 11726) wherein position 1 corresponds to the first aa residue, i.e., the N-terminus aa residue of an F0 precursor protein of HRSV(A2) or an F0 precursor protein of HRSV(Memphis37).
[0137] In preferred embodiments, at least one RNA coding sequence of the first aspect encodes at least one antigenic peptide or protein of RSV F protein, wherein the RSV F protein is a full-length F protein (F0) or an F protein with a deleted C-terminus (F-del) or a fragment or variant thereof.
[0138] In this context, any full-length F protein of RSV (precursor protein called F0) may be used as a suitable antigen and may preferably be derived from any of the NCBI Protein Accession numbers provided in Listing 2 or may be chosen from any of the SEQ ID Nos: 68, 8279-8967 or 11726. In preferred embodiments of the invention, the protein Full-length F (F0) protein from HRSV(A2) (SEQ ID NO: 68) is suitably used, see Overview Table 1. In other preferred embodiments of the invention, full-length F (F0) protein from HRSV (Memphis-37) (SEQ ID NO: 8937 or 11726) is suitably used, see Table 1. Petition 870260029351, dated 03 / 28 / 2026, page 152 / 555 89 / 372 overview.
[0139] In this context, any F of RSV with a deleted C-terminus (F-del) can be used as a suitable antigen and can preferably be derived from any NCBI Protein Accession numbers provided in Listing 2 or can be chosen from any of the SEQ ID Nos: 483, 8968-9683, or 12095. An example of such a deletion mutant is the RSV-Fdel554-574 protein according to (Oomens et al. 2006. J. Virol. 80(21):10465-77) in which aa residues 554574 of the full-length F0 protein are removed. Deletion of the main cytoplasmic tail portion (aa 554574) of F0 leads to enhanced intracellular trafficking / cell surface transport in vitro and significantly increases cell surface expression of RSV F. The increased cell surface presentation results in enhanced B cell recognition (aligned with published data; see document WO2015024668).In preferred embodiments of the invention, the C-terminal deleted F protein referred to as F-del herein (SEQ ID NO: 483, 9653 or 12095) is suitably used, see Overview Table 1. In light of the high level of structural conservation of the RSV F protein among different RSV strains (see, for example, Hause et al., 2017, PLOS ONE 12(6): e0180623), the 554-574 aa deletion is applicable to different RSV F protein sequences from different RSV isolates.
[0140] In particularly preferred embodiments, the artificial RNA of the first aspect encodes at least one antigenic peptide or protein derived from RSV F protein, wherein said RSV F protein is engineered to Petition 870260029351, dated 03 / 28 / 2026, page 153 / 555 90 / 372 stabilize the antigen in the pre-fusion conformation. A pre-fusion conformation is particularly advantageous in the context of an efficient RSV vaccine, since several potential epitopes for neutralizing antibodies are merely accessible in the so-called protein conformation.
[0141] In several embodiments, the RSV F protein includes one or more amino acid substitutions that stabilize the F protein in the pre-fusion conformation, for example, substitutions that stabilize the distal membrane portion of the F protein (including the N-terminal region of the F1 polypeptide) in the pre-fusion conformation. For example, the amino acid substitution may introduce an unnatural disulfide bond or may be a cavity-filling substitution.
[0142] Consequently, in several embodiments, a preferred RSV F protein includes S155C and S290C substitutions that form an unnatural disulfide bond that stabilizes the protein in a pre-fusion conformation; that is, in a conformation that specifically binds to one or more pre-fusion specification antibodies, and / or presents a suitable antigenic site that is present in the pre-fusion conformation but not in the post-fusion conformation of RSV F protein. In further embodiments, the recombinant RSV F protein may additionally include F, L, W, Y, H or M in position 190, position 207, or in positions 190 and 207.
[0143] An example of an RSV F protein designed to stabilize the antigen in the pre-fusion conformation is the RSV F protein comprising a DSCav1 mutation (S155C, S290C, S190F and V207L) or a fragment or a Petition 870260029351, dated 03 / 28 / 2026, p. 154 / 555 91 / 372 variant of the same. Such RSV F DSCavl proteins were described in the art (document WO2014160463).
[0144] Consequently, in particularly preferred embodiments, the artificial RNA of the first aspect encodes at least one antigenic peptide or protein derived from RSV F protein, wherein the RSV F protein comprises a DSCav1 mutation (S155C, S290C, S190F and V207L) or a fragment or variant thereof.
[0145] It should be understood in the context of the invention that any RSV F can be mutated at positions S155C, S290C, S190F and V207L to stabilize the protein in the pre-fusion conformation and can be suitably used in the context of the invention. Consequently, any NCBI Protein Accession numbers provided above or any protein selected from SEQ ID NOs: 68, 8279-8967, 483, 8968-9683, 12095 or 11726 or fragments or variants thereof can be chosen by the skilled individual to introduce such amino acid changes according to S155C, S290C, S190F and V207L to generate various RSV F DSCav1 proteins.
[0146] In preferred embodiments, the full-length RSV F protein (precursor protein, F0) of HRSV(A2) (SEQ ID NO: 68) is used to introduce amino acid changes S155C, S290C, S190F and V207L, leading to an amino acid sequence according to SEQ ID NO: 898. Such RSV F protein is referred to as FO_DSCav1 in the present document throughout the present invention (see, Overview Table 1 (Preferred RSV F Protein Antigen Designs)).
[0147] In other preferred modalities, the protein Petition 870260029351, dated 03 / 28 / 2026, page 155 / 555 92 / 372 of F_del of RSV (cytoplasmic tail deleted (aa 554574)) of HRSV(A2) (SEQ ID NO: 483) is used to introduce amino acid changes S155C, S290C, S190F and V207L, leading to an amino acid sequence according to SEQ ID NO: 1267. Such RSV F protein is referred to as Fdel_DSCav1 in the present document throughout the present invention (see Overview Table 1 (Preferred RSV F Protein Antigen Designs)).
[0148] In preferred embodiments, the full-length F protein of RSV (precursor protein, “F0”) from HRSV (Memphis-37) (SEQ ID NO: 8937 or 11726) is used to introduce S155C, S290C amino acid changes, S190F and V207L, leading to an amino acid sequence according to SEQ ID NO: 12464. Such RSV F protein is referred to as FO_DSCav1 in the present document throughout the present invention (see, Overview Table 1 (Preferred RSV F Protein Antigen Designs)).
[0149] In other preferred embodiments, the protein The F_del of RSV (cytoplasmic tail deleted (aa 554-574)) from HRSV (Memphis-37) (SEQ ID NO: 9653 or 12095) is used to introduce amino acid changes S155C, S290C, S190F and V207L, leading to an amino acid sequence according to SEQ ID NO: 12833. Such RSV F protein is referred to as F-del_DSCav1 in the present document throughout the present invention (see Overview Table 1 (Preferred RSV F Protein Antigen Designs)).
[0150] In preferred embodiments, the at least one antigenic peptide or protein may be a engineered protein comprising the two subunits, F1 and F2 of mature F as a single polypeptide chain, wherein F2 and Petition 870260029351, dated 03 / 28 / 2026, p. 156 / 555 93 / 372 F1 proteins are preferably linked via a linker (GS). Examples of so-called manipulated F2 linker-linked F1 proteins (e.g., F(1-103)-GS-F(145-574) or F(1103)-GS-F(145-553)) have been described in the art (Joyce, M. Gordon, et al. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nature Structural & Molecular Biology 23.9 (2016): 811; document WO2017172890). The aforementioned F proteins of RSV F1 ligand of F2 proteins lack aa104-144 (comprising the furin cleavage site and Pep27) and comprise a linker element between F2 polypeptide and F1 polypeptide (e.g., GS linker). So-called F2-linker F1 proteins may exhibit superior properties in terms of stability and / or antigenicity.
[0151] Consequently, in preferred embodiments, the RSV F protein comprises the two F2 and F1 subunits fused into a single polypeptide chain, wherein F2 and F1 are connected via a linker element, preferably a GS linker as specified herein, preferably generating stable F2-linker F1 proteins.
[0152] Preferably, said F1 fusion proteins of F2 ligand, for example, F(1-103)-GS-F(145-574) or F(1103)-GS-F(145-553) additionally comprise a DScavl mutation as highlighted above (referred to as “mut0” in this document; for example, SEQ ID Nos: 3850, 4219 or 13940, 14309).
[0153] In particularly preferred embodiments, the RSV F protein may additionally comprise at least one additional selected mutation of (S46G, Petition 870260029351, dated 03 / 28 / 2026, p. 157 / 555 94 / 372 A149C, S215P, Y458C, K465Q), (S46G, E92D, A149C, S215P, Y458C, K465Q), (S46G, N67I, E92D, A149C, S215P, Y458C, K465Q), (A149C, Y458C), (N183GC, N428C), (Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q), (Q98C, Q361C, L95M, I221M, R429K) or (N183GC, N428C, S46G, N67I, E92D, S215P, K465Q) or a fragment or variant thereof.
[0154] In particularly preferred embodiments, the so-called F1 F2 ligand proteins (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145-553)) may additionally comprise, preferably in addition to the DSCav1 mutation, at least one selected mutation of S46G, A149C, S215P, Y458C, K465Q, referred to as “multiple” in this document, for example, SEQ ID Nos: 1636, 2005 or 14678, 15047; or S46G, E92D, A149C, S215P, Y458C, K465Q, referred to as mut2 in this document, for example, SEQ ID Nos: 2374, 2743 or 15416, 15785; or S46G, N67I, E92D, A149C, S215P, Y458C, K465Q, referred to as "mut3" in this document, for example, SEQ ID Nos: 3112, 3481 or 13202, 13571, or a fragment or variant of any of these mutations (see Overview Table 1 (Preferred RSV F protein antigen designs)).
[0155] In other embodiments, said F2 ligand F1 proteins (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145553)) may additionally comprise, preferably in addition to the DSCav1 mutation, at least one mutation selected from A149C, Y458C, referred to as “mut4” herein, for example, SEQ ID NOs: 4588, 4957 or 16154, 16523; or N183GC, N428C, referred to as “mut5” in this document, for example, SEQ ID Nos: 5326, 5695 or Petition 870260029351, dated 03 / 28 / 2026, p. 158 / 555 95 / 372 16892, 17261; or Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q, referred to as mut6 in this document, for example, SEQ ID Nos: 6064, 6433 or 17630, 17999; or Q98C, Q361C, L95M, I221M, R429K, referred to as mut7” in this document, for example, SEQ ID Nos: 6802, 7171 or 18368, 18737; or N183GC, N428C, S46G, N67I, E92D, S215P, K465Q, referred to as "mut8" in this document, for example, SEQ ID Nos: 7540, 7909 or 19106, 19475, or a fragment or variant thereof.
[0156] In the context of the invention, it should be understood that any RSV F can be adapted in such a way that the two subunits, F1 and F2, are comprised in a single polypeptide chain, wherein F2 and F1 can be connected via a linker, for example, a linker (GS) to improve protein stability as explained for mutations mut1”, mut2” and mut3”, for example, by deleting aa104-144 from the F0 polypeptide chain (as explained above), by introducing a linker element between F2 and F1 as explained above, and by introducing suitable amino acid substitutions as explained above. Consequently, any NCBI Protein Accession numbers provided above (see List 2) or any protein selected from SEQ ID Nos: 68, 8279-8967, 483, 8968-9683, 11726, 12095 or fragments or variants thereof may be adapted by the expert to generate F1 fusion proteins of F2 ligand as highlighted in this document, and may be further adapted by introducing amino acid substitutions (S46G, A149C, S215P, Y458C, K465Q), (S46G, E92D, A149C, S215P, Y458C, K465Q), (S46G, N67I, E92D, A149C, S215P, Y458C, K465Q), (A149C, Y458C), Petition 870260029351, dated 03 / 28 / 2026, p. 159 / 555 96 / 372 (N183GC, N428C), (Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q), (Q98C, Q361C, L95M, I221M, R429K) or (N183GC, N428C, S46G, N67I, E92D, S215P, K465Q) and / or a DSCav1 mutation. Furthermore, in addition to using a GS linker as highlighted above, the expert can obviously choose from several linkers to arrive at similarly suitable RSV F protein variants (e.g., selected from SEQ ID Nos: 117-162 of patent application WO2017 / 172890 or fragments or variants of these sequences, or selected from SEQ ID Nos: 1509-1565 of patent application WO2017 / 172890). WO2017 / 081082, or fragments or variants of these sequences).
[0157] In preferred embodiments, the F1 F2-linker proteins (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145553)) comprise a DSCav-1 mutation as highlighted above, referred to as F_DSCav1_mut0 or F-del_DSCav1_mut0 herein. In preferred embodiments, the F1 F2-linker proteins (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145-553)) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut1 as defined above, referred to as F_DSCav1_mut1 or F-del_DSCav1_mut1 herein. In preferred embodiments, the F1 F2-linker proteins (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145-553) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut2 as defined above, referred to as F_DSCav1_mut2 or Fdel_DSCav1_mut2 in this document. In preferred embodiments, the F1 F2 ligand proteins (F(1-103) Petition 870260029351, dated 03 / 28 / 2026, p. 160 / 555 97 / 372 GS-F(145-574) or F(1-103)-GS-F(145-553) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut3 as defined above, referred to as F_DSCav1_mut3 or F-del_DSCav1_mut3 in this document. In preferred embodiments, the F1 F2-linker proteins (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145553)) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut4 as defined above, referred to as F_DSCav1_mut4 or F-del_DSCav1_mut4 herein. In preferred embodiments, the F1 F2-linker proteins (F(1-103)GS-F(145-574) or F(1-103)-GS-F(145-553)) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut5 as defined above, referred to as F_DSCav1_mut5 or F-del_DSCav1_mut5 herein.In preferred embodiments, the F1 proteins of F2 ligand (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145553)) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut6 as defined above, referred to as F_DSCav1_mut6 or F-del_DSCav1_mut6 herein. In preferred embodiments, the F1 proteins of F2 ligand (F(1-103)GS-F(145-574) or F(1-103)-GS-F(145-553)) comprise a DSCav-1 mutation as highlighted above, and additionally, an amino acid substitution mut7 as defined above, referred to as F_DSCav1_mut7 or F-del_DSCav1_mut7 herein. In preferred embodiments, the F1 proteins The F2 ligand (F(1-103)-GS-F(145-574) or F(1-103)-GS-F(145553)) comprises a DSCav-1 mutation as highlighted above, and, additionally, a mut8 substitution. Petition 870260029351, dated 03 / 28 / 2026, page 161 / 555 98 / 372 amino acid as defined above, called F DSCavl mut8 or F-del_DSCav1_mut8 in this document.
[0158] A detailed description of particularly preferred RSV F proteins is provided in Table 1.
[0159] In Table 1, all references to amino acid (aa) residues and their position in an RSV F protein refer to the position of the respective aa residue in a corresponding HRSV(A2) F0 precursor protein (SEQ ID NO: 68) or
[0160] HRSV (Memphis-37) (SEQ ID NO: 8937 or 11726). Furthermore, the abbreviations for suitable RSV F protein antigen designs in Table 1 are used throughout the description of the invention (e.g., "F0", "F-del", "F0_DSCav1", "F-del_DSCav1", "F_DSCav1_mut1", "Fdel_DSCav1_mut1", "F_DSCav1_mut2", "F-del_DSCav1_mut2") F_DSCav1_mut3, „F-del_DSCav1_mut3, „F_DSCav1_mut4, „Fdel_DSCav1_mut4, „F_DSCav1_mut5, „F-del_DSCav1_mut5, „F_DSCav1_mut6, „F-del_DSCav1_mut6, „F_DSCav1_mut7, „Fdel_DSCav1_mut7, „F_DSCav1_mut8, „F-del_DSCav1_mut8, „F_DSCav1_mut0, „F-del_DSCav1_mut0). Column A of Table 1 provides SEQ ID NOs of the respective HRSV(A2) derived RSV F protein antigen designs; Column B of Table 1 provides SEQ ID NOs of the respective HRSV-derived RSV F protein antigen designs (Memphis-37). Notably, the invention description explicitly includes the information provided under the identifier. <223> from the ST25 sequence listing of this application. Table 1: Preferred RSV F protein antigen designs Petition 870260029351, dated 03 / 28 / 2026, page 162 / 555 99 / 372 Antigen Name Protein Design Description AB F0 aal-574, Full-length RSV F0 precursor 68 8937, 11726 F-del aa1-553, C-terminal aa 554-574 deletion 483 9653, 12095 F0_DSCav1 aa1-574, aa substitutions: S155C, S290C, S190F and V207L 898 12464 F-del_DSCavl aa1-553, C-terminal aa 554-574 deletion, aa substitutions: S155C, S290C, S190F and V207L 1267 12833 F_DSCav1_mut0 aa1-103 - GS(ligand) - aa145-574 F1 construct of F2 ligand substitutions of aa: S155C, S290C, S190F and V207L 3850 13940 F- del_DSCav1_mut0 aa1-103 - GS(ligand) - aa145-553 deletion of aa 554-574 from C terminal, F1 construct of F2 ligand substitutions of aa: S155C, 4219 14309 Petition 870260029351, dated 03 / 28 / 2026, p. 163 / 555 100 / 372 Antigen Name Protein Design Description AB S290C, S190F and V207L F_DSCav1_mut1 aa1-103 - GS(ligand) - aa145-574, F1 construct of F2 linker, aa substitutions: S155C, S290C, S190F and V207L; S46G, A149C, S215P, Y458C, K465Q 1636 14678 F- del_DSCav1_mut1 aa1-103 - GS(ligand) - aa145-553 C-term aa deletion 554-574, F1 construct of F2 linker, aa substitutions: S155C, S290C, S190F and V207L; S46G, A149C, S215P, Y458C, K465Q 2005 15047 F_DSCav1_mut2 aa1-103 - GS(linker) - aa145-574 F2 linker F1 construct, aa substitutions: S155C, S290C, S190F and V207L; S46G, E92D, A149C, S215P, Y458C, K465Q 2374 15416 Petition 870260029351, dated 03 / 28 / 2026, p. 164 / 555 101 / 372 Antigen Name Protein Design Description AB F- del_DSCav1_mut2 aa1-103 - GS(ligand) - aa145-553 deletion of aa 554-574 from the C-terminus, F1 construct from F2 linker, aa substitutions: S155C, S290C, S190F and V207L; S46G, E92D, A149C, S215P, Y458C, K465Q 2743 15785 F_DSCav1_mut3 aa1-103 - GS(ligand) - aa145-574 F1 construct from F2 linker, aa substitutions: S155C, S290C, S190F and V207L; S46G, N67I, E92D, A149C, S215P, Y458C, K465Q 3112 13202 F- del_DSCav1_mut3 aa1-103 - GS(ligand) - aa145-553 deletion of aa 554-574 from C terminal, F1 construct of F2 ligand, aa substitutions: S155C, S290C, S190F and V207L; S46G, N67I, E92D, A149C, S215P, Y458C, K465Q 3481 13571 Petition 870260029351, dated 03 / 28 / 2026, p. 165 / 555 102 / 372 Antigen Name Protein Design Description AB F_DSCav1_mut4 aa1-103 - GS(ligand) - aa145-574 F1 construct from F2 ligand, amino acid substitutions: S155C, S290C, S190F and V207L; A149C, Y458C 4588 16154 F- del_DSCav1_mut4 aa1-103 - GS(ligand) - aa145-553 C-terminus 554-574 aa deletion, F1 construct from F2 ligand, amino acid substitutions: S155C, S290C, S190F and V207L; A149C, Y458C 4957 16523 F_DSCav1_mut5 aa1-103 - GS(ligand) - aa145-574 F1 construct of F2 ligand, aa substitutions: S155C, S290C, S190F and V207L; N183GC, N428C 5326 16892 F- del_DSCav1_mut5 aa1-103 - GS(ligand) - aa145-553 deletion of aa 554-574 from C terminal, F1 construct of 5695 ligand 17261 Petition 870260029351, dated 03 / 28 / 2026, p. 166 / 555 103 / 372 Antigen name Protein design description AB F2, amino acid substitutions: S155C, S290C, S190F and V207L; N183GC, N428C F_DSCav1_mut6 aa1-103 - GS(ligand) - aa145-574 F1 construct of F2 ligand, amino acid substitutions: S155C, S290C, S190F and V207L; Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q 6064 17630 F- del_DSCav1_mut6 aa1-103 - GS(ligand) - aa145-553 deletion of aa 554-574 from terminal C, F1 construct of F2 ligand, aa substitutions: S155C, S290C, S190F and V207L; Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q 6433 17999 F_DSCav1_mut7 aa1-103 - GS(ligand) - aa145-574 F2 ligand F1 construct, 6802 18368 Petition 870260029351, dated 03 / 28 / 2026, p. 167 / 555 104 / 372 Antigen Name Protein design description AB amino acid substitutions: S155C, S290C, S190F and V207L; Q98C, Q361C, L95M, I221M, R429K F- del_DSCav1_mut7 aa1-103 - GS(ligand) - aa145-553 C-term 554-574 amino acid deletion, F2 ligand F1 construct, amino acid substitutions: S155C, S290C, S190F and V207L; Q98C, Q361C, L95M, I221M, R429K 7171 18737 F_DSCav1_mut8 aa1-103 - GS(ligand) - aa145-574 F1 construct of F2 ligand, aa substitutions: S155C, S290C, S190F and V207L; N183GC, N428C, S46G, N67I, E92D, S215P, K465Q 7540 19106 F- del_DSCav1_mut8 aa1-103 - GS(ligand) - aa145-553 deletion of aa 554-574 from C terminal, F1 construct of F2 ligand, 7909 19475 Petition 870260029351, dated 03 / 28 / 2026, p. 168 / 555 105 / 372 Antigen Name Protein Design Description AB amino acid substitutions: S155C, S290C, S190F and V207L; N183GC, N428C, S46G, N67I, E92D, S215P, K465Q
[0161] In particularly preferred embodiments, the artificial RNA according to the first aspect encodes at least one antigenic peptide or protein derived from an RSV fusion protein (F), wherein the RSV F protein is selected from
[0162] F0, F-del, F0_DSCav1, F_DSCav1_mut0, F_DSCav1_mut1, F_DSCav1_mut2, F_DSCav1_mut3, F_DSCav1_mut4, F_DSCav1_mut5, F_DSCav1_mut6, F_DSCav1_mut7, F_DSCav1_mut8, F-del_DSCav1, F-del_DSCav1_mut0, F-del_DSCav1_mut1, Fdel_DSCav1_mut2, F-del_DSCav1_mut3, F-del_DSCav1_mut4, Fdel_DSCav1_mut5, F-del_DSCav1_mut6, F-del_DSCav1_mut7, Fdel_DSCav1_mut8 or a fragment or variant thereof (see, for example, Table 1).
[0163] In the context of the invention, particularly preferred and advantageous are the RSV F proteins selected from F-del_DSCav1, F-del_DSCav1_mut0, F-del_DSCav1_mut1, F-del_DSCav1_mut2, F-del_DSCav1_mut3, Fdel_DSCav1_mut4, F-del_DSCav1_mut5, F-del_DSCav1_mut6, Fdel_DSCav1_mut7, F-del_DSCav1_mut8 or a fragment or variant thereof (see, for example, Table 1).
[0164] In preferred embodiments, the artificial RNA of the first aspect comprises at least one coding sequence encoding at least one peptide or protein. Petition 870260029351, dated 03 / 28 / 2026, page 169 / 555 106 / 372 antigenic comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ ID Nos: 68, 483, 898, 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999, 18368, 18737, 19106, 19475 (see, for example, Table 1), or 82799683 or a fragment or variant of any of these sequences. Additional information relating to each of these appropriate amino acid sequences that encode RSV proteins can also be derived from the sequence listing, in particular, from details provided therein under the identifier. <223> as explained below.
[0165] In preferred embodiments, the artificial RNA of the first aspect comprises at least one coding sequence encoding at least one antigenic peptide or protein comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ ID Nos: 68, 483, 898, 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999, 18368, 18737, 19106, 19475 (see, for example, Table 1) or a Petition 870260029351, dated 03 / 28 / 2026, p. 170 / 555 107 / 372 fragment or variant of any of these sequences. Additional information relating to each of these appropriate amino acid sequences encoding RSV proteins can also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> as explained below.
