RU2774677C2 - Rna for cancer therapy - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: use of immunostimulatory RNA (hereinafter – isRNA), which contains a nucleotide sequence presented in SEQ ID NO: 433, is described for the treatment or prevention of a tumor or cancer disease selected from a group that consists of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell cancer (VSCC), where the tumor or cancer disease is at a late stage and/or is resistant to standard therapy by means of the administration of isRNA into tumor. A pharmaceutical composition is also described for the treatment of a tumor or cancer disease preferably selected from a group that consists of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell cancer (VSCC), where the tumor or cancer disease is at a late stage and/or is resistant to standard therapy, containing immunostimulatory RNA (isRNA), which contains a nucleotide sequence presented in SEQ ID NO: 433 and a pharmaceutically acceptable carrier and/or filler. In addition, a kit is presented for the treatment of a tumor or cancer disease preferably selected from a group that consists of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphomas of the mycotic fungoid subtype, and vulvar squamous cell cancer (VSCC), where the tumor or cancer disease is at a late stage and/or is resistant to standard therapy. The kit contains isRNA, which contains a nucleotide sequence presented in SEQ ID NO: 433, or the corresponding pharmaceutical composition, and technical instructions with information on administration and administered doses when administered into the tumor. A method for the treatment of the specified diseases by the specified means is also presented.

EFFECT: invention expands the arsenal of means to fight cancer.

66 cl, 13 dwg, 16 tbl, 13 ex

Description

The present invention relates to RNA, especially immunostimulatory RNA (isRNA), encoding RNA or combinations thereof, for use in the treatment or prevention of a disease, especially a tumor and/or cancer. The present invention also relates to pharmaceutical compositions and kits containing the specified(s) RNA. In addition, the invention also relates to the use in medicine of the specified(s) RNA and compositions containing the specified(s) RNA.

Cancers, also called malignant tumors, are a group of diseases characterized by abnormal growth of cells that have the ability to invade or spread to other parts of the body. In 2012, there were approximately 14.1 million new cases of cancer worldwide (not including skin cancers other than melanoma).

Conventional cancer treatments include chemotherapy, radiation therapy, and surgery or immunotherapy, and these treatments are used alone or in combination. Cancer immunotherapy focuses on stimulating the immune system through vaccination, adaptive cellular immunotherapy, blockade of immune checkpoints, or other immunostimulants or immunomodulators to induce an antitumor response.

Some approaches for the treatment of cancer or other neoplastic diseases use gene therapy and genetic vaccination. Gene therapy and genetic vaccination are molecular medicine methods based on the introduction of a nucleic acid into a patient's cells or tissues. As a result, the information encoded by the introduced nucleic acid is processed in the body, i.e. results in the expression of a therapeutic peptide or protein, or the expression of an antigen encoded by the nucleic acid.

Conventional genetic therapeutic methods, including gene therapy and genetic vaccination, are based on the use of DNA molecules to transfer the required genetic information into the cell. Various methods have been developed for the introduction of DNA into cells, such as calcium phosphate transfection, polybrene transfection, protoplast fusion, electroporation, microinjection, and lipofection. Virus DNA can also be used as carrier DNA, allowing very high levels of transfection to be achieved. The use of DNA entails the risk of inserting the DNA into an intact gene of the host cell genome, for example by recombination. In this case, the affected gene may mutate and become inactivated or may encode erroneous information. Another risk of using DNA as a pharmaceutical agent is the risk of inducing pathogenic anti-drug antibodies (anti-DNA antibodies) in a patient, which can lead to autoimmune side effects.

The use of RNA as a gene therapeutic agent or genetic vaccine is practically safe, since there is no risk for RNA to integrate into the genome, inducing unwanted pathogenic induction of anti-drug antibodies.

Thus, RNA expression systems have distinct advantages over DNA expression systems for use in gene therapy and genetic vaccination, although it has long been assumed that the instability of mRNA or RNA in general can be a serious problem when used in medical methods based on expression systems. RNA.

The instability of RNA is caused, in particular, by RNA-cleaving enzymes (ribonucleases - RNases). There are also many other processes that lead to destabilization of RNA, with interactions between RNA and proteins likely often playing a critical role. Some means have been proposed to increase the stability of RNA, which allows it to be used as a gene therapy agent or RNA vaccine.

To solve the problem of ex vivo stability of RNA, European patent application EP 1083232 A1 describes a method for introducing RNA, in particular mRNA, into cells and organisms in which the RNA forms a complex with a cationic peptide or protein.

Known use of mRNA for the treatment and/or prevention of cancer. For example, international patent application WO 03/051401 A2 describes a pharmaceutical composition containing at least one mRNA that contains at least one region encoding an antigen from a tumor, in combination with an aqueous solvent and preferably with a cytokine, for example, GM- CSF. A pharmaceutical composition for use in therapy and/or prevention of cancer is also proposed.

International patent application WO 2006/008154 A1 describes an mRNA mixture for vaccination against tumor diseases, in which at least one type of mRNA contains at least one region encoding a tumor antigen. At least one other mRNA contains at least one type of immunogenic protein coding region.

However, there is still a need for effective treatment of cancerous or neoplastic diseases. Thus, the invention was based on the task of developing an approach for the effective treatment of tumor diseases, in which tumor tissue and cancer cells undergo specific destruction.

This problem is solved with the help of the object of the invention set forth in the claims. In particular, the problem underlying the present invention is solved by using isRNA, coding RNA or combinations thereof, intended for use in the treatment or prevention of neoplastic and/or cancerous diseases. According to other objects of the invention, the problem is solved using a pharmaceutical composition, a kit or a kit consisting of components, and using a method for treating tumor or cancerous diseases.

For purposes of clarity and readability, definitions are provided below. All technical features mentioned herein may be a component of each and every single embodiment of the invention. In the context of these embodiments of the invention, additional definitions and explanations may be specifically given.

Immune System: The immune system can protect organisms from infection. If the pathogen has managed to pass through the body's physical barrier and enter the target organism, then the innate immune system provides an immediate but non-specific response. In case a pathogen eludes this innate response, vertebrates have a second layer of defense, which is the adaptive immune system. In this case, the immune system adapts its response during infection to improve recognition of the pathogen. In addition to infections caused by pathogens, this response can also be directed against malignant tumor cells in the body. This improved response is then stored after elimination of the pathogen in the form of an immunological memory and allows the adaptive immune system to mount faster and stronger attacks each time that pathogen enters. Thus, the immune system includes the innate and adaptive immune systems. Each of these two parts includes the so-called humoral and cellular components.

Immune Response: An immune response can generally be either a specific reaction of the adaptive immune system to an antigen, such as a tumor-derived antigen (so-called specific or adaptive immune response), or a non-specific reaction of the innate immune system (so-called non-specific or innate immune response). answer).

Adaptive immune system: The adaptive immune system consists of highly specialized system cells and processes that eliminate or prevent the growth of pathogens. The adaptive immune response provides the ability of the vertebrate immune system to recognize and remember specific pathogens (to create immunity) and organize a stronger attack in each case when a pathogen is detected. The system is highly adaptable due to somatic hypermutation (a process of accelerated somatic mutations) and V(D)J recombination (irreversible genetic recombination of antigen receptor gene segments). This mechanism allows a small number of genes to create a huge number of different antigen receptors, which are then uniquely expressed on each individual lymphocyte. Since the rearrangement of a gene results in an irreversible change in the DNA of each cell, then all progeny of such a cell must then inherit genes encoding the same receptor specificity, including memory B cells and memory T cells, which are critical for long-term specific immunity. The immune network theory is a theory explaining the operation of the adaptive immune system based on interactions between the variable regions of T cell receptors, B cells and molecules formed by T cells and B cells that have variable regions.

Adaptive immune response: Typically, adaptive immune response is understood to be an antigen-specific response. Antigen specificity allows for responses tailored to specific antigens, pathogens, or pathogen-infected cells. The ability to create such adapted responses is usually maintained in the body by "memory cells". If the pathogen infects the body more than once, then these specific memory cells are used for its rapid elimination. In this context, the first stage of an adaptive immune response is the activation of naïve antigen-specific T cells, or various immune cells capable of inducing an antigen-specific immune response, by antigen-presenting cells. This occurs in lymphoid tissues and organs, through which naive T cells constantly pass. Cell types that can serve as antigen presenting cells are, among others, dendritic cells, macrophages, and B cells. Each of these cells performs a separate function in inducing immune responses. Dendritic cells can take up antigens through phagocytosis and macropinocytosis, and upon contact with, for example, a foreign antigen, they can be stimulated to migrate to the local lymphoid tissue, where they differentiate into mature dendritic cells. Macrophages take up particulate antigens such as bacteria and are induced by infectious agents or other appropriate stimuli and thereby express MHC molecules. The unique ability of B cells to bind and internalize soluble protein antigens through their receptors may also be important for T cell induction. Presentation of the antigen on MHC molecules leads to the activation of T cells, which induces their proliferation and differentiation into “armed” effector T cells. The most important function of effector T cells is the killing of infected cells by cytotoxic CD8 ⁺ -T cells and the activation of macrophages by Th1 cells, which together create cell-mediated (cellular) immunity, and the activation of B cells, both Th2- and Th1- cells, leading to the formation of various classes of antibodies, resulting in a humoral immune response. T cells recognize an antigen through their T cell receptors, which do not recognize or bind to an antigen directly, but instead recognize short peptide fragments, such as pathogen-derived protein antigens, that bind to MHC molecules on the surfaces of other cells.

Cellular Immunity/Cellular Immune Response: Cellular immunity generally refers 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. In a more general sense, cellular immunity is not based on antibodies, but on the activation of cells of the immune system. The cellular immune response is characterized, for example, by the activation of antigen-specific cytotoxic T-lymphocytes, which are capable of inducing apoptosis of body cells displaying antigen epitopes on their surface, such as virus-infected cells or cells with intracellular bacteria, and cancer cells displaying tumor antigens; activation of macrophages and natural killer cells, allowing them to destroy pathogens; and stimulating cells to secrete various cytokines that affect the function of other cells involved in adaptive immune responses and innate immune responses.

Humoral Immunity/Humoral Immune Response: Humoral immunity generally refers to the production of antibodies, and not necessarily to ancillary processes that accompany antibody production. The humoral immune response can typically be characterized by, for example, Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation, and memory cell formation. Humoral immunity, as a rule, can also refer to the effector functions of antibodies, including the neutralization of pathogens and toxins, classical complement activation, and the stimulation of phagocytosis and elimination of pathogens by opsonins.

Innate immune system: The innate immune system, also called the non-specific immune system, includes cells and mechanisms that non-specifically protect the host from infection by other organisms. This means that the cells of the innate system can recognize and respond to pathogens in the usual way, but, unlike the adaptive immune system, it does not provide long-term or protective immunity to the host. The innate immune system can, for example, be activated by receptor ligands that recognize pathogen-associated molecular patterns (PAMPs), such as Toll-like receptors (TLRs), or other accessory substances such as lipopolysaccharides, TNF-alpha, CD40 ligand, or cytokines, monokines, lymphokines, interleukins or chemokines, immunostimulatory nucleic acids, immunostimulatory RNA (isRNA), CpG DNA, antibacterial agent or antiviral agent. Typically, the response of the innate immune system involves the recruitment of immune cells to areas of infection through the production of chemical factors, including specialized chemical mediators called cytokines; activation of the complement cascade; identification and removal of foreign substances present in organs, tissues, blood and lymph by specialized leukocytes; activation of the adaptive immune system through a process known as antigen presentation; and/or functioning as a physical and chemical barrier to infectious agents.

Adjuvant/adjuvant component: An adjuvant or adjuvant component in the broadest sense, as a rule, is a (for example, pharmacological and/or immunological) agent or composition that/which can modify, for example, enhance, the effectiveness of other agents, such as a drug or a vaccine. Generally, the term in the context of the present invention refers to a compound or composition which/which serves as a carrier or excipient for immunogens and/or other pharmaceutically active compounds. This concept should be considered in a broad sense, and it refers to a wide range of substances that have the ability to increase the immunogenicity of antigens included in the considered adjuvant or co-administered with it. In the context of the present invention, the adjuvant should preferably enhance the specific immunogenic effect of the active substances proposed in the present invention. As a rule, the terms "adjuvant" or "adjuvant component" have the same meaning and can be used interchangeably. Adjuvants can be classified into, for example, immunopotentiators, antigen delivery systems, or even combinations thereof.

The term "adjuvant" is usually understood as substances that do not contain agents that themselves cause immunity. The adjuvant helps the immune system non-specifically enhance an antigen-specific immune response, for example, by stimulating antigen presentation to the immune system or inducing a non-specific innate immune response. In addition, the adjuvant may preferably, for example, modulate the antigen-specific immune response, for example, by shifting the dominant Th2-based antigen-specific response towards increasing the Th1-based antigen-specific response, or vice versa. Thus, the adjuvant can preferably modulate cytokine expression/secretion, antigen presentation, type of immune response, etc.

Immunostimulatory/immunostimulatory RNA: In the context of the invention, an immunostimulatory/immunostimulatory RNA (isRNA) can generally be an RNA that itself has the ability to induce an innate immune response. It usually does not have an open reading frame and thus does not encode an antigen peptide or immunogen, but elicits an innate immune response, for example, by binding to a specific type of Toll-like receptor (TLR) or other suitable receptors. Thus, the immunostimulatory/immunostimulatory RNAs are preferably non-coding RNAs. However, of course, also mRNAs having an open reading frame and encoding a peptide/protein (eg antigenic function) can induce an innate immune response.

Antigen: In the context of the present invention, the term "antigen" refers generally to a substance that can be recognized by the immune system and that can have the ability to trigger an antigen-specific immune response, for example, through the formation of antibodies and/or antigen-specific T cells, as a component of an adaptive immune response. The antigen may be a protein or a peptide. In this context, the first stage of the adaptive immune response is the activation of naive antigen-specific T cells by antigen-presenting cells. This occurs in lymphoid tissues and organs, through which naive T cells constantly pass. Three cell types that can serve as antigen presenting cells are dendritic cells, macrophages, and B cells. Each of these cells performs a separate function in inducing immune responses. The dendritic cells present in the tissue take up antigens by phagocytosis and macropinocytosis, and upon infection, they are stimulated to migrate to the local lymphoid tissue, where they can differentiate into mature dendritic cells. Macrophages engulf particulate antigens such as bacteria and are induced by infectious agents to express class II MHC molecules. The unique ability of B cells to bind and internalize soluble protein antigens through their receptors may be important for T cell induction. Presentation of the antigen on MHC molecules leads to the activation of T cells, which induces their proliferation and differentiation into “armed” effector T cells. The most important function of effector T cells is the killing (cytolysis) of infected cells by cytotoxic CD8 ⁺ T cells and the activation of macrophages by Th1 cells, which together create cell-mediated immunity, and the activation of B cells by both Th2 and Th1 cells. , leading to the formation of various classes of antibodies, which leads to the launch of a humoral immune response. T cells recognize an antigen through their T cell receptors, which do not recognize or bind to an antigen directly, but instead recognize short peptide fragments, such as pathogen-derived protein antigens, that bind to MHC molecules on the surfaces of other cells.

T cells are divided into two main classes, which have different effector functions. The two classes differ in the expression of the cell surface proteins CD4 and CD8. These two types of T cells differ in the class of MHC molecule they recognize. Two classes of MHC molecules are known: MHC class I and MHC class II molecules, which differ in structure and expression pattern in body tissues. CD4 ⁺ T cells bind to the MHC class II molecule, and CD8 ⁺ T cells to the MHC class I molecule. MHC class I and MHC class II molecules differ in their distribution among cells, which reflects the different effector functions of T cells, which they are recognized. Class I MHC molecules present peptides of cytosolic and nuclear origin, eg, from pathogens, usually viruses, to CD8 ⁺ T cells, which differentiate into cytotoxic T cells that specialize in the cytolysis of any cell they specifically recognize. Almost all cells express class I MHC molecules, although the level of constitutive expression varies from one cell type to another. But not only pathogenic peptides from viruses are presented by class I MHC molecules, but autoantigens such as tumor antigens are also presented by them. MHC class I molecules bind peptides from proteins cleaved in the cytosol and are transported to the endoplasmic reticulum. CD8 ⁺ T cells, which recognize MHC class I:peptide complexes on the surface of infected cells, are specialized to cytolyze any cells displaying foreign peptides and therefore rid the body of cells infected with viruses and other cytosolic pathogens. The main function of CD4 ⁺ T cells (CD4 ⁺ T helper cells), which recognize MHC class II molecules, is to activate other effector cells of the immune system. Thus, MHC class II molecules are normally present on B-lymphocytes, dendritic cells and macrophages, cells that are involved in immune responses, but not on other tissue cells. Macrophages, for example, are activated to destroy the pathogens they carry within the vesicles, and B cells to secrete immunoglobulins against foreign molecules. Class II MHC molecules lack binding to peptides in the endoplasmic reticulum and therefore class II MHC molecules bind peptides from proteins cleaved in endosomes. They can capture peptides from pathogens that have invaded the macrophage vesicular system or from antigens internalized by immature dendritic cells or B cell immunoglobulin receptors. Pathogens that accumulate in large quantities inside macrophage vesicles and dendritic cells tend to stimulate Th1 cell differentiation, while extracellular antigens tend to stimulate Th2 cell production. Th1 cells activate the microbiocidal properties of macrophages and induce the production of IgG-type antibodies by B cells, which are very efficient at opsonizing extracellular pathogens leading to their uptake by phagocytic cells, while Th2 cells initiate a humoral response by activating naïve B cells. against IgM secretion and induce the production of weakly opsonizing antibodies such as IgG1 and IgG3 (mouse) and IgG2 and IgG4 (human) as well as IgA and IgE (mouse and human).

Epitope (also referred to as "antigenic determinant"): T-cell epitopes may contain fragments, preferably having a length of from about 6 to about 20 amino acids or even more, for example, fragments processed and presented by MHC class I molecules, preferably have a length of from about 8 up to about 10 amino acids, e.g. 8, 9 or 10, (or even 11 or 12 amino acids), or fragments processed and presented by MHC class II molecules are preferably about 13 amino acids or more in length, e.g. 13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids, these fragments can be selected from any part of the amino acid sequence. These fragments are usually recognized by T cells in the form of a complex consisting of a peptide fragment and an MHC molecule. B-cell epitopes, as a rule, are fragments localized on the outer surface of (native) protein or peptide antigens.

Vaccine: A vaccine is generally understood to mean a composition that contains a compound derived from an antigenic substance, preferably derived from a pathogen, where the compound is used to confer immunity against one or more diseases. In the context of the present invention, the term "vaccine" may preferably also refer to a (synthetic/artificial) compound that is not derived from an antigenic substance from a pathogen, and where the compound is used to confer immunity against one or more diseases. For example, the term "vaccine" in the context of the present description may refer to a composition containing as an active ingredient a (synthetic/artificial) compound, such as an (artificial) nucleic acid, peptide or protein molecule (which preferably does not originate from an antigenic substance). derived from the pathogen), wherein said compound induces an immune response, preferably an innate immune response. In this context, a vaccine may contain as active ingredient a (synthetic/artificial) compound which preferably acts as an adjuvant and/or immunomodulator. In this context, the term "immunomodulator" refers to a compound that enhances or inhibits an immune response, for example, through specific interaction with a signal transduction pathway in certain immune cells. Thus, in the context of the present invention, a vaccine can stimulate the creation of an immune response by the adaptive and/or innate immune system of the body, for example, an immune response against a tumor (cell).

Antigen-producing mRNA: An antigen-producing mRNA can generally be an mRNA having at least one open reading frame that can be translated by the cell or organism that/which contains such mRNA. The product of said translation is a peptide or protein that can act as an antigen, preferably an immunogen. The product may also be a fusion protein consisting of several immunogens, for example, a fusion protein that consists of two or more epitopes, peptides or proteins, wherein the epitopes, peptides or proteins may be linked by linker sequences.

Bi/polycistronic mRNA: Bi/polycistronic mRNA can typically have two (bicistronic) or more (polycistronic) coding sequences (cds) (often referred to as open reading frames (ORFs)). In this context, a coding sequence/open reading frame is a sequence consisting of several nucleotide triplets (codons) that can be translated into a peptide or protein. Translation of said mRNA results in two (bicistronic) or more (polycistronic) different translation products (provided the coding sequences/ORFs are not identical). For expression in eukaryotes, such mRNAs may, for example, contain an internal ribosome entry (IRES) sequence.

5'-Cap Structure: The 5'-Cap is usually a modified nucleotide (analogous to the cap structure), primarily a guanine nucleotide added to the 5' end of the mRNA molecule. Preferably, the 5' cap is added using a 5'-5' triphosphate bond (also referred to as m7GpppN). Other examples of 5'-cap structures are glyceryl, inverted deoxy group (fragment) devoid of a nitrogenous base, 4',5'-methylene nucleotide, 1-(beta-D-erythrofuranosyl) nucleotide, 4'-thionucleotide, carbocyclic nucleotide, 1, 5-anhydrohexitol nucleotide, L-nucleotides, alpha-nucleotide, base-modified nucleotide, treopentofuranosyl nucleotide, acyclic 3',4'-seconucleotide, acyclic 3,4-dihydroxybutyl nucleotide, acyclic 3,5-dihydroxypentyl nucleotide, 3'-3 '-Inverted Nucleotide Fragment, 3'-3'-Inverted Nucleotide Fragment, 3'-2'-Inverted Nucleotide Fragment, 3'-2'-Inverted Nucleotide Fragment, 1,4-Butanediol Phosphate, 3'-Phosphoramidate , hexylphosphate, aminohexylphosphate, 3'-phosphate, 3'-phosphorothioate, phosphorodithioate, or a bridged or unbridged methylphosphonate moiety. These modified structures of the 5'-cap in the context of the present invention can be used to modify the mRNA sequence in the composition of the invention. Other modified 5'-cap structures that can be used in the context of the present invention are CAP1 (methylation of the nucleotide ribose adjacent to m7G), CAP2 (methylation of the 2nd nucleotide ribose downstream of m7G), CAP3 (methylation of the ribose 3 -its nucleotide downstream of m7G), CAP4 (methylation of the 4th nucleotide ribose downstream of m7G), ARCA (correctly oriented cap analog), modified by ARCA (e.g. modified by ARCA phosphothioate), inosine, N1-methylguanosine, 2'-fluoroguanosine, 7-deazaguanosine, 8-oxoguanosine, 2-aminoguanosine, LNA-guanosine and 2-azidoguanosine.

In the context of the present invention, the structure of the 5'-cap can also be obtained by chemical synthesis of RNA or transcription of RNA in vitro (co-transcriptional capping) using cap analogs, or the structure of the cap can be obtained in vitro using capping enzymes (for example, commercial kits for capping).

Cap analogs: A cap analog means a non-polymerizable dinucleotide that has a cap functionality that facilitates translation or localization and/or prevents cleavage of the RNA molecule when inserted at the 5' end of the RNA molecule. Non-polymerizable means that the cap analog can only be included at the 5' end because it lacks a 5' triphosphate and therefore cannot be extended in the 3' direction by a template-dependent RNA polymerase.

Cap analogs include, but are not limited to, a chemical structure selected from the group consisting of m7GpppG, m7GpppA, m7GpppC; unmethylated cap analogs (eg GpppG); dimethylated cap analog (e.g., m2.7GpppG), trimethylated cap analog (e.g., m2.2.7GpppG), dimethylated symmetrical cap analogs (e.g., m7Gpppm7G), or anti-reverse cap analogs (e.g., ARCA; m7,2'OmeGpppG, m7,2'dGpppG, m7,3'OmeGpppG, m7,3'dGpppG and their tetraphosphate derivatives) (Stepinski et al., RNA 7(10), 2001, pp. 1486-1495) .

Other analogues of cap structures have been previously described (US 7074596, WO 2008/016473, WO 2008/157688, WO 2009/149253, WO 2011/015347 and WO 2013/059475). In recent years, the synthesis of substituted N ⁷ -(4-chlorophenoxyethyl) analogues of cap structures has been described (Core et al., Bioorg. Med. Chem. 21(15), 2013, pp. 4570-4574).