[0166] In particularly preferred embodiments, the artificial RNA of the first aspect comprises at least one coding sequence encoding at least one antigenic peptide or protein comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ ID Nos: 1267, 2005, 2743, 3481, 4219, 4957, 5695, 6433, 7171, 7909, 12833, 14309, 15047, 15785, 13571, 16523, 17261, 17999, 18737, 19475 (see, for example, Table 1) or a fragment or variant of any of these sequences. Additional information relating to each of these suitable amino acid sequences encoding RSV proteins can also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> as explained below.
[0167] In other embodiments, artificial RNA according to the first aspect comprises at least one coding sequence encoding at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following sequences: Petition 870260029351, dated 03 / 28 / 2026, p. 171 / 555 108 / 372 ID Nos: 8279-9683 or a fragment or variant of any of these sequences. Additional information relating to each of these suitable amino acid sequences encoding RSV proteins can also be derived from the sequence listing, in particular, from details provided therein under the identifier. <223> as explained below.
[0168] In other embodiments, artificial RNA as defined herein comprises at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of SEQ ID Nos: 1-1428 of patent application WO2014 / 160463 or a fragment or variant of any of these sequences. In this context, the SEQ IDs NOs: 1-1428 of patent application WO2014 / 160463 and the disclosure related thereto are incorporated by reference thereto.
[0169] In other embodiments, artificial RNA as defined herein comprises at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of SEQ ID Nos: 1-11 of patent application WO2015 / 024668 or a fragment or variant of any of these sequences. Petition 870260029351, dated 03 / 28 / 2026, p. 172 / 555 109 / 372 In this context, the SEQ IDs NOS: 1-11 of patent application WO2015 / 024668 and the disclosure related thereto are incorporated by reference thereto.
[0170] In other embodiments, the artificial RNA as defined herein comprises at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of SEQ ID Nos: 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 243 or 245 of the patent application. WO2017 / 070622 or a fragment or variant of any of these sequences. In this context, the SEQ ID NOs: 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 243 or 245 of patent application WO2017 / 070622 and the disclosure related thereto are incorporated by reference thereto.
[0171] In other embodiments, artificial RNA as defined herein comprises at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein comprising or consisting of at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of SEQ ID Nos: 1-65, 81-95, 110-116 of patent application WO2017 / 172890 or a fragment or variant of any of these sequences. In this context, the SEQ IDs NOs: 1-65, 8195, 110-116, of patent application WO2017 / 172890 and the Petition 870260029351, dated 03 / 28 / 2026, p. 173 / 555 110 / 372 disclosures related to them are incorporated by way of reference to the same.
[0172] According to another preferred embodiment, the artificial RNA of the invention encodes at least one antigenic peptide or protein as defined above and may additionally encode at least one additional heterologous peptide or protein element.
[0173] Suitably, at least one additional peptide or protein element may promote secretion of the encoded antigenic peptide or protein of the invention (e.g., through secretory signal sequences), promote anchoring of the encoded antigenic peptide or protein of the invention to the plasma membrane (e.g., through transmembrane elements), promote antigen complex formation (e.g., through multimerization domains), promote virus-like particle formation (VLP formation sequence). Furthermore, the artificial nucleic acid sequence according to the present invention may additionally encode peptide-binding elements, self-cleaving peptides, immune adjuvant sequences, or cell-targeting sequences.Suitable multimerization domains can be selected from the list of amino acid sequences according to SEQ ID NOs: 11161167 of patent application WO2017 / 081082, or fragments or variants of these sequences. Trimerization and tetramerization elements can be selected from, for example, manipulated leucine zippers (manipulated α-helical coiled peptide that adopts a parallel trimeric state), fibritin fold domain. Petition 870260029351, dated 03 / 28 / 2026, page 174 / 555 111 / 372 of Enterobacteriaceae T4 phage, GCN4pII, GCN4-pLI and p53. In this context, the fibritin fold domain of Enterobacteriaceae T4 phage, GCN4pII, GCN4-pLI and p53 are preferred. Suitable transmembrane elements may be selected from the list of amino acid sequences according to SEQ ID NOs: 1228-1343 of patent application WO2017 / 081082, or fragments or variants of these sequences. Suitable VLP-forming sequences may be selected from the list of amino acid sequences according to SEQ ID NOs: 1168-1227 of patent application WO2017 / 081082, or fragments or variants of these sequences. Suitable peptide ligands may be selected from the list of amino acid sequences according to SEQ ID Nos: 1509-1565 of patent application WO2017 / 081082, or fragments or variants of these sequences.Suitable self-cleaving peptides may be selected from the list of amino acid sequences according to SEQ ID Nos: 1434-1508 of patent application WO2017 / 081082, or fragments or variants of these sequences. Suitable immune adjuvant sequences may be selected from the list of amino acid sequences according to SEQ ID Nos: 1360-1421 of patent application WO2017 / 081082, or fragments or variants of these sequences. Suitable dendritic cell (DC) targeting sequences may be selected from the list of amino acid sequences according to SEQ ID Nos: 1344-1359 of patent application WO2017 / 081082, or fragments or variants of these sequences. Suitable secretory signaling peptides may be selected from the list of sequences according to... Petition 870260029351, dated 03 / 28 / 2026, page 175 / 555 112 / 372 amino acids according to SEQ ID Nos: 1-1115 and SEQ ID No: 1728 of patent application WO2017 / 081082, or fragments or variants of these sequences. At the nucleic acid level, any nucleic acid sequence (e.g., RNA sequence) encoding such amino acid sequences may be selected. In this context, the disclosure of document WO2017 / 081082 is incorporated by reference hereto. The heterologous secretory signal sequence may enhance the secretion of the encoded antigenic peptide or protein.
[0174] According to the embodiments, the secretory signal sequence comprises an amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, % or 99% identical to any of the SEQ ID NOS: 2132921362 or a fragment or variant of any of these sequences. Additional information relating to each of these suitable amino acid sequences encoding secretory signal sequences may also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> .
[0175] According to preferred embodiments, the artificial nucleic acid, particularly the artificial RNA, comprises at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein as defined herein, preferably derived from RSV F protein or fragments and variants thereof. In this context, any coding sequence encoding at least one RSV-derived antigenic peptide or protein, preferably derived from Petition 870260029351, dated 03 / 28 / 2026, page 176 / 555 113 / 372 RSV F protein or fragments and variants thereof can be understood as a suitable coding sequence and, therefore, can be included in the artificial RNA of the first aspect.
[0176] In preferred embodiments, the artificial RNA of the first aspect may comprise or consist of at least one coding sequence encoding at least one antigenic peptide or protein derived from RSV F protein as defined herein, preferably encoding any of the following SEQ ID Nos: 68, 483, 898, 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999, 18368, 18737, 19106, 19475 or fragments of variants thereof. It should be understood that, at the nucleic acid level, any nucleic acid sequence, in particular, any RNA sequence that codes for amino acid sequences that are identical to the SEQ ID NOs: 68, 483, 898, 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999, 18368, 18737, 19106, 19475 or fragments or variants thereof, or any nucleic acid sequence (e.g., DNA sequence, RNA sequence) encoding amino acid sequences that is at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ ID Nos: 68, 483, 898, Petition 870260029351, dated 03 / 28 / 2026, p. 177 / 555 114 / 372 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999 18368, 18737, 19106, 19475 or fragments or variants thereof may be selected and, consequently, may be understood as a suitable coding sequence and, therefore, may be included in the artificial RNA of the first aspect of the invention.
[0177] In other embodiments, the artificial RNA of the first aspect may comprise or consist of at least one coding sequence encoding any of SEQ ID NOs: 8279-9683 or fragments of variants thereof.It should be understood that, at the nucleic acid level, any nucleic acid sequence, in particular, any RNA sequence encoding amino acid sequences that are identical to SEQ ID NOs: 8279-9683 or fragments or variants thereof, or any nucleic acid sequence (e.g., DNA sequence, RNA sequence) encoding amino acid sequences that are at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of SEQ ID NOs: 8279-9683 or fragments or variants thereof may be selected and, consequently, may be understood as a suitable coding sequence and, therefore, may to be understood in the artificial RNA of the first aspect of the invention.
[0178] In other embodiments, the artificial RNA of the first aspect may comprise or consist of at least one coding sequence that encodes any Petition 870260029351, dated 03 / 28 / 2026, p. 178 / 555 115 / 372 one of SEQ ID Nos: 1-1428 of patent application WO2014 / 160463 or fragments or variants thereof. It should be understood that, at the nucleic acid level, any nucleic acid sequence, in particular, any RNA sequence encoding amino acid sequences that are identical to SEQ ID Nos: 1-1428 of patent application WO2014 / 160463 or fragments or variants thereof, or any nucleic acid sequence (e.g., DNA sequence, RNA sequence) encoding amino acid sequences that are at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the SEQ ID Nos: 1-1428 of patent application WO2014 / 160463 or fragments or Variants of these can be selected and, consequently, can be understood as a suitable coding sequence and, therefore, can be understood in the artificial RNA of the first aspect of the invention.
[0179] In other embodiments, the artificial RNA of the first aspect may comprise or consist of at least one coding sequence encoding any of the SEQ ID Nos: 1-11 of patent application WO2015 / 024668 or fragments or variants thereof. It should be understood that, at the nucleic acid level, any nucleic acid sequence, in particular, any RNA sequence encoding amino acid sequences that are identical to the SEQ ID Nos: 1-11 of patent application WO2015 / 024668 or fragments or variants thereof, or any nucleic acid sequence (e.g., DNA sequence, RNA sequence) encoding amino acid sequences that are at least 70%, 80%, 85%, 86%, 87%, 88%, 89 Petition 870260029351, dated 03 / 28 / 2026, p. 179 / 555 116 / 372%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or % identical to any of SEQ ID Nos: 1-11 of patent application WO2015 / 024668 or fragments or variants thereof may be selected and, consequently, may be understood as a suitable coding sequence and, therefore, may be understood in the artificial RNA of the first aspect of the invention.
[0180] In other embodiments, the artificial RNA of the first aspect may comprise or consist of at least one coding sequence encoding any of the following SEQ ID Nos: 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 243 or 245 of patent application WO2017 / 070622 or fragments or variants thereof. It should be understood that, at the nucleic acid level, any nucleic acid sequence, in particular, any RNA sequence encoding amino acid sequences that are identical to the SEQ ID Nos: 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 243 or 245 of patent application WO2017 / 070622 or fragments or variants thereof, or any nucleic acid sequence (e.g., DNA sequence, RNA sequence) encoding amino acid sequences that are at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of SEQ ID Nos: 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 243 or 245 of the patent application WO2017 / 070622 or fragments or variants thereof may be selected and, consequently, may be understood as a suitable coding sequence and, therefore, may be understood in the artificial RNA of the first aspect of the invention. Petition 870260029351, dated 03 / 28 / 2026, p. 180 / 555 117 / 372
[0181] In other embodiments, the artificial RNA of the first aspect may comprise or consist of at least one coding sequence encoding any of SEQ ID NOs: 1-65, 81-95, 110-116 of patent application WO2017 / 172890 or fragments or variants thereof. It should be understood that, at the nucleic acid level, any nucleic acid sequence, in particular, any RNA sequence encoding amino acid sequences that are identical to SEQ ID NOs: 1-65, 81-95, Sequences 1-116 of patent application WO2017 / 172890, or fragments or variants thereof, or any nucleic acid sequence (e.g., DNA sequence, RNA sequence) encoding amino acid sequences that are at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any of the SEQ ID Nos. 1-65, 81-95, 110-116 of patent application WO2017 / 172890, or fragments or variants thereof may be selected and, consequently, may be understood as a suitable coding sequence and, therefore, may be understood as artificial RNA. of the first aspect of the invention.
[0182] Suitablely, in particularly preferred embodiments, the artificial RNA of the first aspect comprises a coding sequence located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3' UTR.
[0183] In preferred embodiments, the artificial RNA of the first aspect comprises a coding sequence comprising at least one of the nucleic acid sequences that are identical or at least 70%, 80%, 85%, Petition 870260029351, dated 03 / 28 / 2026, p. 181 / 555 118 / 372%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NOs: 69-482, 484-897, 899-1266, 1268-1635, 1637-2004, 2006-2373, 2375-2742, 2744-3111, 3113-3480, 3482-3849, 3851-4218, 4220-4587, 4589-4956, 4958-5325, 5327-5694, 5696-6063, 60656432, 6434-6801, 6803-7170, 7172-7539, 7541-7908, 79108277, 8278, 11727-12094, 12096-12463, 12465-12832, 1283413201, 13941-14308, 14310-14677, 14679-15046, 15048-15415, 15417-15784, 15786-16153, 13203-13570, 13572-13939, 1615516522, 16524-16891, 16893-17260, 17262-17629, 17631-17998, 18000-17998, 18369-18736, 18738-19105, 19107-19474, 1947619843, 21363-21706 or a fragment or variant of any of these sequences (see also Table 3-6). Additional information relating to each of these suitable nucleic acid sequences they encode can also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> .
[0184] In particularly preferred embodiments, the artificial RNA of the first aspect comprises a coding sequence comprising at least one of the nucleic acid sequences that are identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the SEQ ID NOs: 69-77, 484-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596, 4958-4965, 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 21363-21384, 11727-11734, 12096-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679 Petition 870260029351, dated 03 / 28 / 2026, p. 182 / 555 119 / 372 14686, 15048-15055, 15417-15424, 15786-15793, 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376, 18738-18745, 19107-19114, 19476-19483, 21389-21410 or a fragment or a fragment or variant of any of these sequences (see also Tables 3 and 4). Additional information relating to each of these appropriate nucleic acid sequences they encode can also be derived from the sequence listing, in particular, from details provided therein under the identifier. <223> .
[0185] In other embodiments, the artificial RNA of the first aspect comprises a coding sequence comprising at least one of the nucleic acid sequences that are identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID Nos: 383-388 of patent application WO2014 / 160463 or a fragment or a fragment or variant of any of these sequences.
[0186] In other embodiments, the artificial RNA of the first aspect comprises a coding sequence comprising at least one of the nucleic acid sequences that are identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID Nos: 12-22 of patent application WO2015 / 024668 or a fragment or a fragment or variant of any of these sequences.
[0187] In other embodiments, the artificial RNA of the first aspect comprises a coding sequence comprising at least one of the nucleic acid sequences that are identical or at least 70%, 80%, 85%, Petition 870260029351, dated 03 / 28 / 2026, p. 183 / 555 120 / 372%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, %, 97%, 98% or 99% identical to SEQ ID NOs: 1, 2, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 242, 244, 246, 257, 258-280 of patent application WO2017 / 070622 or a fragment or a variant of any of these sequences.
[0188] In other embodiments, the artificial RNA of the first aspect comprises a coding sequence comprising at least one of the nucleic acid sequences that are identical or at least 70%, 80%, 85%, %, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, %, 97%, 98% or 99% identical to SEQ ID Nos: 96-99 of patent application WO2017 / 172890 or a fragment or a fragment or variant of any of these sequences.
[0189] According to preferred embodiments, artificial RNA is modified and / or stabilized artificial RNA.
[0190] According to preferred embodiments, the artificial RNA of the present invention can thus be provided as a “stabilized artificial RNA,” that is, an RNA that exhibits enhanced resistance to degradation in vivo and / or an artificial RNA that exhibits enhanced stability in vivo, and / or an artificial RNA that exhibits enhanced translation capability in vivo. Specific suitable modifications in this context that are suitable for stabilizing the artificial RNA are described below.
[0191] Such stabilization can be achieved by providing “dry RNA” and / or “purified RNA” as specified in this document. Alternatively or in addition, such stabilization can be achieved, for example, by a Petition 870260029351, dated 03 / 28 / 2026, p. 184 / 555 121 / 372 Modified phosphate backbone of the artificial RNA of the present invention. A backbone modification in conjunction with the present invention consists of a modification in which phosphates of the backbone of the nucleotides contained in the RNA are chemically modified. The nucleotides that may preferably be used in this connection contain, for example, a phosphorothioate-modified backbone, preferably with at least one of the phosphate oxygens contained in the backbone being replaced by a sulfur atom. The stabilized RNAs may further include, for example: non-ionic phosphate analogs, such as, for example, alkyl and aryl phosphonates, in which the charged phosphonate oxygen is replaced by an alkyl or aryl group, or phosphodiesters and alkylphosphotriesters, in which the charged oxygen residue is present in the alkylated form.Such modifications to the main chain typically include, without implying any limitation, modifications of the group consisting of methylphosphonates, phosphoramidates and phosphorothioates (e.g., cytidine-5'-O-(1-thiophosphate)).
[0192] Suitable modifications that have the capacity to stabilize the artificial RNA of the invention are described below.
[0193] According to the embodiments, the artificial RNA according to the invention is a modified artificial RNA, wherein the modification refers to chemical modifications comprising modifications to the backbone as well as sugar modifications or base modifications.
[0194] In this context, a modified artificial RNA such Petition 870260029351, dated 03 / 28 / 2026, page 185 / 555 122 / 372 defined in this document may contain nucleotide analogs / modifications, for example, back-strand modifications, sugar modifications, or base modifications. A back-strand modification in conjunction with the present invention consists of a modification in which the back-strand phosphates of the nucleotides contained in a nucleic acid, for example, an artificial RNA, are chemically modified. A sugar modification in conjunction with the present invention is a chemical modification of the sugar of the RNA nucleotides as defined in this document. Additionally, a base modification in conjunction with the present invention consists of a chemical modification of the base moiety of the RNA nucleotides. In this context, nucleotide analogs or modifications are preferably selected from nucleotide analogs that are applicable to transcription and / or translation.
[0195] In particularly preferred embodiments of the present invention, the nucleotide analogs / modifications that can be incorporated into a nucleic acid or, particularly, into a modified RNA, as described herein, are preferably selected from 2-amino-6-chloropurinariboside-5'-triphosphate, 2-aminopurine-riboside-5'-triphosphate; 2-aminoadenosine-5'-triphosphate, 2'-Amino-2'-deoxycytidine-triphosphate, 2-thiocytidine-5'-triphosphate, 2-thiouridine-5'-triphosphate, 2'-Fluorothymidine-5'-triphosphate, 2'-O-Methyl-inosine-5'-triphosphate, 4-thiouridine-5'-triphosphate, 5-aminoallylcytidine-5'-triphosphate, 5-aminoallyluridine-5'-triphosphate, 5-bromocytidine-5'-triphosphate, 5-bromouridine-5'-triphosphate, Petition 870260029351, dated 03 / 28 / 2026, page 186 / 555 123 / 372 5-Bromo-2'-deoxycytidine-5'-triphosphate, 5-Bromo-2'deoxyuridine-5'-triphosphate, 5-iodocytidine-5'-triphosphate, 5-Iodo-2'-deoxycytidine-5'-triphosphate, 5-iodouridine-5'-triphosphate, 5-Iodo-2'-deoxycytidine-5'-triphosphate, 5methylcytidine-5'-triphosphate, 5-methyluridine-5'-triphosphate, 5-Propinyl-2'-deoxycytidine-5'-triphosphate, 5-Propinyl-2'deoxyuridine-5'-triphosphate, 6-azacytidine-5'-triphosphate, 6-azauridine-5'-triphosphate, 6-choropurineribosideum-5'-triphosphate, 7-deazaadenosine-5'-triphosphate, 7deazaguanosine-5'-triphosphate, 8-azaadenosine-5'-triphosphate, 8-azidoadenosine-5'-triphosphate, benzimidazole-riboside-5'triphosphate, N1-methyladenosine-5'-triphosphate, N1methylguanosine-5'-triphosphate, N6-methyladenosine-5'triphosphate, O6-methylguanosine-5'-triphosphate, pseudouridine5'-triphosphate or puromycin-5'-triphosphate, xanthosine-5'-triphosphate.Particular preference is given to nucleotides for base modifications selected from the group of base-modified nucleotides consisting of 5-methylcytidine-5'-triphosphate, 7-deazaguanosine-5'-triphosphate, 5-bromocytidine-5'-triphosphate and pseudouridine-5'-triphosphate, pyridin-4-one ribonucleoside, 5-azauridine, 2-thio-5-aza-uridine, 2-thiouridine, 4-thiopseudouridine, 2-thio-pseudouridine, 5-hydroxyuridine, 3-methyluridine, 5-carboxymethyl-uridine, 1-carboxymethylpseudouridine, 5-propynyl-uridine, 1-propynylpseudouridine, 5-taurinomethyluridine, 1-taurinomethylpseudouridine, 5-taurinomethyl-2-thio-uridine, 1taurinomethyl-4-thio-uridine, 5-methyl-uridine, 1-methylpseudouridine, 4-thio-1-methyl-pseudouridine, 2-thio-1-methylpseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1. Petition 870260029351, dated 03 / 28 / 2026, page 187 / 555 124 / 372 methyl-1-deaza-pseudouridine, di-hydrouridine, dihidropseudouridina, 2-thio-di-hydrouridine, 2-thio-dihidropseudouridina, 2-methoxyuridine, 2-methoxy-4-thiouridine, 4-methoxy-pseudouridine and 4-methoxy-2-thiopseudouridine, 5-aza-cytidine, pseudoisocytidine, 3-methylcytidine, N4-acetylcytidine, 5-formylcytidine, N4methylcytidine, 5-hydroxymethylcytidine, 1-methylpseudoisocytidine, pyrrolo-cytidine, pyrrolopseudoisocytidine, 2-thio-cytidine, 2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-1-deaza-pseudoisocytidine, 1-methyl-1-deazapseudoisocytidine, zebularine, 5-aza-zebularine, 5-methylzebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine, 2methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxypseudoisocytidine and 4-methoxy-1-methyl-pseudoisocytidine, 2aminopurine, 2, 6-diaminopurine, 7-deaza-adenine, 7-deaza8-aza-adenine, 7-deaza-2-aminopurine, 7-deaza-8-aza-2aminopurine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6diaminopurine, 1-methyladenosine,N6-methyladenosine, N6isopentenyladenosine, N6-(cis-hydroxyisopentenyl)adenosine, 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine, N6-glycinylcarbamoyladenosine, N6threonylcarbamoyladenosine, 2-methylthio-N6-threonyl carbamoyladenosine, N6,N6-dimethyladenosine, 7-methyladenine, 2-methylthio-adenine and 2-methoxy-adenine, inosine, 1-methylinosine, wiosine, wibutosine, 7-deaza-guanosine, 7-deaza-8aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine, 6-thio-7methyl-guanosine, 7-methylinosine, 6-methoxy-guanosine, 1methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, Petition 870260029351, dated 03 / 28 / 2026, page 188 / 555 125 / 372 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thioguanosine, N2-methyl-6-thio-guanosine and N2,N2-dimethyl-6-thioguanosine, 5'-O-(1-thiophosphate)-adenosine, 5'-O-(1-thiophosphate)-cytidine, 5'-O-(1-thiophosphate)-guanosine, 5'-O(1-thiophosphate)-uridine, 5'-O-(1-thiophosphate)-pseudouridine, 6-aza-cytidine, 2-thio-cytidine, alpha-thio-cytidine, Pseudoiso-cytidine, 5-aminoallyl-uridine, 5-iodo-uridine, N1-methyl-pseudouridine, 5,6-dihydrouridine, alpha-thiouridine, 4-thio-uridine, 6-aza-uridine, 5-hydroxy-uridine, deoxythymidine, 5-methyl-uridine, pyrrolo-cytidine, inosine, alpha-thio-guanosine, 6-methyl-guanosine, 5-methyl-cytidine, 8-oxo-guanosine, 7-deaza-guanosine, N1-methyl-adenosine, 2-amino-6-chloro-purine, N6-methyl-2-amino-purine, pseudo-isocytidine, 6-chloro-purine, N6-methyl-adenosine, alpha-thioadenosine, 8-azido-adenosine, 7-deaza-adenosine. In the context of the invention, pseudouridine (ψ), N1-methylpseudouridine (η1ψ), 5-methylcytosine and 5-methoxyuridine are particularly preferred and suitable.Consequently, the artificial RNA as defined herein may comprise at least one modified nucleotide selected from pseudouridine (ψ), N1-methylpseudouridine (η1ψ), 5-methylcytosine and 5-methoxyuridine.