Protein Fragments: In the context of the present invention, "fragments" of proteins or peptides may generally contain a protein or peptide sequence as defined herein, which, with respect to its amino acid sequence (or the nucleic acid molecule encoding it), is shortened by N- end, C-terminus and/or within the sequence compared to the amino acid sequence of the original (native) protein (or the nucleic acid molecule encoding it). Thus, said truncation can take place either at the amino acid level or, respectively, at the nucleic acid level. Therefore, sequence identity with respect to such a fragment, as defined herein, preferably refers to the complete protein or peptide, as defined herein, or to the complete (coding) nucleic acid molecule of said protein or peptide. For antigens, said fragment may contain from about 6 to about 20 or even more amino acids, for example, fragments processed and presented by MHC class I molecules are preferably from about 8 to about 10 amino acids in length, for example, 8, 9 or 10 (or even 6, 7, 11, or 12 amino acids), or fragments processed and presented by MHC class II molecules, preferably consist of about 13 or more amino acids, e.g., 13, 14, 15, 16, 17, 18, 19, 20 or even more amino acids, while these fragments can be selected from any region of the amino acid sequence. These fragments are usually recognized by T cells in the form of a complex consisting of a peptide fragment and MHC molecules, i.e. fragments are generally not recognized in their native form. Fragments of proteins or peptides (eg, in the context of antigens) may contain at least one epitope of said proteins or peptides. In addition, it is contemplated that a protein fragment may also contain protein domains such as extracellular domain, intracellular domain or transmembrane domain and truncated or truncated versions of the protein. Preferably, the protein fragment contains a functional protein fragment, which means that the fragment has the same effect or the same functionality as the complete protein from which it is derived. More preferably, in the context of the present description, "fragment" is at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88 %, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the peptide or protein from which it is derived.

Protein Variants: As is apparent from the context of the present invention, "variants" of proteins or peptides can be created having an amino acid sequence that differs from the original sequence by the presence of one or more mutations, such as substitutions, insertions and/or deletions of the amino acid(s). Preferably, said fragments and/or variants have the same biological function or specific activity as the full-length native protein, eg, an inherent specific antigenic characteristic. As follows from the context of the present invention, "variants" of proteins or peptides may contain conservative(s) amino acid(s) substitution(s) compared to their native, ie. unmutated, physiological sequence. Such amino acid sequences, and in particular the nucleotide sequences encoding them, fall within the meaning of "variants" as used herein. Substitutions that replace amino acids belonging to the same class with each other are called conservative substitutions. In particular, such classes are amino acids having aliphatic side chains, positively or negatively charged side chains, aromatic groups in the side chains, or amino acids whose side chains can be hydrogen bridged, for example, whose side chains have a hydroxyl function. This means, for example, that an amino acid having a polar side chain is replaced by another amino acid also having a polar side chain, or, for example, an amino acid having a hydrophobic side chain is replaced by another amino acid also having a hydrophobic side chain (for example, series ( threonine) to threonine (series) or leucine (isoleucine) to isoleucine (leucine)). It is possible to carry out insertions and substitutions, first of all, at those positions in the sequence that do not lead to a modification of the three-dimensional structure or do not affect the binding region. Modifications in the three-dimensional structure due to insertion(s) or deletion(s) can be easily determined, for example, using CD spectra (Circular Dichroism Spectra) (Urry, Absorption, Circular Dichroism and ORD of Polypeptides, in: Modern Physical Methods in Biochemistry, edited by Neuberger et al., Elsevier, Amsterdam, 1985).

The amino acid sequence of a "variant" protein or peptide may be at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to a 10%, 20%, 30%, 50%, 75%, or 100% amino acids to a portion of said protein or peptide. Alternatively, more preferably the term "variant" as used herein is at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85 %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the peptide or protein from which it is received.

In addition, variants of proteins or peptides as defined herein that may be encoded by a nucleic acid molecule may also contain sequences in which nucleic acid nucleotides are exchanged in accordance with the degeneracy of the genetic code, which does not lead to a change in the corresponding amino acid sequence of the protein. or a peptide, i. e. the amino acid sequence, or at least part of it, may not differ from the original sequence in the above sense.

Preferably, the protein variant contains a functional variant of the protein, which means that the variant has the same effect or the same functionality as the complete protein from which it is derived.

Sequence Identity: To determine the percent identity of two sequences, e.g., nucleotide sequences or amino acid sequences as described herein, preferably the amino acid sequences encoded by the nucleic acid molecule of the polymer carrier as described herein, or the amino acid sequences themselves, sequences can be aligned for later comparison. together. Thus, for example, a position in the first sequence can be compared with a corresponding position in the second sequence. If a position in the first sequence is occupied by the same moiety that is at that position in the second sequence, then the two sequences are identical at that position. If this is not the case, then the sequences differ at that position. If there are insertions in the second sequence compared to the first sequence, then gaps can be built into the first sequence, allowing the comparison to continue. If there are deletions in the second sequence compared to the first sequence, then gaps can be built into the second sequence, allowing the comparison to continue. Thus, the percent identity of two sequences is a function of the number of identical positions divided by the total number of positions, including those positions that are occupied in only one sequence. The percent identity of two sequences can be determined using a mathematical algorithm. A preferred example of a mathematical algorithm that can be used is (but not limited to) the algorithm proposed by Karlin et al., PNAS USA, 90, 1993, ss. 5873-5877 or ltschul et al., Nucleic Acids Res., 25, 1997, pp. 3389-3402. This algorithm is included in the BLAST program. Using this program, you can identify sequences that have a specific degree of identity with the sequences proposed in the present invention.

Monocistronic mRNA: Monocistronic mRNA can generally be an mRNA that contains only one coding sequence (open reading frame). In this context, a coding sequence/open reading frame is a sequence consisting of several nucleotide triplets (codons) that can be translated into a peptide or protein.

Nucleic acid: The term "nucleic acid" refers to either a DNA or RNA molecule and is synonymous with the term "polynucleotide". If in the context of the present description, a nucleic acid or nucleotide sequence is mentioned that encodes a specific protein and/or peptide, then said nucleic acid or nucleotide sequence, respectively, also preferably contains regulatory sequences that provide in a suitable host, for example, a human, expression, i.e. transcription and/or translation of a nucleotide sequence that encodes a particular protein or peptide.

Peptide: A peptide is a polymer composed of amino acid monomers. Typically, monomers are linked by peptide bonds. The concept of "peptide" does not impose restrictions on the length of the polymer chain of amino acids. In some embodiments, implementation of the present invention, the peptide may contain, for example, less than 50 monomer units. Longer peptides are also referred to as polypeptides and typically have 50 to 600 monomeric units, more specifically 50 to 300 monomeric units.

Pharmaceutically effective amount: In the context of the invention, a pharmaceutically effective amount is generally understood to mean an amount sufficient to induce an immune response or trigger the desired therapeutic effect.

Protein: A protein typically consists of one or more peptides and/or polypeptides arranged in a 3-dimensional structure, which may be required for the biological function of the protein.

Poly(C) sequence: A poly(C) sequence is typically a long sequence of cytosine nucleotides, typically containing from about 10 to about 200 cytosine nucleotides, preferably from about 10 to about 100 cytosine nucleotides, more preferably from about 10 to about 70 cytosine nucleotides, or even more preferably from about 20 to about 50 or even from about 20 to about 30 cytosine nucleotides. The poly(C) sequence may preferably be located in the 3' direction relative to the coding region contained in the nucleic acid.

Poly(A) tail: The poly(A) tail, also referred to as the "3'-poly(A) tail" or "poly(A) sequence", is generally a long homopolymer sequence of adenosine nucleotides containing up to about 400 adenosine nucleotides, e.g., from about 25 to about 400, preferably from about 50 to about 400, more preferably from about 50 to about 300, even more preferably from about 50 to about 250, most preferably from about 60 to about 250 adenosine nucleotides added to the 3' end of the mRNA. In the context of the present invention, the mRNA poly(A) tail is preferably obtained from a DNA template by in vitro transcription into RNA. Alternatively, the poly(A) sequence can also be generated in vitro by conventional chemical synthesis without the need for transcription from a precursor DNA. In addition, poly(A) sequences or poly(A) tails can be created by enzymatic polyadenylation of RNA.

Stabilized nucleic acid: A stabilized nucleic acid typically has a modification that increases resistance to in vivo cleavage (e.g., exo- or endonuclease cleavage) and/or ex vivo cleavage (e.g., during manufacture prior to vaccine administration, e.g., during preparation vaccine solution to be administered). RNA stabilization can, for example, be provided using a 5' cap structure, a poly(A) tail and/or any other UTR modification. It can also be provided by modifying the framework and/or modifying the G/C content or C content of the nucleic acid. Various other methods are known in the art and may be considered in the context of the invention.

Carrier/Polymer Carrier: In the context of the invention, a carrier can generally be a compound that facilitates transport and/or incorporation into the complex of another compound. Said carrier may form a complex with said other compound. A polymeric carrier is a carrier that forms a polymer.

Cationic component: The term "cationic component" generally refers to a charged molecule that is positively charged (cation) at a pH value typically between 1 and 9, preferably at or below pH 9 (e.g., 5 to 9) equal to or less than 8 (eg 5 to 8), equal to or less than 7 (eg 5 to 7), most preferably at physiological pH, eg 7.3 to 7.4. Thus, according to the present invention, the cationic peptide, protein or polymer is positively charged under physiological conditions, especially at physiological salt concentrations in the cell in vivo. The cationic peptide or protein preferably contains more cationic amino acids, for example, more Arg, His, Lys or Orn, than other amino acid residues (in particular, more cationic amino acids than anionic amino acid residues like Asp or Glu), or contains blocks, formed predominantly from cationic amino acid residues. The term "cationic" can also refer to "polycationic" components.

Excipient: An excipient is an agent, such as a carrier, that can generally be used in a pharmaceutical composition or vaccine to facilitate administration of the components of the pharmaceutical composition or vaccine to an individual.

3'-untranslated region (3'-UTR): The 3'-UTR is typically the part of the mRNA located between the protein-coding region (ie, open reading frame) and the mRNA poly(A) sequence. The 3'-UTR of mRNA is not translated into an amino acid sequence. The 3'-UTR sequence is typically encoded by a gene that is transcribed into the corresponding mRNA during gene expression. The genomic sequence is first transcribed into immature mRNA, which contains optional introns. The immature mRNA is then further processed into mature mRNA during maturation. Said maturation process includes the steps of 5' capping, splicing of immature mRNA with excision of optional introns, and 3' end modifications such as subdiadenylation of the 3' end of immature mRNA and optional endo-/or exonuclease cleavages, etc. In the context of the present invention, the 3'-UTR corresponds to a mature mRNA sequence which is located 3'-side of the stop code of the protein-coding region, preferably immediately adjacent 3'-side to the stop codon of the protein-coding region, and which extends to 5' side of the poly(A) sequence, preferably up to the nucleotide immediately adjacent on the 5' side to the poly(A) sequence. The term "corresponds" means that the 3'-UTR sequence may be an RNA sequence, such as the mRNA sequence specified in the definition of the 3'-UTR sequence, or a DNA sequence that corresponds to the specified RNA sequence. In the context of the present invention, the term "3'-UTR of a gene", for example, "3'-UTR of the albumin gene", means a sequence that corresponds to the 3'-UTR of the mature mRNA derived from the indicated gene, i.e. mRNA obtained by transcription of a gene and maturation of immature mRNA. The term "3'-UTR of a gene" includes a DNA sequence and an RNA 3'-UTR sequence.

5'-untranslated region (5'-UTR): By 5'-UTR, as a rule, understand a specific segment of messenger RNA (mRNA). It is located at the 5' end of the mRNA open reading frame. Typically, the 5'-UTR starts at the site of transcription initiation and is inserted one nucleotide before the start codon of the open reading frame. The 5'-UTR may contain elements designed to control gene expression, so-called regulatory elements. Said regulatory elements may be, for example, ribosome binding sites or a 5'-oligopyrimidine tract. The 5'-UTR may be subject to post-transcriptional modifications, for example by adding a 5'-cap. In the context of the present invention, the 5'-UTR corresponds to the mature mRNA sequence located between the 5'-cap and the start codon. Preferably the 5'-UTR corresponds to a sequence that extends from the nucleotide located on the 3' side of the 5' cap, preferably from the nucleotide immediately adjacent on the 3' side of the 5' cap, to the nucleotide located on the 5' side the start code of the protein coding region, preferably up to the nucleotide immediately adjacent 5' to the start codon of the protein coding region. The nucleotide immediately adjacent on the 3' side to the 5' cap of the mature mRNA usually corresponds to the site of transcription initiation. The term "corresponds" means that the 5'-UTR sequence may be an RNA sequence, such as the mRNA sequence specified in the definition of the 5'-UTR sequence, or a DNA sequence that corresponds to the specified RNA sequence. In the context of the present invention, the term "5'-UTR of a gene", such as "5'-UTR of the TOP gene", means a sequence that corresponds to the 5'-UTR of the mature mRNA derived from this gene, i. mRNA obtained by transcription of a gene and maturation of immature mRNA. The term "5'-UTR of the gene" includes the DNA sequence and the RNA sequence of the 5'-UTR.

5' oligopyrimidine tract (TOR): The 5' oligopyrimidine tract (TOR) generally refers to a segment of pyrimidine nucleotides located at the 5' end of a nucleic acid molecule, such as the 5' end of some mRNA molecules. or in the 5'-terminal region of a functional element, for example, the transcribed region of some genes. The sequence begins with a cytidine, which typically corresponds to the site of transcription initiation, and is followed by a segment typically consisting of about 3-30 pyrimidine nucleotides. For example, TOP can contain 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 , 26, 27, 28, 29, 30 or even more nucleotides. The pyrimidine segment, and hence the 5'-TOP, terminates at one nucleotide adjacent on the 5' side to the first purine nucleotide located in the forward direction relative to the TOP. mRNA that contains the 5' oligoprimidine tract is often referred to as TOP mRNA. Thus, the genes from which these messenger RNAs are derived are referred to as TOP genes. TOP sequences, for example, are found in genes and mRNAs encoding peptide elongation factors and ribosomal proteins.

TOP motif: In the context of the present invention, the TOP motif refers to a nucleotide sequence that corresponds to the 5'-TOP described above. Thus, the TOP motif in the context of the present invention preferably denotes a segment consisting of pyrimidine nucleotides of 3-30 nucleotides in length. 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, more preferably at least 7 nucleotides, most preferably at least 8 pyrimidine nucleotides, with the pyrimidine nucleotide segment preferably beginning at its 5' end with a cytosine nucleotide. In TOP genes and TOP mRNA, the TOP motif preferably starts at its 5' end from the site of transcription initiation and ends with one nucleotide adjacent 5' to the first purine residue in said gene or said mRNA. The TOP motif in the context of the present invention is preferably located at the 5'end of the sequence which is the 5'UTR or at the 5'end of the sequence which encodes the 5'UTR. Thus, in the context of the present invention, a segment of 3 or more pyrimidine nucleotides is referred to as a "TOP motif" if the segment is located at the 5' end of a corresponding sequence such as an mRNA of the invention, the 5'UTR element of an mRNA of the invention in the invention, or a nucleotide sequence that is obtained from the 5'-UTR of the TOP gene specified in the present description. In other words, a segment of 3 or more pyrimidine nucleotides that is not located at the 5' end of the 5'-UTR or 5'-UTR element, but is located somewhere within the 5'-UTR or 5'-UTR- element is preferably not referred to as a "TOP motif".

TOP gene: TOP genes are generally characterized by the presence of a 5'-terminal oligoprimidine tract. In addition, most TOP genes are characterized by growth-associated regulation of translation. However, TOP genes with tissue-specific regulation of translation are also known. As indicated above, the 5'-UTR of the TOP gene corresponds to the sequence of the 5'-UTR of the mature mRNA derived from the TOP gene, which preferably extends from the nucleotide located on the 3' side of the 5' cap to the nucleotide located on the 5' side of the start codon. The 5'UTR of the TOP gene generally does not contain any start codons, preferably no upstream (u) AUG (uAUG) or upstream open reading frames (uOPC). In this context, reversed AUGs and reversed open reading frames are generally understood to mean AUGs and open reading frames that are 5' to the start codon (AUG) of the open reading frame to be translated. The 5'UTRs of TOP genes are generally relatively short. The lengths of the 5'UTRs of TOP genes can vary from 20 nucleotides up to 500 nucleotides and are typically less than about 200 nucleotides, preferably less than about 150 nucleotides, more preferably less than about 100 nucleotides. Examples of the 5'-UTRs of TOP genes in the context of the present invention are nucleotide sequences extending from the nucleotide at position 5 to the nucleotide immediately adjacent 5' to the start codon (e.g., ATG), these sequences are shown in SEQ ID NO: 1 -1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of international patent application WO 2013/143700, or are homologues or variants thereof, the description of this document is incorporated herein by reference. In this context, the most preferred fragment of the 5'UTR of the TOP gene is the 5'UTR of the TOP gene without the 5'TOP motif. The term "5'UTR of the TOP gene" preferably refers to the 5'UTR of the naturally occurring TOP gene.

Chemical Synthesis of RNA: The chemical synthesis of relatively short fragments of oligonucleotides with a defined chemical structure is a fast and inexpensive approach to custom oligonucleotides having any desired sequence. While enzymes provide DNA and RNA synthesis only in the 5' to 3' direction, the chemical synthesis of oligonucleotides is not subject to this restriction, although it is most often carried out in the opposite direction, i.e. from 3' to 5' end. The process is currently carried out as a solid phase synthesis using the phosphoramidite method and phosphoramidite building blocks from protected nucleosides (A, C, G and U) or chemically modified nucleosides.

To obtain the desired oligonucleotide, the building blocks are sequentially linked to the growing oligonucleotide strand on the solid phase in the order required by the product sequence using a fully automated process. After completion of chain assembly, the product is released from the solid phase into solution, the protecting groups are removed and collected. The presence of side reactions imposes a practical limit on the length of synthetic oligonucleotides (up to about 200 nucleotide residues), since the number of errors increases with increasing length of the oligonucleotide to be synthesized. The products are often isolated by HPLC to obtain the desired high purity oligonucleotides.

Chemically synthesized oligonucleotides have found wide application in molecular biology and medicine. They are most commonly used as antisense oligonucleotides, small interfering RNAs, primers for DNA sequencing and amplification, probes for detecting complementary DNA or RNA by molecular hybridization, tools for targeted introduction of mutations and restriction sites, and for the synthesis of artificial genes.

In vitro RNA transcription: The terms "in vitro RNA transcription" or "in vitro transcription" refer to the process by which RNA is synthesized in a cell-free system (in vitro). DNA, in particular plasmid DNA, is used as a template for generating RNA transcripts. RNA can be obtained by DNA-dependent in vitro transcription of an appropriate DNA template, which according to the present invention is preferably a linearized plasmid DNA template. The promoter for controlling in vitro transcription can be any promoter for any DNA-dependent RNA polymerase. Specific examples of DNA-dependent RNA polymerases are T7, T3 and SP6 RNA polymerases. A DNA template for in vitro transcription of RNA can be obtained by cloning a nucleic acid, in particular cDNA, corresponding to the desired RNA to be transcribed in vitro and introduced into an appropriate vector for in vitro transcription, for example into plasmid DNA. In a preferred embodiment of the present invention, the template DNA is linearized with acceptable restriction enzymes prior to in vitro transcription. cDNA can be obtained by reverse transcription of mRNA or by chemical synthesis. Besides. A DNA template for in vitro RNA synthesis can also be obtained by gene synthesis.

In vitro transcription methods are known in the art (see, for example, Geall et al., Semin. Immunol. 25(2), 2013, pp. 152-159; Brunelle et al., Methods Enzymol. 530, 2013, pp. 101-114). Reagents used in this method typically include:

1) a linearized DNA template with a promoter sequence that has a high binding affinity for an appropriate RNA polymerase, such as a bacteriophage-encoded RNA polymerase;

2) ribonucleoside triphosphates (NTPs) for four bases (adenine, cytosine, guanine and uracil);

3) optionally analogous to the cap structure above (eg m7G(5')ppp(5')G(m7G));

4) a DNA-dependent RNA polymerase that has the ability to bind to a promoter sequence in a linearized DNA template (eg T7, T3 or SP6 RNA polymerase);

5) optionally a ribonuclease (RNase) inhibitor to inactivate any contaminating RNase;

6) optionally pyrophosphatase to cleave pyrophosphate, which can inhibit transcription;

7) MgCl ₂ supplementing Mg ^{2+ ions} as a cofactor for the polymerase;

8) a buffer to maintain an acceptable pH, which may also contain antioxidants (eg DTT) and/or polyamines such as spermidine at optimal concentrations.

RNA, mRNA: RNA is a common shorthand for ribonucleic acid. It is a nucleic acid molecule, i.e. a polymer composed of nucleotide monomers. These nucleotides are typically adenosine monophosphate (AMP), uridine monophosphate (UMP), guanosine monophosphate (GMP) and cytidine monophosphate (CMP) monomers or their analogs, linked together along a so-called backbone. The framework is formed by phosphodiester bonds between sugars, i.e. ribose, the first and phosphate residue of the second neighboring monomer. The specific arrangement of monomers, i.e. the order of the bases associated with the sugar/phosphate backbone is called the RNA sequence. Typically, RNA can be obtained by transcription of a DNA sequence, for example, within a cell. In eukaryotic cells, transcription typically occurs within the nucleus or mitochondria. In vivo transcription of DNA generally results in the formation of so-called immature RNA (also referred to as pre-mRNA, progenitor mRNA or heterogeneous nuclear RNA), which must be processed to form so-called messenger RNA, the common abbreviation for which is mRNA. Processing of immature RNA, for example in eukaryotic organisms, involves a wide variety of different post-transcriptional modifications such as splicing, 5' capping, polyadenylation, nuclear or mitochondrial export, and the like. The combination of these processes is also called RNA maturation. Mature messenger RNA typically has a nucleotide sequence that can be translated into the amino acid sequence of a particular peptide or protein. Typically, the mature mRNA contains a 5'cap, optionally a 5'UTR, an open reading frame, an optional 3'UTR, and a poly(A) tail.

In addition to messenger RNA, there are several non-coding RNA types that may be involved in the regulation of transcription and/or translation and immunostimulation. In the context of the present invention, the term "RNA" also includes any type of single-stranded (ssRNA) or double-stranded RNA (dsRNA) molecule known in the art, such as viral RNA, retroviral RNA and replicon RNA, small interfering RNA (siRNA), antisense RNA (asRNA), circular RNA (circPHK), ribozymes, aptamers, riboswitches (RNA switches), immunostimulatory/immunostimulatory RNA, transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA ), miRNA (miRNA), and RNA interacting with the Piwi complex (piRNA).

Fragment of a nucleotide sequence, in particular RNA: A fragment of a nucleotide sequence consists of a continuous nucleotide segment, which corresponds to a continuous nucleotide segment of a full-length nucleotide sequence, which is the basis of the nucleotide sequence of the fragment, the length of which is at least 20%, preferably at least 30%, more preferably at least 40%, more preferably at least 50%, even more preferably at least 60%, even more preferably at least 70%, even more preferably at least 80% and most preferably 90% of the total nucleotide sequence . The specified fragment in the context of the present invention is preferably a functional fragment of a full-length nucleotide sequence.

Nucleotide sequence variant, in particular RNA: Nucleotide sequence variant refers to a variant of the nucleotide sequences that form the basis of a nucleotide sequence. For example, a nucleotide sequence variant may have one or more nucleotide deletions, insertions, additions, and/or substitutions compared to the nucleotide sequence from which the variant is derived. Preferably the nucleotide sequence variant is at least 40% identical, preferably at least 50% identical, more preferably at least 60% identical, more preferably at least 70% identical, even more preferably at least 80% identical, even more preferably at least 90%, most preferably at least 95% of the nucleotide sequence from which the variant is derived. Preferably, the variant is a functional variant. A nucleotide sequence "variant" may have at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical nucleotides on a 10, 20, 30 , 50, 75 or 100 nucleotides segment of the specified nucleotide sequence.

Intratumoral administration/use: The term "intratumoral administration/use" refers to the direct delivery of a pharmaceutical composition to or adjacent to a tumor or cancerous tissue and/or to an area in close proximity to the tumor or cancerous tissue. Thus, in the context of the present invention, the term "intratumoral administration/application" generally also refers to locoregional or peritumoral administration/administration. This also includes multiple injections into different areas of the tumor or cancerous tissue. In addition, intratumoral administration/use includes delivery of the pharmaceutical composition to one or more metastases. Methods for intratumoral drug delivery are known in the art (Brincker, Crit. Rev. Oncol. Hematol. 15(2), 1993, pp. 91-98; Celikoglu et al., Cancer Therapy 6, 2008, pp. 545-552) . For example, the pharmaceutical composition can be administered by conventional needle injection, needleless jet injection, or electroporation, or combinations thereof, into tumor or cancerous tissue. The pharmaceutical composition can be injected directly into the tumor or cancerous tissue with great precision using computed tomography, ultrasound, gamma camera imaging, positron emission tomography, or magnetic resonance imaging of the tumor. Other procedures are selected from the group including (but not limited to) direct intratumoral injection using endoscopy, bronchoscopy, cytoscopy, colonoscopy, laparoscopy, and catheterization.

In addition, the pharmaceutical composition can be injected locoregional or peritumoral using the same methods. Tumor or cancerous tissue includes metastases from primary tumors, for example, to lymph nodes, skin, soft tissues, bone, visceral organs, or other organs of the body.