[0196] In preferred embodiments, the artificial RNA of the invention comprises at least one coding sequence, wherein at least one coding sequence is a pseudouridine (ψ) modified coding sequence.
[0197] Consequently, in preferential modalities, the artificial RNA of the invention, or at least a sequence Petition 870260029351, dated 03 / 28 / 2026, page 189 / 555 The 126 / 372 coding pattern comprises a nucleic acid sequence in which at least one or more, preferably all, uracil nucleotides are replaced by pseudouridine (ψ) nucleotides.
[0198] In further preferred embodiments, the artificial RNA of the invention comprises at least one coding sequence, wherein at least one coding sequence is a coding sequence modified with N1-methylpseudouridine (η1ψ).
[0199] Consequently, in preferred modalities, the The artificial RNA of the invention, or at least one coding sequence, comprises a nucleic acid sequence in which at least one or more, preferably all, uracil nucleotides are replaced by N1-methylpseudouridine (m^) nucleotides.
[0200] In preferred embodiments, the artificial RNA of the invention comprises at least one coding sequence, wherein at least one coding sequence is a codon-modified coding sequence.
[0201] In preferred embodiments, at least one coding sequence of the invention is a codon-modified coding sequence, wherein the amino acid sequence encoded by at least one codon-modified coding sequence is preferably not modified compared to the amino acid sequence encoded by the corresponding wild-type coding sequence.
[0202] The term “modified encoding sequence by Petition 870260029351, dated 03 / 28 / 2026, page 190 / 555 "127 / 372 codon" refers to coding sequences that differ in at least one codon (nucleotide triplets that code for an amino acid) compared to the corresponding wild-type coding sequence. Appropriately, in the context of the invention, a codon-modified coding sequence may exhibit enhanced resistance to degradation in vivo and / or enhanced stability in vivo and / or enhanced translation capability in vivo. Codon modifications in the broadest sense utilize the degeneracy of the genetic code where multiple codons can code for the same amino acid and can be used interchangeably (see Table 2) to optimize / modify the coding sequence for in vivo applications as highlighted above.
[0203] In particularly preferred embodiments of the first aspect, at least one sequence is a codon-modified coding sequence, wherein the codon-modified coding sequence is selected from the C-maximized coding sequence, CAI-maximized coding sequence, human codon-adapted coding sequence, G / C A-content modified coding sequence and G / C-optimized coding sequence or any combination thereof.
[0204] According to preferred embodiments, the artificial RNA of the invention can be modified in that the C content of at least one coding sequence can be increased, preferably maximized, compared to the C content of the corresponding wild-type coding sequence (referred to as the “coding sequence”). Petition 870260029351, dated 03 / 28 / 2026, page 191 / 555 128 / 372 maximized with C” in the present document). The amino acid sequence encoded by the C-maximized RNA coding sequence is preferably not modified when compared to the amino acid sequence encoded by the respective wild-type coding nucleic acid sequence. The generation of C-maximized nucleic acid sequences can be suitably performed using a modification method according to document WO2015 / 062738. In this context, the disclosure of document WO2015 / 062738 is included by reference thereto. Throughout the invention disclosure, including the identifier <223> From the sequence listing, C-maximized encoding sequences of suitable RSV nucleic acid sequences are indicated by the abbreviation “opt2”.
[0205] According to the embodiments, the artificial RNA of the present invention can be modified, wherein the G / C ratio of at least one coding sequence of the invention can be modified compared to the G / C ratio of the corresponding wild-type coding sequence (referred to as the “G / C ratio-modified coding sequence” in this document). In this context, the term “G / C optimization” or “G / C ratio modification” refers to a nucleic acid, preferably an artificial nucleic acid of the invention, comprising an increased, preferably modified, number of guanosine and / or cytosine nucleotides when compared to the corresponding wild-type nucleic acid sequence. Such an increased number can be generated by replacing codons containing adenosine or thymidine nucleotides with codons Petition 870260029351, dated 03 / 28 / 2026, page 192 / 555 129 / 372 containing guanosine or cytosine nucleotides. If the enriched G / C ratio occurs in a DNA or RNA coding sequence, it uses the degeneracy of the genetic code. In particular, in the case of RNA, sequences with an increased G (guanosine) / C (cytosine) ratio are more stable than sequences with an increased A (adenosine) / U (uracil) ratio. The amino acid sequence encoded by the modified coding sequence with the G / C ratio of the nucleic acid sequence is preferably not modified when compared to the amino acid sequence encoded by the respective wild-type coding nucleic acid sequence.Preferably, the G / C content of the coding sequence of the artificial nucleic acid sequence, for example, the RNA sequence of the present invention, is increased by at least 10%, preferably by at least 30%, most preferably by at least 40% compared to the content of... G / C of the coding sequence of the corresponding wild-type nucleic acid sequence (e.g., RNA sequence) that encodes an RSV antigen as defined herein, or a fragment or variant thereof.
[0206] According to preferred embodiments, the artificial RNA of the present invention can be modified wherein the G / C content of at least one coding sequence of the invention can be optimized compared to the G / C content of the corresponding wild-type coding sequence (referred to as the “optimized G / C content coding sequence” in this document). “Optimized” in this context Petition 870260029351, dated 03 / 28 / 2026, p. 193 / 555 130 / 372 refers to a coding sequence in which the G / C ratio is preferably increased to the possible higher G / C ratio. The amino acid sequence encoded by the G / C-optimized nucleic acid sequence is preferably not modified when compared to the amino acid sequence encoded by the respective wild-type coding nucleic acid sequence. The generation of a G / C-optimized nucleic RNA sequence can be suitably performed using a G / C ratio optimization method according to document WO2002 / 098443. In this context, the disclosure of document WO2002 / 098443 is included in its entirety in the present invention.Throughout the invention disclosure process, including the identifier <223> From the sequence listing, the G / C-optimized encoding sequences of the appropriate RSV nucleic acid sequences are indicated by the abbreviation “opt1, opt5, opt6, opt11”.
[0207] According to the embodiments, the artificial RNA of the invention can be modified, wherein the codons in at least one coding sequence of the invention can be adapted for human codon use (referred to as the “human codon-adapted coding sequence” in this document). Codons encoding the same amino acid occur at different frequencies in an individual, for example, a human being. Consequently, the coding sequence of the artificial RNA is preferably modified so that the frequency of the codons encoding the same amino acid corresponds to the naturally occurring frequency of that codon according to the use of Petition 870260029351, dated 03 / 28 / 2026, p. 194 / 555 131 / 372 human codon, for example, as shown in Table 2. For example, in the case of the amino acid Ala, the wild-type coding sequence is preferably adapted in such a way that the codon GCC is used with a frequency of 0.40, the codon GCT” is used with a frequency of 0.28, the codon GCA” is used with a frequency of 0.22 and the codon GCG” is used with a frequency of 0.10 etc. (see Table 2). Consequently, such a procedure (as exemplified for Ala) is applied to each amino acid encoded by the artificial nucleic acid coding sequence of the invention to obtain sequences adapted to the use of human codons. <223> From the sequence listing, encoding sequences adapted for use with human codons from suitable RSV nucleic acid sequences are indicated by the abbreviation opt3. Table 2: Table of human codon usage with frequencies indicated for each amino acid. Amino acid codon frequency Amino acid codon frequency Ala GCG 0.10 Pro CCG 0.11 Ala GCA 0.22 Pro CCA 0.27 Ala GCT 0.28 Pro CCT 0.29 Ala GCC* 0.40 Pro CCC* 0.33 Cys TGT 0.42 Gln CAG* 0.73 Cys TGC* 0.58 Gln CAA 0.27 Asp GAT 0.44 Arg AGG 0.22 Asp GAC* 0.56 Arg AGA* 0.21 Glu GAG* 0.59 Arg CGG 0.19 Glu GAA 0.41 Arg CGA 0.10 Phe TTT 0.43 Arg CGT 0.09 Petition 870260029351, dated 03 / 28 / 2026, p. 195 / 555 132 / 372 Amino acid codon frequency Amino acid codon frequency Phe TTC* 0.57 Arg CGC 0.19 Gly GGG 0.23 Ser AGT 0.14 Gly GGA 0.26 Ser AGC* 0.25 Gly GGT 0.18 Ser TCG 0.06 Gly GGC* 0.33 Ser TCA 0.15 His CAT 0.41 Ser TCT 0.18 His CAC* 0.59 Ser TCC 0.23 Ile ATA 0.14 Thr ACG 0.12 Ile ATT 0.35 Thr ACA 0.27 Ile ATC* 0.52 Thr ACT 0.23 Lys AAG* 0.60 Thr ACC* 0.38 Lys AAA 0.40 Val GTG* 0.48 Leu TTG 0.12 Val GTA 0.10 Leu TTA 0.06 Val GTT 0.17 Leu CTG* 0.43 Val GTC 0.25 Leu CTA 0.07 Trp TGG* 1 Leu CTT 0.12 Tyr TAT 0.42 Leu CTC 0.20 Tyr TAC* 0.58 Met ATG* 1 Parada TGA* 0.61 Asn AAT 0.44 Parada TAG 0.17 Asn AAC* 0.56 Parada TAA 0.22 most frequent human codon
[0208] According to the embodiments, the artificial RNA of the present invention can be modified in that the codon adaptation index (CAI) can be increased or, preferably, maximized in at least one coding sequence of the invention (referred to as the “CAI-maximized coding sequence” in this document). Consequently, it is preferred that all codons of the wild-type nucleic acid sequence that are Petition 870260029351, dated 03 / 28 / 2026, p. 196 / 555 133 / 372 relatively rare codons, for example, in a human cell, are replaced by a respective codon that is frequent, for example, in a human cell, wherein the frequent codon codes for the same amino acid as the relatively rare codon. Suitably, the most frequent codons are used for each encoded amino acid (see Table 2, the most frequent human codons are marked with asterisks). Suitably, the artificial RNA of the invention comprises at least one coding sequence in which the codon adaptation index (CAI) of at least one coding sequence is at least 0.5, at least 0.8, at least 0.9, or at least 0.95. Most preferably, the codon adaptation index (CAI) of at least one coding sequence is 1. For example, in the case of the amino acid Ala, the wild-type coding sequence is adapted in such a way that the most frequent human codon GCC is always used for said amino acid.Consequently, such a procedure (as exemplified for Ala) is applied to each amino acid encoded by the artificial RNA coding sequence of the invention to obtain CAI-maximized coding sequences. Throughout the disclosure of the invention, including the identifier <223> From the sequence listing, CAI-maximized encoding sequences of suitable RSV nucleic acid sequences are indicated by the abbreviation opt4.
[0209] Consequently, in a particularly preferred embodiment, the artificial RNA of the first aspect comprises at least one coding sequence comprising a codon-modified nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86 Petition 870260029351, dated 03 / 28 / 2026, p. 197 / 555 134 / 372%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a codon-modified nucleic acid sequence selected from the group consisting of SEQ ID NOs: 70-77, 485-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596 4958-4965, 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 11728-11734, 12097-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679-14686, 15048-15055, 15417-15424, 15786-15793 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376 18738-18745, 19107-19114, 19476-19483, 21363-21384, 21389-21410 or a fragment or variant of any of these sequences (see also Tables 3 and 4). Additional information relating to each of these suitable nucleic acid sequences they encode can also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> .
[0210] In the particularly preferred embodiment, the artificial RNA of the first aspect comprises at least one coding sequence comprising a codon-modified nucleic acid sequence that is identical or at least 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the G / C content-modified nucleic acid sequences or the G / C optimized nucleic acid sequences according to SEQ ID NOs: 70-71, 75-77, 485-486, 490-492, 899-900, 904-906, Petition 870260029351, dated 03 / 28 / 2026, p. 198 / 555 135 / 372 1268-1269 1273-1275 1637-1638 1642-1644 2006-2007 2011-2013 2375-2376 2380-2382 2744-2745 2749-2751 3113-3114 3118-3120 3482-3483 3487-3489 3852 4221 4590,4959 5328,5697 6066,6435 6804,7173 7542,7911 3856-3858 4225-4227 4594-4596 4963-4965 5332-5334 5701-5703 6070-6072 6439-6441 6808-6810 7177-7179 7546-7548, 7915-7917, 11728, 11732-11734, 12097, 12101-12103, 12465, 12466, 12470-12472, 12834, 12835, 12839-12841, 13941, 13942, 13946-13948, 14310, 14311, 14315-14317, 14679, 14680, 14684-14686, 15048, 15049, 15053-15055, 15417, 15418 15422-15424, 15786, 15787, 15791-15793, 13203, 13204, 13208-13210, 13572, 13573, 13577-13579, 16155, 16156, 16160-16162, 16524, 16525, 16529-16531, 16893, 16894, 16898-16900, 17262, 17263, 17267-17269, 17631, 17632, 17636-17638, 18000, 18001, 18005- 18007, 18369, 18370, 18374-18376, 18738, 18739, 18743- 18745, 19107, 19108, 19112-19114, 19476, 19477, 19481-19483, 21363-21384, 21389-21410 or a fragment or variant of any of these sequences (see also Tables 3 and 4; opt1, 5, 6, 11). Additional information relating to each of these suitable nucleic acid sequences they encode can also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> .
[0211] In the preferred embodiment, the artificial RNA of the first aspect comprises at least one coding sequence comprising a codon-modified nucleic acid sequence that is identical to, or at least 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to Petition 870260029351, dated 03 / 28 / 2026, p. 199 / 555 136 / 372 any of the nucleic acid sequences adapted with the use of human codons according to SEQ ID Nos: 73,488, 902, 1271, 1640, 2009, 2378, 2747, 3116, 3485, 3854, 4223, 4592, 4961, 5330, 5699, 6068, 6437, 6806, 7175, 7544, 7913, 11730, 12099, 12468, 12837, 13944, 14313, 14682, 15051, 15420, 15789, 13206, 13575, 16158, 16527, 16896, 17265, 17634, 18003, 18372, 18741, 19110, 19479 or a fragment or variant of any of these sequences (see also Tables 3 and 4; opt3). Additional information relating to each of these suitable nucleic acid sequences they encode can also be derived from the sequence listing, in particular, from details provided therein under the identifier <223> .
[0212] In the particularly preferred embodiment, the artificial RNA of the first aspect comprises at least one coding sequence comprising a codon-modified nucleic acid sequence that is identical or at least 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, %, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the C-maximized nucleic acid sequences according to the SEQ ID NOs: 72, 487, 901, 1270, 1639, 2008, 2377, 2746, 3115, 3484, 3853, 4222, 4591, 4960, 5329, 5698, 6067, 6436, 6805, 7174, 7543, 7912, 11729, 12098, 12467, 12836, 13943, 14312, 14681, 15050, 15419, 15788, 13205, 13574, 16157, 16526, 16895, 17264, 17633, 18002, 18371, 18740, 19109, 19478 or a fragment or variant of any of these sequences (see also Tables 3 and 4; opt2). Additional information relating to each of these suitable nucleic acid sequences they encode may also be Petition 870260029351, dated 03 / 28 / 2026, page 200 / 555 137 / 372 derived from the sequence listing, in particular, from details provided therein under the identifier <223> .
[0213] In the preferred embodiment, the artificial RNA of the invention comprises at least one coding sequence comprising a codon-modified nucleic acid sequence that is identical or at least 50%, 60%, 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the CAI-maximized nucleic acid sequences according to SEQ IDs 74, 489, 903, 1272, 1641, 2010, 2379, 2748, 3117, 3486, 3855, 4224, 4593, 4962, 5331, 5700, 6069, 6438, 6807, 7176, 7545, 7914, 11731, 12100, 12469, 12838, 13945, 14314, 14683, 15052, 15421, 15790, 13207, 13576, 16159, 16528, 16897, 17266, 17635, 18004, 18373, 18742, 19111, 19480 or a fragment or variant of any of these sequences (see also Tables 3 and 4; opt4).Additional information relating to each of these suitable nucleic acid sequences that they encode can also be derived from the sequence listing, in particular, from details provided therein under the identifier. <223> .
[0214] In embodiments, the A / U content in the environment of the ribosome binding site of the artificial nucleic acid, particularly the artificial RNA of the invention, can be increased compared to the A / U content in the environment of the ribosome binding site of its respective wild-type nucleic acid. This modification (an increased A / U content around the ribosome binding site) increases the efficiency of the ribosome binding to the nucleic acid, preferably RNA. Effective binding of Petition 870260029351, dated 03 / 28 / 2026, p. 201 / 555 138 / 372 ribosomes to the ribosome binding site has, in turn, the effect of efficient RNA translation. Consequently, in a particularly preferred embodiment, the artificial nucleic acid of the invention comprises a ribosome binding site, also called a “Kozak sequence,” identical or at least 80%, 85%, 90%, 95% identical to any of the sequences SEQ ID NOs: 41, 42 or fragments or variants thereof.
[0215] The nucleic acid and polypeptide coding sequences of RSV (“cds”) are provided in Tables 3A and 3B and in Tables 4A and 4B.
[0216] In Tables 3A and 3B, Columns A to J represent specific suitable constructs of the invention derived from the Fusion (F) protein wherein Column A provides suitable sequences for F0, Column B provides suitable sequences for F-del, Column C provides suitable sequences for F0_DSCav1, Column D provides suitable sequences for Fdel_DSCav1, Column E provides suitable sequences for F_DSCav1_mut1, Column F provides suitable sequences for F-del_DSCav1_mut1, Column G provides suitable sequences for F_DSCav1_mut2, Column H provides suitable sequences for F-del_DSCav1_mut2, Column I provides suitable sequences for F_DSCav1_mut3, Column J provides suitable sequences for F-del_DSCav1_mut3. The specific protein SEQ ID NOs, as provided in the sequence listing, are in row 2 (“PRT”). The corresponding unmodified / wild-type coding sequence SEQ ID NOs are provided in row 3 (“wt”).The SEQ ID numbers of modified coding sequences with corresponding codons for each protein construct are: Petition 870260029351, dated 03 / 28 / 2026, page 202 / 555 139 / 372 provided in rows 4 to 10 (opt1, “opt2, “opt3, “opt4, “opt5, “opt6, “opt11). In Table 3A, the encoding sequences derived from HRSV(A2) are provided, in Table 3B, the encoding sequences derived from HRSV(Memphis-37) are provided. Additional information is provided in the identifier. <223> for each of the respective SEQ ID NOs in the sequence listing. Table 3A: Preferred encoding sequences that encode F from RSV (columns AJ) derived from HRSV(A2) ABCDEFGHIJ PRT 68 483 898 1267 1636 2005 2374 2743 3112 3481 weight 69 484 opt1 70, 485, 899, 1268, 1637, 2006, 2375, 2744, 3113, 3482, 71, 486, 900, 1269, 1638, 2007, 2376, 2745, 3114, 3483, 21363 21364 21365 21366 21369 21370 21371 21372 21373 21374 opt2 72 487 901 1270 1639 2008 2377 2746 3115 3484 opt3 2379 2748 3117 3486 opt5 75 490 904 1273 1642 2011 2380 2749 3118 3487 opt6 76 491 905 1274 1643 2012 2381 2750 3119 3488 opt11 77 492 906 1275 1644 2013 2382 2751 3120 3489 Table 3B: Preferred encoding sequences that encode F from RSV (columns AJ) derived from HRSV(Memphis37) ABCDEFGHIJ PRT 11726 12095 12464 12833 13940 14309 14678 15047 15416 15785 weight 11727 12096 opt1 11728, 12097, 12465, 12834, 13941, 14310, 14679, 15048, 15417, 15786, 21389 21390 12466, 12835, 13942, 14311, 14680, 15049, 15418, 15787, 21391 21392 21395 21396 21397 21398 21399 21400 opt2 11729 12098 12467 12836 13943 14312 14681 15050 15419 15788 opt3 11730 12099 12468 12837 13944 14313 14682 15051 15420 15789 Petition 870260029351, dated 03 / 28 / 2026, p. 203 / 555 140 / 372 ABCDEFGHIJ opt4 11731 12100 12469 12838 13945 14314 14683 15052 15421 15790 opt5 11732 12101 12470 12839 13946 14315 14684 15053 15422 15791 opt6 11733 12102 12471 12840 13947 14316 14685 15054 15423 15792 opt11 11734 12103 12472 12841 13948 14317 14686 15055 15424 15793
[0217] In Tables 4A and 4B, Columns K to V represent suitable constructs specific to the invention derived from RSV Fusion protein (F), wherein Column K provides suitable sequences for F_DSCav1_mut0, Column L provides suitable sequences for F-del_DSCav1_mut0, Column M provides suitable sequences for F_DSCav1_mut4, Column N provides suitable sequences for F-del_DSCav1_mut4, Column O provides suitable sequences for F_DSCav1_mut5, Column P provides suitable sequences for Fdel_DSCav1_mut5, Column Q provides suitable sequences for F_DSCav1_mut6, Column R provides suitable sequences for F-del_DSCav1_mut6, Column S provides suitable sequences for F_DSCav1_mut7, Column T provides suitable sequences for F-del_DSCav1_mut7, a Column U provides suitable sequences for F_DSCav1_mut8, and Column V provides suitable sequences for F-del_DSCav1_mut8. The specific protein SEQ ID NOs, as provided in the sequence listing, are in row 2 (PRT).The SEQ ID NOs of modified coding sequences with corresponding codons for each protein construct are provided in rows 3 to 9 (opt1, “opt2, “opt3, “opt4, opt5, opt6, “opt11). In Table 4A, the coding sequences derived from HRSV(A2) are provided, in Table 4B, the coding sequences derived from HRSV(Memphis-37) are provided. Information. Petition 870260029351, dated 03 / 28 / 2026, page 204 / 555 141 / 372 additional information is provided in the identifier. <223> for each of the respective SEQ ID NOs in the sequence listing. Table 4A: Preferred encoding sequences that encode F of RSV (KV columns) derived from HRSV(A2) KLMNOPQRSTUV PRT 3850 4219 4588 4 957 5326 5695 6064 6433 6802 7171 7540 7 909 opt1 3851, 4220, 4589, 4 958, 5327, 5696, 6065, 6434, 6803, 7172, 7541, 7910, 3852, 4221, 4590, 4959, 5328, 5697, 6066, 6435, 6804, 7173, 7542, 7911, 21367 21368 21375 21376 21377 21378 21379 21380 21381 21382 21383 21384 opt2 3853 4222 4591 4 960 5329 5698 6067 6436 6805 7174 7543 7912 opt3 3854 4223 4592 4 961 5330 5699 6068 6437 6806 7175 7544 7913 opt4 3855 4224 4593 4 962 5331 5700 6069 6438 6807 7176 7545 7914 opt5 3856 4225 4594 4 963 5332 5701 6070 6439 6808 7177 754 6 7915 opt6 3857 4226 4595 4 964 5333 5702 6071 64 4 0 6809 7178 7547 7916 opt11 3858 4227 4596 4 965 5334 5703 6072 64 4 1 6810 7179 7548 7917 Table 4B: Preferred encoding sequences that encode F of RSV (KV columns) derived from HRSV(Memphis37) KLMNOPQRSTUV PRT 13202 13571 16154 16523 16892 17261 17 630 17 999 18368 18737 19106 19475 opt1 13203 13572 16155 16524 16893 17262 17 631 18000 18369 18738 19107 1947 6 , 13204 , 13573 , 16156 , 16525 , 16894 , 17263 , 17 632 , 18001 , 18370 , 18739 , 19108 , 19477 , 21393 , 21394 , 21401 , 21402 , 21403 , 21404 , 21405 , 21406 , 21407 , 21408 , 21409 , 21410 opt2 13205 13574 16157 16526 16895 17264 17 633 18002 18371 18740 19109 19478 opt3 13206 13575 16158 16527 16896 17265 17 634 18003 18372 18741 19110 1947 9 opt4 13207 13576 16159 16528 16897 17266 17 635 18004 18373 18742 19111 19480 opt5 13208 13577 16160 16529 16898 17267 17 636 18005 18374 18743 19112 19481 opt6 13209 13578 16161 16530 16899 17268 17 637 18006 18375 18744 19113 19482 opt1 1 13210 13579 16162 16531 16900 17269 17 638 18007 1837 6 18745 19114 19483
[0218] In modalities, the artificial RNA of the first aspect is monocistronic, bicistronic or multicistronic.