Decoy receptors: Decoy receptors recognize some growth factors or cytokines with high affinity and specificity, but they are not structurally capable of signaling or presenting an agonist to signaling receptor complexes. They act as a molecular trap for the agonist and signaling receptor components. A decoy or shell receptor is a receptor that binds a ligand by inhibiting its binding to its normal receptor. For example, the VEGFR-1 receptor can interfere with the binding of vascular endothelial growth factor (VEGF) to VEGFR-2.

Dominant Negative Receptors: Dominant negative receptors are variants of a particular receptor that contain dominant negative (DN) mutations resulting in mutant polypeptides that, when overexpressed, disrupt wild-type receptor activity.

The first object of the present invention is an immunostimulatory RNA (isRNA) intended for use in the treatment or prevention of neoplastic and/or cancerous diseases. In particular, isRNA is provided for use in the treatment or prevention of neoplastic and/or cancerous diseases when isRNA is administered inside tumors. In the course of the invention, it has been found that intratumoral administration of isRNA as described herein can be used to treat or prevent neoplastic or cancerous diseases and related disorders. It has been found that the treatment of neoplastic or cancerous diseases with isRNA surprisingly proved to be effective, in particular when administered intratumorally, in reducing the size of the tumor. In addition, the use of the isRNA of the invention may improve survival in animal models and protect surviving animals from reinfection with the same tumor, although treatment with the pharmaceutical compositions was discontinued after reinfection. These data indicate the creation of long-term immunological memory. This was not to be expected since isRNA does not directly induce an adaptive immune response.

As used herein, "tumor", "cancer", or "cancerous disease" refers to a malignant disease which is preferably selected from the group consisting of adenoid cystic carcinoma (adenoid cystic carcinoma), adrenocortical carcinoma, AIDS-related cancers, AIDS-associated lymphoma. , anus cancer, appendix cancer, astrocytoma, basal cell carcinoma, bile duct cancer, bladder cancer, bone cancer, osteosarcoma/malignant fibrous histocytoma, brainstem glioma, brain tumor, cerebellar astrocytoma, astrocytoma/malignant cerebellar glioma, ependymoma, medulloblastoma , supratentorially located primitive neuroectodermal tumors, glioma of the optic tract and hypothalamus, breast cancer, bronchial adenomas/carcinoids, Burkitt's lymphoma, carcinoid tumor in children, carcinoid tumor of the gastrointestinal tract, carcinoma of unknown origin, primary lymphoma of the central nervous system cerebellar astrocytoma, pediatric astrocytoma/malignant glioma of the cerebellum, cervical cancer, various childhood cancers, chronic lymphocytic leukemia, colon cancer, cutaneous T-cell lymphoma including mycotic fungoid and Cesari syndrome, dermaplastic small round cell tumor, cancer endometrium, ependymoma, esophageal cancer, Ewing's sarcoma from the Ewing tumor family, extracranial germ cell tumor in children, extragonadal germ cell tumor, extrahepatic bile duct cancer, intraocular melanoma, retinoblastoma, bladder cancer, gastric cancer (stomach cancer), carcinoid gastrointestinal tumor, gastrointestinal stromal tumor (GIST), extracranial, extragonadal or ovarian germ cell tumor, gestational trophoblastic tumor, brainstem glioma, pediatric cerebellar astrocytoma, pediatric optic pathway and hypothalamic glioma, gastric carcinoid , hairy cell leukemia, head and neck cancer, heart cancer, hepatocellular (liver) cancer, Hodgkin's lymphoma, human papillomavirus (HPV) associated cancer, hypopharynx cancer, glioma of the hypothalamus and optic pathway in children, intraocular melanoma, islet carcinoma cells (pancreatic endocrine carcinoma), Kaposi's sarcoma, kidney cancer (renal cell carcinoma), kidney cancer (renal cell carcinoma), larynx cancer, lip and mouth cancer, liposarcoma, liver cancer, non-small cell lung cancer, small cell lung cancer , lymphomas, AIDS-related lymphoma, Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphomas, primary central nervous system lymphoma, malignant fibrous bone histiocytoma/osteosarcoma, childhood medulloblastoma, melanoma, intraocular (ocular) melanoma, Merkel cell carcinoma, adult malignant mesothelioma , childhood mesothelioma, head or neck cancer, oral cavity cancer, pediatric multiple endocrine neoplasia syndrome, multiple myeloma/n Plasma cell neoplasm, multiple myeloma/plasma cell neoplasm, multiple myeloma (bone marrow cancer), nasal cavity and paranasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma, oral cancer, oropharyngeal cancer, osteosarcoma/malignant fibrous histiocytoma of bone, ovarian cancer, epithelial ovarian cancer (superficial stromal epithelial tumour), ovarian germ cell cancer, low potential ovarian tumor, pancreatic cancer, pancreatic islet cell cancer, paranasal sinus and nasal cavity cancer, parathyroid cancer, penis cancer, pharyngeal cancer , pheochromocytoma, pineal astrocytoma, pineal germinoma, pinealoblastoma and supratentorially located primitive neuroectodermal tumors in children, pituitary adenoma, plasma cell neoplasia/multiple myeloma, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer cancer, rectal cancer, renal cell carcinoma (kidney cancer), cancer of the renal pelvis and ureter, retinoblastoma, rhabdomyosarcoma in children, salivary gland cancer, Ewing's tumor family sarcoma, Kaposi's sarcoma, soft tissue sarcoma, uterine sarcoma, skin cancer (not melanoma), skin cancer (melanoma), Merkel cell carcinoma of the skin, small intestine cancer, squamous cell carcinoma, asymptomatic onset metastatic squamous cell carcinoma of the neck, soft tissue sarcoma (STS), supratentorially located primitive neuroectodermal tumor in children, testicular cancer ( seminoma and non-seminoma), laryngeal cancer, childhood thymoma, thymoma and thymic carcinoma, thyroid cancer, childhood thyroid cancer, transitional cell carcinoma of the renal pelvis and ureter, gestational trophoblastic tumor, urethral cancer, uterine endometrial cancer, uterine sarcoma, vaginal cancer, glioma of the optic pathway and hypothalamus in children, vulvar cancer and Wilms tumor (kidney cancer) in children th.

Particularly preferred examples of tumors or cancers that can be treated with intratumoral, including peritumoral or locoregional administration, preferably image-guided locoregional administration, are prostate cancer, lung cancer, breast cancer, brain cancer, head and neck cancer, including cancer. lips, mouth or tongue, nasopharyngeal cancers or lymphomas, thyroid cancer, thymus cancer, colon cancer, stomach cancer, esophageal cancer, liver cancer, biliary tract cancer, pancreatic cancer, ovarian cancer, skin cancer (melanoma and non-melanoma skin cancer) ), bladder and urothelial cancer, uterine and cervical cancer, anus cancer, bone cancers, kidney cancer, adrenal cancer, testicular cancer, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, plasmacytoma, other Hodgkin and non-Hodgkin lymphomas with single lesions that can be injected, adenoid cystic carcinoma, other salivary gland cancers, tumors of the neuroendocrine system, cancer to the vulva, sarcoma (including pediatric sarcoma), cancer (lymphomas) of the penis.

Preferably, the neoplastic or cancerous disease is selected from the group consisting of breast cancer (hormone receptor positive (hormone positive) or hormone negative forms); melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL); squamous cell skin cancer (SCC), preferably unresectable and/or advanced SCC, most preferably squamous cell skin carcinoma (cSCC) or other forms of malignant skin cancer; adenoid cystic carcinoma (ACC), preferably advanced ACC; cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype (CTCL-MF); head and neck squamous cell carcinoma (HNSCC), preferably an advanced or limited-advanced form of HNSCC; follicular lymphoma (FL); marginal zone lymphoma, preferably nodal marginal zone lymphoma (nMZL); mantle cell lymphoma; primary cutaneous anaplastic large cell lymphoma (PC-ALCL); vulvar carcinoma, preferably vulvar squamous cell carcinoma (VSCC); soft tissue sarcoma; mammary cancer; hepatocellular carcinoma; colorectal cancer (including CRC with high microsatellite instability status MSI-H); neuroendocrine tumors; pancreas cancer; gastoroesophageal cancer; uveal melanoma; cancer (lymphoma) of the penis; salivary gland cancer; cancers of the nasopharynx; lung cancer, preferably limited or advanced form of non-small cell lung cancer or small cell limited or extensive lung cancer, lung metastases from other malignant diseases; mesothelioma; urothelial or bladder cancer; thyroid cancer; cancer of the esophagus and stomach; stomach cancer, esophageal cancer, liver cancer; malignant diseases with liver metastases; ovarian cancer; cervical cancer; kidney cancer; adrenal malignancies, soft tissue sarcomas, hematologic malignancies with injectable lesions such as cutaneous T-cell lymphoma; solitary or multiple myeloma; Hodgkin's disease; non-Hodgkin's lymphoma, preferably indolent (painless) skin detectable non-Hodgkin's lymphoma (CTCL) or non-Hodgkin's lymphoma with injectable lesions; sarcoma, including its various subtypes; glioma degree I-IV; colorectal, rectal, or anal cancer. In particular, the terms "tumor", "cancer" or "cancer" as used herein, refer to basal cell carcinoma; or melanoma, preferably advanced and/or metastatic melanoma; squamous cell carcinoma (SCC), preferably skin SCC, more preferably inoperable and/or advanced skin SCC; or head and neck squamous cell carcinoma (HNSCC), preferably advanced and/or platinum-resistant and/or immunotherapy-resistant HNSCC; or vulvar carcinoma or vulvar squamous cell carcinoma (VSCC), preferably unresectable and/or advanced VSCC, more preferably advanced and/or platinum resistant and/or immunotherapy resistant VSCC; or adenoid cystic carcinoma (ACC), preferably advanced ACC; or cutaneous T cell lymphoma, preferably advanced cutaneous T cell lymphoma or cutaneous T cell lymphoma of the mycotic fungoid subtype (CTCL-MF), preferably CTCL-MF advanced, preferably cutaneous T cell lymphoma resistant to topical treatment or chemotherapy; or follicular lymphoma; or marginal zone lymphoma, preferably nodal marginal zone lymphoma (nMZL); or mantle cell lymphoma; or primary cutaneous anaplastic large cell lymphoma (PC-ALCL); or soft tissue sarcoma (STS); or associated with human papillomavirus (HPV) cancer; or breast cancer; or hepatocellular carcinoma; or colorectal cancer (including CRC with high MSI status); or neuroendocrine tumors; or pancreatic cancer; or gastroesophageal cancer; or uveal melanoma; or cancer (lymphoma) of the penis. In some embodiments of the invention, the terms "tumor", "cancer" or "cancer" when used in the present description, refer to basal cell carcinoma; or melanoma, preferably advanced and/or metastatic melanoma; squamous cell carcinoma (SCC), preferably skin SCC, more preferably inoperable and/or advanced skin SCC; or head and neck squamous cell carcinoma (HNSCC), preferably advanced and/or platinum-resistant and/or immunotherapy-resistant HNSCC; or vulvar carcinoma or vulvar squamous cell carcinoma (VSCC), preferably unresectable and/or advanced VSCC, more preferably advanced and/or platinum resistant and/or immunotherapy resistant VSCC; or adenoid cystic carcinoma (ACC), preferably advanced ACC; or cutaneous T cell lymphoma, preferably advanced cutaneous T cell lymphoma or cutaneous T cell lymphoma of the mycotic fungoid subtype (CTCL-MF), more preferably CTCL-MF advanced, more preferably T cell lymphoma resistant to topical treatment or chemotherapy; or follicular lymphoma; or marginal zone lymphoma, preferably nodal marginal zone lymphoma (nMZL); or primary cutaneous anaplastic large cell lymphoma (PC-ALCL); or soft tissue sarcoma (STS); or associated with human papillomavirus (HPV) cancer.

Thus, a preferred embodiment of the invention is an isRNA for the treatment or prevention of neoplastic and/or cancerous diseases, wherein the neoplastic or cancerous disease is selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, preferably advanced cutaneous melanoma (cMEL) , skin squamous cell carcinoma (SCC), more preferably unresectable and/or advanced SCC, or cutaneous squamous cell carcinoma (cSCC), and/or head and neck squamous cell carcinoma (HNSCC), preferably advanced and/or immunotherapy-resistant, platinum-resistant HNSCC , and/or adenocystic carcinoma (ACC), preferably advanced ACC, and/or cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy.

Another preferred embodiment of the invention is isRNA, preferably as described herein, for use in the treatment and/or prevention of a tumor and/or cancer, where the tumor or cancer is selected from the group consisting of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably triggered by immunotherapy-resistant HNSCC or triggered by platinum-resistant HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy.

Thus, the most preferred embodiment of the invention is isRNA, preferably as described herein, for use in the treatment and/or prevention of a tumor and/or cancer, wherein the tumor or cancer is selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the tumor or the cancer is preferably advanced and/or resistant to standard therapy.

The next most preferred embodiment of the invention is isRNA for use in the treatment or prevention of a neoplastic and/or cancerous disease, wherein the neoplastic or cancerous disease is selected from the group consisting of advanced melanoma, preferably advanced cutaneous melanoma (cMEL), skin squamous cell carcinoma (SCC ), preferably cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), and adenoid cystic carcinoma (adenocystic carcinoma (ACC)).

An alternative preferred embodiment of the invention is an isRNA for use in the treatment or prevention of a neoplastic and/or cancerous disorder, wherein the neoplastic or cancerous disorder is selected from the group consisting of advanced cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head squamous cell carcinoma, and neck (HNSCC) and adenoid cystic carcinoma (ACC).

According to a preferred embodiment of the invention, the isRNA provided herein is for use in the treatment of advanced melanoma, preferably advanced cutaneous melanoma (cMEL) that is histologically confirmed, preferably unresectable and/or metastatic (cutaneous) melanoma. More preferably, the melanoma is resistant to standard therapy, in particular checkpoint inhibitor or immunostimulant immunotherapy, or targeted chemotherapy, or a combination thereof.

According to another embodiment of the invention, the isRNA provided herein is for use in the treatment of advanced SCC, preferably cutaneous squamous cell carcinoma (cSCC) that is histologically confirmed, preferably unresectable and/or metastatic SCC. More preferably, SCC is resistant to standard therapy, or no therapy exists for SCC.

According to a preferred embodiment of the invention, the isRNA provided herein is for use in the treatment of limitedly advanced or advanced HNSCC that is histologically confirmed, preferably unresectable and/or recurrent and/or metastatic HNSCC. More preferably, the HNSCC is resistant to standard therapies, in particular platinum or radiotherapy, or checkpoint inhibitor or immunostimulant immunotherapy, or a combination of any of these.

According to another preferred embodiment of the invention, the isRNA provided herein is for use in the treatment of adenocystic carcinoma (ACC) that is histologically confirmed, preferably unresectable and/or recurrent and/or metastatic adenocystic carcinoma (ACC). More preferably, the ACC is resistant to standard therapy, in particular platinum-based therapy or radiation therapy, or immunotherapy based on the use of a checkpoint inhibitor or immunostimulant, or a combination of any of them.

According to another embodiment of the invention, the isRNA provided herein is for use in the treatment of cutaneous T-cell lymphoma that is histologically confirmed, preferably unresectable and/or recurrent and/or metastatic cutaneous T-cell lymphoma. More preferably, the cutaneous T-cell lymphoma is resistant to standard therapy, in particular platinum or radiation therapy, or checkpoint inhibitor or immune stimulant immunotherapy, or a combination of any of these.

In another embodiment, the isRNA provided herein is for use in the treatment of vulvar squamous cell carcinoma (VSCC) that is histologically confirmed, preferably inoperable and/or recurrent and/or metastatic VSCC. More preferably, the VSCC is resistant to standard therapies, in particular platinum or radiotherapy, or checkpoint inhibitor or immunostimulant immunotherapy, or a combination of any of these.

In a preferred embodiment of the invention, the isRNA for use in the treatment or prevention of neoplastic and/or cancerous diseases, preferably as described herein, elicits an innate immune response that can support an adaptive immune response.

isRNA for the treatment or prevention of a tumor and/or cancer described herein may preferably be any (double-stranded or single-stranded) RNA, such as the coding RNA described herein. In a preferred embodiment of the invention isRNA, intended for the treatment or prevention of tumor and/or cancer described in the present description, is a non-coding RNA. In this context, the term "non-coding" refers to the fact that the isRNA preferably does not encode a peptide or protein, or that the isRNA preferably does not contain a coding sequence, preferably specified in the present description.

In some embodiments, the isRNA for the treatment or prevention of a tumor and/or cancer described herein is single-stranded, double-stranded or partially double-stranded RNA, more preferably single-stranded RNA, and/or circular or linear RNA, more preferably linear RNA. More preferably, the isRNA may be a (linear) single stranded RNA. Even more preferably, the isRNA may be a (long) (linear) (single stranded) non-coding RNA. In this context, it is particularly preferred that the isRNA carries a triphosphate at its 5' end, which is generally the case for in vitro transcribed RNA. isRNA can also be in the form of a short RNA oligonucleotide as described herein.

isRNA intended for the treatment or prevention of the tumor and/or cancer described in the present description, you can also choose from any class of RNA molecules present in nature or obtained by synthesis, and which can induce an innate immune response and can support an adaptive immune response, antigen induced. In this context, the immune response can be generated in a variety of ways. An essential factor for obtaining an appropriate (adaptive) immune response is the stimulation of various T-cell subpopulations. T lymphocytes are generally divided into two subpopulations, type 1 helper T cells (Th1) and type 2 helper T cells (Th2), through which the immune system is able to destroy intracellular (Th1) and extracellular (Th2) pathogens (eg, antigens). The two populations of T helper cells differ in the pattern of effector proteins (cytokines) they produce. Thus, Th1 cells stimulate the cellular immune response by activating macrophages and cytotoxic T cells. On the other hand, Th2 cells initiate the humoral immune response by stimulating the conversion of B cells to plasma cells and by generating antibodies (eg against antigens). Thus, the Th1 cell/Th2 cell ratio is essential for inducing and maintaining an adaptive immune response. In the context of the present invention, the ratio of Th1 cell/Th2 cell in the (adaptive) immune response is preferably shifted towards a cellular response (Th1 response) and thereby a cellular immune response is induced. In one example, the innate immune system, which can support an adaptive immune response, can be activated by Toll-like receptor (TLR) ligands. TLRs are a family of highly conserved pattern recognition receptor (PRR) polypeptides that recognize pathogen-associated molecular patterns (PAMPs) and play a critical role in mammalian innate immunity. Currently, at least 13 members of the family have been identified, designated TLR1-TLR13 (Toll-like receptors: TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, or TLR13). In addition, a number of specific TLR ligands have been identified. For example, unmethylated bacterial DNA and its synthetic analogues (CpG-DNA) have been found to be TLR9 ligands (Hemmi H. et al., Nature 408, 2000, pp. 740-745; Bauer S. et al., Proc NatlAcadSci USA 98 , 2001, pp. 9237-9242). In addition, data have been published that ligands for certain TLRs include certain nucleic acid molecules and that certain types of RNA are immunostimulatory and act in a sequence-independent or sequence-dependent manner, wherein said various immunostimulatory RNAs can, for example, stimulate TLR3 , TLR7 or TLR8 or intracellular receptors such as RIG-I, MDA-5, etc. For example, Lipford et al found that certain G,U-containing oligoribonucleotides are immunostimulatory in their action through TLR7 and TLR8 (see WO 03/086280). The immunostimulatory G,U-containing oligoribonucleotides described by Lipford et al can probably be made using RNA sources including ribosomal RNA, transfer RNA, messenger RNA and viral RNA.

Preferably, an isRNA for the treatment or prevention of a tumor and/or cancer described herein may contain any RNA sequence known to be immunostimulatory, including (but not limited to) RNA sequences representing and/ or encoding TLR ligands, preferably selected from members of the human TLR1-TLR10 family or members of the murine TLR1-TLR13 family, more preferably selected from members of the (human) TLR1-TLR10 family, even more preferably TLR7 and TLR8, ligands for intracellular RNA receptors (such like RIG-I or MDA-5, etc.) (see e.g. Meylan, E., Tschopp, J., Toll-like receptors and RNA helicases: two parallel ways to trigger antiviral responses. Mol. Cell 22 , 2006, pp. 561-569), or any other immunostimulatory RNA sequences. In addition, (classes) of immunostimulatory RNA molecules intended for the treatment or prevention of tumor and/or cancer described in the present description may include any other RNA with the ability to induce an immune response. Said isRNA for the treatment or prevention of the tumor and/or cancer described herein may include, but is not limited to, ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), and viral RNA (vRNA). In preferred embodiments, the isRNA may comprise 1000 to 5000, 500 to 5000, 5 to 5000, or 5 to 1000, 5 to 500, 5 to 250, 5 to 100, 5 to 50, or 5 up to 30 nucleotides.

According to the most preferred embodiment of the invention, the isRNA intended for the treatment or prevention of the neoplastic and/or cancerous disease specified in the present description consists of or contains a nucleic acid of the following formula (I) or (II):

wherein:

G is guanosine (guanine), uridine (uracil), or an analogue of guanosine (guanine) or uridine (uracil);

X is guanosine (guanine), (uridine) uracil, adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of the above nucleotides (nucleosides);

l denotes an integer from 1 to 40,

where,

when l=1, then G denotes guanosine (guanine) or its analogue,

when l>1, then at least 50% of the nucleotides (nucleosides) are guanosine (guanine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X denotes uridine (uracil) or its analogue,

when m>3, then at least 3 consecutive nucleotides are present, representing uridine (uracil) or an analogue of uridine (uracil);

n is an integer from 1 to 40,

where,

when n=1, then G denotes guanosine (guanine) or its analogue,

when n>1, then at least 50% of the nucleotides (nucleosides) are guanosine (guanine) or its analogue;

where:

C is cytidine (cytosine), uridine (uracil), or an analogue of cytidine (cytosine) or uridine (uracil);

X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of the above nucleotides (nucleosides);

l denotes an integer from 1 to 40,

where,

when l=1, then C denotes cytidine (cytosine) or its analogue,

when l>1, then at least 50% of the nucleotides (nucleosides) are cytidine (cytosine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X denotes uridine (uracil) or its analogue,

when m>3, then at least 3 consecutive nucleotides are present, representing uridine (uracil) or an analogue of uridine (uracil);

n is an integer from 1 to 40,

where,

when n=1, then C denotes cytidine (cytosine) or its analogue,

when n>1, then at least 50% of the nucleotides (nucleosides) are cytidine (cytosine) or its analogue.

Nucleic acids of formula (I) or (II) that can be used as isRNAs can be relatively short nucleic acid molecules, typically consisting of about 5-100 (but in particular embodiments of the invention, they can consist of more than 100 nucleotides, e.g. up to 200 nucleotides), of 5-90 or of 5-80 nucleotides, may preferably be about 5 to 70 in length, more preferably about 8 to 60 in length, and more preferably in about 15 to 60 nucleotides in length , more preferably 20 to 60, most preferably 30 to 60 nucleotides. If the nucleic acid of the invention is a nucleic acid included in the complex as a cargo molecule, has a maximum length, for example, 100 nucleotides, then, as a rule, m≤98. The number of nucleotides G in the nucleic acid of formula (I) is determined by the value of l or n. The symbol l and n each independently of each other denotes an integer from 1 to 40, while when l or n=1, then G denotes guanosine or its analogue, and when l or n>1, then at least 50% of the nucleotides are guanosine or its analogue. For example (but not limited to), when l or n=4, then G _l or G _n may be, for example, GUGU, GGUU, UGUG, UUGG, GUUG, GGGU, GGUG, GUGG, UGGG or GGGG, etc. d.; when l or n=5, then G _l or G _n may be, for example, GGGUU, GGUGU, GUGGU, UGGGU, UGGUG, UGUGG, UUGGG, GUGUG, GGGGU, GGGUG, GGUGG, GUGGG, UGGGG or GGGGG, etc. ; etc. The nucleotide adjacent to X _m in the nucleic acid of formula (I) according to the invention is preferably not uracil. Similarly, the number of nucleotides C in the nucleic acid of formula (II) according to the invention is determined by the value of l or n. The symbol l and n each independently of one another denotes an integer from 1 to 40, while when l or n=1, then C denotes cytidine or its analogue, and when l or n>1, then at least 50% of the nucleotides are cytidine or its analogue. For example (but not limited to), when l or n=4, then C _l or C _n may be, for example, CUCU, CCUU, UCUC, UUCC, CUUC, CCCU, CCUC, CUCC, UCCC, or CCCC, etc. d.; when l or n=5, then C _l or C _n may be, for example, CCCUU, CCUCU, CUCCU, UCCCU, UCCUC, UCUCC, UUCCC, CUCUC, CCCCU, CCCUC, CCUCC, CUCCC, UCCCC or CCCCC, etc. ; etc. The nucleotide adjacent to X _m in the nucleic acid of formula (II) according to the invention is preferably not uracil. Preferably in formula (I), when l or n>1, then at least 60%, 70%, 80%, 90% or even 100% of the nucleotides are guanosine or its analogue, as indicated above. The remaining nucleotides required until 100% (when the guanosine constituents account for less than 100% of all nucleotides) in the flanking G _l and/or G _n sequences are uridine or an analog thereof, as above. It is also preferred that l and n are each independently an integer from 2 to 30, more preferably an integer from 2 to 20, and even more preferably an integer from 2 to 15. The lower limit of l or n can be varied as needed, and represents is at least 1, preferably at least 2, more preferably at least 3, 4, 5, 6, 7, 8, 9 or 10. The foregoing applies accordingly to formula (II).

According to a particularly preferred embodiment of the invention, a nucleic acid having any of the above formulas (I) or (II), which can be used as an isRNA in the context of the present invention, can be selected from a nucleotide sequence that consists of or contains any of the following SEQ sequences ID NO: 471-554 or from sequences that are at least 60%, 70%, 80%, 90% or even 95% identical to any of these sequences. In some embodiments, the isRNA is selected from a nucleotide sequence that consists of or contains any of the nucleotide sequences of SEQ ID NO: 471-554, or a fragment or variant of any of these sequences.

According to another preferred embodiment of the invention, the isRNA intended for the treatment or prevention of the neoplastic and/or cancerous disease specified in the present description consists of or contains a nucleic acid of formula (III) or (IV):

wherein:

G is guanosine (guanine), uridine (uracil) or an analogue of guanosine (guanine) or uridine (uracil), preferably guanosine (guanine) or an analogue thereof;

X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (pitosine) or analogs of said nucleotides (nucleosides), preferably uridine (uracil) or an analog thereof;

N denotes a nucleotide sequence consisting of about 4-50, preferably about 4-40, more preferably about 4-30 or 4-20 nucleic acids, with each N independently selected from guanosine (guanine), uridine ( uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of these nucleotides (nucleosides);

a is an integer from 1 to 20, preferably from 1 to 15, most preferably from 1 to 10;

l denotes an integer from 1 to 40,

where,

when l=1, then G denotes guanosine (guanine) or its analogue,

when l>1, then at least 50% of these nucleotides (nucleosides) are guanosine (guanine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X is uridine (uracil) or an analogue thereof, and

when m>3, then there are at least 3 consecutive nucleotides representing uridine (uracil) or an analogue of uridine (uracil);

n is an integer from 1 to 40,

where,

when n=1, then G denotes guanosine (guanine) or its analogue,

when n>1, then at least 50% of these nucleotides (nucleosides) are guanosine (guanine) or its analogue;

u, v can independently denote an integer from 0 to 50,

preferably, when u=0, then v≥1 or

when v=0, then u≥1;

wherein the nucleic acid molecule of formula (III) is at least 50 nucleotides, preferably at least 100 nucleotides, more preferably at least 150 nucleotides, even more preferably at least 200 nucleotides, and most preferably at least 250 nucleotides.

wherein:

C is cytidine (cytosine), uridine (uracil) or an analog of cytidine (cytosine) or uridine (uracil), preferably cytidine (cytosine) or an analog thereof;

X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analog of the above nucleotides (nucleosides), preferably uridine (uracil) or an analog thereof;

N denotes a nucleotide sequence consisting of about 4-50, preferably about 4-40, more preferably about 4-30 or 4-20 nucleic acids, with N each independently selected from guanosine (guanine), uridine ( uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of these nucleotides (nucleosides);

a is an integer from 1 to 20, preferably from 1 to 15, most preferably from 1 to 10;

l denotes an integer from 1 to 40,

where,

when l=1, then C denotes cytidine (cytosine) or its analogue,

when l>1, then at least 50% of these nucleotides (nucleosides) are cytidine (cytosine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X denotes uridine (uracil) or its analogue,

when m>3, then at least 3 consecutive uridine (uracil) or uridine analogs (uracil) are present;

n is an integer from 1 to 40,

where,

when n=1, then C denotes cytidine (cytosine) or its analogue,

when n>1, then at least 50% of these nucleotides (nucleosides) are cytidine (cytosine) or its analogue;

u, v can independently denote an integer from 0 to 50,

preferably, when u=0, then v≥1 or

when v=0, then u≥1;

wherein the nucleic acid molecule of formula (IV) consists of at least 50 nucleotides, preferably at least 100 nucleotides, more preferably at least 150 nucleotides, even more preferably at least 200 nucleotides, and most preferably at least 250 nucleotides.

In formula (IV), any of the definitions given above for the elements N (i.e. N _u and N _v ) and X (X _m ), especially for the above core structure, and also for the integers a, l, m , n, u and v, is also applicable to the elements of formula (IV), respectively, while in the formula (IV) the core structure is described by the formula C _l X _m C _n . The definition of boundary elements N _u and N _v is identical to the definitions given above for N _u and N _v .

According to the most preferred embodiment of the invention, the nucleic acid molecule, preferably the immunostimulatory RNA of formula (III), can be selected from any of the sequences of SEQ ID NO: 555-563 or from a sequence identical to at least 60%, 70%, 80%, 90 % or even 95% of any of the indicated sequences.

Preferably isRNA, which is used according to the present description, contains or consists of a nucleotide sequence corresponding to any of SEQ ID NO: 555-563, or a fragment or variant of any of these sequences.

In this context, immunostimulatory RNAs having one of SEQ ID NOs: 433-437, 1014-1016, 1055, or 1056 are particularly preferred. SEQ ID NO: 433-437, 1014-1016, 1055 or 1056, or a fragment or variant of one of the indicated sequences. Even more preferably, the immunostimulatory RNA contains or consists of a nucleotide sequence that is at least 60%, 70%, 80%, 90%, or even 95% identical to one of the nucleotide sequences of SEQ ID NO: 433-437, 1014-1016, 1055 or 1056.

According to the most preferred embodiment of the invention immunostimulatory RNA, which is used according to the present description, contains or consists of a nucleotide sequence corresponding to one of SEQ ID NO: 433; 434 or 1014-1016, or a fragment or variant of one of these sequences. Even more preferably, the immunostimulatory RNA contains or consists of a nucleotide sequence that is at least 60%, 70%, 80%, 90% or even 95% identical to one of the nucleotide sequences of SEQ ID NO: 433, 434 or 1014-1016.

According to another most preferred embodiment of the invention, the nucleic acid molecule of formula (IV) can be selected from any of the sequences of SEQ ID NO: 433; 434 or 1014-1016, or from a sequence that is at least 60%, 70%, 80%, 90%, or even 95% identical to any of these sequences. Preferably isRNA, which is used according to the present description, contains or consists of a nucleotide sequence corresponding to SEQ ID NO: 433; 434 or 1014-1016, or a fragment or variant of one of these sequences.

All modifications mentioned in the context of coding RNA can also be applied to non-coding RNA, if this is acceptable.

isRNA for use as described herein can be used as naked RNA without association with any additional excipient, carrier, transfection or complexing agent.

In a preferred embodiment of the invention, an isRNA intended for the treatment or prevention of a tumor and/or cancer described herein is formulated in combination with additional compounds to increase the transfection efficiency and/or immunostimulatory properties of the isRNA. These compounds in the context of the present description are called carriers, fillers or agents for transfection or complexation. Preferably, the isRNA for the treatment or prevention of a tumor and/or cancer as defined herein is complexed with a cationic or polycationic compound, preferably a cationic or polycationic polymer, a cationic or polycationic peptide or protein, such as a protamine, a cationic or polycationic a polysaccharide and/or a cationic or polycationic lipid.

According to a specific preferred embodiment of the invention, an isRNA intended for the treatment or prevention of a neoplastic and/or cancerous disease specified in the present description is complexed with a cationic or polycationic compound, where the cationic or polycationic compound is a polymeric carrier.

In the context of the present invention, said cationic or polycationic polymers, cationic or polycationic peptides or proteins, cationic or polycationic polysaccharides, cationic or polycationic lipids or polymeric carriers can be used as carriers, excipients, agents for transfection or complexation of nucleic acids, in particular isRNA, intended for the application specified in the present description. Thus, in a further embodiment of the invention, it is preferred that the isRNA be associated with or complexed with a cationic or polycationic compound or polymeric carrier, optionally in a weight ratio of RNA and cationic or polycationic compound and/or polymeric carrier selected from the range of about 6:1 to about 0.25:1 (w/w), more preferably from about 5:1 to about 0.5:1 (w/w), even more preferably from about 4:1 to about 1:1 (w/w), or about 3:1 to about 1:1 (w/w), and most preferably in a ratio of about 3:1 to about 2:1 (w/w). /wt.); or optionally in a nitrogen/phosphate ratio of the RNA and the cationic or polycationic compound and/or polymeric carrier in the range of at least about 0.1-10, preferably in the range of about. 0.3-4 or 0.3-1 and most preferably in the range of about 0.5-1 or 0.7-1, and even most preferably in the range of about 0.3-0.9 or 0.5-0.9.

The ratio of isRNA intended for the treatment or prevention of tumor and/or cancer described in the present description, and cationic or polycationic compounds can be calculated based on the ratio of nitrogen/phosphate (N/P-ratio) of all these components. In the context of the present invention, the N/P ratio is preferably in the range of about 0.01-4, 0.01-2, 0.1-2 or 0.1-1.5 regarding the ratio of nucleic acids: cationic or polycationic peptide included in the vaccine of the present invention, and most preferably in the range of about 0.1-1. Alternatively, the N/P ratio of isRNA to cationic or polycationic compound, preferably a cationic or polycationic peptide or protein, is in the range of about 0.1-10, including a range of about 0.3-4, about 0.5 -2, about 0.7-2 and about 0.7-1.5. This N/P ratio is preferably created to obtain a high capacity for transfection in vivo and transport into and across cell membranes. Preferably, for this purpose, the basis of the cationic or polycationic compounds and/or polymeric carriers used according to the present description, are peptide sequences.

полипептиды, обладающие способностью проникать в клетку пептиды (СРР), такие как ВИЧ-связывающие пептиды, Tat ВИЧ-1 (ВИЧ), происходящие из Tat пептиды, пенетратин, полученные из VP22 пептиды или аналоги, VP22 HSV (вирус герпеса простого), MAP, KALA или домены трансдукции белков (PTD), РрТ620, богатые пролином пептиды, богатые аргинином пептиды, богатые лизином пептиды, MPG-пептид(ы), Pep-1, L-олигомеры, пептид(ы) кальцитонина, происходящие из Antennapedia пептиды (прежде всего, происходящие из Drosophila antennapedia), pAntp, pIsl, FGF, лактоферрин, транспортан, буфорин-2, Вас715-24, SynB, SynB(1), pVEC, происходящие из hCT пептиды, SAP или гистоны. В этом контексте наиболее предпочтительным является протамин.Cationic or polycationic compounds which are the most preferred agents in this context include protamine, nucleolin, spermine or spermidine or other cationic peptides or proteins such as poly-L-lysine (PLL), polyarginine,

cell-penetrating peptides (CPPs) such as HIV-binding peptides, HIV-1 Tat (HIV), Tat-derived peptides, penetratin, VP22-derived peptides or analogs, VP22 HSV (herpes simplex virus), MAP , KALA or protein transduction domains (PTDs), PpT620, proline-rich peptides, arginine-rich peptides, lysine-rich peptides, MPG peptide(s), Pep-1, L-oligomers, calcitonin peptide(s), Antennapedia-derived peptides ( especially those derived from Drosophila antennapedia), pAntp, pIsl, FGF, lactoferrin, transportan, buforin-2, Bac715-24, SynB, SynB(1), pVEC, hCT-derived peptides, SAP or histones. In this context, protamine is most preferred.

In addition, preferred cationic or polycationic proteins or peptides may be selected from the following proteins or peptides which have the general formula (V) below:

wherein l+m+n+o+x are 8-15 and l, m, n or o can each independently be any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provided that the total content of Arg, Lys, His and Orn is at least 50% of the total amino acid content of the oligopeptide; and Xaa can be any amino acid selected from native (ie, naturally occurring) or non-naturally occurring amino acids with the exception of Arg, Lys, His, or Orn; and x may be any number selected from 0, 1, 2, 3, or 4, provided that the total Xaa content does not exceed 50% of the total amino acid content of the oligopeptide. In this context, the most preferred cationic peptides are, for example, Arg ₇ , Arg ₈ , Arg ₉ , H ₃ R ₉ , R ₉ H ₃ , H ₃ R ₉ H ₃ , YSSR ₉ SSY, (RKH) ₄ , Y(RKH) _2R etc. In this context, the contents of WO 2009/030481 are incorporated herein by reference.

The polymeric carrier used according to the invention may be a polymeric carrier formed by connecting cationic components with disulfide bridges.

According to another particularly preferred embodiment of the invention, the cationic or polycationic peptides or proteins of the polymeric carrier having the empirical general formula (V) above and which contain or are further modified so as to contain at least one -SH group can be selected from (but not limited to), subgroups of general formulas Arg ₇ (also referred to as R ₇ ), Arg ₉ (also referred to as R ₉ ), Arg ₁₂ (also referred to as R ₁₂ ).

According to another particularly preferred embodiment of the invention, cationic or polycationic peptides or polymeric carrier proteins, when they are described by the formula {(Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x } (formula (V )) above, and which contain or are further modified to contain at least one -SH group, may be selected from, but not limited to, subformula (Va):

in which (Arg) _l ; (Lys) _m ; (His) _n ; (Orn) _o and x have the meanings specified in the present description, Xaa' denotes any amino acid selected from native (i.e., naturally occurring) or non-naturally occurring amino acids other than Arg, Lys, His, Orn, or Cys, and y is any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-90, provided that the total content of Arg (arginine), Lys (lysine), His (histidine) and Orn (ornithine) is at least 10% of all amino acids of the oligopeptide.

представленную выше, содержит или модифицирован так, что содержит по меньшей мере один остаток цистеина в качестве -SH-группы, указанной выше, в результате чего указанный катионный или поликатионный пептид в качестве катионного компонента несет по меньшей мере один остаток цистеина, который может образовывать дисульфидную связь с другими компонентами полимерного носителя.This embodiment of the invention can be applied to situations where a cationic or polycationic peptide or polymeric carrier protein, for example, falling within the empirical formula

above, contains or is modified so that it contains at least one cysteine residue as the -SH group indicated above, whereby the specified cationic or polycationic peptide, as a cationic component, carries at least one cysteine residue, which can form a disulfide connection with other components of the polymer carrier.

Examples thereof may include any of the following sequences: Cys(Arg ₇ ) (SEQ ID NO: 581), Cys(Arg ₈ ) (SEQ ID NO: 582), Cys(Arg ₉ ) (SEQ ID NO: 583), Cys( Arg ₁₀ ) (SEQ ID NO: 584), Cys(Arg ₁₁ ) (SEQ ID NO: 585), Cys(Arg ₁₂ ) (SEQ ID NO: 580) (SEQ ID NO: 571), Cys(Arg ₁₃ ) ( SEQ ID NO: 586), Cys(Arg ₁₄ ) (SEQ ID NO: 587), Cys(Arg ₁₅ ) (SEQ ID NO: 588), Cys(Arg ₁₆ ) (SEQ ID NO: 589), Cys(Arg ₁₇ ) (SEQ ID NO: 590), Cys(Arg ₁₈ ) (SEQ ID NO: 591), Cys(Arg ₁₉ ) (SEQ ID NO: 592), Cys(Arg ₂₀ ) (SEQ ID NO: 593).

представленной выше, можно выбирать из подформулы (Vb) (но, не ограничиваясь только ею):According to another most preferred embodiment of the invention, the cationic or polycationic peptides or polymeric carrier proteins, when described by the formula

above can be selected from (but not limited to) sub-formula (Vb):

определена в настоящем описании и образует ядро аминокислотной последовательности, соответствующей (полуэмпирической) формуле (V), и в которой Cys₁ и Cys₂ представляют собой остатки цистеина, расположенные проксимально или терминально относительно (Arg)_l;(Lys)_m;(His)_n;(Orn)_o;(Xaa)_x. Примеры могут содержать любую из вышеуказанных последовательностей, фланкированных двумя остатками Cys, и имеют следующие последовательности:in which the empirical formula

is defined herein and forms the core of the amino acid sequence corresponding to (semi-empirical) formula (V), and in which Cys ₁ and Cys ₂ are cysteine residues located proximal or terminal relative to (Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x . Examples may contain any of the above sequences flanked by two Cys residues and have the following sequences:

Cys(Arg ₇ )Cys (SEQ ID NO: 566), Cys(Arg ₈ )Cys (SEQ ID NO: 567), Cys(Arg ₉ )Cys (SEQ ID NO: 568), Cys(Arg ₁₀ )Cys (SEQ ID NO: 569, Cys(Arg ₁₁ )Cys (SEQ ID NO: 570), Cys(Arg ₁₂ )Cys (SEQ ID NO: 579), Cys(Arg ₁₃ )Cys (SEQ ID NO: 571), Cys(Arg ₁₄ )Cys (SEQ ID NO: 572), Cys(Arg ₁₅ )Cys (SEQ ID NO: 573), Cys(Arg ₁₆ )Cys (SEQ ID NO: 574), Cys(Arg ₁₇ )Cys (SEQ ID NO: 575), Cys(Arg ₁₈ )Cys (SEQ ID NO: 576), Cys(Arg ₁₉ )Cys (SEQ ID NO: 577), Cys(Arg ₂₀ )Cys (SEQ ID NO: 578).

, которая представлена выше, модифицирован с помощью по меньшей мере двух остатков цистеина в качестве -SH-групп, как указано выше, в результате чего указанный катионный или поликатионный пептид, который входит в предлагаемый в изобретении комплекс, содержащий полимерный носитель и карго-молекулу, в качестве катионного компонента, содержит по меньшей мере два остатка (терминальных) цистеина, которые могут образовывать дисульфидную связь с другими компонентами полимерного носителя.This embodiment of the invention can be applied to situations where a cationic or polycationic peptide or polymeric carrier protein, such as those described by empirical formula

, which is presented above, is modified with at least two cysteine residues as -SH groups, as indicated above, as a result of which the specified cationic or polycationic peptide, which is included in the inventive complex containing a polymer carrier and a cargo molecule, as a cationic component, contains at least two (terminal) cysteine residues, which can form a disulfide bond with other components of the polymer carrier.

In a preferred embodiment, the polymeric carrier is formed from, contains or consists of a CysArg ₁₂ Cys peptide (CRRRRRRRRRRRRC) (SEQ ID NO: 579) or CysArg ₁₂ (CRRRRRRRRRRRR) (SEQ ID NO: 580). In some embodiments, the polymeric carrier is formed from, contains, or consists of a (R12C)-(R12C) dimer (Arg ₁₂ Cys-CysArg ₁₂ dimer), wherein the individual peptide monomers in the dimer (CR12 (CysArg ₁₂ ; SEQ ID NO: 580)) connected via -SH groups. In another preferred embodiment of the invention, the polymeric carrier is formed from, contains or consists of a (WR12C)-(WR12C) dimer (TrpArg ₁₂ Cys-CysArg ₁₂ Trp dimer) wherein the individual peptide monomers in the dimer (WR12C (TrpArg ₁₂ Cys; SEQ ID NO: 1017)), connected via -SH groups. According to some embodiments of the invention, the polymeric carrier is formed from, contains or consists of a trimer (CR12)-(CR12C)-(CR12) (trimer Arg ₁₂ Cys-CysArg ₁₂ Cys-CysArg ₁₂ ), where the individual peptide monomers in the dimer (CR12C (CysArg ₁₂ Cys; SEQ ID NO: 579) and CR12 (CysArg ₁₂ ; SEQ ID NO: 580)) are connected via -SH groups. In specific embodiments, the polymer carrier consists of a (R12C)-(R12C) dimer, (WR12C)-(WR12C) dimer, or (CR12)-(CR12C)-(CR12) trimer, where the individual cationic peptides (elements) in the dimer ( eg (WR12C)) or trimer (eg (CR12)) are connected via -SH groups of their cysteine residues.

According to a second alternative, the at least one cationic (or polycationic) polymeric carrier component may be selected, for example, from any (non-peptide) cationic or polycationic polymer suitable for the purpose, provided that the (non-peptide) cationic or polycationic polymer contains or modified so that it contains at least one -SH-group, which is suitable for the formation of a disulfide bond connecting the cationic or polycationic polymer with another component of the polymer carrier specified in the present description. Thus, according to the present invention, the polymer carrier may contain the same or different cationic or polycationic polymers.

In the particular case where the cationic carrier polymer component comprises a (non-peptide) cationic or polycationic polymer, the cationic properties of the (non-peptide) cationic or polycationic polymer may be determined by the level of cationic charges compared to the total charge level of the cationic polymer components. Preferably, the level of cationic charges in the cationic polymer at the (physiological) pH value specified in the present description is at least 10%, 20% or 30%, preferably at least 40%, more preferably at least 50%, 60% or 70%, but also preferably at least 80%, 90% or even 95%, 96%, 97%, 98%, 99% or 100%, most preferably at least 30%, 40%, 50%, 60% , 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%, or may be in the range of about 10% to 90%, more preferably in the range of about 30% to 100%, even more preferably in the range of from about 50% to 100%, such as 50%, 60%, 70%, 80%, 90%, or 100%, or in the range of any two of the above values, provided that the level of all charges, for example, positive and negative charges at the (physiological) pH value specified in the present description, in the entire cationic polymer is 100%.

Preferably, the (non-peptide) cationic component of the polymeric carrier is a cationic or polycationic polymer, typically having a molecular weight of from about 0.1 or 0.5 kDa to about 100 kDa, preferably from about 1 to about 75 kDa, more preferably from about 5 kDa. up to about 50 kDa, even more preferably from about 5 to about 30 kDa, or a molecular weight from about 10 to about 50 kDa, even more preferably from about 10 to about 30 kDa. In addition, the (non-peptide) cationic or polycationic polymer typically bears at least one -SH group which can form a disulfide bond when condensed with either any of the other cationic components or other components of the polymeric carrier referred to herein.

In the above context, the (non-peptide) cationic component of the polymer carrier may be selected from the group consisting of acrylates, modified acrylates such as pDMAEMA (poly(dimethylaminoethyl methyl acrylate)), chitosans, aziridines, or 2-ethyl-2-oxazoline (forming oligoethyleneimines or modified oligoethyleneimines), polymers obtained by reacting bisacrylates with amines, which form oligo-beta-amino esters or polyamidoamines, or other polymers such as polyesters, polycarbonates, etc. Each molecule of said (non-peptide) cationic or polycationic polymers typically carries at least one -SH group, while at least one -SH group can be introduced into the (non-peptide) cationic or polycationic polymer through chemical modifications, for example, using iminothiolane, 3-thiopropionic acid, or introduce -SH-containing amino acids such as cysteine, or any other (modified) amino acid. Said -SH groups are preferably those already described above.

The cationic components crosslinked by disulfide bonds may be the same or may be different from each other. The polymeric carrier may also contain additional components. In addition, it is particularly preferred that the polymeric carrier used according to the present invention contains mixtures of cationic peptides, proteins or polymers, and optionally other components referred to in the present description, which are cross-linked with disulfide bonds, as indicated in the present description. In this context, the description of WO 2012/013326 is incorporated herein by reference.

In this context, the cationic components that form the backbone of the polymeric carrier by cross-linking with a disulfide bond are generally selected from any suitable cationic or polycationic peptide, protein or polymer suitable for this purpose, in particular any cationic or polycationic peptide, protein or a polymer that has the ability to form a complex with the isRNA intended for the use specified in the present description, and thereby preferentially condenses the isRNA. The cationic or polycationic peptide, protein or polymer is preferably a linear molecule, however branched cationic or polycationic peptides, proteins or polymers can also be used.

Each disulfide-crosslinked cationic or polycationic protein, peptide or carrier polymer polymer that can be used to form the isRNA complex for use herein contains at least one -SH group, most preferably at least one cysteine a residue or any other chemical group bearing a -SH group that can form a disulfide bond when condensed with at least one other cationic or polycationic protein, peptide or polymer as a cationic component of the polymer carrier referred to herein.

As indicated above, the polymeric carrier that can be used to produce the isRNA complex for the use described herein can be formed from disulfide crosslinked cationic (or polycationic) components.

A complex containing a nucleic acid, such as an isRNA, for the use described herein, which forms a complex with said polymeric carriers, is also referred to as "carrier-polymer complexes".