[0219] In preferred embodiments, the artificial RNA of Petition 870260029351, dated 03 / 28 / 2026, page 205 / 555 142 / 372 invention is monocistronic.
[0220] The term “monocistronic nucleic acid” or “monocistronic nucleic acid” will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to an artificial RNA comprising only coding sequences as defined herein. The term “bicistronic nucleic acid, multicistronic nucleic acid” or “monocistronic RNA” as used herein will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to an artificial RNA that may have two coding sequences (bicistronic) or even more coding sequences (multicistronic).
[0221] In embodiments, the artificial RNA of the invention is monocistronic and the coding sequence of said monocistronic artificial RNA encodes at least two different antigenic peptides or proteins derived from RSV F as defined herein or a fragment or variant thereof. Consequently, at least one coding sequence of the monocistronic artificial RNA may encode at least two, three, four, five, six, seven, eight and more antigenic peptides or proteins derived from an RSV, preferably from an RSV F as defined herein linked or without an amino acid linker sequence, wherein said linker sequence may comprise rigid linkers, flexible linkers, cleavable linkers (e.g., autocleavable peptides) as defined above or a combination thereof (referred to as “multiantigen / nucleic acid constructs” herein). Petition 870260029351, dated 03 / 28 / 2026, page 206 / 555 143 / 372
[0222] In embodiments, the artificial RNA of the invention is bicistronic or multicistronic and comprises at least two coding sequences, wherein the at least two coding sequences encode two or more different antigenic peptides or proteins derived from RSV, preferably from RSV F as defined herein, or a fragment or variant thereof. Consequently, the coding sequences in a bicistronic or multicistronic artificial RNA suitably encode distinct antigenic proteins or peptides as defined herein, or a fragment or variant thereof. Preferably, the coding sequences in said bicistronic or multicistronic artificial RNA may be separated by at least one IRES (internal ribosomal entry site) sequence.Thus, the term “encoding two or more antigenic peptides or proteins” may mean, without limitation, that the bicistronic or multicistronic artificial RNA encodes, for example, at least two, three, four, five, six or more (preferably different) antigenic peptides or proteins from different RSVs or their fragments or variants within the definitions provided in this document. Alternatively, the bicistronic or multicistronic artificial RNA may encode, for example, at least two, three, four, five, six or more (preferably different) antigenic peptides or proteins derived from the same RSV or fragments or variants within the definitions provided in this document. In this context, suitable IRES sequences may be selected from the list of sequences. Petition 870260029351, dated 03 / 28 / 2026, page 207 / 555 144 / 372 nucleic acids according to SEQ ID Nos: 1566-1662 of patent application WO2017 / 081082, or fragments or variants of these sequences. In this context, the disclosure of document WO2017 / 081082 relating to IRES sequences is incorporated by reference hereto.
[0223] It should be understood that, in the context of the invention, certain combinations of coding sequences can be generated by any combination of monocistronic, bicistronic and multicistronic artificial nucleic acids and / or multiantigen / nucleic acid constructs to obtain a nucleic acid composition encoding multiple antigenic peptides or proteins as defined herein.
[0224] Preferably, the artificial RNA comprising at least one coding sequence as defined herein typically comprises a length of about 50 to about 20000, or 500 to about 20000 nucleotides, or about 500 to about 20000 nucleotides, or about 500 to about 10000 nucleotides, or about 1000 to about 10000 nucleotides, or preferably from about 1000 to about 5000 nucleotides, or even more preferably from about 1000 to about 2500 nucleotides.
[0225] According to preferred embodiments, the artificial RNA of the first aspect can be an mRNA, a self-replicating RNA, a circular RNA or a replicon RNA.
[0226] In embodiments, artificial RNA is circular RNA. As used in this document, circular RNA or circRNAs should be understood as a circular polynucleotide that can encode at least one peptide or Petition 870260029351, dated 03 / 28 / 2026, p. 208 / 555 145 / 372 antigenic protein as defined herein. Consequently, in preferred embodiments, said circular RNA comprises at least one coding sequence encoding at least one RSV-derived antigenic peptide or protein or a fragment or variant thereof as defined herein. The production of circRNAs can be accomplished using various methods provided in the art. For example, US6210931 teaches a method of synthesizing circRNAs by inserting DNA fragments into a plasmid containing sequences that have the capability for spontaneous cleavage and autocircularization. US5773244 teaches how to produce circRNAs by fabricating a DNA construct encoding an RNA ribozyme, expressing the DNA construct as an RNA, and then allowing the RNA to self-splice, which produces an intron-free circRNA in vitro.Document WO1992 / 001813 teaches a process for manufacturing single-stranded circular nucleic acids by synthesizing a linear polynucleotide, combining the linear nucleotide with a complementary linking oligonucleotide under hybridization conditions, and then ligating the linear polynucleotide. Those skilled in the art may also use methods provided in documents WO2015 / 034925 or WO2016 / 011222 to produce circular RNA. Consequently, methods for producing circular RNA as provided in documents US6210931, US5773244, etc. WO1992 / 001813, WO2015 / 034925 and WO2016 / 011222 are incorporated by reference herein.
[0227] In embodiments, artificial RNA is replicon RNA. The term “replicon RNA” will be recognized and understood by the element of common skill in the technique, and Petition 870260029351, dated 03 / 28 / 2026, page 209 / 555 146 / 372 is, for example, intended to be optimized self-replicating artificial RNA constructs. Such constructs include replication elements (replicase) derived from alphaviruses and the replacement of structural viral proteins with the artificial nucleic acid of interest (in the context of the invention, an artificial nucleic acid comprising at least one coding sequence encoding at least one antigenic peptide or protein derived from RSV). Alternatively, the replicase may be provided in a stand-alone construct comprising a replicase RNA sequence derived from, for example, Semliki Forest Virus (SFV), Sindbis Virus (SIN), Venezuelan Equine Encephalitis Virus (VEE), Ross River Virus (RRV), or other viruses belonging to the alphavirus family.Downstream of the replicase is a subgenomic promoter that controls replication of the artificial nucleic acid of the invention, that is, an artificial nucleic acid comprising at least one coding sequence encoding at least one antigenic peptide or protein derived from RSV.
[0228] In preferred embodiments, the artificial RNA of the first aspect is an mRNA.
[0229] The terms RNA and mRNA will be recognized and understood by the element of common skill in the art, and are, for example, intended to be a ribonucleic acid molecule, that is, a polymer consisting of nucleotides. These nucleotides are monomers of adenosine monophosphate, uridine monophosphate, guanosine monophosphate, and cytidine monophosphate that are linked together along the so-called backbone. The backbone is formed by phosphodiester bonds between the Petition 870260029351, dated 03 / 28 / 2026, page 210 / 555 147 / 372 sugar, that is, ribose, from a first moiety and a phosphate moiety from a second adjacent monomer. The specific succession of monomers is called the RNA sequence. mRNA (messenger RNA) usually provides the nucleotide sequence that can be translated into an amino acid sequence of a particular peptide or protein.
[0230] The artificial RNA, preferably the mRNA of the invention, can be prepared using any method known in the art, including chemical synthesis, such as solid-phase RNA synthesis, as well as in vitro methods, such as in vitro RNA transcription reactions.
[0231] In a preferred embodiment, the artificial RNA, preferably mRNA, is obtained by in vitro transcription of RNA.
[0232] Consequently, the RNA of the invention is preferably an RNA transcribed in vitro.
[0233] The term “in vitro RNA transcription” or “in vitro transcription” refers to a process in which RNA is synthesized in a cell-free system (in vitro). The RNA can be obtained through in vitro DNA-dependent transcription of a suitable DNA template which, according to the present invention, is a linearized plasmid DNA template or a PCR-amplified DNA template. The promoter to control in vitro RNA transcription can be any promoter for any DNA-dependent RNA polymerase. Particular examples of DNA-dependent RNA polymerases are T7, T3, SP6 or RNA polymerases. Syn5. In a preferred embodiment of the present invention, the DNA template is linearized with a suitable restriction enzyme before being subjected to transcription in Petition 870260029351, dated 03 / 28 / 2026, p. 211 / 555 148 / 372 vitro RNA.
[0234] The reagents used in in vitro transcription of RNA typically includes: a DNA template (linearized plasmid DNA or PCR product) with a promoter sequence that has a high binding affinity with its respective RNA polymerase, such as bacteriophage-encoded RNA polymerases (T7, T3, SP6, or Syn5); ribonucleotide triphosphates (NTPs) for four bases (adenine, cytosine, guanine, and uracil); optionally, a termination analog as defined herein (e.g., m7G(5')ppp(5')G (m7G, m7G(5')ppp(5')(2'OMeG)pG or m7G(5')ppp(5')(2'OMeA)pG)); optionally, additionally modified nucleotides as defined herein; a DNA-dependent RNA polymerase that has the ability to bind to the promoter sequence contained in the DNA template (e.g., T7, T3, SP6, or Syn5 RNA polymerase); Optionally, a ribonuclease (RNase) inhibitor to inactivate any potentially contaminating RNase; optionally, a pyrophosphate to degrade pyrophosphate which may inhibit in vitro RNA transcription; MgCl2, supplies Mg2+ ions as a cofactor for the polymerase; a buffer (TRIS or HEPES) to maintain an appropriate pH value which may also contain antioxidants (e.g., DTT), and / or polyamines, such as spermidine in ideal concentrations, for example, a buffer system comprising TRIS citrate as disclosed in document WO2017 / 109161.
[0235] In embodiments, the nucleotide mixture used in in vitro RNA transcription may additionally contain modified nucleotides as defined herein. Petition 870260029351, dated 03 / 28 / 2026, page 212 / 555 149 / 372 document. In this context, the preferred modified nucleotides comprise pseudouridine (ψ), N1-methylpseudouridine (m^), 5-methylcytosine and / or 5-methoxyuridine.
[0236] In preferred embodiments, the nucleotide mixture (i.e., the fraction of each nucleotide in the mixture) used for in vitro RNA transcription reactions can be optimized for the given RNA sequence, preferably as described in WO2015 / 188933.
[0237] In the embodiment in which more than one different artificial RNA as defined in this document must be produced, for example, in which 2, 3, 4, 5, 6, 7, 8, 9, 10 or even more different artificial RNAs must be produced (for example, encoding different RSV F antigens, or, for example, a combination of RSV F and RSV G; see second aspect), the procedures as described in WO2017 / 109134 may be appropriately used.
[0238] In the context of RNA vaccine production, it may be required to supply GMP-grade RNA. GMP-grade RNA can be produced using a manufacturing process approved by regulatory authorities. Consequently, in a particularly preferred embodiment, RNA production is carried out under Good Manufacturing Practices (GMP), implementing various quality control steps at the DNA and RNA level, preferably in accordance with WO2016 / 180430. In preferred embodiments, the RNA of the invention is a GMP-grade RNA, particularly a GMP-grade mRNA.
[0239] The RNA products obtained are preferably, Petition 870260029351, dated 03 / 28 / 2026, page 213 / 555 150 / 372 purified using PureMessenger® (CureVac, Tübingen, Germany; RP-HPLC according to document WO2008 / 077592) and / or tangential flow filtration (as described in document WO2016 / 193206).
[0240] In a further preferred embodiment, the RNA, particularly the purified RNA, is lyophilized in accordance with WO2016 / 165831 or WO2011 / 069586 to produce a temperature-stable, dry artificial RNA (powder) as defined herein. The RNA of the invention, particularly the purified RNA, can also be dried using spray drying or spray drying and freeze-drying in accordance with WO2016 / 184575 or WO2016184576 to produce a temperature-stable RNA (powder) as defined herein. Consequently, in the context of RNA fabrication and purification, the disclosures in documents WO2017 / 109161, WO2015 / 188933, WO2016 / 180430, WO2008 / 077592, WO2016 / 193206, WO2016 / 165831, WO2011 / 069586, WO2016 / 184575 and WO2016 / 184576 are incorporated by reference thereto.
[0241] Consequently, in preferred embodiments, the RNA is dry RNA, particularly dry mRNA.
[0242] The term “dry RNA” as used in this document should be understood as RNA that has been lyophilized, or spray-dried, or spray-dried and freeze-dried as defined above to obtain a temperature-stable dry RNA (powder).
[0243] In preferred embodiments, the artificial RNA of the invention is purified RNA, in particular, purified mRNA.
[0244] The term “purified RNA” or “purified mRNA” Petition 870260029351, dated 03 / 28 / 2026, p. 214 / 555 151 / 372 as used in this document should be understood as RNA that has a higher purity after certain purification steps (e.g., HPLC, TFF, Oligo d(T) purification, precipitation steps) than the initial material (e.g., RNA transcribed in vitro). Typical impurities that are not essentially present in purified RNA comprise peptides or proteins (e.g., enzymes derived from in vitro transcription of DNA-dependent RNA, e.g., RNA polymerases, RNases, pyrophosphatase, restriction endonuclease, DNase), spermidine, BSA, abortive RNA sequences, RNA fragments (short double-stranded RNA fragments, abortive sequences, etc.), free nucleotides (modified nucleotides, conventional NTPs, termination analog), template DNA fragments, buffer components (HEPES, TRIS, MgCl2), etc.Other potential impurities that may be derived from, for example, fermentation procedures include bacterial impurities (bioburden, bacterial DNA) or impurities derived from purification procedures (organic solvents, etc.). Consequently, in this regard, it is desirable that the "RNA purity grade" be as close as possible to 100%. It is also desirable that the RNA purity grade, which is the amount of full-length RNA transcripts, be as close as possible to 100%. Consequently, “purified RNA” as used in this document has a degree of purity of more than 75%, 80%, 85%, and very particularly 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and most favorably 99% or more. The degree of purity can be determined, for example, by analytical HPLC, where the percentages given above Petition 870260029351, dated 03 / 28 / 2026, p. 215 / 555 152 / 372 corresponds to the ratio between the peak area for the target RNA and the total area of all peaks representing the byproducts. Alternatively, the degree of purity can be determined, for example, by analytical agarose gel electrophoresis or capillary gel electrophoresis.
[0245] It should be understood that “dry RNA” as defined herein and “purified RNA” as defined herein or “GMP-grade mRNA” as defined herein may have superior stability characteristics (in vitro, in vivo) and enhanced efficiency (e.g., improved mRNA translation capability in vivo) and are therefore particularly suitable in the context of the invention. Furthermore, “dry RNA” as defined herein and “purified RNA” as defined herein or “GMP-grade mRNA” may be particularly suitable for medical use as defined herein.
[0246] The artificial RNA can be suitably modified by adding a 5'-cap structure that preferably stabilizes the nucleic acid as described in this document. Consequently, in preferred embodiments, the artificial RNA of the first aspect comprises a 5'-cap structure, preferably m7G, cap0 (e.g., m7G(5')ppp(5')G), cap1 (e.g., m7G(5')ppp(5')(2'OMeG) or m7G(5')ppp(5')(2'OMeA)), cap2, a modified cap0, or a modified cap1 structure (generated using a termination analog as defined below).
[0247] The term “5'-cap structure” as used in this document will be recognized and understood by the element of Petition 870260029351, dated 03 / 28 / 2026, page 216 / 555 153 / 372 common skill in the art, and is, for example, intended to refer to a modified nucleotide (termination analog), particularly a guanine nucleotide, added to the 5' end of an RNA molecule, for example, an mRNA molecule. Preferably, the 5' termination is added using a 5'-5'triphosphate linkage (also called m7GpppN).Additional examples of 5'-cap structures include glyceryl, inverted deoxyabasic residue (portion), 4',5'-methylene nucleotide, 1-(beta-D-erythrofuranosyl) nucleotide, 4'-thionucleotide, carbocyclic nucleotide, 1,5-anhydrohexitol nucleotide, L-nucleotides, alpha-nucleotide, base-modified nucleotide, threo-pentofuranosyl nucleotide, 3',4'-seco acyclic nucleotide, 3,4-dihydroxybutyl acyclic nucleotide, 3,5-dihydroxypentyl acyclic nucleotide, 3'-3'-inverted nucleotide fraction, 3'-3'-inverted nucleotide abasic fraction, 3'-2'-inverted nucleotide fraction, abasic fraction 3'-2'-inverted, 1,4-butanediol phosphate, 3'-phosphoramidate, hexyl phosphate, aminohexyl phosphate, 3'-phosphate, 3'-phosphorothioate, phosphorodithioate, or methylphosphonate fraction, bridged or unbridged.
[0248] 5'-cap structures that may be suitable in the context of the present invention are cap1 (additional methylation of the ribose of the adjacent nucleotide of m7GpppN), cap2 (additional methylation of the ribose of the 2nd nucleotide downstream of m7GpppN), cap3 (additional methylation of the ribose of the 3rd nucleotide downstream of m7GpppN), cap4 (additional methylation of the ribose of the 4th nucleotide downstream of m7GpppN), ARCA (antireverse termination analog), modified ARCA (e.g., phosphothioate-modified ARCA), Petition 870260029351, dated 03 / 28 / 2026, page 217 / 555 154 / 372 inosine, N1-methyl-guanosine, 2'-fluoro-guanosine, 7-deazaguanosine, 8-oxo-guanosine, 2-amino-guanosine, LNAguanosine and 2-azido-guanosine.
[0249] A 5'-cap structure (cap0 or cap1) can also be formed in chemical RNA synthesis or, preferably, in vitro RNA transcription (cotranscriptional termination) using termination analogs.
[0250] The term “termination analog” as used in this document will be recognized and understood by the common skill element in the art, and is, for example, intended to refer to a non-polymerizable dinucleotide that has termination functionality in which it facilitates translation and localization, and / or prevents degradation of a nucleic acid molecule, particularly an RNA molecule, when incorporated into the 5' end of the nucleic acid molecule. Non-polymerizable means that the termination analog will only be incorporated into the 5' end due to not having a 5' triphosphate and therefore cannot be extended in the 3' direction by a template-dependent polymerase, particularly by a template-dependent RNA polymerase.Examples of termination analogs include, but are not limited to, a chemical structure selected from the group consisting of m7GpppG, m7GpppA, m7GpppC; non-methylated termination analogs (e.g., GpppG); dimethylated termination analogs (e.g., m2,7GpppG), trimethylated termination analogs (e.g., m2,2,7GpppG), dimethylated symmetrical termination analogs (e.g., m7Gpppm7G) or anti-reverse termination analogs (e.g., ARCA; m7,2'OmeGpppG, m7,2'dGpppG, m7,3'OmeGpppG). Petition 870260029351, dated 03 / 28 / 2026, page 218 / 555 155 / 372 m7,3'dGpppG and its tetraphosphate derivatives). Additional termination analogs have been previously described (documents WO2008 / 016473, WO2008 / 157688, WO2009 / 149253, WO2011 / 015347 and WO2013 / 059475). Suitable termination analogues in this context are described in documents WO2017 / 066793, WO2017 / 066781, WO2017 / 066791, WO2017 / 066789, WO2017 / 053297, WO2017 / 066782, WO2018075827 and WO2017 / 066797 in which the disclosures relating to termination analogues are incorporated by reference thereto.
[0251] The 5'-cap structure can be suitably added in a cotranscriptional manner using termination analogs as defined herein in an in vitro RNA transcription reaction as defined herein.
[0252] In preferred embodiments, a modified cap1 structure is generated using a termination analog as disclosed in WO2017 / 053297, WO2017 / 066793, WO2017 / 066781, WO2017 / 066791, WO2017 / 066789, WO2017 / 066782, WO2018075827 and WO2017 / 066797. In particular, any termination structures derivable from the structure disclosed in claims 1-5 of WO2017 / 053297 can be suitably used to cotranscriptionally generate a modified cap1 structure. Additionally, any termination structures derivable from the structure defined in claim 1 or claim 21 of document WO2018075827 can be suitably used to cotranscribeally generate a modified cap1 structure.
[0253] The preferred termination analogs are the Petition 870260029351, dated 03 / 28 / 2026, page 219 / 555 156 / 372 dinucleotide termination analogs m7G(5')ppp(5')G (m7G) or 3'-O-Me-m7G(5')ppp(5')G to cotranscriptionally generate cap0 structures. Particularly preferred termination analogs are the trinucleotide termination analogs m7G(5')ppp(5'(2'OMeA)pG or m7G(5')ppp(5')(2'OMeG)pG to cotranscriptionally generate cap1 structures.
[0254] In this context, it is preferable that the RNA of the invention comprises a Cap1 structure as defined above which preferably results in protein expression through, for example, high termination efficiencies and increased translation efficiencies. Also suitably, the RNA of the invention comprising a Cap1 structure exhibits decreased stimulation of the innate immune system when compared to Cap0 constructs of the same nucleic acid sequence. The common skill element knows how to determine translation efficiencies, degree of termination, and immune stimulation.
[0255] In a particularly preferential modality, the The artificial RNA of the first aspect of the invention comprises a cap1 structure, wherein said cap1 structure can be formed enzymatically or cotranscriptionally (for example, using m7G(5')ppp(5')(2'OMeA)pG or m7G(5')ppp(5')(2'OMeG)pG analogs).
[0256] In preferred embodiments, the first-appearance artificial RNA comprises an m7G(5')ppp(5')(2'OMeA)pG termination structure. In such embodiments, the coding RNA comprises a 5'-terminal m7G termination, and further methylation of the adjacent m7GpppN nucleotide ribose, in this case, a 2'O adenosine. Petition 870260029351, dated 03 / 28 / 2026, p. 220 / 555 157 / 372 methylated.
[0257] In other preferred embodiments, the first-appearance artificial RNA comprises an m7G(5')ppp(5')(2'OMeG)pG termination structure. In such embodiments, the coding RNA comprises a 5'-terminal m7G termination, and additional methylation of the adjacent nucleotide ribose, in this case, a 2'O methylated guanosine.
[0258] Consequently, whenever any reference is made to suitable RNA or mRNA sequences in the context of the invention, the first nucleotide of said RNA or mRNA sequence, i.e., the nucleotide downstream of the m7G(5')ppp structure, may be a methylated 2'O guanosine or a methylated 2'O adenosine.
[0259] Consequently, in other embodiments, the artificial RNA of the invention may comprise a 5'-cap sequence element according to SEQ ID NO: 43 or 21321 or a fragment or variant thereof.
[0260] In other embodiments, the 5'-cap structure is added via enzymatic termination using termination enzymes (e.g., vaccinia virus termination enzymes, commercially available termination kits) to generate cap0 or cap1 or cap2 structures. In other embodiments, the 5'-cap structure (cap0, cap1) is added via enzymatic termination using immobilized termination enzymes, for example, using a termination reactor (WO2016 / 193226 document).
[0261] In preferred embodiments, the artificial RNA of the invention comprises at least one poly(A) sequence comprising, preferably, 30 to 150 nucleotides of Petition 870260029351, dated 03 / 28 / 2026, page 221 / 555 158 / 372 adenosine.
[0262] In preferred embodiments, the poly(A) sequence suitably located at the 3' terminus comprises 10 to 500 adenosine nucleotides, 10 to 200 adenosine nucleotides, 40 to 200 adenosine nucleotides, or 40 to 150 adenosine nucleotides. In a particularly preferred embodiment, the poly(A) sequence comprises about 64 adenosine nucleotides. In further particularly preferred embodiments, the poly(A) sequence comprises about 75 adenosine nucleotides. In further particularly preferred embodiments, the poly(A) sequence comprises about 100 adenosine nucleotides.
[0263] The term “poly(A) sequence”, “poly(A) tail” or “3’ poly(A) tail” as used herein shall be recognized and understood by the element of common skill in the art, and is, for example, intended to be an adenosine nucleotide sequence typically located at the 3’ end of an RNA of up to about 1000 adenosine nucleotides. Preferably, said poly(A) sequence is essentially homopolymeric, for example, a poly(A) sequence of, for example, 100 adenosine nucleotides is essentially 100 nucleotides long. In other embodiments, the poly(A) sequence may be interrupted by at least one nucleotide other than an adenosine nucleotide; for example, a poly(A) sequence of, say, 100 adenosine nucleotides may have a length of more than 100 nucleotides (comprising 100 adenosine nucleotides and, in addition, at least one nucleotide other than an adenosine nucleotide). Petition 870260029351, dated 03 / 28 / 2026, page 222 / 555 159 / 372 adenosine nucleotide).