In this context, it is particularly preferred that the isRNA intended for use in the treatment or prevention of a neoplastic and/or cancerous disease as defined herein is complexed with a polymeric carrier as defined above. Preferably isRNA (for example, containing an RNA sequence having one of formulas I-IV), more preferably containing an RNA sequence indicated by one of SEQ ID NO: 433-437, 1014-1016, or a fragment or variant of one of these sequences, most preferably containing the RNA sequence specified in one of SEQ ID NOs: 433, 434 or 1014-1016, or a fragment or variant of one of these sequences, is complexed with a polymeric carrier containing or formed by cross-linked via a disulfide bond peptides of formulas V, Va or Vb, preferably a polymeric support formed by Cys(Arg ₁₂ )Cys or Cys(Arg ₁₂ ). This particularly preferred variant is also referred to in the context of the present description as "RNAdjuvant".

In another specific embodiment of the invention, the polymeric carrier that can be used to obtain a complex with an isRNA intended for use in the treatment or prevention of a tumor and/or cancer described in the present description can be selected from a polymeric carrier molecule of general formula (VI):

wherein

P ¹ and P ³ are different or identical to each other and represent a linear or branched hydrophilic polymer chain, each P ¹ and P ³ carries at least one -SH-group capable of forming a disulfide bond when condensed with the P ² component, or alternatively to this with (AA) (amino acid component), (AA) _x or [(AA) _x ] _z if these components are used as a linker between P ¹ and P ² or P ³ and P ² ) and / or with other components ( for example, (AA), (AA) _x , [(AA) _x ] _z or L), a linear or branched hydrophilic polymer chain, selected independently from polyethylene glycol (PEG), poly-N-(2-hydroxypropyl) methacrylamide , poly-2-(methacryloyloxy)ethylphosphorylcholines, poly(hydroxyalkyl-L-asparagine), poly(2-(methacryloyloxy)ethylphosphorylcholine), hydroxyethyl starch or poly(hydroxyalkyd-L-glutamine), where the hydrophilic polymer chain has a molecular weight of from about 1 up to about 100 kDa, preferably from about 2 to about 25 kDa and or more preferably from about 2 to about 10 kDa, for example, from about 5 to about 25 kDa or from 5 to about 10 kDa;

P ² is a cationic or polycationic peptide or protein, for example as defined above for a polymeric carrier formed by cross-linked disulfide-crosslinked cationic components, and is preferably about 3 to about 100 amino acids long, more preferably about 3 to about 50 amino acids long, still more preferably about 3 to about 25 amino acids in length, e.g., about 3 to 10, 5 to 15, 10 to 20, or 15 to 25 amino acids in length, more preferably about 5 to about 20 amino acids in length, and more more preferably having a length of from about 10 to about 20 amino acids; or

denotes a cationic or polycationic polymer, for example, as defined above for a polymer carrier formed by cross-linked disulfides of cationic components, typically having a molecular weight of from about 0.5 to about 30 kDa, including a molecular weight of from about 1 to about 20 kDa, even more preferably from about 1.5 to about 10 kDa, or having a molecular weight from about 0.5 to about 100 kDa, including a molecular weight from about 10 to about 50 kDa, even more preferably from about 10 to about 30 kDa;

each P ² carries at least two —SH-groups capable of forming a disulfide bond when condensed with other components of P ² or with component (s) P ¹ and / or P ³ , or alternatively with other components (for example, (AA) , (AA) _x or [(AA) _x ] _z );

-SS- denotes a (reversible) disulfide bond (brackets omitted for readability), in which S is preferably sulfur or a bearing -SH group which forms a (reversible) disulfide bond. The disulfide bond (reversible) is preferably obtained by condensation of -SH groups of either the components P ¹ and P ² or P ² and P ² or P ² and P ³ , or optionally other components specified in the present description (for example, L, ( AA), (AA) _x , [(AA) _x ] _z etc.); -SH-group may be part of the structure of these components or may be added by modification, as indicated below;

L is an optional ligand which may or may not be present and can be selected independently from RGD, transferrin, folate, signal peptide or signal sequence, localization signal or sequence, nuclear localization signal or sequence (NLS), antibody penetrating into peptide cell (eg, TAT or KALA), receptor ligand (eg, cytokines, hormones, growth factors, etc.), small molecules (eg, carbohydrates such as mannose or galactose, or synthetic ligands), small molecule agonists, inhibitors, or antagonists receptors (eg, analogues of RGD-peptidomimetics) or any other proteins mentioned in the present description, etc.;

n is an integer, typically selected from the range of about 1 to 50, preferably from the range of about 1, 2, or 3 to 30, more preferably from the range of about 1, 2, 3, 4, or 5 to 25, or a range of about 1, 2, 3, 4, or 5 to 20, or a range of about 1, 2, 3, 4, or 5 to 15, or a range of about 1, 2, 3, 4, or 5 to 10, including, for example, the range about 4 to 9, 4 to 10, 3 to 20, 4 to 20, 5 to 20, or 10 to 20, or a range of about 3 to 15, 4 to 15, 5 to 15, or 10 to 15, or a range of about 6 to 11 or 7 to 10. Most preferably, n is in the range of about 1, 2, 3, 4, or 5 to 10, more preferably in the range of about 1, 2, 3, or 4 to 9, in the range from about 1, 2, 3, or 4 to 8, or in the range from about 1, 2, or 3 to 7.

In this context, the description of WO 2011/026641 and WO 2012/116811 is incorporated herein by reference. Each of the hydrophilic polymers P ¹ and P ³ typically carries at least one -SH group, where at least one -SH group can form a disulfide bond when interacting with the P ² component or with the component (AA) or ( AA) _x when used as a linker between P ¹ and P ² or P ³ and P ² as indicated below, and optionally with another component, for example, L and/or (AA) or (AA) _x , for example, if it carries two or more -SH groups. The following subformulas "P ¹ -SS-P ² " and "P ² -SSP ³ " in the above general formula, in which all S, P ¹ and P ³ have the above meanings, as a rule, describe the situation when one -SH -group of hydrophilic polymers P ¹ and P ³ is fused with one -SH group of component P ² in the above general formula, where both sulfur atoms in said -SH groups form a disulfide bond -SS-. Said -SH groups are generally present in each of the hydrophilic polymers P ¹ and P ³ , for example present in the cysteine localized therein, or any other (modified) amino acid or compound which/which bears a -SH group. Therefore, the subformulas "P ¹ -SSP ² " and "P ² SSP ³ " can also be written as "P ¹ -Cys-Cys-P ² " and "P ² -Cys-Cys-P ³ ", if -SH- the group is present in cysteine, where the term Cys-Cys refers to two cysteines linked by a disulfide bond, but not by a peptide bond. In this case, the concept of "-SS-" in these formulas can also be written as "-S-Cys", as "-Cys-S" or as "-Cys-Cys-". In this context, the term "-Cys-Cys-" does not describe a peptide bond, but the linkage of two cysteines through their -SH groups to form a disulfide bond. Thus, the concept "-Cys-Cys-" can also be written in general form as "-(Cys-S)-(S-Cys)-", where in this particular case S denotes the sulfur atom of the -SH group of cysteine. Similarly, the terms "-S-Cys" and "-Cys-S" refer to the disulfide bond between the fragment containing the -SH group and cysteine, which can also be written as "-S-(S-Cys)" and "-(Cys- S)-S". Alternatively, the hydrophilic polymers P ¹ and P ³ can be modified with a -SH group, preferably by chemical reaction with a compound bearing an -SH group, such that each of the hydrophilic polymers P ¹ and P ³ carries at least one of said -SH- group. Such a compound bearing an -SH group may be, for example, an (additional) cysteine or any other (modified) amino acid which carries an -SH group. Such a compound may also be a non-amino acid compound or group which/which contains or allows the introduction of a -SH group into the hydrophilic polymers P ¹ and P ³ described herein. Such non-amino acid compounds can be attached to the hydrophilic polymers P ¹ and P ^{3 of} the carrier polymer by chemical interactions or by coupling with compounds, for example by coupling with 3-thiopropionic acid or thioimolane, by forming an amide (for example, carboxylic acids, sulfonic acids, amines, etc.), by Michael addition reaction (e.g. maleimide groups, unsaturated carbonyls, etc.), by click chemistry (e.g. azides or alkynes), by alkene/alkyne metathesis (e.g. alkenes or alkynes), formation of imines or hydrozones (aldehydes or ketones, hydrazines, hydroxylamines, amines), complexation reactions (avidin, biotin, protein G) or with components that allow S _n -type substitution reactions (e.g. haloalkanes, thiols, alcohols, amines, hydrazines, hydrazides, sulfonic acid esters, oxyphosphonium salts) or other chemical groups that can be used to add other components in. In this context, the most preferred PEG derivative is alpha-methoxy-omega-mercapto-poly(ethylene glycol). In each case, the SH group, for example, cysteine or any other (modified) amino acid or compound, may be present at the ends or at any position within the hydrophilic polymers P ¹ and P ³ . As described herein, each of the hydrophilic polymers P ¹ and P ³ typically carries at least one -SH group, preferably at one end, but may also contain two or even more -SH groups, which can be be used to additionally attach other components specified in the present description, preferably other functional peptides or proteins, for example, a ligand, an amino acid component (AA) or (AA) _x , antibodies, cell-penetrating peptides or enhancer peptides (for example, TAT, KALA) etc.

полипептиды, химерные СРР, такие как транспортан, или MPG-пептиды, ВИЧ-связывающие пептиды, Tat, ВИЧ-1 Tat (ВИЧ), происходящие из Tat пептиды, олигоаргинины, представители семейства пенетратина, например, пенетратин, происходящие из Antennapedia пептиды (прежде всего из Drosophila antennapedia), pAntp, pIsl и т.д., происходящие из антимикробных пептидов СРР, например, буфорин-2, Вас715-24, SynB, SynB(1), pVEC, происходящие из hCT пептиды, SAP, MAP, KALA, PpTG20, богатые пролином пептиды, L-олигомеры, богатые аргинином пептиды, пептиды кальцитонина, FGF, лактоферрин, поли-L-лизин, полиаргинин, гистоны, полученные из VP22 пептиды или аналоги, Erns пестивирусов, HSV, VP22 (вирус герпеса простого), MAP, KALA или домены трансдукции белков (PTD), РрТ620, богатые пролином пептиды, богатые аргинином пептиды, богатые лизином пептиды, Рер-1, L-олигомеры, пептид(ы) кальцитонина и т.д. Особенно предпочтительной в этом контексте является манноза в качестве лиганда для антигенпрезентирующих клеток-мишеней, которые несут на их клеточной поверхности рецепторы маннозы. В другом предпочтительном аспекте первого варианта осуществления настоящего изобретения в качестве оптимального лиганда можно применять галактозу для направленного переноса к гепатоцитам. Указанные лиганды можно присоединять к компоненту Р¹ и/или Р³ с помощью обратимых дисульфидных связей, указанных ниже, или с помощью других возможных путей химического присоединения, путем образования амида (например, карбоновые кислоты, сульфоновые кислоты, амины и т.д.), путем реакции присоединения по Михаэлю (например, малеимидные группы, α,β-ненасыщенные карбонилы и т.д.), с помощью клик-химии (например, азиды или алкины), с помощью метатезиса алкенов/алкинов (например, алкены или алкины), формирования иминов или гидразонов (альдегиды или кетоны, гидразины, гидроксиламины, амины), реакций комплексообразования (авидин, биотин, белок G) или с компонентами, которые допускают реакции замещения S_n-типа (например, галогеналканы, тиолы, спирты, амины, гидразины, гидразиды, эфиры сульфоновых кислот, соли оксифосфония) или другими химическими группами, которые можно использовать для присоединения других компонентов.As indicated above, ligands (L) can optionally be used in a polymer carrier molecule of general formula (VI), for example, to direct the carrier polymer of the invention and its complete "cargo molecule" (for example, isRNA intended for the treatment or prevention of tumor and/or cancer specified in the present description) in specific cells. They can be independently selected from RGD, transferrin, folate, signal peptide or signal sequence, localization signal or sequence, nuclear localization signal or sequence (NLS), antibody, cell-penetrating peptide (e.g., TAT or KALA), receptor ligand (eg, cytokines, hormones, growth factors, etc.), small molecules (eg, carbohydrates such as mannose or galactose, or synthetic ligands), small molecule agonists, inhibitors, or antagonists of receptors (eg, RGD peptidomimetic analogues), or any other such molecules as indicated below, etc. Particularly preferred are cell-penetrating peptides (CPPs) that induce a pH-mediated conformational change in the endosome and result in improved release of the polymeric carrier (in complex with the nucleic acid) from the endosome by incorporation into the lipid layer of the liposome. Said so-called CPP or cationic transport peptides may be, but not limited to, protamine, nucleolin, spermine or spermidine, poly-L-lysine (PLL),

polypeptides, chimeric CPPs such as transportan or MPG peptides, HIV-binding peptides, Tat, HIV-1 Tat (HIV), Tat-derived peptides, oligoarginines, members of the penetratin family, e.g. penetratin, Antennapedia-derived peptides (formerly total from Drosophila antennapedia), pAntp, pIsl, etc., derived from CPP antimicrobial peptides, e.g. Buforin-2, Bac715-24, SynB, SynB(1), pVEC, hCT derived peptides, SAP, MAP, KALA , PpTG20, proline-rich peptides, L-oligomers, arginine-rich peptides, calcitonin peptides, FGF, lactoferrin, poly-L-lysine, polyarginine, histones derived from VP22 peptides or analogues, pestivirus Erns, HSV, VP22 (herpes simplex virus) , MAP, KALA or protein transduction domains (PTDs), PpT620, proline-rich peptides, arginine-rich peptides, lysine-rich peptides, Pep-1, L-oligomers, calcitonin peptide(s), etc. Particularly preferred in this context is mannose as a ligand for antigen-presenting target cells that carry mannose receptors on their cell surface. In another preferred aspect of the first embodiment of the present invention, galactose can be used as the optimal ligand for targeted transport to hepatocytes. Said ligands can be attached to the P ¹ and/or P ³ component via the reversible disulfide bonds listed below, or via other possible chemical addition routes, via amide formation (e.g. carboxylic acids, sulfonic acids, amines, etc.) , by Michael addition reaction (e.g. maleimide groups, α,β-unsaturated carbonyls, etc.), by click chemistry (e.g. azides or alkynes), by alkene/alkyne metathesis (e.g. alkenes or alkynes ), formation of imines or hydrazones (aldehydes or ketones, hydrazines, hydroxylamines, amines), complexation reactions (avidin, biotin, protein G) or with components that allow S _n -type substitution reactions (e.g. haloalkanes, thiols, alcohols, amines , hydrazines, hydrazides, sulfonic acid esters, oxyphosphonium salts) or other chemical groups that can be used to attach other components.

In the context of formula (VI) in the present invention, the components P ¹ and P ³ are a linear or branched hydrophilic polymer chain containing at least one -SH group, each P ¹ and P ³ are independently selected from polyethylene glycol (PEG) , poly-N-(2-hydroxypropyl)methacrylamide, poly-2-(methacryloyloxy)ethylphosphorylcholines, poly(hydroxyalkyl-L-asparagine), poly(2-(methacryloyloxy)ethylphosphorylcholine), hydroxyethyl starch, or poly(hydroxyalkyd-L-glutamine) . R ¹ and R ³ may be identical or different from each other. Preferably, the hydrophilic polymers P ¹ and P ³ each have a molecular weight of from about 1 to about 100 kDa, preferably from about 1 to about 75 kDa, or more preferably from about 5 to about 50 kDa, even more preferably from about 5 to about 25 kDa . In addition, each of the hydrophilic polymers P ¹ and P ³ typically bears at least one -SH group, where at least one -SH group can form a disulfide bond when interacting with the P ² component or with the (AA ) or (AA) _x if used as a linker between P ¹ and P ² or P ³ and P ² as indicated below, and optionally with another component, for example, L and/or (AA) or (AA) _x , for example, if it carries two or more -SH groups. The following subformulas "P ¹ -SS-P ² " and "P ² -SSP ³ " in the above general formula (VI) (brackets omitted for readability), in which all S, P ¹ and P ³ have the above meanings, as generally describe the situation where one -SH group of hydrophilic polymers P ¹ and P ³ is fused with one -SH group of component P ² in the above general formula (VI), where both sulfur atoms in said -SH groups form a disulfide bond -SS-. Said -SH groups are generally present in each of the hydrophilic polymers P ¹ and P ³ , for example present in the cysteine localized therein, or any other (modified) amino acid or compound which/which bears a -SH group. Therefore, the subformulas "P ¹ -SSP ² " and "P ² -SSP ³ " can also be written as "P ¹ -Cys-Cys-P ² " and "P ² -Cys-Cys-P ³ ", if -SH - group is present in cysteine, where the term Cys-Cys refers to two cysteines linked by a disulfide bond, but not by a peptide bond. In this case, the concept of "-SS-" in these formulas can also be written as "-S-Cys", as "-Cys-S" or as "-Cys-Cys-". In this context, the term "-Cys-Cys-" does not describe a peptide bond, but the linkage of two cysteines through their -SH groups to form a disulfide bond. Thus, the concept "-Cys-Cys-" can also be written in general form as "-(Cys-S)-(S-Cys)-", where in this particular case S denotes the sulfur atom of the -SH group of cysteine. Similarly, the terms "-S-Cys" and "-Cys-S" refer to the disulfide bond between the fragment containing the -SH group and cysteine, which can also be written as "-S-(S-Cys)" and "-(Cys- S)-S". Alternatively, the hydrophilic polymers P ¹ and P ³ can be modified with a -SH group, preferably by chemical reaction with a compound bearing an -SH group, such that each of the hydrophilic polymers P ¹ and P ³ carries at least one of said -SH- group. Such a compound bearing an -SH group may be, for example, an (additional) cysteine or any other (modified) amino acid which carries an -SH group. Such a compound may also be a non-amino acid compound or group which/which contains or allows the introduction of a -SH group into the hydrophilic polymers P ¹ and P ³ described herein. Such non-amino acid compounds can be attached to the hydrophilic polymers P ¹ and P ^{3 of} formula (VII) of the carrier polymer of the present invention by chemical interactions or by coupling with compounds, for example by coupling with 3-thiopropionic acid or thioimolane, by forming amide (e.g. carboxylic acids, sulfonic acids, amines, etc.), by Michael addition reaction (e.g., maleimide groups, α,β-unsaturated carbonyls, etc.), by click chemistry (e.g., azides or alkynes), via alkene/alkyne metathesis (e.g. alkenes or alkynes), imine or hydrozone formation (aldehydes or ketones, hydrazines, hydroxylamines, amines), complexation reactions (avidin, biotin, protein G), or with components that allow substitution reactions of S _n -type (for example, haloalkanes, thiols, alcohols, amines, hydrazines, hydrazides, sulfonic acid esters, oxyphosphonium salts) or other chemical groups that These can be used to attach other components. In this context, the most preferred PEG derivative is alpha-methoxy-omega-mercapto-poly(ethylene glycol). In each case, the SH group, for example, cysteine or any other (modified) amino acid or compound, may be present at the ends or at any position within the hydrophilic polymers P ¹ and P ³ . As described herein, each of the hydrophilic polymers P ¹ and P ³ typically carries at least one -SH group, preferably at one end, but may also contain two or even more -SH groups, which can be be used to additionally attach other components specified in the present description, preferably other functional peptides or proteins, for example, a ligand, an amino acid component (AA) or (AA) _x , antibodies, cell-penetrating peptides or enhancer peptides (for example, TAT, KALA) etc.

полипептиды, полиаргинин, химерные СРР, такие как транспортан, или MPG-пептиды, ВИЧ-связывающие пептиды, Tat, ВИЧ-1 Tat (ВИЧ), происходящие из Tat пептиды, олигоаргинины, представители семейства пенетратина, например, пенетратин, происходящие из Antennapedia пептиды (прежде всего из Drosophila antennapedia), pAntp, pIsl и т.д., происходящие из антимикробных пептидов СРР, например, буфорин-2, Вас715-24, SynB, SynB(1), pVEC, происходящие из hCT пептиды, SAP, MAP, KALA, PpTG20, богатые пролином пептиды, L-олигомеры, богатые аргинином пептиды, пептиды кальцитонина, FGF, лактоферрин, поли-L-лизин, полиаргинин, гистоны, полученные из VP22 пептиды или аналоги, Erns пестивирусов, HSV, VP22 (вирус герпеса простого), MAP, KALA или домены трансдукции белков (PTD), РрТ620, богатые пролином пептиды, богатые аргинином пептиды, богатые лизином пептиды, Рер-1, L-олигомеры, пептид(ы) кальцитонина и т.д.According to one preferred alternative, said additional functional peptides or proteins may comprise so-called cell-penetrating peptides (CPPs) or cationic transport peptides. Most preferred are CPPs that induce a pH-mediated conformational change in the endosome and result in improved release of the inventive polymer carrier (in complex with nucleic acid) from the endosome by insertion into the lipid layer of the liposome. Said CPP or cationic transport peptides may be, but are not limited to, protamine, nucleolin, spermine or spermidine, poly-L-lysine (PLL),

polypeptides, polyarginine, chimeric CPPs such as transportan or MPG peptides, HIV-binding peptides, Tat, HIV-1 Tat (HIV), Tat-derived peptides, oligoarginines, members of the penetratin family, e.g. penetratin, Antennapedia-derived peptides (primarily from Drosophila antennapedia), pAntp, pIsl, etc., derived from CPP antimicrobial peptides, e.g. Buforin-2, Bac715-24, SynB, SynB(1), pVEC, hCT derived peptides, SAP, MAP , KALA, PpTG20, proline-rich peptides, L-oligomers, arginine-rich peptides, calcitonin peptides, FGF, lactoferrin, poly-L-lysine, polyarginine, histones derived from VP22 peptides or analogs, Pestivirus Erns, HSV, VP22 (herpes virus simple), MAP, KALA or protein transduction domains (PTD), PpT620, proline-rich peptides, arginine-rich peptides, lysine-rich peptides, Pep-1, L-oligomers, calcitonin peptide(s), etc.

According to a further preferred embodiment of the present invention, each of the hydrophilic polymers P ¹ and P ^{3 of} formula (VI) of the polymer carrier used according to the present invention may also contain at least one additional functional group, which allows the addition of additional components specified in the present description, e.g., the above ligand, or functionality which allows addition of additional components, e.g. by amide formation (e.g. carboxylic acids, sulfonic acids, amines, etc.), by Michael addition reaction (e.g. maleimide groups, unsaturated carbonyls etc.), via click chemistry (e.g. azides or alkynes), via alkene/alkyne metathesis (e.g. alkenes or alkynes), formation of imines or hydrozones (aldehydes or ketones, hydrazines, hydroxylamines, amines), complex formation reactions (avidin, biotin, protein G), or with components which allow S _n -type substitution reactions (eg, haloalkanes, thiols, alcohols, amines, hydrazines, hydrazides, sulfonic acid esters, oxyphosphonium salts), or other chemical groups that can be used to attach other components. Additional functional groups may contain the amino acid component (AA) specified in the present description, or (AA) _x , where (AA) preferably represents an amino group-containing component specified above. In the above context, x is preferably an integer and can be selected from the range of about 1 to 100, preferably from the range of about 1 to 50, more preferably from 1 to 30, and even more preferably can be selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15-30, for example, from a range of about 1 to 30, from a range of about 1 up to 15, or from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, or may be selected from a range formed by any two of the above. Most preferably, x is 1. Said amino acid component (AA) or (AA) _x may be present in each part of the inventive polymeric carrier of formula (VI) above, and therefore may be attached to all components of the inventive polymeric carrier of formula (VI). Particularly preferably, the amino acid component (AA) or (AA) _x is present as a ligand or part of the [SP ² -S] _n repeating component in formula (VI) of the polymeric carrier according to the invention.

In the context of the overall formula (VI), the preferred polymeric carrier may be defined by the following formula:

in which L, R ¹ , R ² , R ³ and n have the meanings specified in the present description, S denotes a sulfur atom and each Cys bears one -SH-group to form a disulfide bond.