[0264] In the context of the present invention, a poly(A) sequence may be located in an mRNA or in any other nucleic acid molecule, such as, for example, in a DNA vector, for example, in a vector that serves as a template for the generation of an RNA, preferably from an mRNA, for example, through transcription of said DNA vector.
[0265] Preferably, the poly(A) sequence of the artificial RNA is obtained from a DNA template during in vitro RNA transcription. In other embodiments, the poly(A) sequence is obtained in vitro by common chemical synthesis methods without necessarily being transcribed from a DNA template. In other embodiments, the poly(A) sequences are generated by enzymatic polyadenylation of RNA (after in vitro RNA transcription) using commercially available polyadenylation kits and corresponding protocols known in the art, or alternatively, through the use of immobilized poly(A) polymerases, for example, using a polyadenylation reactor (as described in WO2016 / 174271).
[0266] In embodiments, the artificial RNA of the invention may contain a poly(A) sequence derived from a vector and may comprise at least one additional poly(A) sequence generated by enzymatic polyadenylation, for example, as described in document WO2016 / 091391.
[0267] In preferred embodiments, the artificial RNA of the invention comprises at least one poly(C) sequence comprising, preferably, 10 to 40 cytosine nucleotides. Petition 870260029351, dated 03 / 28 / 2026, page 223 / 555 160 / 372
[0268] In preferred embodiments, the poly(C) sequence suitably located at the 3' terminus comprises 10 to 200 cytosine nucleotides, 10 to 100 cytosine nucleotides, 20 to 70 cytosine nucleotides, 20 to 60 cytosine nucleotides, or 10 to 40 cytosine nucleotides. In a particularly preferred embodiment, the poly(C) sequence comprises about 30 cytosine nucleotides.
[0269] The term “poly(C) sequence” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to be a cytosine nucleotide sequence typically located at the 3' end of an RNA of up to about 200 cytosine nucleotides. In the context of the present invention, a poly(C) sequence may be located in an mRNA or in any other nucleic acid molecule, such as, for example, in a DNA vector, for example, in a vector that serves as a template for the generation of an RNA, preferably from an mRNA, for example, through transcription of the vector.
[0270] Preferably, the poly(C) sequence in the RNA sequence of the present invention is derived from a DNA template by in vitro RNA transcription. In other embodiments, the poly(C) sequence is obtained in vitro by common chemical synthesis methods without necessarily being transcribed from a DNA template.
[0271] In other embodiments, the artificial RNA of the invention does not comprise a poly(C) sequence as defined herein.
[0272] In preferred embodiments, the artificial RNA of Petition 870260029351, dated 03 / 28 / 2026, p. 224 / 555 161 / 372 first aspect comprises at least one histone stem-loop.
[0273] The term “histone stem-loop” as used in this document will be recognized and understood by the element of common skill in the art, and is, for example, intended to refer to nucleic acid sequences that are predominantly found in histone mRNAs. Exemplary histone stem-loop sequences are described in Lopez et al. (Davila Lopez et al, (2008), RNA, 14(1)). Histone stem-loop premRNAs are typically followed by a purine-rich sequence known as the histone downstream element (HDE). These premRNAs are processed in the nucleus by a single endonucleolytic cleavage of approximately 5 nucleotides downstream of the stem-loop structure, catalyzed by U7 snRNP via base pairing of U7 snRNA with the HDE.
[0274] Histone stem-loop sequences / structures can be appropriately selected from histone stem-loop sequences as disclosed in document WO2012 / 019780, the disclosure relating to histone stem-loop sequences / structures incorporated by reference thereto. The histone stem-loop sequence that can be used in the present invention can preferably be derived from formulas (I) or (II) of patent application WO2012 / 019780.According to a further preferred embodiment, the RNA as defined herein may comprise at least one histone stem-loop sequence derived from at least one of the specific formulas (Ia) or (IIa) of patent application WO2012 / 019780. Petition 870260029351, dated 03 / 28 / 2026, p. 225 / 555 162 / 372
[0275] In the particularly preferred embodiment, the artificial RNA of the invention comprises at least one histone stem-loop, wherein said histone stem-loop comprises a nucleic acid sequence according to SEQ ID NO: 39 or 40 or fragments or variant thereof.
[0276] In other embodiments, the artificial RNA of the first aspect does not comprise a histone stem-loop as defined in this document.
[0277] In further embodiments, the artificial RNA of the invention comprises a 3'-terminal sequence element. Said 3'-terminal sequence element is to be understood as a sequence element comprising a poly(A) sequence and a histone stem-loop sequence, wherein said sequence element is located at the 3' terminus of the artificial RNA of the invention.
[0278] In other embodiments, the artificial RNA of the invention may comprise a 3' terminal sequence element according to SEQ ID Nos: 44-63 or 2132221328 or a fragment or variant thereof.
[0279] In preferred embodiments, the artificial RNA of the invention comprises at least one coding sequence modified by pseudouridine (ψ).
[0280] Consequently, in preferred embodiments, the artificial RNA of the invention, or at least one coding sequence, comprises a nucleic acid sequence in which at least one or more, preferably all, uracil nucleotides are replaced by pseudouridine (ψ) nucleotides.
[0281] In further preferred embodiments, the artificial RNA of the invention comprises at least one sequence Petition 870260029351, dated 03 / 28 / 2026, page 226 / 555 163 / 372 modified encoding by Nl-methylpseudouridine (η1ψ).
[0282] Consequently, in preferred embodiments, the The artificial RNA of the invention, or at least one coding sequence, comprises a nucleic acid sequence in which at least one or more, preferably all, uracil nucleotides are replaced by N1-methylpseudouridine (m^) nucleotides.
[0283] In preferred embodiments of the first aspect, artificial RNA, preferably mRNA, preferably comprises, in the 5' to 3' direction, the following elements a)-i): a) 5'-cap structure, preferably as specified in this document; b) optionally, a 5' UTR as specified in this document, preferably at least one selected from SEQ ID Nos: 1-22; c) a ribosome binding site, preferably as specified in this document. d) at least one encoding sequence as specified in this document, preferably as specified in Table 3 and Table 4; e) 3' UTR as specified in this document, preferably at least one selected from SEQ IDs 23-38; f) optionally, the poly(A) sequence, preferably as specified in this document; g) optionally, the poly(C) sequence, preferably as specified in this document; h) optionally, the histone stem-loop, preferably, Petition 870260029351, dated 03 / 28 / 2026, p. 227 / 555 164 / 372 as specified in this document; (i) optionally, a 3' terminal sequence element as specified in this document, preferably according to SEQ ID Nos: 44-63 or 21322-21328; and where, optionally, at least one or more of the uracil nucleotides are replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (η1ψ) nucleotides.
[0284] In additional preferred embodiments of the first aspect, artificial RNA, preferably mRNA, comprises the following preferred elements in the 5' to 3' direction: a) 5'-cap structure, preferably, as specified in this document, with maximum preference, a Cap1 structure; b) a 3' UTR and a 5' UTR element according to a-1, a-4, c-1, e-4, g-2, i-2, or i-3 as specified herein; c) a ribosome binding site, preferably as specified in this document; (d) at least one encoding sequence as specified herein, wherein said encoding sequence is located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3' UTR, wherein said encoding sequence is preferably selected from a sequence specified in Table 3 and Table 4; (e) optionally, a poly(A) sequence, preferably Petition 870260029351, dated 03 / 28 / 2026, page 228 / 555 165 / 372 as specified in this document; f) optionally, poly(C) sequence, preferably as specified in this document; (g) optionally, histone handle, preferably as specified in this document; h) optionally, a 3' terminal sequence element as specified herein, preferably in accordance with SEQ ID Nos: 44-63, 21322- 21328, and wherein, optionally, at least one or more of the uracil nucleotides are preferably replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (η1ψ) nucleotides.
[0285] In additional preferred embodiments of the first aspect, artificial RNA, preferably mRNA, comprises the following preferred elements in the 5' to 3' direction: a) 5'-cap structure, preferably, as specified in this document, with maximum preference, a Cap1 structure; b) a 3' UTR and a 5' UTR element according to a-1 or i-3 as specified in this document; c) a ribosome binding site, preferably as specified in this document. (d) at least one encoding sequence as specified herein, wherein said encoding sequence is located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3' UTR, wherein the encoding sequence is preferably, Petition 870260029351, dated 03 / 28 / 2026, page 229 / 555 166 / 372 selected from a sequence specified in Table 3 and Table 4; (e) optionally, a histone handle, preferably as specified in this document; f) a poly(A) sequence comprising, preferably, about 100 adenosine nucleotides; (g) optionally, a 3' terminal sequence element as specified in this document, preferably in accordance with SEQ ID Nos: 21322-21328, and wherein, optionally, at least one or more of the uracil nucleotides are preferably replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (η1ψ) nucleotides.
[0286] In further preferred embodiments of the first aspect, the artificial RNA, preferably mRNA, comprises the following elements in the 5' to 3' direction: a) 5'-cap structure, preferably, as specified herein, most preferably a Cap1 structure; b) a 3' UTR and a 5' UTR element according to a-1, a-4, c-1, e-4, g-2, i-2, or i-3 as specified in this document; c) a ribosome binding site, preferably as specified in this document; (d) at least one encoding sequence as specified herein, wherein said encoding region is located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3' UTR, wherein the encoding sequence is preferably selected from Petition 870260029351, dated 03 / 28 / 2026, page 230 / 555 167 / 372 of any of the SEQ ID Nos: 69-77, 484-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596 4958-4965, 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 11727-11734, 12096-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679-14686, 15048-15055, 15417-15424, 15786-15793, 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376, 18738-18745, 19107-19114, 19476-19483, 21363-21384, 21389-21410 (or fragments or variants thereof)]; e) a poly(A) sequence comprising approximately 64 adenosines; f) a poly(C) sequence comprising approximately 30 cysteines; (g) a histone stem-loop according to SEQ ID NO: 39 or 40, and wherein, optionally, at least one or more of the uracil nucleotides are preferably replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (η1ψ) nucleotides.
[0287] In further preferred embodiments of the first aspect, the artificial RNA, preferably mRNA, comprises the following elements in the 5' to 3' direction: a) 5'-cap structure, preferably, as specified herein, most preferably a Cap1 structure; b) a 3' UTR and a 5' UTR element according to a-1, a-4, c-1, e-4, g-2, i-2, or i-3 as specified Petition 870260029351, dated 03 / 28 / 2026, p. 231 / 555 168 / 372 in this document; c) a ribosome binding site, preferably as specified in this document; (d) at least one encoding sequence as specified in this document, wherein said encoding region is located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3' UTR, wherein the encoding sequence is preferably selected from any of the SEQ ID Nos: 69-77, 484-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596 4958-4965, 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 11727-11734, 12096-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679-14686, 15048-15055, 15417-15424, 15786-15793, 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376, 18738-18745, 19107-19114, 19476-19483, 21363-21384, 21389-21410 (or fragments or variants thereof)]; e) a poly(A) sequence comprising approximately 64 adenosines; f) a histone stem-loop according to SEQ ID NO: 39 or 40, and wherein, optionally, at least one or more of the uracil nucleotides are preferably replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (m^) nucleotides.
[0288] RSV polypeptide, nucleic acid and Petition 870260029351, dated 03 / 28 / 2026, p. 232 / 555 169 / 372 preferred mRNA sequences are provided in Tables 5A, 5B and Tables 6A, 6B.
[0289] In Tables 5A and 5B, the protein designs are indicated in row 1. In the same, Columns A to J represent specific suitable constructs of the invention derived from the Fusion protein (F) wherein Column A provides suitable sequences for F0, Column B provides suitable sequences for F-del, Column C provides suitable sequences for F0_DSCav1, Column D provides suitable sequences for F-del_DSCav1, Column E provides suitable sequences for F_DSCav1_mut1, Column F provides suitable sequences for F-del_DSCav1_mut1, Column G provides suitable sequences for F_DSCav1_mut2, Column H provides suitable sequences for Fdel_DSCav1_mut2, Column I provides suitable sequences for F_DSCav1_mut3, Column J provides suitable sequences for F-del_DSCav1_mut3.
[0290] Protein designs are indicated in row (Columns A to J), the specific protein SEQ ID NOs as provided in the sequence listing are in row 2 (protein). The SEQ ID NOs of coding sequences corresponding to each protein construct are provided in row 3 (cds, compare with Table 3 for different cds optimizations). Additional information, for example, related to the type of codon-modified coding sequence (opt1, opt2, opt3, opt4, opt5, opt6, opt11 etc.) is provided in the identifier. <223> of the respective SEQ ID NO in the sequence listing and in Table 3. The SEQ ID NOs of corresponding mRNA constructs comprising said coding sequences and the 3' UTRs and UTRs of Petition 870260029351, dated 03 / 28 / 2026, page 233 / 555 170 / 372 Suitable 5' sequences according to the invention are provided in rows 4 to 47 (mRNA designs a-1 to i-3 as specified herein). Table 5A provides mRNA sequences derived from HRSV(A2), and Table 5B provides mRNA sequences derived from HRSV(Memphis37). Additional information, for example, regarding the type of coding sequence (wt, opt1, opt2, opt3, opt4, opt5, opt6, opt11, etc.) included in the mRNA constructs, is provided in the identifier. <223> of the respective SEQ ID NO in the sequence listing. Table 5A: Preferred mRNA constructs encoding F of RSV (columns AJ) derived from HRSV(A2) 1 ABCDEFGHIJ 2 Protein 68 483 898 1267 1636 2005 2374 2743 3112 3481 3 cds 69-77, 21363 4 84- 4 92, 21364 899- 906, 21365 1268- 1275, 21366 1637- 164 4 , 21369 2006- 2013, 21370 2375- 2382, 21371 2744- 2751, 21372 3113- 3120, 21373 3482- 3489, 21374 4 mRNA project a-1 78-86, 2141521417, 2156121563 4 93- 501, 21418- 21420, 21564- 21566 907- 914, 21421- 21423, 21567- 21569 127 6- 1283, 21424- 21426, 21570- 21572 1645- 1652, 21433- 21435, 21579- 21581 2014- 2021, 21436- 21438, 21582- 21584 2383- 2390, 21439- 21441, 21585- 21587 2752- 2759, 21442- 21444, 21588- 21590 3121- 3128, 21445- 21447, 21591- 21593 34 90- 34 97 , 21448- 21450,21594- 21596 5 mRNA Project a-2 87-95 502- 510 915- 922 1284- 1291 1653- 1660 2022- 2029 2391- 2398 27 60- 27 67 3129- 3136 34 98- 3505 6 mRNA Project a-3 96-104 511- 519 923- 930 1292- 1299 1661- 1668 2030- 2037 2399- 2406 27 68- 2775 3137- 3144 3506- 3513 7 mRNA Project a-4 105- 113 520- 528 931- 938 1300- 1307 1669- 1676 2038- 2045 2407- 2414 277 6- 2783 3145- 3152 3514- 3521 8 mRNA Project a-5 114- 122 529- 537 939- 946 1308- 1315 1677- 1684 204 6- 2053 2415- 2422 2784- 27 91 3153- 3160 3522- 3529 9 mRNA Project b-1 123- 131 538- 546 947- 954 1316- 1323 1685- 1692 2054- 2061 2423- 2430 2792- 2799 3161- 3168 3530- 3537 Petition 870260029351, dated 03 / 28 / 2026, page 234 / 555 171 / 372 1 ABCDEFGHIJ 10 b-2 mRNA Project 132-140 547-555 955-962 1324-1331 1693-1700 2062-2069 2431-2438 2800-2807 3169-3176 3538-3545 11 b-3 mRNA Project 141-149 556-564 963-970 1332-1339 1701-1708 2070-2077 2439-2446 2808-2815 3177-3184 3546-3553 12 b-4 mRNA Project 150- 158 5 65- 573 971- 978 1340- 1347 1709- 1716 2078- 2085 2447- 2454 2816- 2823 3185- 3192 3554- 3561 13 mRNA b-5 Project 159- 167 574- 582 97 9- 986 1348- 1355 1717- 1724 2086- 2093 2455- 24 62 2824- 2831 3193- 3200 3562- 3569 14 mRNA c-1 Project 168- 176 583- 591 987- 994 1356- 1363 1725- 1732 2094- 2101 24 63- 2470 2832- 2839 3201- 3208 3570- 3577 15 c-2 mRNA Project 177- 185 592- 600 995- 1002 1364- 1371 1733- 1740 2102- 2109 2471- 2478 2840- 2847 3209- 3216 3578- 3585 16 c-3 mRNA Project 186- 194 601- 609 1003- 1010 1372- 1379 1741- 1748 2110- 2117 247 9- 2486 2848- 2855 3217- 3224 3586- 3593 17 c-4 mRNA Project 195- 203 610- 618 1011- 1018 1380- 1387 174 9- 17562118- 2125 2487- 2494 2856- 2863 3225- 3232 3594- 3601 18 c-5 mRNA Project 204- 212 619- 627 1019- 1026 1388- 1395 1757- 1764 2126- 2133 2495- 2502 2864- 2871 3233- 3240 3602- 3609 19 d-1 mRNA Project 213- 221 628- 636 1027- 1034 1396- 1403 1765- 1772 2134- 2141 2503- 2510 2872- 287 9 3241- 3248 3610- 3617 20 d-2 mRNA Project 222- 230 637- 645 1035- 1042 14 04- 1411 1773- 1780 2142- 2149 2511- 2518 2880- 2887 324 9- 3256 3618- 3625 21 d-3 mRNA Project 231- 239 64 6- 654 1043- 1050 1412- 1419 1781- 1788 2150- 2157 2519- 2526 2888- 2895 3257- 3264 3626- 3633 22 d-4 mRNA Project 240- 248 655- 663 1051- 1058 1420- 1427 1789- 1796 2158- 2165 2527- 2534 2896- 2903 3265- 3272 3634- 3641 23 d-5 mRNA Project 24 9- 257 6 64- 672 1059- 1066 1428- 1435 17 97- 1804 2166- 2173 2535- 2542 2904- 2911 3273- 3280 3642- 364 9 24 Project 258- 673- 1067- 1436- 1805- 2174- 2543- 2912- 3281- 3650- Petition 870260029351, dated 03 / 28 / 2026, page 235 / 555 172 / 372 1 ABCDEFGHIJ mRNA e-1 266 681 1074 1443 1812 2181 2550 2919 3288 3657 25 mRNA e-2 Project 267- 275 682- 690 1075- 1082 14 4 4- 1451 1813- 1820 2182- 2189 2551- 2558 2920- 2927 3289- 3296 3658- 3665 26 mRNA e-3 Project 27 6- 284 691- 699 1083- 1090 1452- 1459 1821- 1828 2190- 2197 2559- 2566 2928- 2935 3297- 3304 3 6 6 6- 3673 27 e-4 mRNA Project 285- 293 700- 708 1091- 1098 14 60- 1467 1829- 1836 2198- 2205 2567- 2574 2936- 2943 3305- 3312 3674- 3681 28 e-5 mRNA Project 294- 302 709- 717 1099- 1106 14 68- 1475 1837- 1844 2206- 2213 2575- 2582 2944- 2951 3313- 3320 3682- 3689 29 mRNA e-6 Project 303- 311 718- 726 1107- 1114 147 6- 1483 1845- 1852 2214- 2221 2583- 2590 2952- 2959 3321- 3328 3690- 3697 30 mRNA f-1 Project 312- 320 727- 735 1115- 1122 14 84- 1491 1853- 1860 2222- 2229 2591- 2598 2960- 2967 3329- 3336 3698- 3705 31 f-2 mRNA Project 321- 329 736- 744 1123- 1130 14 92- 1499 1861- 1868 2230- 2237 2599- 2606 2968- 2975 3337- 3344 3706- 3713 32mRNA Project f-3 330- 338 745- 753 1131- 1138 1500- 1507 1869- 1876 2238- 2245 2607- 2614 297 6- 2983 3345- 3352 3714- 3721 33 mRNA Project f-4 339- 347 754- 762 1139- 1146 1508- 1515 1877- 1884 224 6- 2253 2615- 2622 2984- 2991 3353- 3360 3722- 3729 34 mRNA Project f-5 348- 356 7 63- 771 1147- 1154 1516- 1523 1885- 1892 2254- 2261 2623- 2630 2992- 2999 3361- 3368 3730- 3737 35 g-1 mRNA Project 357- 365 772- 780 1155- 1162 1524- 1531 1893- 1900 2262- 2269 2631- 2638 3000- 3007 3369- 3376 3738- 3745 36 g-2 mRNA Project 3 6 6- 374 781- 789 1163- 1170 1532- 1539 1901- 1908 2270- 2277 2639- 264 6 3008- 3015 3377- 3384 374 6- 3753 37 g-3 mRNA Project 375- 383 7 90- 798 1171- 1178 1540- 1547 1909- 1916 2278- 2285 2647- 2654 3016- 3023 3385- 3392 3754- 37 61 38 mRNA Project 384- 392 7 99- 807 1179- 1186 1548- 1555 1917- 1924 2286- 2293 2655- 2662 3024- 3031 3393- 3400 3762- 3769 Petition 870260029351, dated 03 / 28 / 2026, page 236 / 555 173 / 372 1 ABCDEFGHIJ g-4 39 mRNA design g-5 393- 401 808- 816 1187- 1194 1556- 1563 1925- 1932 2294- 2301 2663- 2670 3032- 3039 3401- 3408 3770- 3777 40 mRNA design h-1 402- 410 817- 825 1195- 1202 1564- 1571 1933- 1940 2302- 2309 2671- 2678 3040- 3047 3409- 3416 3778- 3785 41 Design of mRNA h-2 411- 419 826- 834 1203- 1210 1572- 1579 1941- 1948 2310- 2317 267 9- 2686 3048- 3055 3417- 3424 3786- 37 93 42 mRNA h-3 Project 420- 428 835- 843 1211- 1218 1580- 1587 194 9- 1956 2318- 2325 2687- 2694 3056- 3063 3425- 3432 37 94- 3801 43 mRNA h-4 Project 429- 437 84 4- 852 1219- 1226 1588- 1595 1957- 1964 2326- 2333 2695- 2702 3064- 3071 3433- 3440 3802- 3809 44 mRNA h-5 project 438- 446 853- 861 1227- 1234 1596- 1603 1965- 1972 2334- 2341 2703- 2710 3072- 307 9 3441- 3448 3810- 3817 45 mRNA i-1 project 4 47- 455 862- 870 1235- 1242 1604- 1611 1973- 1980 2342- 234 9 2711- 2718 3080- 3087 344 9- 3456 3818- 3825 46 mRNA i-2 Project 456- 473 871- 888 1243- 1258 1612- 16271981- 1996 2350- 2365 2719- 2734 3088- 3103 3457- 3472 3826- 3841 47 mRNA Project i-3 47 4- 482 889- 897 1259- 1266 1628- 1635 1997- 2004 2366- 2373 2735- 2742 3104- 3111 3473- 3480 3842- 384 9 48 mRNA Project i-4 8278 Table 5B: Preferred mRNA constructs encoding F of RSV (columns AJ) derived from HRSV (Memphis-37) 1 ABCDEFGHIJ 2 Protein 11726 12095 124 64 12833 13940 14309 14 678 15047 15416 15785 3 cds 11727- 12096- 12465- 12834- 13941- 14310- 14679- 15048- 15417- 15786- 11734, 12103, 12472, 12841, 13948, 14317, 14686, 15055, 15424, 15793, 21389 21390 21391 21392 21395 21396 21397 21398 21399 21400 4 Project 11735- 12104- 12473- 12842- 13949- 14318- 14687- 15056- 15425- 15794- of mRNA 11742, 12111, 12480, 12849, 13956, 14325, 14694, 15063, 15432, 15801, Petition 870260029351, dated 03 / 28 / 2026, page 237 / 555 174 / 372 1 ABCDEFGHIJ a-1 21489, 21490, 21635, 21636 21491, 21492, 21637, 21638 21493- 21495, 21639- 21641 21496- 21498, 21642- 21644 21505- 21507, 21651- 21653 21508- 21510, 21654- 21656 21511- 21513, 21657- 21659 21514- 21516, 21660- 21662 21517- 21519, 21663- 21665 21520- 21522, 21666- 21668 5 mRNA a-2 Project 11743- 11750 12112- 12119 12481- 12488 12850- 12857 13957- 13964 14326- 14333 14695- 14702 15064- 15071 15433- 15440 15802- 15809 6 mRNA a-3 Project 11751- 11758 12120- 12127 12489- 12496 12858- 12865 13965- 13972 14334- 14341 14703- 14710 15072- 15079 15441- 15448 15810- 15817 7 mRNA a-4 Project 11759- 11766 12128- 12135 12497- 12504 12866- 12873 13973- 13980 14342- 1434 9 14711- 14718 15080- 15087 15449- 15456 15818- 15825 8 mRNA a-5 Project 11767- 11774 12136- 12143 12505- 12512 12874- 12881 13981- 13988 14350- 14357 14719- 14726 15088- 15095 15457- 15464 15826- 15833 9 mRNA b-1 Project 11775- 11782 12144- 12151 12513- 12520 12882- 12889 13989- 1399614358- 14365 14727- 14734 15096- 15103 15465- 15472 15834- 15841 10 mRNA b-2 Project 11783- 11790 12152- 12159 12521- 12528 12890- 12897 13997- 14004 14366- 14373 14735- 14742 15104- 15111 15473- 15480 15842- 15849 11 mRNA b-3 Project 11791- 11798 12160- 12167 12529- 12536 12898- 12905 14005- 14012 14374- 14381 14743- 14750 15112- 15119 15481- 15488 15850- 15857 12 mRNA b-4 Project 11799- 11806 12168- 12175 12537- 12544 12906- 12913 14013- 14020 14382- 14389 14751- 14758 15120- 15127 15489- 15496 15858- 15865 13 mRNA b-5 Project 11807- 11814 12176- 12183 12545- 12552 12914- 12921 14021- 14028 14390- 14397 14759- 14766 15128- 15135 15497- 15504 15866- 15873 14 mRNA c-1 Project 11815- 11822 12184- 12191 12553- 12560 12922- 12929 14029- 14036 14398- 14405 14767- 14774 15136- 15143 15505- 15512 15874- 15881 15 c-2 mRNA Project 11823- 11830 12192- 12199 12561- 12568 12930- 12937 14037- 1404 4 14406- 14413 14775- 14782 15144- 15151 15513- 15520 15882- 15889 16c-3 mRNA Project 11831- 11838 12200- 12207 12569- 12576 12938- 12945 14045- 14052 14414- 14421 14783- 14790 15152- 15159 15521- 15528 15890- 15897 17 c-4 mRNA Project 11839- 11846 12208- 12215 12577- 12584 12946- 12953 14053- 14060 14422- 14429 14791- 14798 15160- 15167 15529- 15536 15898- 15905 Petition 870260029351, dated 03 / 28 / 2026, page 238 / 555 175 / 372 1 ABCDEFGHIJ 18 c-5 mRNA Project 11847- 11854 12216- 12223 12585- 12592 12954- 12961 14061- 14068 14430- 14437 14799- 14806 15168- 15175 15537- 15544 15906- 15913 19 d-1 mRNA Project 11855- 11862 12224- 12231 12593- 12600 12962- 12969 14069- 1407 6 14438- 14 4 45 14807- 14814 15176- 15183 15545- 15552 15914- 15921 20 d-2 mRNA Project 11863- 11870 12232- 12239 12601- 12608 12970- 12977 14077- 14084 14446- 14453 14815- 14822 15184- 15191 15553- 15560 15922- 15929 21 d-3 mRNA Project 11871- 11878 12240- 12247 12609- 12616 12978- 12985 14085- 14092 14454- 14 4 61 14823- 14830 15192- 15199 15561- 15568 15930- 15937 22 d-4 mRNA Project 11879- 11886 12248- 12255 12617- 12624 12986- 12993 14093- 14100 14462- 14 4 69 14831- 14838 15200- 15207 15569- 15576 15938- 15945 23 d-5 mRNA Project 11887- 11894 12256- 12263 12625- 12632 12994- 13001 14101- 14108 14470- 14477 14839- 14846 15208- 15215 15577- 15584 15946- 15953 24 mRNA e-1 Project 11895- 11902 12264- 1227112633- 12640 13002- 13009 14109- 14116 14478- 14 4 85 14847- 14854 15216- 15223 15585- 15592 15954- 15961 25 e-2 mRNA Project 11903- 11910 12272- 12279 12641- 12648 13010- 13017 14117- 14124 14486- 14 4 93 14855- 14862 15224- 15231 15593- 15600 15962- 15969 26 e-3 mRNA Project 11911- 11918 12280- 12287 12649- 12656 13018- 13025 14125- 14132 14494- 14501 14863- 14870 15232- 15239 15601- 15608 15970- 15977 27 e-4 mRNA Project 11919- 11926 12288- 12295 12657- 12664 13026- 13033 14133- 14140 14502- 14509 14871- 14878 15240- 15247 15609- 15616 15978- 15985 28 e-5 mRNA Project 11927- 11934 12296- 12303 12665- 12672 13034- 13041 14141- 14148 14510- 14517 14879- 14886 15248- 15255 15617- 15624 15986- 15993 29 e-6 mRNA Project 11935- 11942 12304- 12311 12673- 12680 13042- 1304 9 14149- 14156 14518- 14525 14887- 14894 15256- 15263 15625- 15632 15994- 16001 30 mRNA f-1 Project 11943- 11950 12312- 12319 12681- 12688 13050- 13057 14157- 14164 14526- 14533 14895- 14902 15264-15271 15633- 15640 16002- 16009 31 mRNA f-2 Project 11951- 11958 12320- 12327 12689- 12696 13058- 13065 14165- 14172 14534- 14541 14903- 14910 15272- 15279 15641- 15648 16010- 16017 32 Project 11959- 12328- 12697- 13066- 14173- 14542- 14911- 15280- 15649- 16018- Petition 870260029351, dated 03 / 28 / 2026, page 239 / 555 176 / 372 1 ABCDEFGHIJ mRNA f-3 11966 12335 12704 13073 14180 1454 9 14918 15287 15656 16025 33 mRNA f-4 Project 11967- 11974 12336- 12343 12705- 12712 13074- 13081 14181- 14188 14550- 14557 14919- 14926 15288- 15295 15657- 15664 16026- 16033 34 mRNA f-5 Project 11975- 11982 12344- 12351 12713- 12720 13082- 13089 14189- 14196 14558- 14565 14927- 14934 15296- 15303 15665- 15672 16034- 16041 35 g-1 mRNA Project 11983- 11990 12352- 12359 12721- 12728 13090- 13097 14197- 14204 14566- 14573 14935- 14942 15304- 15311 15673- 15680 16042- 1604 9 36 g-2 mRNA Project 11991- 11998 12360- 12367 12729- 12736 13098- 13105 14205- 14212 14574- 14581 14943- 14950 15312- 15319 15681- 15688 16050- 16057 37 g-3 mRNA Project 11999- 12006 12368- 12375 12737- 12744 13106- 13113 14213- 14220 14582- 14589 14951- 14 958 15320- 15327 15689- 15696 16058- 16065 38 g-4 mRNA Project 12007- 12014 12376- 12383 12745- 12752 13114- 13121 14221- 14228 14590- 14597 14959- 14966 15328- 15335 15697-15704 16066- 16073 39 g-5 mRNA Project 12015- 12022 12384- 12391 12753- 12760 13122- 13129 14229- 14236 14598- 14605 14967- 14974 15336- 15343 15705- 15712 16074- 16081 40 h-1 mRNA Project 12023- 12030 12392- 12399 12761- 12768 13130- 13137 14237- 14244 14606- 14613 14975- 14 982 15344- 15351 15713- 15720 16082- 16089 41 h-2 mRNA Project 12031- 12038 12400- 12407 12769- 1277 6 13138- 13145 14245- 14252 14614- 14 621 14983- 14 990 15352- 15359 15721- 15728 16090- 16097 42 h-3 mRNA Project 12039- 1204 6 12408- 12415 12777- 12784 13146- 13153 14253- 14260 14622- 14629 14991- 14998 15360- 15367 15729- 15736 16098- 16105 43 mRNA h-4 Project 12047- 12054 12416- 12423 12785- 12792 13154- 13161 14261- 14268 14630- 14637 14999- 15006 15368- 15375 15737- 15744 16106- 16113 44 mRNA Project h-5 12055- 12062 12424- 12431 12793- 12800 13162- 13169 14269- 1427 6 14638- 14 645 15007- 15014 15376- 15383 15745- 15752 16114- 16121 45 mRNA Project i-1 12063- 12070 12432- 1243912801- 12808 13170- 13177 14277- 14284 14646- 14653 15015- 15022 15384- 15391 15753- 15760 16122- 16129 46 mRNA Project 12071- 12086 12440- 12455 12809- 12824 13178- 13193 14285- 14300 14654- 14669 15023- 15038 15392- 15407 15761- 15776 16130- 16145 Petition 870260029351, dated 03 / 28 / 2026, p. 240 / 555 177 / 372 1 ABCDEFGHIJ i-2 47 mRNA Project i-3 12087- 12094 12456- 124 63 12825- 12832 13194- 13201 14301- 14308 14670- 14 677 15039- 1504 6 15408- 15415 15777- 15784 16146- 16153
[0291] In Tables 6A and 6B, the protein designs are indicated in row 1. In these, Columns K to V represent specific suitable constructs of the invention derived from RSV Fusion protein (F), wherein Column K provides suitable sequences for F_DSCav1_mut0, Column L provides suitable sequences for F-del_DSCav1_mut0, Column M provides suitable sequences for F_DSCav1_mut4, Column N provides suitable sequences for Fdel_DSCav1_mut4, Column O provides suitable sequences for F_DSCav1_mut5, Column P provides suitable sequences for F-del_DSCav1_mut5, Column Q provides suitable sequences for F_DSCav1_mut6, Column R provides suitable sequences for F-del_DSCav1_mut6, Column S provides suitable sequences for F_DSCav1_mut7, Column T provides suitable sequences For F-del_DSCav1_mut7, Column U provides suitable sequences; for F_DSCav1_mut8, Column V provides suitable sequences.
[0292] Protein designs are indicated in the first row (Columns K to V), the specific protein SEQ ID NOs as provided in the sequence listing are in row 2, PRT. The SEQ ID NOs of coding sequences corresponding to each protein construct are provided in row 3, cds” (compare with Table 4 for different cds optimizations). Additional information, for example, relating to sequence type. Petition 870260029351, dated 03 / 28 / 2026, page 241 / 555 178 / 372 modified codon encodings (optl, opt2, opt3, opt4, opt5, opt6, opt11, etc.) are provided in the identifier. <223> The respective SEQ ID NOs are listed in the sequence list and in Table 4. The SEQ ID NOs of corresponding mRNA constructs comprising said coding sequences and the appropriate 3' and 5' UTRs according to the invention are provided in each row below (mRNA designs “a-1” to “i-3” as specified herein). In Table 6A, the mRNA sequences derived from HRSV(A2) are provided, in Table 6B, the mRNA sequences derived from HRSV (Memphis-37) are provided.
[0293] Additional information, for example, relating to the type of coding sequence (wt, opt1, opt2, opt3, opt4, opt5, opt6, opt11 etc.) included in the mRNA constructs is provided in the identifier. <223> of the respective SEQ ID NO in the sequence listing. Table 6A: Preferred mRNA constructs encoding RSV F (KV columns) derived from HRSV(A2) KLMNOPQRSTUV PR T 3850 4219 4588 4 957 5326 5695 6064 6433 6802 7171 7540 7 909 cd 3851- 4220- 4589- 4 958- 5327- 5696- 6065- 6434- 6803- 7172- 7541- 7910- s 3858, 4227, 4596, 4965, 5334, 5703, 6072, 64 4 1, 6810, 7179, 7548, 7917, 21367 21368 21375 21376 21377 21378 21379 21380 21381 21382 21383 21384 a- 3859- 4228- 4597- 4 966- 5335- 5704- 6073- 6442- 6811- 7180- 754 9- 7918- 1 3866, 4235, 4 604, 4 973, 5342, 5711, 6080, 644 9, 6818, 7187, 7556, 7925, 21427 21430 21451 21454 21457 21460 21463 21466 21469 21472 21475 21478 21429 21432 21453 21456 21459 21462 21465 21468 21471 21474 21477 21480 , 21573 , 21576 , 21597 , 21600 , 21603 , 21606 , 21609 , 21612 , 21615 , 21618 , 21621 , 21624 21575 21578 21599 21602 21605 21608 21611 21614 21617 21620 21623 21626 Petition 870260029351, dated 03 / 28 / 2026, p. 242 / 555 179 / 372 K L M N O P Q R S T U V a- 2 3867- 3874 4236- 4243 4 605- 4612 4 974- 4 981 5343- 5350 5712- 5719 6081- 6088 6450- 6457 6819- 6826 7188- 7195 7557- 7564 7 926- 7 933 a- 3 3875- 3882 4244- 4251 4613- 4 620 4 982- 4 989 5351- 5358 5720- 5727 6089- 6096 6458- 64 65 6827- 6834 7196- 7203 7565- 7572 7 934- 7 941 a- 4 3883- 3890 4252- 4259 4 621- 4 628 4 990- 4 997 5359- 5366 5728- 5735 6097- 6104 64 6 6- 6473 6835- 6842 7204- 7211 7573- 7580 7 942- 7 94 9 a- 5 3891- 3898 4260- 4267 4 629- 4 636 4 998- 5005 5367- 5374 5736- 5743 6105- 6112 6474- 6481 6843- 6850 7212- 7219 7581- 7588 7950- 7957 b- 1 3899- 3906 4268- 4275 4 637- 4 64 4 5006- 5013 5375- 5382 5744- 5751 6113- 6120 6482- 6489 6851- 6858 7220- 7227 7589- 7596 7958- 7 965 b- 2 3907- 3914 427 6- 4283 4 645- 4 652 5014- 5021 5383- 5390 5752- 5759 6121- 6128 64 90- 64 97 6859- 6866 7228- 7235 7597- 7 604 7 966- 7 973 b- 3 3915- 3922 4284- 4291 4653- 4 660 5022- 5029 5391- 5398 5760- 5767 6129- 6136 64 98- 6505 6867- 6874 7236- 72437605- 7612 7 974- 7 981 b- 4 3923- 3930 4292- 4299 4 661- 4 668 5030- 5037 5399- 5406 5768- 5775 6137- 6144 6506- 6513 6875- 6882 7244- 7251 7613- 7 620 7 982- 7 989 b- 5 3931- 3938 4300- 4307 4 669- 4 67 6 5038- 5045 5407- 5414 5776- 5783 6145- 6152 6514- 6521 6883- 6890 7252- 7259 7 621- 7 628 7 990- 7 997 o- I 3939- 394 6 4308- 4315 4 677- 4 684 504 6- 5053 5415- 5422 5784- 5791 6153- 6160 6522- 6529 6891- 6898 7260- 7267 7 629- 7 636 7 998- 8005 c- 2 3947- 3954 4316- 4323 4 685- 4 692 5054- 5061 5423- 5430 5792- 5799 6161- 6168 6530- 6537 6899- 6906 7268- 7275 7 637- 7 644 8006- 8013 c- 3 3955- 3962 4324- 4331 4 693- 4700 5062- 5069 5431- 5438 5800- 5807 6169- 6176 6538- 6545 6907- 6914 727 6- 7283 7 645- 7652 8014-8021c-4 3963- 3970 4332- 4339 4701- 4708 5070- 5077 5439- 544 6 5808- 5815 6177- 6184 654 6- 6553 6915- 6922 7284- 7291 7653- 7 660 8022- 8029 c- 5 3971- 3978 4340- 4347 4709- 4716 5078- 5085 5447- 5454 5816- 5823 6185- 6192 6554- 6561 6923- 6930 7292- 7299 7 661- 7668 8030- 8037 d- 1 397 9- 3986 4348- 4355 4717- 4724 5086- 5093 5455- 54 62 5824- 5831 6193- 6200 6562- 6569 6931- 6938 7300- 7307 7 669- 7 67 6 8038- 8045 d- 2 3987- 3994 4356- 4363 4725- 4732 5094- 5101 5463- 5470 5832- 5839 6201- 6208 6570- 6577 6939- 694 6 7308- 7315 7 677- 7 684 804 6- 8053 d- 3 3995- 4002 4364- 4371 4733- 47 4 0 5102- 5109 5471- 5478 5840- 5847 6209- 6216 6578- 6585 6947- 6954 7316- 7323 7685- 7 692 8054- 8061 d- 4 4003- 4010 4372- 437 9 47 4 1- 47 4 8 5110- 5117 547 9- 5486 5848- 5855 6217- 6224 6586- 6593 6955- 6962 7324- 7331 7 693- 7700 8062- 8069 d- 5 4011- 4018 4380- 4387 474 9- 4756 5118- 5125 5487- 54 94 5856- 5863 6225- 6232 6594- 6601 6963- 6970 7332- 7339 7701- 7708 8070- 8077 e- 1 4019- 4026 4388- 4395 4757- 47 64 5126- 5133 5495- 5502 5864- 5871 6233- 6240 6602- 6609 6971- 6978 7340- 7347 7709- 7716 8078- 8085 e- 2 4027- 4034 4396- 4 4 03 47 65- 4772 5134- 5141 5503- 5510 5872- 5879 6241- 6248 6610- 6617 697 9- 6986 7348- 7355 7717- 7724 8086- 8093 Petition 870260029351, dated 03 / 28 / 2026, p. 243 / 555 180 / 372 K L M N O P Q R S T U V e- 3 4035- 4 042 4 4 04- 4411 4773- 4780 5142- 5149 5511- 5518 5880- 5887 624 9- 6256 6618- 6625 6987- 6994 7356- 7363 7725- 7732 8094- 8101 e- 4 4043- 4050 4412- 4419 4781- 4788 5150- 5157 5519- 5526 5888- 5895 6257- 6264 6626- 6633 6995- 7002 7364- 7371 7733- 7740 8102- 8109 e- 5 4051- 4058 4420- 4427 4789- 47 96 5158- 5165 5527- 5534 5896- 5903 6265- 6272 6634- 6641 7003- 7010 7372- 737 9 7741- 7748 8110- 8117 e- 6 4059- 4066 4428- 4435 47 97- 4804 5166- 5173 5535- 5542 5904- 5911 6273- 6280 6642- 664 9 7011- 7018 7380- 7387 774 9- 7756 8118- 8125 f- 1 4067- 4074 4436- 4 4 43 4805- 4812 5174- 5181 5543- 5550 5912- 5919 6281- 6288 6650- 6657 7019- 7026 7388- 7395 7757- 77 64 8126- 8133 f- 2 4075- 4082 4 4 4 4- 4451 4813- 4820 5182- 5189 5551- 5558 5920- 5927 6289- 6296 6658- 6 6 65 7027- 7034 7396- 7403 7765- 7772 8134- 8141 f- 3 4083- 4090 4452- 4459 4821- 4828 5190- 5197 555 9- 5566 5928- 5935 6297- 6304 6 6 6 6- 6673 7035- 7042 7404- 7411 7773- 7780 8142-8149 f- 4 4091- 4098 44 60- 4 4 67 4829- 4836 5198- 5205 5567- 5574 5936- 5943 6305- 6312 6674- 6681 7043- 7050 7412- 7419 7781- 7788 8150- 8157 f- 5 4099- 4106 44 68- 4 475 4837- 4 84 4 5206- 5213 5575- 5582 5944- 5951 6313- 6320 6682- 6689 7051- 7058 7420- 7427 7789- 77 96 8158- 8165 g- 1 4107- 4114 447 6- 4 4 83 4845- 4852 5214- 5221 5583- 5590 5952- 5959 6321- 6328 6690- 6697 7059- 7066 7428- 7435 77 97- 7804 8166- 8173 g- 2 4115- 4122 4 4 84- 4 4 91 4853- 4860 5222- 5229 5591- 5598 5960- 5967 6329- 6336 6698- 6705 7067- 7074 7436- 7 4 43 7805- 7812 8174- 8181 g- 3 4123- 4130 44 92- 4 4 99 4861- 4868 5230- 5237 5599- 5606 5968- 5975 6337- 6344 6706- 6713 7075- 7082 7 4 4 4- 7451 7813- 7820 8182- 8189 g- 4 4131- 4138 4500- 4507 4869- 487 6 5238- 5245 5607- 5614 5976- 5983 6345- 6352 6714- 6721 7083- 7090 7452- 7459 7821- 7828 8190- 8197 g- 5 4139- 4146 4508- 4515 4877- 4884 5246- 5253 5615- 5622 5984- 5991 6353- 6360 6722- 6729 7091- 7098 74 60- 74 67 7829- 7836 8198- 8205 h- 14147- 4154 4516- 4523 4885- 4892 5254- 5261 5623- 5630 5992- 5999 6361- 6368 6730- 6737 7099- 7106 74 68- 7475 7837- 7844 8206- 8213 h- 2 4155- 4162 4524- 4531 4893- 4 900 5262- 5269 5631- 5638 6000- 6007 6369- 637 6 6738- 6745 7107- 7114 747 6- 7483 7845- 7852 8214- 8221 h- 3 4163- 4170 4532- 4539 4 901- 4 908 5270- 5277 5639- 564 6 6008- 6015 6377- 6384 674 6- 6753 7115- 7122 7484- 74 91 7853- 7860 8222- 8229 h- 4 4171- 4178 4540- 4547 4 909- 4916 5278- 5285 5647- 5654 6016- 6023 6385- 6392 6754- 67 61 7123- 7130 74 92- 74 99 7861- 7868 8230- 8237 h- 5 4179- 4186 4548- 4555 4917- 4 924 5286- 5293 5 655- 5662 6024- 6031 6393- 6400 67 62- 67 69 7131- 7138 7500- 7507 7869- 787 6 8238- 8245 i- 1 4187- 4194 4556- 4563 4925- 4 932 5294- 5301 5663- 5670 6032- 6039 6401- 6408 6770- 6777 7139- 7146 7508- 7515 7877- 7884 824 6- 8253 i- 2 4195- 4210 4564- 457 9 4 933- 4 94 8 5302- 5317 5671- 5686 6040- 6055 6409- 6424 6778- 67 93 7147- 7162 7516- 7531 7885- 7 900 8254- 8269 Petition 870260029351, dated 03 / 28 / 2026, p. 244 / 555 181 / 372 KLMNOPQRSTUV i- 3 4211- 4218 4580- 4587 4 94 9- 4 956 5318- 5325 5687- 5694 6056- 6063 6425- 6432 67 94- 6801 7163- 7170 7532- 7539 7 901- 7 908 8270- 8277 Table 6B: Preferred mRNA constructs encoding RSV F (KV columns) derived from HRSV (Memphis-37) K L M N O P Q R S T U V PRT 13202 13571 16154 16523 168 92 17261 17630 17 999 18368 18737 19106 19475 cds 13203- 13210, 21393 13572 - 13579 , 21394 16155- 16162, 21401 16524- 16531, 21402 16893- 16900, 21403 17262- 17269, 21404 17631- 17638, 21405 18000- 18007, 21406 18369- 18376, 21407 18738- 18745, 21408 19107- 19114, 21409 19476- 19483, 21410 a-1 13211- 13218, 21499- 21501, 21645- 21647 13580 - 13587 , 21502 - 21504 , 21648 - 21650 16163- 16170, 21523- 21525, 21669- 21671 16532- 16539, 21526- 21528, 21672- 21674 16901- 16908, 21529- 21531, 21675- 21677 17270- 17277, 21532- 21534, 21678- 21680 17639- 17646, 21535- 21537, 21681- 21683 18008- 18015, 21538- 21540, 21684- 21686 18377- 18384, 21541- 21543, 21687- 21689 18746- 18753, 21544- 21546, 21690- 21692 19115- 19122, 21547- 21549, 21693- 21695 19484- 19491, 21550- 21552, 21696- 21698 a-2 13219- 13226 13588 - 13595 16171- 16178 16540- 16547 16909- 16916 17278- 17285 17647- 17654 18016- 18023 18385- 18392 18754- 18761 19123- 1913019492- 19499 a- 3 13227- 13234 13596 - 13603 16179- 16186 16548- 16555 16917- 16924 17286- 172 93 17655- 17662 18024- 18031 18393- 18400 18762- 18769 19131- 19138 19500- 19507 a-4 13235- 13242 13604 - 13611 16187- 16194 16556- 16563 16925- 16932 17294- 17301 17663- 17670 18032- 18039 18401- 18408 18770- 18777 19139- 19146 19508- 19515 a- 5 13243- 13250 13612 - 13619 16195- 16202 16564- 16571 16933- 16940 17302- 17309 17671- 17678 18040- 18047 18409- 18416 18778- 18785 19147- 19154 19516- 19523 b-1 13251- 13258 13620 - 13627 16203- 16210 16572- 16579 16941- 16948 17310- 17317 17679- 17686 18048- 18055 18417- 18424 18786- 18793 19155- 19162 19524- 19531 b-2 13259- 13266 13628 - 13635 16211- 16218 16580- 16587 16949- 16956 17318- 17325 17687- 17694 18056- 18063 18425- 18432 18794- 18801 19163- 19170 19532- 19539 b-3 13267- 13274 13636 - 13643 16219- 16226 16588- 16595 16957- 16964 17326- 17333 17695- 17702 18064- 18071 18433- 18440 18802- 18809 19171- 19178 19540- 19547 b-4 13275- 1328213644 - 16227- 16234 16596- 16603 16965- 16972 17334- 17341 17703- 17710 18072- 1807 9 18441- 18448 18810- 18817 19179- 19186 19548- 19555 Petition 870260029351, dated 03 / 28 / 2026, pp. 245 / 555 182 / 372 K L M N O P Q R S T U V 13651 b-5 13283- 13290 13652 - 13659 16235- 16242 16604- 16611 16973- 16980 17342- 17349 17711- 17718 18080- 18087 18449- 18456 18818- 18825 19187- 19194 19556- 19563 c-1 13291- 13298 13660 - 13667 16243- 16250 16612- 16619 16981- 16988 17350- 17357 17719- 17726 18088- 18095 18457- 18464 18826- 18833 19195- 19202 19564- 19571 c-2 13299- 13306 13668 - 13675 16251- 16258 16620- 16627 16989- 16996 17358- 17365 17727- 17734 18096- 18103 18465- 18472 18834- 18841 19203- 19210 19572- 1957 9 c-3 13307- 13314 13676 - 13683 16259- 16266 16628- 16635 16997- 17004 17366- 17373 17735- 17742 18104- 18111 18473- 18480 18842- 1884 9 19211- 19218 19580- 19587 c-4 13315- 13322 13684 - 13691 16267- 16274 16636- 16643 17005- 17012 17374- 17381 17743- 17750 18112- 18119 18481- 18488 18850- 18857 19219- 19226 19588- 19595 c-5 13323- 13330 13692 - 13699 16275- 16282 16644- 16651 17013- 17020 17382- 17389 17751- 17758 18120- 18127 18489- 18496 18858- 18865 19227- 19234 19596- 19603d-1 13331- 13338 13700 - 13707 16283- 162 90 16652- 16659 17021- 17028 17390- 17397 17759- 17766 18128- 18135 18497- 18504 18866- 18873 19235- 19242 19604- 19611 d-2 13339- 13346 13708 - 13715 16291- 162 98 16660- 16667 17029- 17036 17398- 17405 17767- 17774 18136- 18143 18505- 18512 18874- 18881 19243- 19250 19612- 19619 d-3 13347- 13354 13716 - 13723 16299- 16306 16668- 16675 17037- 17044 17406- 17413 17775- 17782 18144- 18151 18513- 18520 18882- 1888 9 19251- 19258 19620- 19627 d-4 13355- 13362 13724 - 13731 16307- 16314 16676- 16683 17045- 17052 17414- 17421 17783- 17790 18152- 18159 18521- 18528 18890- 18897 19259- 19266 19628- 19635 d-5 13363- 13370 13732 - 13739 16315- 16322 16684- 16691 17053- 17060 17422- 17429 17791- 17798 18160- 18167 18529- 18536 18898- 18 905 19267- 19274 19636- 19643 e-1 13371- 13378 13740 - 13747 16323- 16330 16692- 16699 17061- 17068 17430- 17437 17799- 17806 18168- 18175 18537- 18544 18906- 18913 19275- 19282 19644- 19651 e-2 13379- 13386 13748 - 1375516331- 16338 16700- 16707 17069- 17076 17438- 17445 17807- 17814 18176- 18183 18545- 18552 18914- 18921 19283- 19290 19652- 19659 e- 3 13387- 13394 13756 - 13763 16339- 16346 16708- 16715 17077- 17084 17446- 17453 17815- 17822 18184- 18191 18553- 18560 18922- 18 92 9 19291- 19298 19660- 19667 e- 4 13395- 13402 13764 - 13771 16347- 16354 16716- 16723 17085- 17092 17454- 17461 17823- 17830 18192- 18199 18561- 18568 18930- 18 937 19299- 19306 19668- 19675 e-5 13403- 13410 13772 - 13779 16355- 16362 16724- 16731 17093- 17100 17462- 17469 17831- 17838 18200- 18207 18569- 18576 18938- 18945 19307- 19314 19676- 19683 Petition 870260029351, dated 03 / 28 / 2026, page 246 / 555 183 / 372 K L M N O P Q R S T U V e- 6 13411- 13418 13780 - 13787 16363- 16370 16732- 16739 17101- 17108 17470- 17477 17839- 17846 18208- 18215 18577- 18584 18946- 18 953 19315- 19322 19684- 19691 f-1 13419- 13426 13788 - 137 95 16371- 16378 16740- 16747 17109- 17116 17478- 17485 17847- 17854 18216- 18223 18585- 18592 18954- 18 961 19323- 19330 19692- 19699 f-2 13427- 13434 137 96 - 13803 16379- 16386 16748- 16755 17117- 17124 17486- 174 93 17855- 17862 18224- 18231 18593- 18600 18962- 18 969 19331- 19338 19700- 19707 f-3 13435- 13442 13804 - 13811 16387- 16394 16756- 16763 17125- 17132 17494- 17501 17863- 17870 18232- 18239 18601- 18608 18970- 18 977 19339- 19346 19708- 19715 f-4 13443- 13450 13812 - 13819 16395- 16402 16764- 16771 17133- 17140 17502- 17509 17871- 17878 18240- 18247 18609- 18616 18978- 18 985 19347- 19354 19716- 19723 f-5 13451- 13458 13820 - 13827 16403- 16410 16772- 16779 17141- 17148 17510- 17517 17879- 17886 18248- 18255 18617- 18624 18986- 18 993 19355- 19362 19724- 19731g-1 13459- 13466 13828 - 13835 16411- 16418 16780- 16787 17149- 17156 17518- 17525 17887- 17894 18256- 18263 18625- 18632 18994- 19001 19363- 19370 19732- 19739 g-2 13467- 13474 13836 - 13843 16419- 16426 16788- 167 95 17157- 17164 17526- 17533 17895- 17 902 18264- 18271 18633- 18640 19002- 19009 19371- 19378 19740- 19747 g-3 13475- 13482 13844 - 13851 16427- 16434 16796- 16803 17165- 17172 17534- 17541 17903- 17910 18272- 1827 9 18641- 18648 19010- 19017 19379- 19386 19748- 19755 g-4 13483- 13490 13852 - 13859 16435- 16442 16804- 16811 17173- 17180 17542- 17549 17911- 17918 18280- 18287 18649- 18656 19018- 19025 19387- 19394 19756- 19763 g-5 13491- 13498 13860 - 13867 16443- 16450 16812- 16819 17181- 17188 17550- 17557 17919- 17 926 18288- 18295 18657- 18664 19026- 19033 19395- 19402 19764- 19771 h-1 13499- 13506 13868 - 13875 16451- 16458 16820- 16827 17189- 17196 17558- 17565 17927- 17 934 18296- 18303 18665- 18672 19034- 19041 19403- 19410 19772- 1977 9 h-2 13507- 13514 13876 -13883 16459- 16466 16828- 16835 17197- 17204 17566- 17573 17935- 17 942 18304- 18311 18673- 18680 19042- 1904 9 19411- 19418 19780- 19787 h-3 13515- 13522 13884 - 138 91 16467- 16474 16836- 16843 17205- 17212 17574- 17581 17943- 17 950 18312- 18319 18681- 18688 19050- 19057 19419- 19426 19788- 19795 h-4 13523- 13530 138 92 - 138 99 16475- 16482 16844- 16851 17213- 17220 17582- 17589 17951- 17 958 18320- 18327 18689- 18696 19058- 19065 19427- 19434 19796- 19803 h-5 13531- 13538 13900 - 13907 16483- 164 90 16852- 16859 17221- 17228 17590- 17597 17959- 17 966 18328- 18335 18697- 18704 19066- 19073 19435- 19442 19804- 19811 i-1 13539- 13908 16491- 16860- 17229- 17598- 17967- 18336- 18705- 19074- 19443- 19812- Petition 870260029351, dated 03 / 28 / 2026, p. 247 / 555 184 / 372 K L M N O P Q R S T U V 13546 - 13915 164 98 16867 17236 17605 17 974 18343 18712 19081 19450 19819 i-2 13547- 13562 13916 - 13931 16499- 16514 16868- 16883 17237- 17252 17606- 17621 17975- 17 990 18344- 18359 18713- 18728 19082- 19097 19451- 19466 19820- 19835 i-3 13563- 13570 13932 - 13939 16515- 16522 16884- 168 91 17253- 17260 17622- 17629 17991- 17 998 18360- 18367 18729- 18736 19098- 19105 19467- 19474 19836- 19843