According to a particular embodiment of the invention, the polymeric carrier of formula (VI) above may contain at least one amino acid component (AA) or (AA) _x as defined above. Said amino acid component (AA) or (AA) _x may be contained in each part of the inventive polymeric carrier of formula (VI) above, and therefore may be attached to all components of the polymeric carrier of formula (VI). Particularly preferably, the amino acid component (AA) or (AA) _x is present as a ligand or part of the repeating component [SP ² -S] _n in formula (VI) of the polymer carrier. The amino acid component (AA) or (AA) _x preferably contains or is flanked (for example, at the end) by at least one containing -SH group, which allows the introduction of this component (AA) or (AA) _x using a disulfide bond into the polymer carrier of the formula (VI) specified in the present description. Said -SH-containing group may be any -SH-containing group (or, of course, one sulfur atom of a disulfide bond), such as a cysteine residue. In the particular case where said -SH-containing group refers to cysteine, the amino acid component (AA) _x may also be referred to as -Cys-(AA) _x - or -Cys-(AA) _x -Cys-, where Cys is cysteine and contains the -SH group necessary for the formation of a disulfide bond. The -SH-containing group can also be introduced into the amino acid component (AA) _x by any of the modifications or reactions described above for the P ¹ , P ² or P ³ components. In the particular case where the amino acid component (AA) _x is linked to two polymeric carrier components of formula (VI), it is preferred that (AA) or (AA) _x contain at least two -SH groups, for example at least two cysteines , preferably at their ends. It is especially preferred if (AA) or (AA) _x is part of the repeating component [SP ² -S] _n . Alternatively, the amino acid component (AA) or (AA) _x is introduced into the polymer carrier of formula (VI) as defined herein by any chemically possible addition reaction. To do this, the amino acid component (AA) or (AA) _x contains at least one additional functional group, which allows it to be attached to an additional component specified in the present description, for example, component P ¹ or P ³ , P ² , L, or another amino acid component (AA) or (AA) _x , etc. Said functional groups can be selected from functionalities that allow the addition of additional components, such as the functionalities specified herein, for example, by amide formation (for example, carboxylic acids, sulfonic acids, amines, etc.), by Michael addition reaction ( e.g. maleimide groups, α,β-unsaturated carbonyls, etc.), via click chemistry (e.g. azides or alkynes), via alkene/alkyne metathesis (e.g. alkenes or alkynes), formation of imines or hydrozones ( aldehydes or ketones, hydrazines, hydroxylamines, amines), complexation reactions (avidin, biotin, protein G) or with components that allow S _n -type substitution reactions (e.g. haloalkanes, thiols, alcohols, amines, hydrazines, hydrazides, sulfonic esters acids, hydroxyphosphonium salts), or other chemical groups that can be used to attach other components.

The amino acid component (AA) or (AA) _x in the polymeric carrier of formula (VI) may also be in the form of a mixed repeating amino acid component [(AA) _x ] _z , in which the number of amino acid components (AA) or (AA) _x is additionally determined by integer number z. In this context, z may be selected from the range of about 1 to 30, preferably from the range of about 1 to 15, more preferably 1 to 10 or 1 to 5, and even more preferably selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, or may be selected from a range defined by any two of the above values.

In a specific and most preferred embodiment, the amino acid component (AA) or (AA) _x , which is preferably referred to as S-(AA) _x -S or [S-(AA) _x -S], can be used to modify the P ² component, before the total content of the component SP ² -S in the repeating component [SP ² -S] _n of the polymer carrier of the above formula (VI). This can be denoted in the context of the entire polymeric carrier of formula (VI), for example, using the following formula (VIa):

in which x, S, L, AA, R ¹ , R ² and R ³ preferably have the meanings specified in the present description. In formula (VIa) above, any of the individual components [SP ² -S] and [S-(AA) _x -S] may be present in any order in the subformula {[SP ² -S] _a [S-(AA) _x -S] _b }. The numbers of individual components [SP ² -S] and [S-(AA) _x -S] in the subformula {[SP ² -S] _a [S-(AA) _x -S] _b } are determined by integers a and b, where a+b=n. n is an integer and is as defined above for formula (VI).

The symbol a denotes an integer, generally selected independently from integer b, from the range of about 1 to 50, preferably from the range of about 1, 2, or 3 to 30, more preferably from the range of about 1 , 2, 3, 4, or 5 to 25, or a range of about 1, 2, 3, 4, or 5 to 20, or a range of about 1, 2, 3, 4, or 5 to 15, or a range of about 1, 2, 3, 4, or 5 to 10, including, for example, a range of about 3 to 20, 4 to 20, 5 to 20, or 10 to 20, or a range of about 3 up to 15, 4 to 15, 5 to 15, or 10 to 15, or a range of about 6 to 11 or 7 to 10. Most preferably, a is in the range of about 1, 2, 3, 4 or 5 to 10, more preferably in the range of about 1, 2, 3, or 4 to 9, in the range of about 1, 2, 3, or 4 to 8, or in the range of ranging from about 1, 2 or 3 to 7.

The symbol b denotes an integer, generally selected independently from integer a, from a range of about 0 to 50 or 1 to 50, preferably a range of about 0, 1.2, or 3 to 30, more preferably from a range of about 0, 1, 2, 3, 4, or 5 to 25, or a range of about 0, 1, 2, 3, 4, or 5 to 20, or a range of about 0, 1, 2 , 3, 4, or 5 to 15, or a range of about 0, 1, 2, 3, 4, or 5 to 10, including, for example, a range of about 3 to 20, 4 to 20, 5 to 20, or 10 to 20, or a range of about 3 to 15, 4 to 15, 5 to 15, or 10 to 15, or a range of about 6 to 11, or 7 to 10. Most preferably , b is in the range of about 1, 2, 3, 4 or 5 to 10, more preferably in the range of about 1, 2, 3 or 4 to 9, in the range of about 1, 2, 3 or 4 to 8, or in the range of about 1, 2, or 3 to 7.

In this context, it is particularly preferred that the isRNA intended for use in the treatment or prevention of the neoplastic and/or cancerous disease described herein is complexed at least in part with a cationic or polycationic compound and/or a polymeric carrier, preferably cationic proteins or peptides. . In this context, the contents of WO 2010/037539 and the contents of WO 2012/113513 are incorporated herein by reference. "Partly" means that only a portion of the RNA is complexed with the cationic compound and that the rest of the RNA (preferably in the same composition) is not complexed (i.e., in "free" form). Preferably, the ratio of complexed RNA:free RNA (in the composition of the invention) is selected from the range of from about 5:1 to about 1:10 (w/w), more preferably from the range of from about 4:1 up to about 1:8 (w/w), even more preferably in the range of from about 3:1 to about 1:5 (w/w) or 1:3 (w/w), and most preferably, the ratio of complexed RNA : free RNA in the composition according to the invention is selected from a ratio of about 1:1 (w/w).

According to a preferred embodiment of the invention, an isRNA for use in the treatment or prevention of a tumor and/or cancer described herein may be complexed with lipids to form one or more liposomes, lipid nanoparticles and/or lipoplexes.

There is increasing evidence that lipid-based formulations should be considered as the most promising RNA delivery systems due to their biocompatibility and ease of large-scale production. Cationic lipids have been extensively studied as synthetic materials for RNA delivery. After mixing, nucleic acids are condensed with cationic lipids to form lipid/nucleic acid complexes known as lipoplexes. These lipid complexes can protect the genetic material from the effects of nucleases and be delivered to cells by interacting with a negatively charged cell membrane. Lipoplexes can be obtained directly by mixing positively charged lipids at physiological pH with negatively charged nucleic acids.

Conventional liposomes are composed of a lipid bilayer, which may be composed of cationic, anionic, or neutral (phospho)lipids, and cholesterol surrounding an aqueous core. Both the lipid bilayer and the water space may include hydrophobic or hydrophilic compounds, respectively. The in vivo characteristics and behavior of liposomes can be modified by adding a hydrophilic polymeric coating, such as polyethylene glycol (PEG), to the surface of the liposomes to impart steric stabilization. In addition, liposomes can be used for specific targeting by attaching ligands (eg, antibodies, peptides and carbohydrates) to their surface or to the ends of attached PEG chains (Front Pharmacol., 6, December 1, 2015, p. 286).

Liposomes are lipid-based and surfactant-based colloidal delivery systems consisting of a phospholipid bilayer surrounding an aqueous compartment. They may be in the form of spherical bubbles and may range in size from 20 nm to several microns. Liposomes based on cationic lipids can complex with negatively charged nucleic acids through electrostatic interactions, resulting in the formation of complexes with biocompatibility, low toxicity and the possibility of their large-scale production necessary for clinical applications in vivo. Liposomes can fuse with the plasma membrane for entry; Once inside the liposome cell, they are processed through the endocytic pathway, and then the genetic material is released from the endosome/carrier into the cytoplasm. Liposomes have long been regarded as drug delivery vehicles due to their very high biocompatibility based on the fact that liposomes are in general analogues of biological membranes and can be obtained from naturally occurring and synthetic phospholipids (Int J Nanomedicine. 9, 2014, pp. 1833-1843).

Cationic liposomes have traditionally been most widely used as non-viral delivery systems for oligonucleotides, including plasmid DNA, antisense oligonucleotides, and siRNA/small hairpin RNA (shRNA)). Cationic lipids such as DOTAP (1,2-dioleoyl-3-trimethylammonium propane) and DOTMA (N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate) can form complexes or lipoplexes with negatively charged nucleic acids with the formation of nanoparticles through electrostatic interaction, which ensures high efficiency of transfection in vitro. In addition, lipid-neutral RNA delivery nanoliposomes have been developed, such as neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes (Adv Drug Deliv Rev. 66, February 2014, cc. 110-116.).

Thus, in one of the embodiments of the invention, an isRNA intended for use in the treatment or prevention of a tumor and/or cancer described in the present description forms a complex with cationic lipids and/or neutral lipids and thereby forms liposomes, lipid nanoparticles, lipoplexes or nanoliposomes based on neutral lipids.

In some embodiments, the isRNA for the use described herein is formulated into a lipid composition. The lipid composition is preferably selected from (but not limited to) liposomes, lipoplexes, copolymers such as PLGA, and lipid nanoparticles.

In one of the preferred embodiments of the invention, the lipid nanoparticle (LNP) contains:

(a) a nucleic acid,

(b) cationic lipid,

(c) an aggregation reducing agent (such as a polyethylene glycol (PEG) lipid or a modified PEG lipid),

(d) optionally a non-cationic lipid (such as a neutral lipid), and

(e) optionally a sterol.

In one of the embodiments of the invention, the lipid nanoparticle composition consists of (I) at least one cationic lipid; (II) neutral lipid; (III) a sterol, eg cholesterol; and (iv) a PEG lipid, in a molar ratio of about 20-60% cationic lipid: 5-25% neutral lipid: 25-55% sterol; 0.5-15% PEG lipid.

Cationic lipids

The lipid nanoparticle preferably includes a cationic lipid suitable for formation of the lipid nanoparticle. Preferably, the cationic lipid carries a frequent positive charge at near physiological pH.

The cationic lipid may be, for example, N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), 1,2-dioleoyltrimethylammonium propane chloride (DOTAP) (also known as N-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride and 1,2-dioleyloxy-3-trimethylaminopropane chloride), N-(1-(2,3-dioleoyloxy)propyl)-N,N, N-trimethylammonium chloride (DOTMA), N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), 1,2-dilinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-dilinoleyloxy-N,N-dimethylaminopropane (DLenDMA), 1,2-di-y-linolenyloxy-N,N-dimethylaminopropane (γ-DLenDMA), 1,2-dilinoleylcarbamoyloxy-3-dimethylaminopropane (DLin-C-DAP), (dimethylamino)acetoxypropane (DLin-DAC), 1,2-dilinoleoyl-3-dimethylaminopropane (DLin-MA), 1,2-dilinoleoyl-3-dimethylaminopropane (DLinDAP), 1,2-dilinoleylthio-3-dimethylaminopropane (DLin- S-DMA), 1-linoleoyl-2-linoleyloxy-3-dimethylaminopropane (DLin-2-DMAP), 1,2-dilinoleyloxy-3-trimethylaminopropane chloride (DLin-TMA.Cl), 1,2-dyl inoleoyl-3-trimethylaminopropane chloride (DLin-TAP.Cl), 1,2-dilinoleyloxy-3-(N-methylpiperazino)propane (DLin-MPZ), or 3-(N,N-dilinoleylamino)-1,2-propanediol (DLinAP ), 3-(N,N-dioleylamino)-1,2-propanediol (DOAP), 1,2-dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DM A), 2, 2-dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA) or analogues thereof, (3aR,5s,6aS)-N,N-dimethyl-2,2-di((9Z,12Z )-octadeca-9,12-dienyl)tetrahydro-3аН-cyclopenta[d][1,3]dioxol-5-amine, (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraene -19-yl-4-(dimethylamino)butanoate (MC3), 1,1'-(2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino )ethyl)piperazin-1-yl)ethylazanediyl)didodecan-2-ol (С12-200), 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-K-C2- DMA), 2,2-dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA), (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen- 19-yl-4-(dimethylamino)butanoate (DLin-M-C3-DMA), 3-((6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yloxy)- N,N-dimethylp ropan-1-amine (MC3-ether), 4-((6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yloxy)-N,N-dimethylbutan-1- amine (MC4 ether) or any combination of any of the above compounds. Other cationic lipids include, but are not limited to, N,N-distearyl-N,N-dimethylammonium bromide (DDAB), 3P-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol), N-(1-(2,3-dioleyloxy)propyl)-N-2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate (DOSPA), dioctadecylamidoglycylcarboxyspermine (DOGS), 1,2-dioleoyl-sn-3- phosphoethanolamine (DOPE), 1,2-dioleoyl-3-dimethylammonium propane (DODAP), N-(1,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethylammonium bromide (DMRIE), and 2,2-dilinoleyl -4-dimethylaminoethyl-[1,3]-dioxolane (XTS). In addition, commercially available cationic lipid preparations such as LIPOFECTIN (including DOTMA and DOPE, commercially available from GIBCO/BRL) and Lipofectamine (containing DOSPA and DOPE, commercially available from GIBCO) can be used. /BRL).

Other suitable cationic lipids are described in international patent applications WO 09/086558, WO 09/127060, WO 10/048536, WO 10/054406, WO 10/088537, WO 10/129709 and WO 2011/153493; U.S. Patent Publication Nos. 2011/0256175, 2012/0128760 and 2012/0027803; US No. 8158601; and Love et al., PNAS, 107(5), 2010, pp. 1864-1869. Other acceptable aminolipids include compounds that have alternative fatty acid groups and other dialkylamino groups, including compounds in which the alkyl substituents are different (eg, N-ethyl-N-methylamino- and N-propyl-N-ethylamino-). In general, aminolipids having less saturated acyl chains are more convenient in size, especially when the complexes need to be smaller than about 0.3 microns for filter sterilization purposes. You can use aminolipids containing unsaturated fatty acids with a carbon chain length in the range from C14 to C22. Other scaffolds may also be used to separate the amino group from the fatty acid or fatty acid alkyl moiety of the amino lipid.

In another preferred embodiment of the invention, the LNP contains a cationic lipid of formula (III) specified in the patent application PCT/EP 2017/064066. In this context, the specification PCT/EP2017/064066 is also incorporated herein by reference.

In some embodiments, the aminolipids or cationic lipids of the invention have at least one protonated or deprotonated group, resulting in the lipid being positively charged at a pH that is at or below the physiological pH (e.g., pH 7 ,4), and neutral at another pH, which preferably corresponds to or exceeds the physiological pH. Naturally, as should be obvious, the addition or removal of protons as a function of pH is an equilibrium process and that reference to a charged or neutral lipid is in the nature of the predominant species and does not require all of the lipid to be present in a charged or neutral form. The invention does not preclude the use of lipids which have more than one protonable or deprotonable group, or which are zwitterionic. In some embodiments, the protonated lipids have a pKa value of the protonated group ranging from about 4 to about 11, for example, a pKa value from about 5 to about 7.

The proportion of cationic lipid can be from about 20 to about 70 or 75 mol. % or from about 45 to about 65 mol. % or about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or about 70 mol. % of the total lipid content in the particle. In another embodiment, the lipid nanoparticles comprise from about 25% to about 75%, based on moles of cationic lipid, for example, from about 20% to about 70%, from about 35% to about 65%, from about 45% to about 65%, about 60%, about 57.5%, about 57.1%, about 50%, or about 40% on a mole basis (based on 100% of all lipid moles in the lipid nanoparticle). In one embodiment, the ratio between cationic lipid and nucleic acid is from about 3 to about 15, for example, from about 5 to about 13, or from about 7 to about 11.

Non-cationic lipids

The non-cationic lipid may be a neutral lipid, an anionic lipid, or an amphipathic lipid. Neutral lipids, if present, can be any of the many types of lipids that exist in either uncharged or neutral zwitterionic form at physiological pH. Such lipids include, for example, diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide, sphingomyelin, dihydrosphingomyelin, cephalin, and cerebrosides. When choosing neutral lipids for use in the particles described in the present description, as a rule, take into account, for example, the size of the lipid particle and the stability of the lipid particle in the bloodstream. Preferably, the neutral lipid is a lipid having two acyl groups (eg, diacylphosphatidylcholine and diacylphosphatidylethanolamine). In one of the embodiments of the invention, neutral lipids contain saturated fatty acids with a carbon chain length in the range from C10 to C20. In another embodiment of the invention, neutral lipids are used with mono- or diunsaturated fatty acids with a carbon chain length ranging from C10 to C20. In addition, neutral lipids containing mixtures of saturated and unsaturated fatty acids can be used.

Acceptable neutral lipids include, but are not limited to, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylethanolaminelcholine (POPC), palmitoyloleoylphosphatidylethanolamine choline (POPC), palmitoyloleoylphosphatidylethanolamine (POPC), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoylphosphatidylcholine (POPC). ), dioleoylphosphatidylethanolamine-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (DOPE-mal), dipalmitoylphosphatidylethanolamine (DPPE), dimyristoylphosphatidylethanolamine (DMPE), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylethanolamine (DSPE), SM, 16-0-monomethyl PE , 16-O-dimethyl PE, 18-1-trans-PE, 1-stearoyl-2-oleoylphosphatidylethanolamine (SOPE), cholesterol, or a mixture thereof. Anionic lipids that can be used in the lipid particles of the invention include, but are not limited to, phosphatidylglycerol, cardiolipin, diacylphosphatidylserine, diacylphosphamide acid, N-dodecanoylphosphatidylethanolamine, N-succinylphosphatidylethanolamine, N-glutarylphosphatidylethanolamine, lysylphosphatidylglycerol, and other anionic modifying groups. associated with neutral lipids. The proportion of non-cationic lipid can be from about 5 to about 90 mol. %, from about 5 to about 10 mol. %, about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 or about 90 mol. % of total lipid present in the particle. In one embodiment, the lipid nanoparticles comprise from about 0% to about 15% or 45%, based on moles of neutral lipid, such as from about 3% to about 12%, or from about 5% to about 10%. For example, the lipid nanoparticles may include about 15%, about 10%, about 7.5%, or about 7.1% neutral lipid on a mole basis (based on 100% of all lipid moles in the lipid nanoparticle).

Sterols

The preferred sterol is cholesterol. The share of the sterol can be from about 10 to about 60 mol. % or from about 25 to about 40 mol. % in the lipid particle. In one of the embodiments of the invention, the proportion of sterol is about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 or about 60 mol. % of the total lipid content present in the lipid particle. In another embodiment, the lipid nanoparticles comprise about 5% to about 50% sterol on a mole basis, e.g., about 15% to about 45%, about 20% to about 40%, about 48%, about 40%, about 38.5%, about 35%, about 34.4%, about 31.5%, or about 31% on a mole basis (based on 100% of all lipid moles in the lipid nanoparticle).

Anti-aggregation agent

The aggregation-reducing agent may be a lipid that has the ability to reduce aggregation. Examples of such lipids include, but are not limited to, polyethylene glycol (PEG) modified lipids, Gml monosialoganglioside, and polyamide oligomers (PAO), such as those described in US No. 6320017, the entire content of which is incorporated herein by reference. Other components with uncharged hydrophilic, steric barrier residues that prevent aggregation during formulation, such as PEG, Gml or TTA, can also be linked to lipids. ATTA lipids are described, for example, in US No. 6320017, and PEG-lipid conjugates are described, for example, in US No. 5820873, 5534499 and 5885613, the full content of each of which is incorporated herein by reference.

The aggregation reducing agent may be, for example, a polyethylene glycol (PEG) lipid, including but not limited to PEG diacylglycerol (DAG), PEG dialkylglycerol, PEG dialkyloxypropyl (DAA), PEG phospholipid, PEG ceramide (Cer) or a mixture thereof (such as, for example, PEG-Cerl4 or PEG-Cer20). The PEG-DAA conjugate may be, for example, PEG dilauryloxypropyl (C12), PEG dimyristyloxypropyl (C14), PEG dipalmityloxypropyl (C16) or PEG distearyloxypropyl (C18). Other pegylated lipids include, but are not limited to, polyethylene glycol-didimyristoylglycerol (C14-PEG or PEG-C14 in which the PEG has an average molecular weight of 2000 Da) (PEG-DMG); (R)-2,3-bis(octadecyloxy)propyl-1-(methoxypoly(ethylene glycol)2000)propylcarbamate) (PEG-DSG); PEG-carbamoyl-1,2-dimyristyloxypropylamine, wherein the PEG has an average molecular weight of 2000 Da (PEG-cDMA); N-acetylgalactosamine-((R)-2,3-bis(octadecyloxy)propyl-1-(methoxypoly(ethyleneglycol))2000)propylcarbamate)) (GalNAc-PEG-DSG); mPEG (mw2000)-diastearoylphosphatidylethanolamine (PEG-DSPE); and polyethylene glycol-dipalmitoylglycerol (PEG-DPG). In one embodiment, the aggregation reducing agent is PEG-DMG. In another embodiment, the anti-aggregation agent is PEG-c-DMA.

The average molecular weight of the PEG moiety in PEG-modified lipids can be from about 500 to about 8000 Da (eg, from about 1000 to about 4000 Da). In one of the preferred embodiments of the invention, the average molecular weight of the PEG fragment is about 2000 Da.

The concentration of anti-aggregation agent may be from about 0.1 to about 15 mol. %, based on 100% of all lipid moles in the lipid particle. In one of the embodiments of the invention, the formulation includes less than about 3, 2, or 1 mol. % PEG or PEG-modified lipid, based on the total number of moles of lipid in the lipid particle. In another embodiment, the lipid nanoparticles comprise from about 0.1% to about 20%, based on moles of PEG-modified lipid, for example, from about 0.5% to about 10%, from about 0.5% to about 5%, about 10 %, about 5%, about 3.5%, about 1.5%, about 0.5% or about 0.3% on a mole basis (based on 100% of all lipid moles in a lipid nanoparticle).

According to a preferred embodiment of the invention, an isRNA for use in the treatment or prevention of a neoplastic and/or cancerous disease as described herein is formulated using the isRNA as described herein and one or more liposomes, lipoplexes, or lipid nanoparticles. . In one of the embodiments of the invention proposed in the invention the composition contains liposomes. Liposomes are typically engineered vesicles that may consist primarily of a lipid bilayer and can be used as delivery vehicles for nutrient and pharmaceutical formulations. Liposomes may vary in size, such as, but not limited to, a multilamellar vesicle (MLV) which may be several hundred nanometers in diameter and may contain a series of concentric bilayers separated by narrow aqueous compartments, a small unicellular vesicle (SUV) , which may be less than 50 nm in diameter, and a large unilamellar vesicle (LUV), which may be 50 to 500 nm in diameter. When creating liposomes, you can include (but not limited to) opsonins or ligands to increase the ability of liposomes to attach to unhealthy tissue or to activate processes such as endocytosis (but not limited to them). Liposomes may have a low or high pH in order to improve the delivery of isRNA for use in the treatment or prevention of a tumor and/or cancer as described herein, particularly when used as a pharmaceutical composition as described herein.

Lipid nanoparticles (LNP)

Preferably, the lipid nanoparticles may have a liposome structure. A liposome typically has a structure comprising lipid-containing membranes that surround an aqueous interior. Liposomes preferably have one or more lipid membranes. In preferred embodiments, the liposomes may be unilamellar, referred to as unilamellar, or multilamellar, referred to as multilamellar. When complexed with nucleic acids (eg, RNA), the lipid particles can also be lipoplexes, which preferably consist of cationic lipid bilayers sandwiched between the nucleic acid layers. Liposomes may be of various sizes, such as, but not limited to, a multilamellar vesicle (MLV) which may be several hundred nanometers in diameter and may contain a series of concentric bilayers separated by narrow aqueous compartments, a small unicellular vesicle (SUV) , which may be less than 50 nm in diameter, and a large unilamellar vesicle (LUV), which may be 50 to 500 nm in diameter. In some embodiments of the invention, when creating liposomes, but not limited to, opsonins or ligands can be included to increase the ability of liposomes to attach to unhealthy tissue or to activate processes such as endocytosis (but not limited to them). Liposomes may have a low (eg, acidic) or high (eg, basic) pH to improve the delivery of pharmaceutical formulations.

Liposomes, such as synthetic membrane vesicles, can be obtained, for example (but not limited to) using the methods, tools and devices described in US patent publications US 20130177638, US 20130177637, US 20130177636, US 20130177635, US 20130177634, US 20130177633 , US 20130183375, US 20130183373 and US 20130183372, the full content of each of which is incorporated herein by reference. In preferred embodiments, the nucleic acid (e.g., RNA as defined herein) may be encapsulated in a liposome and/or may be contained in an aqueous core, which may then be encapsulated in a liposome (see international patent applications WO 2012/031046). , WO 2012/031043, WO 2012/030901 and WO 2012/006378 and US Patent Publication Nos. US 20130189351, US 20130195969 and US 20130202684, the entire contents of each of which are incorporated herein by reference).