[0294] In preferred embodiments, the artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to, a nucleic acid sequence selected from the group consisting of Seq ID NOs: 78-482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 4228-4587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 21415-21480, 21561-21626, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 13949-14308, 1431814677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 16532-16891, 1690117260, 17270-17629, 17639-17998, 18008-18367, 18377-18736, 18746-19105, 19115-19474, 19484-19843, 21489-21552, 2163521698 or one fragment or variant of any of these sequences, where, optionally,at least one or more of the uracil nucleotides, or where all of them are replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (η1ψ) nucleotides.
[0295] In preferred embodiments, the artificial RNA comprises (a) at least one 5' untranslated region Petition 870260029351, dated 03 / 28 / 2026, pp. 248 / 555 185 / 372 heterologous (UTR of 5') and / or at least one untranslated 3' heterologous region (UTR of 3') and
[0296] (b) at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR encoding at least one antigenic peptide or protein derived from an RSV F or a fragment or variant thereof, wherein - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 78-482, 1173512094, 21415-21417, 21561-21563, 21489, 21490, 21635, 21636 (which encodes F0) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 493-897, 1210412463, 21418-21420, 21564-21566, 21491, 21492, 21637, 21638 (which encodes F-del) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the Petition 870260029351, dated 03 / 28 / 2026, p. 249 / 555 186 / 372 group consisting of SEQ ID NOs: 907-1266, 1247312832, 21421-21423, 21567-21569, 21493-21495, 2163921641 (which encodes F0_DSCav1) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 1276-1635, 8278, 12842-13201, 21424-21426, 21570-21572, 21496-21498, 21642-21644 (which encodes F-del_DSCav1) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1645-2004, 1394914308, 21433-21435, 21579-21581, 21505-21507, 2165121653 (encoding F_DSCav1_mut1) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 2014-2373, 1431814677, 21436-21438, 21582-21584, 21508-21510, 21654 Petition 870260029351, dated 03 / 28 / 2026, p. 250 / 555 187 / 372 21656 (which encodes F-del_DSCav1_mut1) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 2383-2742, 1468715046, 21439-21441, 21585-21587, 21511-21513, 2165721659 (encoding F_DSCav1_mut2) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 2752-3111, 1505615415, 21442-21444, 21588-21590, 21514-21516, 2166021662 (encoding F-del_DSCav1_mut2) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 3121-3480, 1542515784, 21445-21447, 21591-21593, 21517-21519, 2166321665 (encoding F_DSCav1_mut3) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of a Petition 870260029351, dated 03 / 28 / 2026, pp. 251 / 555 188 / 372 RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 3490-3849, 1579416153, 21448-21450, 21594-21596, 21520-21522, 2166621668 (encoding F-del_DSCav1_mut3) or a fragment or variant of any of these sequences. - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 3859-4218, 1321113570, 21427-21429, 21573-21575, 21499-21501, 2164521647 (encoding F_DSCav1_mut0) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 4228-4587, 1358013939, 21430-21432, 21576-21578, 21502-21504, 2164821650 (encoding F-del_DSCav1_mut0) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a Petition 870260029351, dated 03 / 28 / 2026, pp. 252 / 555 189 / 372 selected nucleic acid sequence from the group consisting of SEQ ID NOs: 4597-4956, 1616316522, 21451-21453, 21597-21599, 21523-21525, 2166921671 (encoding F_DSCav1_mut4) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 4966-5325, 1653216891, 21454-21456, 21600-21602, 21526-21528, 2167221674 (encoding F-del_DSCav1_mut4) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5335-5694, 1690117260, 21457-21459, 21603-21605, 21529-21531, 2167521677 (which encodes F_DSCav1_mut5) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 5704-6063, 1727017629, 21460-21462, 21606-21608, 21532-21534, 21678 Petition 870260029351, dated 03 / 28 / 2026, p. 253 / 555 190 / 372 21680 (which encodes F-del_DSCav1_mut5) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 6073-6432, 1763917998, 21463-21465, 21609-21611, 21535-21537, 2168121683 (encoding F_DSCav1_mut6) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 6442-6801, 1800818367, 21466-21468, 21612-21614, 21538-21540, 2168421686 (encoding F-del_DSCav1_mut6) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 6811-7170, 1837718736, 21469-21471, 21615-21617, 21541-21543, 2168721689 (which encodes F_DSCav1_mut7) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of a Petition 870260029351, dated 03 / 28 / 2026, pp. 254 / 555 191 / 372 RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 7180-7539, 1874619105, 21472-21474, 21618-21620, 21544-21546, 2169021692 (encoding F-del_DSCav1_mut7) or a fragment or variant fragment of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 7549-7908, 1911519474, 21475-21477, 21621-21623, 21547-21549, 2169321695 (encoding F_DSCav1_mut8) or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 7918-8277, 1948419843, 21478-21480, 21624-21626, 21550-21552, 2169621698 (which encodes F-del_DSCav1_mut8) or a fragment or variant of any of these sequences, and where, Optionally, at least one or more of these, or where all uracil nucleotides are replaced by pseudouridine nucleotides (ψ) or N1-methylpseudouridine nucleotides (ψ). Petition 870260029351, dated 03 / 28 / 2026, pp. 255 / 555 192 / 372
[0297] In particularly preferred modalities, the Artificial RNA comprises (a) at least one heterologous 5' untranslated region (5' UTR) and / or at least one heterologous 3' untranslated region (3' UTR) and
[0298] (b) at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR encoding at least one antigenic peptide or protein derived from an RSV F or a fragment or variant thereof, wherein said artificial RNA comprises or consists of an RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5704-6063, 17270-17629, 21460-21462, 21606-21608, 21532-21534, 21678-21680 (which encodes F-del_DSCav1_mut5) or a fragment or variant of any of these sequences.
[0299] As highlighted throughout the descriptive report, additional information relating to amino acid sequences or suitable nucleic acid sequences (coding sequences, mRNA sequences) can also be derived from the sequence listing, in particular, from the details provided therein under the identifier. <223> as explained below.
[0300] For example, the numeric identifier <223> The listing of sequences for SEQ ID NO: 68 reads as follows:
[0301] “Sequence of a protein derived and / or modified (artificial) from HRSV(A2)_F0. Note that throughout the sequence listing, information provided under Petition 870260029351, dated 03 / 28 / 2026, pp. 256 / 555 193 / 372 the numerical identifier <223> It follows the same structure:<SEQUENCE_DESCRIPTOR> of<CONSTRUCT_IDENTIFIER> The<SEQUENCE_DESCRIPTOR> This refers to the type of sequence (e.g., “derived and / or modified protein sequence,” “derived and / or modified CDS,” “mRNA product design a...
Claims
1. Artificial RNA characterized by comprising a) at least one heterologous 5' untranslated region (5' UTR) and / or at least one heterologous 3' untranslated region (3' UTR); and b) at least one coding sequence operatively linked to said 3' UTR and / or said 5' UTR encoding at least one antigenic peptide or protein derived from an RSV fusion protein (F) or a fragment or variant thereof.
2. Artificial RNA, according to claim 1, characterized in that at least one heterologous 3' UTR comprises a nucleic acid sequence derived from a 3' UTR of a gene selected from PSMB3, ALB7, alpha-globin, CASP1, COX6B1, GNAS, NDUFA1 and RPS9, or from a homolog, fragment or variant of any of these genes or artificial RNA, wherein at least one heterologous 5' UTR comprises a nucleic acid sequence derived from a 5' UTR of a gene selected from HSD17B4, RPL32, ASAH1, ATP5A1, MP68, NDUFA4, NOSIP, RPL31, SLC7A3, TUBB4B and UBQLN2, or from a homolog, fragment or variant of any of these genes.
3. Artificial RNA, according to any of the preceding claims, characterized by comprising a-1. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-2. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-3. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog,fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-4. at least one 5' UTR of a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or a-5. at least one 5' UTR derived from a 5' UTR of an MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-1. at least one 5' UTR derived from a 5' UTR of a UBQLN2 gene, or from a corresponding homologous RNA sequence,a fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-2. at least one 5' UTR derived from a 5' UTR of an ASAH1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-3. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or b-4. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence,a. homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or b-5. at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or c-1. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-2. at least one 5' UTR derived from a 5' UTR of a NOSIP gene,or a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-3. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-4. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or c-5. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence,homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or d-1. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a PSMB3 gene, or from a corresponding RNA sequence, homologous, fragment or Petition 870260029351, dated 03 / 28 / 2026, p. 440 / 555 5 / 38 variant thereof; or d-2. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-3. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene,or a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-4. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or d-5. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-1. at least one 5' UTR derived from a 5' UTR of a TUBB4B gene, or from a corresponding RNA sequence,homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-2. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-3. at least one 5' UTR derived from a 5' UTR of an MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-4. at least one 5' UTR derived from a 5' UTR of a NOSIP gene,or a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-5. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or e-6. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or Petition 870260029351, dated 03 / 28 / 2026,pg. 442 / 555 7 / 38 variant thereof; or f-1. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-2. at least one 5' UTR derived from a 5' UTR of an ATP5A1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-3. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding homologous RNA sequence, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding homologous RNA sequence,fragment or variant thereof; or f-4. at least one 5' UTR derived from a 5' UTR of an HSD17B4 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or f-5. at least one 5' UTR derived from a 5' UTR of an MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or g-1. at least one 5' UTR derived from a 5' UTR of an MP68 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence,homologous, fragment or variant thereof; or g-2. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or g-3. at least one 5' UTR derived from a 5' UTR of an NDUFA4 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or g-4. at least one 5' UTR derived from a 5' UTR of a NOSIP gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog,fragment or variant thereof; or g-5. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-1. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof; or h-2. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a GNAS gene, or from a corresponding RNA sequence,homologous, fragment or variant thereof; or h-3. at least one 5' UTR derived from a 5' UTR of an RPL31 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of an NDUFA1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or h-4. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a CASP1 gene, or from a corresponding RNA sequence, homologous, fragment or variant thereof; or h-5. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, and at least one 3' UTR derived from a 3' UTR of a COX6B1 gene, or from a corresponding RNA sequence, homolog, fragment or Petition 870260029351,from 03 / 28 / 2026, page 445 / 555 10 / 38 variant thereof; or i-1. at least one 5' UTR derived from a 5' UTR of an SLC7A3 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an RPS9 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof i-2. at least one 5' UTR derived from a 5' UTR of an RPL32 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof and at least one 3' UTR derived from a 3' UTR of an ALB7 gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof i-3. at least one 3' UTR derived from a 3' UTR of an alpha-globin gene, or from a corresponding RNA sequence, homolog, fragment or variant thereof, preferably comprising UTR elements according to a-1 (HSD17B4 / PSMB3), a-4 (NDUFA4 / PSMB3), c-1 (NDUFA4 / RPS9), e-4 (NOSIP / RPS9),g-2 (NDUFA4 / CASP1), i-2 (RPL32 / ALB7) or i-3 (alpha-globin), preferably a-1 (HSD17B4 / PSMB3); wherein more preferably - said 5' UTR derived from an HSD17B4 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1 or 2 or a fragment or variant thereof; - the said 5' UTR derived from an ASAH1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 3 or 4 or a fragment or variant thereof; - the said 5' UTR derived from an ATP5A1 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%,93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 5 or 6 or a fragment or variant thereof; - said 5' UTR derived from an MP68 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 7 or 8 or a fragment or variant thereof; - said 5' UTR derived from an NDUFA4 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 9 or 10 or a fragment or variant thereof; - the said 5' UTR derived from a NOSIP gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to SEQ ID NO: 11 or 12 or a fragment or variant thereof; - said 5' UTR derived from an RPL31 gene comprises or consists of a nucleic acid sequence that is Petition 870260029351, dated 03 / 28 / 2026, page 447 / 555 12 / 38 identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13 or 14 or a fragment or variant thereof; - said 5' UTR derived from an RPL32 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 21 or 22 or a fragment or variant thereof; - the said 5' UTR derived from an SLC7A3 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to SEQ ID NO: 15 or 16 or a fragment or variant thereof; - said 5' UTR derived from a TUBB4B gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 17 or 18 or a fragment or variant thereof; - said 5' UTR derived from a UBQLN2 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 19 or 20 or a fragment or variant thereof; - said 3' UTR derived from a PSMB3 gene comprises or consists of a nucleic acid sequence that is Petition 870260029351, dated 03 / 28 / 2026, p. 448 / 555 13 / 38 identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to SEQ ID NO: 23 or 24 or a fragment or variant thereof; - said 3' UTR derived from a CASP1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 25 or 26 or a fragment or variant thereof; - said 3' UTR derived from a COX6B1 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 27 or 28 or a fragment or variant thereof; - said 3' UTR derived from a GNAS gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to SEQ ID NO: 29 or 30 or a fragment or variant thereof; - said 3' UTR derived from an NDUFA1 gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 31 or 32 or a fragment or variant thereof; - said 3' UTR derived from an RPS9 gene comprises or consists of a nucleic acid sequence that is identical Petition 870260029351, dated 03 / 28 / 2026, page 449 / 555 14 / 38 or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 33 or 34 or a fragment or variant thereof; 1 - said 3' UTR derived from an ALB7 gene comprises or consists of a nucleic acid sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to SEQ ID NO: 35 or 36 or a fragment or variant thereof; - said 3' UTR derived from an alpha-globin gene comprises or consists of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 37 or 38 or a fragment or variant thereof.
4. Artificial RNA, according to any of the preceding claims, characterized in that at least one antigenic peptide or protein derived from RSV F protein is a full-length F protein (F0) and an F protein with a deleted C-terminus (F-del), or a fragment or variant thereof, and / or in which the RSV F protein is designed to stabilize the antigen in the pre-fusion conformation, wherein the RSV F protein preferably comprises a DSCav1 mutation (S155C, S290C, S190F and V207L), or a fragment or variant thereof, or wherein the RSV F protein preferably comprises the two F2 and F1 subunits in a single peptide chain, wherein F2 and F1 are connected via a linker element, Petition 870260029351, dated 03 / 28 / 2026, p. 450 / 555 15 / 38 preferably, a GS ligand, to generate a stable F1-binding F2 protein, wherein said F1-binding F2 protein preferably lacks,from aa104-aa144 and / or in which the RSV F protein preferentially comprises at least one additional mutation selected from (S46G, A149C, S215P, Y458C, K465Q), (S46G, E92D, A149C, S215P, Y458C, K465Q), (S46G, N67I, E92D, A149C, S215P, Y458C, K465Q), (A149C, Y458C), (N183GC, N428C), (Q98C, Q361C, S46G, E92D, L95M, S215P, I217P, I221M, R429K, K465Q), (Q98C, Q361C, L95M, I221M, R429K) or (N183GC, N428C, S46G, N67I, E92D, S215P, K465Q) or a fragment or variant thereof, and / or wherein the RSV F protein is preferentially selected from F0, F-del, F0_DSCav1, F_DSCav1_mut0, F_DSCav1_mut1, F_DSCav1_mut2, F_DSCav1_mut3, F_DSCav1_mut4, F_DSCav1_mut5, F_DSCav1_mut6, F_DSCav1_mut7, F_DSCav1_mut8, F-del_DSCav1, F-del_DSCav1_mut0, F-del_DSCav1_mut1, Fdel_DSCav1_mut2, F-del_DSCav1_mut3, F-del_DSCav1_mut4, Fdel_DSCav1_mut5, F-del_DSCav1_mut6, F-del_DSCav1_mut7, Fdel_DSCav1_mut8 or a fragment or variant thereof.
5. Artificial RNA, according to any of the preceding claims, characterized in that at least one coding sequence encodes at least one amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ ID Nos: 68, 483, 898, 1267, 1636, 2005, 2374, 2743, 3112, 3481, 3850, 4219, 4588, 4957, 5326, 5695, 6064, 6433, 6802, 7171, 7540, 7909, 8279-9683, 11726, 12095, 12464, 12833, 13940, 14309, 14678, 15047, 15416, 15785, 13202, 13571, 16154, 16523, 16892, 17261, 17630, 17999, Petition 870260029351, dated 03 / 28 / 2026, page. 451 / 555 16 / 38 18368, 18737, 19106, 19475 or a fragment or variant of any of the sequences, preferably SEQ ID NO. 5695.
6. Artificial RNA, according to any of the preceding claims, characterized in that at least one coding sequence comprises at least one of the nucleic acid sequences being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the sequence identification numbers: 69-77, 484-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596, 4958-4965, 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 11727-11734, 12096-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679-14686, 15048-15055 15417-15424, 15786-15793, 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376, 18738-18745, 19107-19114, 19476-19483, 21363-21384, 21389-21410 or a fragment or a fragment or variant of any of these sequences.
7. Artificial RNA, according to any of the preceding claims, characterized in that at least one coding sequence is a codon-modified coding sequence, wherein the amino acid sequence encoded by at least one codon-modified coding sequence is preferably unmodified compared to the amino acid sequence encoded by the corresponding wild-type coding sequence, or wherein the at least one codon-modified coding sequence is selected from a C-maximized coding sequence, a CAI-maximized coding sequence, a human codon-adapted coding sequence, a G / C-modified coding sequence, and a G / C-optimized coding sequence, or any combination thereof.
8. Artificial RNA, according to claim 7, characterized in that at least one coding sequence comprises a codon-modified coding sequence comprising a nucleic acid sequence identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ identification numbers: 7077, 485-492, 899-906, 1268-1275, 1637-1644, 2006-2013, 2375-2382, 2744-2751, 3113-3120, 3482-3489, 3851-3858, 4220-4227, 4589-4596, 4958-4965, 5327-5334, 5696-5703, 6065-6072, 6434-6441, 6803-6810, 7172-7179, 7541-7548, 7910-7917, 1172-8-11734, 12097-12103, 12465-12472, 12834-12841, 13941-13948, 14310-14317, 14679-14686, 15048-15055 15417-15424, 15786-15793, 13203-13210, 13572-13579, 16155-16162, 16524-16531, 16893-16900, 17262-17269, 17631-17638, 18000-18007, 18369-18376, 18738-18745, 19107-19114, 19476-19483, 21363-21384, 21389-21410 or a fragment or variant of any of these sequences.
9. Artificial RNA according to claim 7 or 8, characterized in that at least one coding sequence comprises a codon-modified coding sequence comprising a nucleic acid sequence identical to or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the same nucleic acid sequence. Petition 870260029351, dated 03 / 28 / 2026, p. 453 / 555 18 / 38 identical to any of the following SEQ ID numbers: 70-71, 75-77, 485-486, 490-492, 899-900, 904-906, 1268-1269, 1273-1275, 1637-1638, 1642-1644, 2006-2007, 2011-2013, 2375-2376, 2380-2382, 2744-2745, 2749-2751, 3113-3114, 3118-3120, 3482-3483, 3487-3489, 3852, 4221, 4590, 4959, 5328, 5697, 6066, 6435, 6804, 7173, 7542, 7911, 3856-3858, 4225-4227, 4594-4596, 4963-4965, 5332-5334, 5701-5703, 6070-6072, 6439-6441, 6808-6810, 7177-7179, 7546-7548, 7915-7917, 11728, 11732-11734, 12097, 12101-12103, 12465, 12466, 12470-12472, 12834, 12835, 12839, 12841, 13941, 13942, 13946-13948, 14310, 14311, 14315-14317, 14679,14680, 14684-14686, 15048, 15049, 15053-15055, 15417, 15418, 15422-15424, 15786, 15787, 15791-15793, 13203, 13204, 13208-13210, 13572, 13573, 13577-13579, 16155, 16156, 16160-16162, 16524, 16525, 16529-16531, 16893, 16894, 16898-16900, 17262 17263, 17267-17269, 17631, 17632, 17636-17638, 18000, 18001, 18005-18007, 18369, 18370, 18374-18376, 18738, 18739, 18743-18745, 19107, 19108, 19112-19114, 19476, 19477, 19481-19483, 21363-21384, 21389-21410 or a fragment or variant of any of these sequences.
10. Artificial RNA, according to any of the preceding claims, wherein the RNA is characterized as being an mRNA, a self-replicating RNA, a circular RNA or a replicon RNA, in which the RNA is preferably an mRNA.
11. Artificial RNA, according to any of the preceding claims, the RNA being characterized by comprising a 5'-cap structure, preferably m7G, cap0, cap1, cap2, a modified cap0 or modified cap1 structure, and / or wherein the RNA comprises at least one poly(A) sequence comprising, preferably, 30 to 150 adenosine nucleotides comprising, more preferably, 100 Petition 870260029351, dated 03 / 28 / 2026, p. 454 / 555 19 / 38 adenosine nucleotides and / or at least one poly(C) sequence comprising, preferably, 10 to 40 cytosine nucleotides and / or wherein the RNA comprises at least one histone stem-loop, wherein the histone stem-loop preferably comprises a nucleic acid sequence according to SEQ ID NO: 39 or 40 or a fragment or variant thereof.
12. Artificial RNA, according to any of the preceding claims, characterized by comprising the following elements, preferably in the 5' to 3' direction: a) 5'-cap structure, preferably as specified herein; b) optionally, a 5' UTR as specified herein, preferably at least one selected from SEQ ID NOs: 1-22; c) a ribosome binding site, preferably as specified herein; d) at least one coding sequence as specified herein, preferably as specified in Table 3 and Table 4; e) a 3' UTR as specified herein, preferably at least one selected from SEQ ID NOs: 23-38; f) optionally, a poly(A) sequence, preferably as specified herein; g) optionally, a poly(C) sequence, preferably as specified herein;h) optionally, a histone stem-loop, preferably as specified in this document; Petition 870260029351, dated 03 / 28 / 2026, p. 455 / 555 20 / 38 i) optionally, a 3' terminal sequence element as specified in this document, preferably according to SEQ ID Nos: 44-63, or 21322-21328; and wherein, optionally, at least one or more of, preferably, all uracil nucleotides are replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (η1ψ) nucleotides, and / or comprising the following elements, preferably in the 5' to 3' direction: a) 5'-cap structure, preferably as defined in claim 11, most preferably a Capl structure; b) 5' UTR and / or 3' UTR according to a-1, a-4, c-1, e-4, g-2, i-2 or i-3;c) at least one coding sequence as defined in any one of claims 5 to 9 or encoding a protein as defined in any one of claim 4; or d) optionally, a poly(A) sequence, preferably as defined in claim 11; e) optionally, a poly(C) sequence, preferably as defined in claim 11; f) optionally, a histone stem-loop, preferably as defined in claim 8;(g) optionally, a 3' terminal sequence according to SEQ ID Nos: 44-63, 21322-21328 and wherein, optionally, at least one or more of, preferably, all uracil nucleotides are replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (m^) nucleotides and / or Petition 870260029351, dated 03 / 28 / 2026, p. 456 / 555 21 / 38 comprising the following elements in the 5' to 3' direction: a) 5'-cap structure, preferably as defined in claim 11, most preferably a Capl structure; b) 5' and / or 3' UTR according to a-1, a-4, c-1, e-4, g-2, i-2 or i-3, preferably a-1;c) at least one coding sequence as defined in any one of claims 5 to 9 or encoding a protein as defined in any one of claims 7 to 12, wherein said coding sequence is located between said 5' UTR and said 3' UTR, preferably downstream of said 5' UTR and upstream of said 3' UTR; d) the histone stem-loop, preferably as defined in claim 11; e) a poly(A) sequence, preferably as defined in claim 11; f) a 3' terminal sequence according to SEQ ID NOs: 21322-21328, wherein, optionally, at least one or more of the uracil nucleotides are preferably replaced by pseudouridine (ψ) nucleotides or N1-methylpseudouridine (m^) nucleotides; 13. Artificial RNA, according to any of the preceding claims, the artificial RNA being characterized by comprising or consisting of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a sequence of amino acids. Petition 870260029351, dated 03 / 28 / 2026, p. 457 / 555 22 / 38 nucleic acids selected from the group consisting of SEQ ID Nos: 78-482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 4228-4587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 13949-14308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 16532-16891, 16901-17260, 17270-17629, 17639-17998, 18008-18367, 18377-18736, 18746-19105, 19115-19474, 19484-19843, 21415-21480,21561-21626, 21489-21552, 21635-21698 or a fragment or variant of any of these sequences, wherein preferably - said artificial RNA comprises or consists of an RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 78-482, 11735-12094, 21415-21417, 21561-21563, 21489, 21490, 21635, 21636 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 493-897, 12104-12463, 21418-21420, 21564-21566, 21491, 21492, 21637,21638 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of a Petition 870260029351, dated 03 / 28 / 2026, page. 458 / 555 23 / 38 RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 907-1266, 12473-12832, 21421-21423, 21567-21569, 21493-21495, 21639-21641 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1276-1635, 8278, 12842-13201, 21424-21426, 21570-21572, 21496-21498,21642-21644 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1645-2004, 13949-14308, 21433-21435, 21579-21581, 21505-21507, 21651-21653 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 2014-2373, 14318-14677, 21436-21438, 21582-21584, 21508-21510, 21654-21656 or a fragment or variant of Petition 870260029351, of 28 / 03 / 2026pg. 459 / 555 24 / 38 of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 2383-2742, 14687-15046, 21439-21441, 21585-21587, 21511-21513, 21657-21659 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 2752-3111, 15056-15415, 21442-21444, 21588-21590, 21514-21516,21660-21662 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 3121-3480, 15425-15784, 21445-21447, 21591-21593, 21517-21519, 21663-21665 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group comprising Petition 870260029351, dated 03 / 28 / 2026, p. 460 / 555 25 / 38 in SEQ ID Nos: 3490-3849, 15794-16153, 21448-21450, 21594-21596, 21520-21522,21666-21668 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 3859-4218, 13211-13570, 21427-21429, 21573-21575, 21499-21501, 21645-21647 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 4228-4587, 13580-13939, 21430-21432, 21576-21578, 21502-21504,21648-21650 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 4597-4956, 16163-16522, 21451-21453, 21597-21599, 21523-21525, 21669-21671 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95% Petition 870260029351, dated 03 / 28 / 2026, p. 461 / 555 26 / 38%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 4966-5325, 16532-16891, 21454-21456, 2160021602, 21526-21528,21672-21674 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5335-5694, 16901-17260, 21457-21459, 21603-21605, 21529-21531, 21675-21677 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5704-6063, 17270-17629, 21460-21462, 21606-21608, 21532-21534, 21678-21680 or a fragment or variant of any of these sequences,preferably 21460 or 21606 - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 6073-6432, 17639-17998, 21463-21465, 21609-21611, 21535-21537, 21681-21683 or a fragment or variant of any of these sequences; Petition 870260029351, dated 03 / 28 / 2026, p. 462 / 555 27 / 38 - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 6442-6801, 18008-18367, 21466-21468, 21612-21614, 21538-21540,21684-21686 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 6811-7170, 18377-18736, 21469-21471, 21615-21617, 21541-21543, 21687-21689 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 7180-7539, 18746-19105, 21472-21474, 21618-21620, 21544-21546,21690-21692 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 7549-7908, 19115-19474, 21475-21477, 21621- Petition 870260029351, dated 03 / 28 / 2026, p. 463 / 555 28 / 38 21623, 21547-21549, 21693-21695 or a fragment or variant of any of these sequences; - said artificial RNA comprises or consists of an RNA sequence that is identical to, or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to, a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 7918-8277, 19484-19843, 21478-21480, 21624-21626, 21550-21552,21696-21698 or a fragment or variant of any of these sequences.
14. Composition characterized by comprising at least one artificial RNA as defined in any of claims 1 to 13, wherein the composition optionally comprises at least one pharmaceutically acceptable carrier, preferably comprising at least one additional artificial RNA comprising at least one coding sequence encoding at least one antigenic peptide or protein derived from RSV selected from matrix protein M, nucleoprotein N, protein M2-1 and / or phosphoprotein P or combinations thereof, preferably selected from M2-1.
15. Composition according to claim 14, characterized in that the coding sequence of the additional artificial RNA encodes at least one of the amino acid sequences that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to any of the following SEQ ID Nos: 9684, 10053-10133, 10134, 10503-10636, 10637, 11006-11182, 11183, 11552-11725, 19844, 20213, 20582, 20951 or a fragment or variant of any of these sequences Petition 870260029351, dated 03 / 28 / 2026, p. 464 / 555 29 / 38 and / or where the encoding sequence is operatively linked to a 3' UTR and a 5' UTR selected from a-1, a-2, a-3, a-4, a-5, b-1, b-2, b-3, b-4, b-5, c-1, c2, c-3, c-4, c-5, d-1, d-2, d-3, d-4, d-5, e-1, e-2, e-3, e4, e-5, e-6, f-1, f-2, f-3, f-4, f-5, g-1, g-2, g-3, g-4, g5, h-1, h-2, h-3, h-4, h-5, i-1,i-2 or i-3 and / or where the coding sequence comprises at least one of the nucleic acid sequences that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID Nos: 9685-9692, 10135-10142, 10638-10645, 11184-11191, 19845-19852, 20214-20221, 20583-20590, 20952-20959, 21385-21388, 21411-21414 or a fragment or variant of any of these sequences, and / or wherein the additional artificial RNA comprises or consists of an RNA sequence that is identical to or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 969310052, 10143-10502, 10646-11005, 11192-11551, 19853-20212, 20222-20581, 20591-20950, 20960-21319, 21481-21634,2155321706 or a fragment or variant of any of these sequences comprising - an artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 78 Petition 870260029351, dated 03 / 28 / 2026, p. 465 / 555 30 / 38 482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 4228-4587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 13949-14308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 16532-16891, 16901-17260, 17270-17629, 17639-17998, 18008-18367 18377-18736, 18746-19105, 19115-19474, 19484-19843, 21415-21480, 21561-21626, 21489-2155221635-21698 and an additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 9693-10052, 19853-20212, 21481, 21482, 21627, 21628, 21553, 21554, 21699, 21700; or - an artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID NOs: 78482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 42284587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 1394914308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939,16163-16522, 1653216891, 16901-17260, 17270-17629, 17639-17998, 18008-18367, 18377-18736, 18746-19105, 19115-19474, 19484-19843, 2141521480, 21561-21626, 21489-21552, 21635-21698 and an RNA Petition 870260029351, dated 03 / 28 / 2026, page. 466 / 555 31 / 38 additional artificial sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 10143-10502, 20222-20581, 21483, 21484, 21629, 21630, 21555, 21556, 21701, 21702; or - an artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID NOs: 78482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 42284587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432,6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 13949-14308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 16532-16891, 16901-17260, 17270-17629, 17639-17998, 18008-18367, 18377-18736, 18746-19105, 19115-19474, 19484-19843, 21415-21480, 21561-21626, 21489-21552, 21635-21698 and an additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 10646-11005, 20591-20950, 21485, 21486, 21631, 21632, 21557, 21558, 21703, 21704; or - an artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 78- Petition 870260029351, dated 03 / 28 / 2026, p. 467 / 555 32 / 38 482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 4228-4587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 13949-14308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 16532-16891, 16901-17260, 17270-17629, 17639-17998, 18008-18367 18377-18736, 18746-19105, 19115-19474, 19484-19843, 214152-1480, 21561-21626, 21489-21552, 21635-21698 and an additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID Nos: 11192-11551, 20960-21319; 21487, 21488, 21633, 21634, 21559, 21560, 21705, 21706 or - an artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 78482, 493-897, 907-1266, 1276-1635, 1645-2004, 2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 4228-4587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 13949-14308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 16532-16891, 16901-17260, 17270-17629, 17639-17998, 18008-18367, 18377-18736, 18746-19105, 19115-19474, 19484-19843, 21415-21480, 21561-21626, 21489-2155221635-21698 and an RNA Petition 870260029351, dated 03 / 28 / 2026, p. 468 / 555 33 / 38 additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID NOs: 969310052, 19853-20212, 21481, 21482, 21627, 21628, 21553, 21554, 21699, 21700 and an additional artificial RNA that is identical or at least 70%, 80%, 85% %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID NOs: 10646-11005, 20591-20950, 21485, 21486, 21631, 21632, 21557, 21558, 21703, 21704; or - an artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 78482, 493-897, 907-1266, 1276-1635, 1645-2004,2014-2373, 2383-2742, 2752-3111, 3121-3480, 3490-3849, 3859-4218, 4228-4587, 4597-4956, 4966-5325, 5335-5694, 5704-6063, 6073-6432, 6442-6801, 6811-7170, 7180-7539, 7549-7908, 7918-8277, 8278, 11735-12094, 12104-12463, 12473-12832, 12842-13201, 1394914308, 14318-14677, 14687-15046, 15056-15415, 15425-15784, 15794-16153, 13211-13570, 13580-13939, 16163-16522, 1653216891, 16901-17260, 17270-17629, 17639-17998, 18008-18367, 18377-18736, 18746-19105, 19115-19474, 19484-19843, 2141521480, 21561-21626, 21489-21552, 21635-21698 and an additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 969310052, 19853-20212, 21481, 21482, 21627, 21628, 21553, Petition 870260029351, of 28 / 03 / 2026, p. 469 / 555 34 / 38 21554, 21699, 21700 and an additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from SEQ ID NOs: 10646-11005, 20591-20950, 21485, 21486, 21631, 21632, 21557, 21558, 21703, 21704 and an additional artificial RNA that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from SEQ ID Nos: 10143-10502, 20222-20581, 21483, 21484, 21629, 21630, 21555, 21556, 21701, 21702.
16. Composition, according to claim 14 or 15, characterized in that at least one artificial RNA and, optionally, additional artificial RNA are complexed or associated or at least partially complexed or partially associated with one or more cationic or polycationic compounds, preferably a cationic or polycationic polymer, cationic or polycationic polysaccharide, cationic or polycationic lipid, cationic or polycationic protein, cationic or polycationic peptide or any combination thereof, wherein the artificial RNA and, optionally, the additional artificial RNA are preferably complexed or associated with one or more lipids, thereby forming liposomes, lipid nanoparticles, lipoplexes and / or nanoliposomes, wherein the artificial RNA and, optionally, the additional artificial RNA are more preferably complexed with one or more lipids, thereby forming nanoparticles. Petition 870260029351, of 28 / 03 / 2026, page.470 / 555 35 / 38 lipids (LNP).
17. Composition according to claim 16, characterized in that the LNP comprises one or more neutral lipids and / or a steroid or steroid analogues, wherein the neutral lipid is more preferably selected from the group comprising distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylethanolamine (DOPE), palmitoylleoylphosphatidylcholine (POPC), palmitoylleoylphosphatidylethanolamine (POPE) and 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate of dioleoyl-phosphatidylethanolamine (DOPE-mal), dipalmitoylphosphatidylethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoylphosphatidylethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, 1-stearioyl-2-oleoylphosphatidiethanolamine (SOPE) and 1,2-dielaidoyl-singlycerol-3-phosphoethanolamine (transDOPE), or wherein the neutral lipid is more preferably 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), wherein the molar ratio of the cationic lipid to DSPC is optionally in the range of about 2:1 to 8:1, wherein the steroid is most preferentially cholesterol, and wherein the molar ratio of the cationic lipid to cholesterol is optionally in the range of about 2:1 to 1:
1.
18. Composition, according to any one of claims 16 or 17, characterized in that the LNP consists essentially of Petition 870260029351, dated 03 / 28 / 2026, page 471 / 555 36 / 38 (i) at least one cationic lipid, (ii) a neutral lipid, preferably as defined in claim 17; (iii) a steroid or steroid analogues, preferably as defined in claim 17; and (iv) a PEG lipid, for example, PEG DMG or PEG cDMA, wherein (i) to (iv) are in a molar ratio of about 20-60% cationic lipid, 5-25% neutral lipid, 25-55% sterol and 0.5-15% PEG lipid.
19. Polypeptide encoded by artificial RNA as defined in any one of claims 1 to 13, characterized by preferably having an amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID Nos: 1267, 2005, 2743, 3481, 4219, 4957, 5695, 6433, 7171, 7909, 12833, 14309, 15047, 15785, 13571, 16523, 17261, 17999, 18737, 19475 or a variant of any of these polypeptides, preferably SEQ ID NO. 2695, or a composition comprising the polypeptide as defined above, wherein the composition optionally comprises at least one pharmaceutically acceptable carrier or at least one artificial RNA as defined in any of claims 1 to 13, or the composition as defined in any of claims 14 to 18.
20. Vaccine characterized by comprising artificial RNA as defined in any one of claims 1 to 13, the composition as defined in any one of claims 14 to 18, the polypeptide Petition 870260029351, dated 03 / 28 / 2026, page 472 / 555 37 / 38 as defined in claim 19 or the composition as defined in claim 19, wherein the artificial RNA as defined in any one of claims 1 to 10, the composition as defined in any one of claims 11 to 18, the polypeptide as defined in claim 19 or the composition as defined in claim 19 preferentially elicits an adaptive immune response, and / or wherein the vaccine further comprises a pharmaceutically acceptable carrier and optionally at least one adjuvant.
21. Kit or kit of parts characterized by comprising the artificial RNA as defined in any one of claims 1 to 13, the composition as defined in any one of claims 14 to 18, the polypeptide as defined in claim 19, the composition as defined in claim 19 and / or the vaccine as defined in claim 20, optionally comprising a liquid vehicle for solubilization, and optionally technical instructions providing information on administration and dosage of the components, preferably comprising at least the following components: a) at least one artificial RNA as defined in any one of claims 1 to 13 encoding at least one antigenic peptide or protein derived from an RSV fusion protein (F), wherein said artificial RNA is preferably complexed with one or more lipids, thereby forming lipid nanoparticles (LNPs);(b) at least one, two or three additional artificial RNA species, each encoding an RSV-derived antigenic peptide or protein selected from M, N, M21 or P, wherein each of said additional artificial RNA species is preferably complexed with one or more lipids, thereby forming lipid nanoparticles (LNPs), wherein components (a) and (b) are provided as separate entities or as a single entity, more preferably comprising Ringer's lactate solution; 22. Use of artificial RNA as defined in any one of claims 1 to 13, the composition as defined in any one of claims 14 to 18, the polypeptide as defined in claim 19, the composition as defined in claim 19, the vaccine as defined in claim 20, or the kit or kit of parts as defined in claim 21, characterized in being used in the manufacture of a medicament, for the treatment or prophylaxis of an infection by a virus, preferably RSV, or of a disorder related to such infection, wherein the individual is in particular a mammalian or human individual, preferably a newborn, a pregnant woman, a lactating woman, an elderly person and / or an immunocompromised human individual.