In another embodiment, the lipid nanoparticles have a median diameter size of about 50 to about 300 nm, eg, about 50 to about 250 nm, eg, about 50 to about 200 nm. In another embodiment of the invention, nucleic acids can be delivered using smaller LNPs, which can have a diameter of from about 1 to about 100 nm, from about 1 to about 10 nm, from about 1 to about 20 nm, from about 1 to about 30 nm , from about 1 to about 40 nm, from about 1 to about 50 nm, from about 1 to about 60 nm, from about 1 to about 70 nm, from about 1 to about 80 nm, from about 1 to about 90 nm, from about 5 to about 100 nm, from about 5 to about 10 nm, from about 5 to about 20 nm, from about 5 to about 30 nm, from about 5 to about 40 nm, from about 5 to about 50 nm, from about 5 to about 60 nm, from about 5 to about 70 nm, from about 5 to about 80 nm, from about 5 to about 90 nm, from about 10 to about 50 nm, from about 20 to about 50 nm, from about 30 to about 50 nm, about 40 to about 50 nm, about 20 to about 60 nm, about 30 to about 60 n m, from about 40 to about 60 nm, from about 20 to about 70 nm, from about 30 to about 70 nm, from about 40 to about 70 nm, from about 50 to about 70 nm, from about 60 to about 70 nm, about 20 to about 80 nm, about 30 to about 80 nm, about 40 to about 80 nm, about 50 to about 80 nm, about 60 to about 80 nm, about 20 to about 90 nm, from about 30 to about 90 nm, about 40 to about 90 nm, about 50 to about 90 nm, about 60 to about 90 nm, about 70 to about 80 nm, and/or about 70 to about 90 nm.

In one embodiment, the weight ratio of lipid to RNA is at least about 0.5:1, at least about 1:1, at least about 2:1, at least about 3:1, at least about 4:1, at least about 5:1, at least about 6:1, at least about 7:1, at least about 11:1, at least about 20:1, at least about 25: 1 at least about 27:1, at least about 30:1, or at least about 33:1. In one embodiment, the weight ratio of lipid to RNA is from about 1:1 to about 35:1, from about 3:1 to about 15:1, from about 4:1 to about 15:1, or from about 5:1 to about 13:1 or from about 25:1 to about 33:1. In one embodiment, the weight ratio of lipid to RNA is from about 0.5:1 to about 12:1.

According to a preferred embodiment of the invention, an isRNA for use in the treatment or prevention of a tumor and/or cancer described herein is administered/administered intratumorally (i.t.), locoregional or peritumorally. In the context of the present description, the term "intratumoral administration/use" refers to the direct delivery of a pharmaceutical active substance, such as isPHK, specified in the present description, for example, in the form of a composition/formulation containing isRNA, specified in the present description, to the tumor, in the neighborhood and / or in the immediate vicinity of the tumor (peritumoral). For said delivery, several methods known in the art can be used, including, but not limited to, injection (such as conventional needle or needleless, eg jet injection) or electroporation, or combinations thereof. Methods for intratumoral drug administration are described in the art (see, e.g., (Brincker, Crit. Rev. Oncol. Hematol. 15(2), 1993, pp. 91-98; Celikoglu et al., Cancer Therapy 6, 2008, pp. 545-552)).

In the context of the present description, the term "intratumoral" may also refer to the introduction of an active pharmaceutical ingredient into an organ that has a tumor or cancer, or into a tissue that has a tumor or cancer. Thus, the term "intratumoral" in the context of the present description may also include peritumoral or locoregional administration, in which the active pharmaceutical ingredient is preferably administered to an organ or tissue, proximal to the tumor or cancer, preferably to an organ or tissue that is / which is in the immediate physical contact with a tumor or cancer. In the context of the present invention, intratumoral, locoregional, or peritumoral administration preferably comprises delivery (ie, by injection) of the active pharmaceutical ingredient to the surface of a tumor or cancer, or to a tumor or cancer that is/are localized within a tissue.

In some embodiments, locoregional administration of an active pharmaceutical ingredient (such as an RNA as defined herein) comprises delivering the active pharmaceutical ingredient to a tumor or cancer or tissue or organ having/having a tumor or cancer by introducing the active pharmaceutical ingredient into a blood vessel ( for example, an artery, such as the hepatic artery, or a vein, such as the pulmonary vein) that carries blood to a tumor or cancer, or to a tissue or organ that has/has a tumor or cancer.

According to a preferred embodiment of the invention, a pharmaceutically active ingredient, such as isRNA, intended for use in the treatment or prevention of a neoplastic and/or cancerous disease as defined herein, is administered intratumorally (i.t.), including locoregional or peritumoral administration, whereby the administration is used injection method. However, a pharmaceutically active ingredient, such as isPHK, for the use described herein may preferably be injected as a single dose per treatment. Alternatively, multiple injections can also be made into the same or different areas of the tumor or cancer or cancer-bearing organ or cancer-bearing tissue. In addition, intratumoral administration/use includes delivery of the pharmaceutically active ingredient to one or more metastases, preferably by injection. Administration of the pharmaceutically active ingredient may be in the form of a single dose treatment or repeated doses using various treatment intervals, preferably as described herein.

In a preferred embodiment of the invention, a pharmaceutically active ingredient such as isRNA for use in the treatment or prevention of a neoplastic and/or cancerous disease as defined herein is administered intratumorally (i.t.), including locoregional or peritumoral administration, by injection. Preferably, intratumoral administration includes an imaging technique, which preferably improves the accuracy of the injection. More preferably, said imaging modality is selected from the group consisting of computed tomography, ultrasound, imaging using a gamma camera, positron emission tomography, and magnetic resonance imaging of tumors. In addition, the intratumoral administration may preferably be a direct intratumoral injection, which preferably includes at least one of the procedures selected from the group consisting of endoscopy, bronchoscopy, cystoscopy, colonoscopy, laparoscopy, and catheterization.

In a preferred embodiment of the invention, a pharmaceutically active ingredient, such as isRNA, for use in the treatment or prevention of a neoplastic and/or cancerous disease as defined herein, is administered locoregional by injection. Preferably, locoregional administration includes an imaging technique that preferably improves the accuracy of administration, preferably intratumoral or peritumoral administration, as described herein. More preferably, said imaging modality is selected from the group consisting of computed tomography, ultrasound, imaging using a gamma camera, positron emission tomography, and magnetic resonance imaging of tumors. In addition, locoregional administration may preferably be direct locoregional injection, which preferably includes at least one of the procedures selected from the group consisting of endoscopy, bronchoscopy, cystoscopy, colonoscopy, laparoscopy, and catheterization. Thus, in the context of the present description, the term "locoregional administration" may also refer to intratumoral or peritumoral administration, preferably injection, of a pharmaceutically active ingredient (for example, the RNA specified in the present description), where the introduction preferably includes an imaging method, where the imaging method preferably includes at least one of the procedures selected from the group consisting of endoscopy, bronchoscopy, cystoscopy, colonoscopy, laparoscopy and catheterization.

A preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isPHK contains the nucleotide sequence of formula (I) (G _l X _m G _n ), formula (II) (C _l X _m C _n ), formula (III) (N _u G _l X _m G _n N _v ) _a or formula (IV) (N _u C _l X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in one of SEQ ID NOs: 433-437 or 1014-1016, or a fragment or variant of one of these sequences, more preferably presented in one of SEQ ID NOs: 433, 434 or 1014-1016, or a fragment or variant of one of the specified nucleotide sequences,

where isPHK is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI) (L-P1-S-[S-P2-S] _n -S-P3-L), more preferably at least one of the disulfide cross-linked cationic Cys-Arg ₁₂ peptides, Cys-Arg ₁₂ -Cys, or Trp-Arg ₁₂ -Cys, and where isPHK is preferably injected into the tumor.

A particularly preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isPHK contains the nucleotide sequence of formula (I) (G _l X _m G _n ), formula (II) (C _l X _m C _n ), formula (III) (N _u G _l X _m G _n N _v )a or formula (IV) (N _u C _l X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in one of SEQ ID NOs: 433-437 or 1014-1016, or a fragment or variant of one of these sequences, more preferably presented in one of SEQ ID NOs: 433, 434 or 1014-1016, or a fragment or variant of one of the specified nucleotide sequences,

where isPHK is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI) (L-P1-S-[S-P2-S] _n -S-P3-L), more preferably at least one of the disulfide cross-linked cationic Cys-Arg ₁₂ peptides, Cys-Arg ₁₂ -Cys, or Trp-Arg ₁₂ -Cys, and where isPHK is preferably injected into the tumor,

and

where the neoplastic or cancerous disease is preferably selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma; squamous cell skin cancer (SCC), preferably unresectable and/or advanced SCC; adenocystic carcinoma (ACC), preferably advanced ACC; cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy; and head and neck cancer (HNSCC), preferably advanced by HNSCC. In this context, the tumor or cancer is preferably selected from the group consisting of advanced melanoma, preferably advanced cutaneous melanoma (cMEL), skin squamous cell carcinoma (SCC), preferably cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), and adenoid cystic carcinoma (adenocystic carcinoma (ACC)).

In an alternative preferred embodiment of the invention, the tumor or cancer is selected from the group consisting of advanced cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (hnSCC), and adenoid cystic carcinoma (ACC).

A particularly preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isPHK contains the nucleotide sequence of formula (I) (G _l X _m G _n ), formula (II) (C _l X _m C _n ), formula (III) (N _u G _l X _m G _n N _v ) _a or formula (IV) (N _u C _l X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in one of SEQ ID NOs: 433-437 or 1014-1016, or a fragment or variant of one of these sequences, more preferably presented in one of SEQ ID NOs: 433, 434 or 1014-1016, or a fragment or variant of one of the specified nucleotide sequences,

where isPHK is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI) (L-P1-S-[S-P2-S] _n -S-P3-L), more preferably at least one of the disulfide cross-linked cationic Cys-Arg ₁₂ peptides, Cys-Arg ₁₂ -Cys, or Trp-Arg ₁₂ -Cys,

where isRNA is preferably injected into the tumor,

where the neoplastic or cancerous disease is preferably selected from the group consisting of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or wherein the tumor or cancer is preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC);

where the tumor or cancer is preferably at an advanced stage and/or is resistant to standard therapy.

Some embodiments of the invention is an isRNA as defined herein for use in the treatment of a neoplastic or cancerous disease, preferably as described herein, wherein the treatment comprises administering at least one additional pharmaceutically active agent, and wherein the isRNA is preferably administered intratumorally, including peritumorally. or locoregional introduction, preferably specified in the present description. In particular, the present invention provides isRNA for use in the treatment or prevention of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises administering at least one additional pharmaceutically active ingredient that is typically used in the treatment and/or prevention of a neoplastic or cancerous disease. , preferably specified in the present description, and where isRNA is preferably injected into the tumor, including peritumoral or locoregional administration. In the context of the present invention, the phrase "a pharmaceutically active ingredient which is usually used for the treatment and/or prevention of a [neoplastic or cancerous disease]" preferably refers to a pharmaceutically active ingredient which is used - preferably according to standard therapy - for the treatment and/or prevention of a neoplastic or cancerous diseases. More preferably, the phrase refers to a pharmaceutically active ingredient for which it is known in the art that it can be used to treat and/or prevent a neoplastic or cancerous disease.

A preferred embodiment of the invention is an isRNA as defined herein for use in the treatment of a neoplastic or cancerous disease, preferably as described herein, wherein the treatment comprises the administration of at least one additional pharmaceutically active ingredient that is typically used for treatment and/or prevention. of the respective disease, and where isRNA is preferably injected into the tumor.

Even more preferably, the isRNA is for use in the treatment of a neoplastic or cancerous disease selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), skin squamous cell carcinoma (SCC), preferably unresectable and/ or running SCC; most preferably cutaneous squamous cell carcinoma (cSCC); adenocystic carcinoma (ACC), preferably advanced ACC; cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy; and head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, wherein the treatment comprises concomitant localized or systemic administration of at least one additional pharmaceutically active ingredient that is typically used to treat and/or prevent any of said diseases, and isRNA is preferably administered orally tumors.

A preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer selected from the group consisting of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for use in the treatment of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC);

where the tumor or cancerous disease is preferably at an advanced stage and / or is resistant to standard therapy, where the treatment includes concomitant localized or systemic administration of at least one additional pharmaceutically active ingredient, which is usually used to treat and / or prevent any of these diseases, and isRNA is preferably injected into the tumor.

The at least one additional pharmaceutically active ingredient may be administered using any acceptable route of administration or route of administration, preferably those described herein, or by intravenous, oral, or topical/topical treatment. In a preferred embodiment of the invention, the isRNA, as well as at least one additional pharmaceutically active ingredient, is administered into the tumor. In a more preferred embodiment, the isRNA is administered intratumorally and at least one additional pharmaceutically active ingredient is administered systemically (orally or intravenously or subcutaneously or intramuscularly or intraperitoneally or intradermally).

In some embodiments of the invention, at least one additional pharmaceutically active ingredient is included in the composition along with isPHK, intended for use specified in the present description. In a particularly preferred embodiment of the invention, at least one additional pharmaceutically active ingredient is included in a composition other than the isRNA composition intended for use as described herein.

At least one additional pharmaceutically active ingredient is not limited to a particular class of compounds. For example, at least one additional pharmaceutically active ingredient may preferably be a compound that is usually used in chemotherapy of a neoplastic or cancerous disease, for which the isRNA specified in the present description is used. Preferably, at least one additional pharmaceutically active ingredient is a compound specified in the present description, intended for use in combination with isPHK, specified in the present description. Alternatively, the at least one additional pharmaceutically active ingredient may preferably be a therapeutic peptide or protein (eg, an antibody or decoy receptor) or a fragment or variant thereof.

In some embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is usually used for the treatment and/or prevention of melanoma, preferably advanced and/or metastatic melanoma, and most preferably advanced cMEL, where the compound is preferably selected from the group consisting of from the following compounds:

nivolumab (opdivo), ipilimumab (winglor, Yervoy®), pembrolizumab (keytruda), dabrafenib mesylate + trametinib dimethyl sulfoxide (tafinlar + mekinist), temozolomide (astromid, temodal, temozolomide), vemurafenib (zelboraf), PEG interferon alfa-2b ( PEG-Intron), Aldesleukin (Proleukin), Bleomycin Sulfate (Bleo, Bleoprim), Carboplatin (Paraplatin), Carmustine (Becenun, Biknu), Cisplatin (Platinol, Cisplatin, Displanor, Nuoxin), Cobimetinib Fumarate (Cotellic), Cyclophosphamide (Endoxan) ), dabrafenib mesylate (tafinlar), dacarbazine (dacarbazine, dacarbazine DBL, DTIC, DTIC-Dome, dacarbazine (Mayne), dacarbazine, dacarbazine, detimedak, dacarb, celdaz, dabase, dakarzine, dakarin, dakmed, onkodak, Dti, dacarbazine (Sandoz), fauldacar, dacarex, dakzin, arzi, tiferomed, acocarb, DTI, evodazine), dactinomycin (cosmegen, cosmegen, cosmegen (Lyovac)), diphenidole hydrochloride (bleocin, raamphen, dimensal), epirubicin hydrochloride (farmorubicin) , fotemustine (muforan, mustoforan, mustoforan, f otemustine), hydroxyurea (hydrin, durea, myelostat, riborea, unidrea, hydran, leukocel, hydroxyurea, hydrea, hydroxyurea), interferon alfa (alfanative, immunox), interferon alfa-2a (itermax alfa, inron-A, intefen, viteron- A, roferon A, alferon), interferon alfa-2b (realfa-2B, shanferon, intron A, viraferon, alfaron, lemoron, liveral, recombinant human interferon alfa-2b, reliferon, Fni 2B, infostat, altevir, lanstion, interferon beta (feron), interleukin-2 (inleusin, recombinant human interleukin-2), irinotecan hydrochloride (camptolem), lomustine (belustine, lomustine, moostin), melanoma cell lysate vaccine (melacin), melphalan (alkacel, alkeran, melphalan) , methotrexate (methotrexate), nivolumab + ipilimumab (opdivo + Yervoy), silatron (PEG-intron, silatron), talimogen lagerparepvek (imglic), tamoxifen citrate (tamoxifen), temozolomide (emzolam, temozolomide, temozolomide LW, tiloshil, temolid, temozod , temozolomide, temizol), trametinib dimethyl sulfoxide (Mekinist), vincristine sulfate (oncovin, vincristine sulfate, vincristine, fauldwincrie, eldizine), (mequinol + tretinoin) (Solage®), dacarbazine (dacarbazine), interferon alfa (biaferon, isiferon), cisplatin; dacarbazine; vindesine sulfate, fibrin sealant, tremelimumab, interferon alfa-2b, recombinant interferon alfa, imiquimod, etanercept, sorafeniba tosylate; sunitinib malate, aldesleukin, imatinib mesylate; nilotinib, sargramostim, aldesleukin, ipilimumab; sargramostim, ipilimumab, pasireotide, aldesleukin; ipilimumab, vemurafenib, melphalan, cetuximab; cisplatin; cyclophosphamide; dacarbazine; docetaxel; doxorubicin; etoposide; fluorouracil; gemcitabine hydrochloride; irinotecan hydrochloride; oxaliplatin; paclitaxel; pemetrexed disodium; temozolomide, interferon alfa-2b; silatron, bleomycin, talimogen lagerparepvec, dabrafenib mesylate; dabrafenib mesylate + trametinib dimethyl sulfoxide; trametinib dimethyl sulfoxide; vemurafenib, trametinib dimethyl sulfoxide, dabrafenib mesylate; trametinib dimethyl sulfoxide, dabrafenib mesylate, granulocyte and macrophage colony stimulating factor; ipilimumab, bleomycin; undeclared chemotherapy, ipilimumab; vemurafenib, nivolumab, bortezomide; cabozantinib s-malate; ceritinib; crizotinib; dasatinib; erlotinib hydrochloride; everolimus; gefitinib; imatinib; lapatinib ditosylate; nilotinib; olaparib; palbociclib; pazopanib hydrochloride; ramucirumab; regorafenib; sorafenib tosylate; sunitinib malate; trametinib dimethyl sulfoxide; vorinostat, bortezomid; cabozantinib s-malate; ceritinib; crizotinib; dasatinib; erlotinib hydrochloride; everolimus; gefitinib; imatinib; lapatinib ditosylate; nilotinib; olaparib; palbociclib; pazopanib hydrochloride; ramucirumab; regorafenib; sorafenib tosylate; sunitinib malate; trametinib dimethyl sulfoxide; vorinostat, aminolevulinic acid hydrochloride, dabrafenib mesylate; vemurafenib, pembrolizumab, GSK-2132231 A, fotemustine, M-Vax, melphalan; tumor necrosis factor alpha, canvaxin, aldesleukin; tumor-infiltrating lymphocytes, interferon alfa-2a, talimogen lagerparepvek, aldesleukin; cisplatin; dacarbazine; filgrastim; interferon alpha; vinblastine, velimogen aliplasmide, oblimersen sodium, metastatic melanoma gp100 antigen targeting vaccine, temozolomide, velimogen aliplasmide, sorafeniba tosylate, DHA-paclitaxel, melphalan, vitespen, cisplatin; dacarbazine, PEG interferon alfa-2b, lenalidomide, melanoma cell lysate vaccine, celecoxib, sodium tazisulam, albumin-bound paclitaxel, sorafeniba tosylate, aldesleukin; histamine dihydrochloride, canvaxin, sorafenib tosylate, GM2-KLH + QS21 vaccine, elesclomol; paclitaxel, PEG interferon alfa-2b, BMS-734019; ipilimumab, aldesleukin; cisplatin; dacarbazine; filgrastim; vinblastine, aldesleukin; cisplatin; dacarbazine; interferon alfa-2b; vinblastine sulfate, dacarbazine; sodium oblimersen, bevacizumab, sodium oblimersen, cisplatin; cytarabine; paclitaxel; treosulfan, melanoma vaccine, melphalan; recombinant tumor necrosis factor, GM2-KLH vaccine; QS-21, polyvalent melanoma vaccine + BCG vaccine, aldesleukin; cisplatin; dacarbazine; interferon alpha; vinblastine, temozolomide, interferon gamma; melphalan; tumor necrosis factor alpha, melanoma cellular immunotherapy, retinol, interferon alpha-2a, Corynebacterium granulosum P40 fraction, melphalan, cisplatin, Bacillus Calmette-Guérin vaccine; cyclophosphamide, aldesleukin; cisplatin; dacarbazine; interferon alpha; vinblastine, ranibizumab, interferon alfa, Bacillus Calmette-Guerin vaccine, Bacillus Calmette-Guerin vaccine, melphalan, interferon alfa, megestrol, interferon alfa-2, cisplatin; dacarbazine, a vaccine based on the bacillus Calmette-Guerin; dacarbazine, aldesleukin; lysophyllin, dabrafenib mesylate, cyclophosphamide; dactinomycin; vincristine, Bacillus Calmette-Guerin vaccine, Bacillus Calmette-Guerin vaccine; dacarbazine, trametinib dimethyl sulfoxide, PV-10, holocalciferol, tumolol maleate, mazitinib, fotemustine; interferon alfa-2b, talimogen lagerparepvec, sodium biselenite, cisplatin; dacarbazine; vindesine, isotretinoin, silatron, fotemustine, seviprotimut-L, dabrafeniba mesylate; trametinib dimethyl sulfoxide, PEG interferon alfa-2a, aldesleukin; isotretinoin; PEG interferon alfa-2b, dabrafenib mesylate; trametinib dimethyl sulfoxide, cobimetinib fumarate; vemurafenib, interferon alfa-2b; M-Vax, nivolumab, dacarbazine; paclitaxel, M-200, holocalciferol, binimetinib, melphalan, sargramostim, pembrolizumab, malignant melanoma gene therapy, eltrapuldensel-T, binimetinib; encorafenib, sargramostim; tyrosinase peptide vaccine, pembrolizumab; talimogen lagerparepvec, autologous tumor-infiltrating lymphocytes, talimogen lagerparepvek, dabrafenib mesylate; ipilimumab; nivolumab; trametinib dimethyl sulfoxide, aldesleukin; cyclophosphamide; fludarabine; lymphocytes, PV-10, talimogen lagerparepvec, HM-95573, dabrafenib mesylate; trametinib dimethyl sulfoxide, interferon beta, ipilimumab; nivolumab, darleukin; fibromun, LN-144, binimetinib, epacadostat; pembrolizumab, sodium oblimersen, sodium agatolimod, lenalidomide, interferon alfa-2a; PEG interferon alfa-2a, CSF-470, melanoma vaccine modified to express ligand for HLA A2/4-1BB (Metastatic Melanoma Cellular Immunotherapy), ipilimumab; nivolumab; sargramostim, ImmuniCell® (cellular immunotherapy for cancer and viral infections), trabedersen, VTH-1677, trametinib dimethyl sulfoxide, melphalan (melblez), AS 15 + recMAGE-A3, binimetinib, binimetinib + encorafenib, cellular immunotherapy for cancer and viral infections, CSF-470 , dabrafenib mesylate (tafinlar), dabrafenib mesylate + trametinib

dimethyl sulfoxide, darleukin, encorafenib, epacadostat, mazitinib, PV-10, sargramostim (leukin), seviprotimut-L, trabedersen, breast cancer, melanoma and soft tissue sarcoma vaccine, and vemurafenib (zelboraf).

In the most preferred embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is generally used for the treatment and/or prevention of melanoma, preferably advanced and/or metastatic melanoma, and most preferably advanced cMEL, where the compound is a PD-1 inhibitor, preferably an anti-PD-1 antagonist antibody, preferably selected from the group consisting of nivolumab (opdivo) and pembrolizumab (keytruda).

In specific embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is generally used for the treatment and/or prevention of squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC, where the compound is preferably selected from the group , consisting of the following compounds: cetuximab (erbitux), albumin-bound paclitaxel (abraksan), (gimeracil + oteracil + tegafur) (TS-1), docetaxel (docetaxel, doxel, taxotere, docetaxel An, docel, nanoxel M, tautax, docetaxel-AS, docetaxel-M, quidadotax, Relidoce™, taxelo, oncodosel, doxotel, pacancer, docetrust, dodetax, dodabur, sulaxcin, taxedol, docefim, docetaxel, ribodocel, critidoc, azodoc, chemodoc, docelibbs, docenate, dincilezan, dostradixinol , docefrez, kamitotic, oncotaxel, somatixel, belotaxel, quidadotax, tactseus, cetadocur, docetaxel ST, tevaxter, dociren, eurotere, axtere, coelotax, taxanite, d robanos, cetado, doxocad, tactseus, aegidox, tedocad, docecad, docelex, docetax, docetaxel, docetere, dotax, taxuba, monotaxel, taceedo, detaxl, docet, docetaxel, ferdotax, vintaxel), (tegafur + uracil) (Uft, Uft E, tefudex, unitoral, luporal, tagracil), fluorouracil (5-FU), (gimeracil + oteracil + tegafur) ODT (OD TS-1 combination), bleomycin sulfate (tecnomycin, cinaleo, bleomycin, bloicin-S, bonar, bleocin , bleomycin sulfate, bleo, bleocel, bleotex, oncobleo, bleonco, bleozol, lyoble, bleomycin sulfate, blenamax, bleomycin, blenoxan, bleomycin, bleomycin bellon, bleoprim), carboplatin (carboplatin, patamin CS, carbachcord, carboplatin, carboplatino, paraplatin, carbosine, tecnocarb, carbomerc, paract, carboplatin CTRS, carboplatin from Intsel Chimos, carboplatin, carbochem, carbotinol, fauldcarbo, evocarbo, cytoplatin, platin), ciprofloxacin (hypoflox, ufexil), ciprofloxacin hydrochloride (ciprofloxacin from Pharma), prodine, cyproxin) , cisplatin (cisplatin, street in, ifapla, accocyt, unistin, carcinotin, cisplan, cytoplax, nuoxin, placis, cisplatino, displanor, randa, cispla, fauldcispla, briplatin, platinex, platinol, platinex, riboplatin, cisplatin, platinum CS, platosin, accocyt, cisplatino), cyclophosphamide (endoxan, cyclophosphamide), doxyuridine (doxyuridine from May Vladimir), doxorubicin (doxorubicin hydrochloride, adriamycin RDF, doxorubicin, doxorubicin PFS), epirubicin, hydrochloride (brecila, epirubicin hydrochloride (Cloridrato De Epirrubicina), epirubicin, farmorubicin, nuovodox, adnexa , 4-eppedo, flavicin), fluorouracil (agicyl, fluorouracil, fouldfluor, oncurcil, flocil, 5 flucel), folic acid + methotrexate (truxophore), human adenovirus type 5 (recombinant) (oncorin), hydroxyurea (oxyurea, durea, myelostat , riborea, unidrea, ondrea, hydran, leucocel, hydroxyurea, hydrea), ifosfamide (goloxan, ifosfamide EG), levamisole (zirzol), methotrexate (tratoben, methotrexate, fresexate, neometo, fouldmetro, methotrexa sodium t, methocel, gytas, metachord, metofill, methotrexato, traxocord, plastomet, tevatrex, metrex, kadytrex, cardiotrex, vibzi, imutrex, biotrexate, metorex, meksat, neotrexate, oncotrex, remtrex, tryxylem, Hi-trex, metorex, track , unitrexate, ebetrexac, fouldexato, lantarel, maxtrex, myantrex CS, rheumatrex, folex, folex PFS, abitrexate, tevameto, trxall, emtrexate, abitrexate, meadow), mitomycin (mitomycin C, mitomycin, mitonko, lyomite), nedaplatin (jiebaishu, aoxanda, akupla), nimesulide (nimulide), nimotuzumab (biomab EGFR, ledemab), nitrofurantoin (furatsilin), ofloxacin (entof), paclitaxel (paclitaxel, taxol), peplomycin sulfate (pepleo), picibanil (picibanil), pyrarubicin (pyrarubicin hydrochloride) , terarubicin, pinorubine), sodium glycidazole (CMNa), tegafur (utephos, icarus, futrafur, tegafur, gimeracil, oteracil potassium), temoporfin (foscan), topotecan hydrochloride (topotecan), ubenimex (ubenimex), vinblastine sulfate (vinblastine, vblastine ), vincristine sulfate (vincristine, vincristine sulfate, vincristine, sutuvin, vindesine sulfate (eldizine), carboplatin (qualimed carboplatin, carboplatin, carboplatino, carboplatin), cisplatin (cisplatin), docetaxel (camidocon, naltoxater, docetaxel), fluorouracil (fluorouracil, fluorouracil, fluorouracil), methotrexate (methotrexate sodium, mexate, mexate Aq, biometrox, medsatrexate, otaxem), vincristine sulfate (oncovin), fluorouracil, sunitinib malate, acitretin, fibrin sealant, cetuximab, cetuximab, erlotinib, cisplatin; docetaxel; fluorouracil, undeclared cancer drug, gefitinib, pravastatin sodium, sirolimus, undeclared chemotherapy, cisplatin; docetaxel; fluorouracil, sirolimus, fluorouracil; undeclared taxane, methylaminolevulinate hydrochloride, cisplatin; docetaxel; fluorouracil, erlotinib hydrochloride, cetuximab, imiquimod, undeclared Chinese herbal medicine, aspirin; enalapril maleate, undeclared chemotherapy, cetuximab, (gimeracil + oteracil + tegafur); carboplatin; cisplatin, cisplatin; fluorouracil; nimotuzumab, carboplatin; albumin-bound paclitaxel, cisplatin; nedaplatin, bleomycin, nedaplatin, cisplatin; paclitaxel, albumin-bound paclitaxel, (gimeracil + oteracil + tegafur), bleomycin; undeclared chemotherapy, apatinib; docetaxel, undeclared immunomodulatory supplement, BCM-95, aminolevulinic acid hydrochloride, nedaplatin, cisplatin; palifermin, cetuximab, gefitinib, bevacizumab, belagenpumatucel-L, cisplatin; tirapazamine, cisplatin; tirapazamine, cisplatin; gemcitabine; paclitaxel; topotecan; vinorelbine, cisplatin; fluorouracil, panitumumab, carboplatin; docetaxel; gemcitabine hydrochloride; vinorelbine tartrate, aminophostin; fluorouracil, cisplatin; fluorouracil, carboplatin; paclitaxel, tirapazamine, cisplatin; epoetin alfa, figitumumab, melphalan; tumor necrosis factor alpha, cisplatin, cisplatin; fluorouracil, cisplatin; undeclared chemotherapy, docetaxel, ladenovec contusugen, cisplatin; fluorouracil; paclitaxel, docetaxel, human papillomavirus vaccine (bivalent) [serotypes 16, 18], isotretinoin, cisplatin; fluorouracil, misonidazole, paclitaxel, palifermin, endostatin, pilocartin, cisplatin; docetaxel; filgrastim; fluorouracil; paclitaxel, cisplatin; docetaxel; filgrastim; fluorouracil; paclitaxel, cisplatin; irinotecan hydrochloride, cisplatin; gemcitabine, cisplatin; epirubicin; fluorouracil; undeclared chemotherapy, methylaminolevulinate hydrochloride, carboplatin; paclitaxel, carbogen; carbon dioxide; niacinamide, cisplatin; fluorouracil, talimogen lagerparepvec, epoetin alfa, cisplatin; fluorouracil; panitumumab, cisplatin; fluorouracil, cisplatin; fluorouracil, aldesleukin, cisplatin; fluorouracil, cisplatin; paclitaxel, cisplatin; fluorouracil, fluorouracil; leucovorin; lobaplatin, cisplatin, cisplatin; ethyl mercaptan; ifosfamide; mesna; mitolactol, doxorubicin; levamisole, (tegafur + uracil), cisplatin; fluorouracil, cisplatin; vinorelbine, carboplatin; cisplatin; gemcitabine hydrochloride, Corynebacterium parvum; doxorubicin, capecitabine; cisplatin; fluorouracil; paclitaxel, fluorouracil; leucovorin; methotrexate, rAd-p53, cetuximab; cisplatin; docetaxel, PV-10, methylaminolevulinate hydrochloride, cisplatin; fluorouracil, paclitaxel; topotecan hydrochloride, carboplatin; cisplatin; paclitaxel, cisplatin; topotecan hydrochloride, cisplatin; etoposide, docetaxel; fluorouracil, aspirin, cisplatin; gemcitabine, Lactobacillus brevis CD2, cisplatin; docetaxel, fosbretabulin tromethamine, panitumumab, fluorouracil, paclitaxel, carboplatin; cisplatin; docetaxel; fluorouracil, fluorouracil, erlotinib hydrochloride, cisplatin; undeclared chemotherapy; vinorelbine, (gimeracil + oteracil + tegafur); carboplatin, cetuximab, contusugen ladenovec, cetuximab, methylaminolevulinate hydrochloride, cyclophosphamide, (gimeracil + oteracil + tegafur); cisplatin, albumin-bound paclitaxel, carboplatin; paclitaxel, cisplatin; gemcitabine, capecitabine; cisplatin, docetaxel, Z-100, cisplatin; ifosfamide; paclitaxel, nimotuzumab, irinotecan hydrochloride, celecoxib; methotrexate, nutrison, carboplatin; cisplatin; fluorouracil; paclitaxel, cisplatin; paclitaxel, cisplatin; docetaxel; vinorelbine, paclitaxel, (gimeracil + oteracil + tegafur); cisplatin, carboplatin; paclitaxel, methylaminolevulinate hydrochloride, aibin, cisplatin; fluorouracil, sodium porfimer, carboplatin; cisplatin; tocotrienol; vinorelbine, (gimeracil + oteracil + tegafur); cisplatin; paclitaxel, docetaxel, ipilimumab, cisplatin, VB-4847, celecoxib; thalidomide, cisplatin; epirubicin; fluorouracil, cisplatin; fluorouracil, fluorouracil, carboplatin; paclitaxel, cetuximab; cisplatin; docetaxel, autologous cytokine-induced killer cells, cisplatin; docetaxel; fluorouracil, cisplatin; epirubicin; fluorouracil, tergenpumatucel-L, cetuximab; cisplatin; docetaxel, elenthal, cisplatin; nimotuzumab; paclitaxel, eicosapentanoic acid; an undeclared nutritional supplement, palbociclib, pembrolizumab (keytruda), nimotuzumab, aptorsen, and dacomitinib.

In the most preferred embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is typically used for the treatment and/or prevention of squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC, where the compound is an inhibitor PD-1, preferably an anti-PD-1 antagonist antibody, preferably selected from the group consisting of nivolumab (opdivo) and pembrolizumab (keytruda).

), карбоплатин; цисплатин; фторурацил; паклитаксел, Биафин, метотрексат, цисплатин; фторурацил, альфа токоферол; изотретиноин; рекомбинантный интерферон альфа, панитумумаб, цисплатин, блеомицин; фторурацил; леуковорин; метотрексат; винкристин, нимотузумаб, панитумумаб, аминофостин; фторурацил, цисплатин; доцетаксел; фторурацил, капецитабин; цисплатин; фторурацил, пеметрексед динатрия, цисплатин; гемцитабин, транексамовая кислота, карбоплатин; фторурацил, цефазолин, эпоэтин альфа, тирапазамин, эрлотиниба гидрохлорид, цетуксимаб; доцетаксел; фторурацил, мегестрол, контусуген ладеновек, цевимелина гидрохлорид, цисплатин; фторурацил, цисплатин; фторурацил; паклитаксел, изотретиноин, порфиромицин, эскиталопрама оксалат, гимерацил + отерацил + тегафур, IntraDose (цисплатин плюс эпинефрин), мизонидазол, тирапазамин, карбоплатин; цисплатин; доцетаксел; фторурацил, гефитиниб, эпоэтин альфа, паклитаксел, гефитиниб, палифермин, пилокартин, целекоксиб, цисплатин; доцетаксел; филграстим; фторурацил; паклитаксел, цисплатин; фторурацил; леуковорин, цисплатин; гемцитабин; маннит, Lactobacillus brevis CD2, глутамин, карбоген; ниацинамидем, цетуксимаб; цисплатин; доцетаксел; фторурацил, карбоген; диоксид углерода; ниацинамид, цисплатин; доцетаксел; фторурацил, растворимый бета-глюкан, контусуген ладеновек, залутумумаб, талимоген лагерпарепвек, сукралфат, доксепин, метотрексат, аминофостин, капсаицин, цисплатин; фторурацил; панитумумаб, алдеслейкин, транексамовая кислота, цинка сульфат, вакцина на основе бациллы Кальметта-Герена [коннаут]; блеомицин; циклофосфамид; фторурацил; метотрексат, аминофостин, фторурацил; гидроксимочевина, бацитрацин; клотримазол; гентамицин, циклофосфамид; доксорубицин, пелареореп, филграстим, энтеральное питание (enteral nutrition!!!), пентоксифиллин, эпирубицин; фторурацил; леуковорин; митомицин, порфиромицин, блеомицин; цисплатин; метотрексат; винкристин, вакцина на основе бациллы Кальметта-Герена; изониазид; метотрексат, фторурацил; леуковорин;метотрексат, rAd-p53, PV-10, Лейкоцитарный интерлейкин, нимотузумаб, афатиниба дималеат, афатиниба дималеат; цисплатин, карбоплатин; цетуксимаб; фторурацил, цетуксимаб; цисплатин, недаплатин, доцетаксел; фторурацил, ниморазол, гемцитабина гидрохлорид, афатиниба дималеат, недаплатин, контусуген ладеновек, Lactobacillus brevis CD2, цетуксимаб, нимотузумаб, Е-10А, цисплатин; гемцитабин, цисплатин; лобаплатин, эндостатин (рекомбинантный)_дапсон; доксициклин; миноциклин, карбоплатин; циклофосфамид; доцетаксел;доксорубицин; паклитаксел, ниволумаб, пелареореп, аутологичные стволовые клетки; карбоплатин; этопозид; ифосфамид, винфлунина дитартрат, гемцитабин, цисплатин; фторурацил; митомицин, порфиромицин, олимел, пембролизумаб, AminoPure (пищевая добавка), недаплатин, Liang Ge San (пищевая добавка), эйкозапентаноевая кислота, целекоксиб; метотрексат, цисплатин; пембролизумаб, (тегафур + урацил); цисплатин; эпирубицин; митомицин, дурвалумаб; тремелимумаб, натрия гипохлорид, цетуксимаб; цисплатин, цисплатин; паклитаксел, амказертиб, капецитабин, R-TPR-033, VB-4847, габапентин, ралтитрексед, цисплатин; фторурацил; леуковорин, цисплатин; доцетаксел, целекоксиб, дурвалумаб; дурвалумаб + тремелимумаб, ТТ-10, (натрия альгинат + натрия карбонат + прополис + алоэ вера + календула + мед + ромашка); цисплатин, пембролизумаб; талимоген лагерпарепвек, авелумаб, ниморазол, эйкозапентаноевая кислота, ловастатин, дексаметазон; этопозид; гемцитабин; ПЭГ-аспаргаза, ипилимумаб; ниволумаб, цетуксимаб; цисплатин; ниволумаб, капецитабин; цисплатин; доцетаксел, изотретиноин, карбоплатин; цисплатин; гемцитабин;паклитаксел, эрлотиниба гидрохлорид, VB-4847 (проксиний плюс наилучший поддерживающий уход), целекоксиб; талидомид, цисплатин; фторурацил, куркумин, целекоксиб, имиквимод, цисплатин; циклофосфамид; этопозид, зотатерцепт, цисплатин; доцетаксел; фторурацил, цетуксимаб; цисплатин; доцетаксел, человеческий эндостатин, мелатонин, эпигаллокатехина галлат, цисплатин; гемцитабин, гемцитабин; паклитаксел, (гимерацил + отерацил + тегафур), эйкозапентаноевая кислота; незаявленная питательная добавка, целекоксиб; метотрексат, пембролизумаб (кейтруда), афатиниба дималеат, цетуксимаб (эрбитукс), дурвалумаб, дурвалумаб + тремелимумаб, Е-10А, энтректиниб, лйкоцитарный интерлейкин (мультикин), нимотузумаб, ниволумаб (опдиво), пелареореп (реолизин), ТТ-10, винфлунина дитартрат (явлор), акалобрутиниб, вакцина AlloVax и алпелизиб.In some embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is typically used for the treatment and/or prevention of head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, where the compound is preferably selected from the group consisting of of the following compounds: nivolumab, cetuximab (erbitux), albumin-bound paclitaxel (abraksan), gimeracil + oteracil + tegafur (TS-1), docetaxel (docetaxel, doxel, taxotere, docetaxel An, nanoxel M, tautax, docetaxel-AS, docetaxel-M, quidadotax, relidoce, taxelo, oncodosel, doxotel, pacancer, docetrust, dodetax, dodabur, sulaxcin, taxedol, docefim, ribodocel, critidoc, azodoc, chemodoc, docelibbs, docenat, dincilezan, dostradixinol, docefrez, kamitotic, oncotaxel, somatixel, belotaxel, quidadotax, takceus, cetadocur, docetaxel ST, tevaxter, dociren, eurotere, axtere, celotax, taxanite, drobanos, cetado, do xocad, tacceus, aegidox, tedocad, docecad, docelex, docetax, docetere, dotax, taxuba, monotaxel, taceedo, detaxl, docet, ferdotax, vintaxel, kamidocon, naltoxater), tegafur + uracil (Uft, Uft E, tefudex, unitoral, luporal tagracil), fluorouracil (bn: 5-FU, fluorouracil, fluorouracil), gimeracil + oteracil + tegafur ODT (OD bn TS-1 combination), bleomycin sulfate (tecnomycin, cinaleo, bleomycin, bloicin-S, bonar, bleocin, bleo , bleomycin sulfate, bleocel, bleotex, oncobleo, bleonco, bleozol, lyoble, bleomycin sulfate, blenamax, blenoxan, bleomycin, bleomycin Bellon!!!, bleoprim), carboplatin , tecnocarb, carbomerc, paract, carboplatin CTRS, carboplatin from Intsel Chimos, carbochem, carbotinol, fauldcarbo, evocarbo, cytoplatin, platinum, carboplatin from Qualimed, carboplatin, carboplatino, carboplatin), ciprofloxacin (hypoflox, ufexil), ciprofloxacin hydrochloride (ciprofloxacin firms s Pharma, prodin, cyproxin), cisplatin (cisplatin, stritin, ifapla, accocyt, unistin, carcinotin, cisplan, cytoplax, nuoxin, placis, cisplatino, displanor, cisplatin, randa, cisplatin, cisplatin, fouldcispla, briplatin, platinex, platinol, riboplatin, platistin CS, platosin, accocyt), cyclophosphamide (endoxan, cyclophosphamide), doxyuridine (May Vladimir's doxyuridine, doxyuridine), doxorubicin (doxorubicin hydrochloride, adriamycin RDF, doxorubicin, doxorubicin hydrochloride, doxorubicin PFS), epirubicin hydrochloride (brecila, Cloridrato De Epirrubicina, epirubicin, farmorubicin, nuovodox, adnexa, 4-eppedo, flavicin), fluorouracil (agicyl, fluorouracil, fauldfluor, oncurcil, flocil, 5-flucel), folic acid + methotrexate (truxophore), human adenovirus type 5 (recombinant) (Oncorin), Hydroxyurea (Oxyurea, Durea, Myelostat, Riborea, Unidrea, Ondrea, Hydran, Leukocel, Hydroxyurea, Hydrea), Ifosfamide (Goloxan, Ifosfamide EG), Levamisole (Zirzol), Methotrexate (Tratobe n, methotrexate, fresexate, neometo, fouldmetro, sodium methotrexate, methocel, gytas, metachord, methophyll, methotrexato, traxocord, plastomet, tevatrex, metrex, cadytrex, cardiotrex, vibzy, imutrex, biotrexate, metorex, meksat, neotrexate, ontrexotrex, remtrex , Trixylem, Hi-Trex, Metorex, Tracke, Unitrexate, Ebetrexac, Fouldexato, Lantarel, Maxtrex, Miantrex CS, Rheumatrex, Folex, Folex PFS, Abitrexate, Trxall, Emtrexate, Abitrexate, Meadow, Mexat Aq, Biometrox, Otaxem), Mitomycin (mitomycin C, mitomycin, mitonko, lyomite), nedaplatin (jiebaishu, aoxanda, akupla), nimesulide (nimulide), nimotuzumab (EGFR biomab, ledemab), nitrofurantoin (furatsilin), ofloxacin (entof), paclitaxel (paclitaxel, taxol), peplomycin sulfate (pepleo), picibanil (picibanil), pyrarubicin (pyrarubicin hydrochloride, terarubicin, pinorubine), sodium glycidazole (CMNa), tegafur (utefos, icarus, futrafur, tegafur, gimeracil, oteracil potassium), temoporfin (foscan), topotecan hydrochloride (topotecan), at benimex (ubenimex), vinblastine sulfate (vinblastine, vblastine, vincristine, vincristine sulfate, vincristine, sutuvin, vincrisane, eldizine), vincristine sulfate (oncovin), gefitinib, escitalopram oxalate, gene therapy to activate p53 in oncology, cevimeline hydrochloride, docetaxel; lenograstim, bortezomid; docetaxel; irinotecan, carboplatin; paclitaxel, cisplatin; docetaxel; fluorouracil, human papillomavirus vaccine (vaccination against human papillomavirus types 16 and 18 and unvaccinated controls), carboplatin; cisplatin; paclitaxel, an undeclared epidermal growth factor receptor inhibitor, cetuximab, sorafenib tosylate; sunitinib malate, aminophostin, cisplatin; dexamethasone; docetaxel; metoclopramide, platinum-based chemotherapy, cetuximab; nimotuzumab, nimotuzumab, dobutamine hydrochloride; dopexamine hydrochloride; epinephrine; norepinephrine bitartrate, cetuximab; cisplatin, cetuximab; cisplatin; docetaxel; fluorouracil, cisplatin; paclitaxel, gendicin, doce oncovis (docetaxel), picibanil, docetaxel; lobaplatin, oxytetracycline hydrochloride, cisplatin; mitomycin, bleomycin, nimotuzumab, cisplatin; fluorouracil; nimotuzumab, cetuximab; cisplatin; cyclophosphamide; dacarbazine; docetaxel; doxorubicin; etoposide; fluorouracil; gemcitabine hydrochloride; irinotecan hydrochloride; oxaliplatin; paclitaxel; pemetrexed disodium; temozolomide, varenicline, acetylcysteine, dopamine; norepinephrine, (gimeracil + oteracil + tegafur), nimotuzumab, icotinib hydrochloride, kushen (kuh-seng), carboxymethylpachymaran, BCM-95, lactofos, PEG-filgrastim, methadone, varanadi grita, cisplatin; palifermin, cetuximab, cisplatin; lapatinib ditosylate, gefitinib, zalutumumab, erlotinib hydrochloride, beta carotene; E-Tabs, bevacizumab, levothyroxine; liothyronine sodium; recombinant human thyroid-stimulating hormone, cisplatin; docetaxel; fluorouracil; hydroxyurea, fluorouracil, docetaxel; hypericum extract (

), carboplatin; cisplatin; fluorouracil; paclitaxel, biafin, methotrexate, cisplatin; fluorouracil, alpha tocopherol; isotretinoin; recombinant interferon alfa, panitumumab, cisplatin, bleomycin; fluorouracil; leucovorin; methotrexate; vincristine, nimotuzumab, panitumumab, aminofostin; fluorouracil, cisplatin; docetaxel; fluorouracil, capecitabine; cisplatin; fluorouracil, pemetrexed disodium, cisplatin; gemcitabine, tranexamic acid, carboplatin; fluorouracil, cefazolin, epoetin alfa, tirapazamine, erlotinib hydrochloride, cetuximab; docetaxel; fluorouracil, megestrol, ladenovec contusugen, cevimeline hydrochloride, cisplatin; fluorouracil, cisplatin; fluorouracil; paclitaxel, isotretinoin, porfiromycin, escitalopram oxalate, gimeracil + oteracil + tegafur, IntraDose (cisplatin plus epinephrine), misonidazole, tirapazamine, carboplatin; cisplatin; docetaxel; fluorouracil, gefitinib, epoetin alfa, paclitaxel, gefitinib, palifermin, pilocartin, celecoxib, cisplatin; docetaxel; filgrastim; fluorouracil; paclitaxel, cisplatin; fluorouracil; leucovorin, cisplatin; gemcitabine; mannitol, Lactobacillus brevis CD2, glutamine, carbogen; niacinamide, cetuximab; cisplatin; docetaxel; fluorouracil, carbogen; carbon dioxide; niacinamide, cisplatin; docetaxel; fluorouracil, soluble beta-glucan, ladenovec contusugen, zalutumumab, talimogen lagerparepvec, sucralfate, doxepin, methotrexate, aminophostin, capsaicin, cisplatin; fluorouracil; panitumumab, aldesleukin, tranexamic acid, zinc sulfate, Bacillus Calmette-Guerin vaccine [connaught]; bleomycin; cyclophosphamide; fluorouracil; methotrexate, aminophostin, fluorouracil; hydroxyurea, bacitracin; clotrimazole; gentamicin, cyclophosphamide; doxorubicin, pelareorep, filgrastim, enteral nutrition (enteral nutrition!!!), pentoxifylline, epirubicin; fluorouracil; leucovorin; mitomycin, porfiromycin, bleomycin; cisplatin; methotrexate; vincristine, a vaccine based on the bacillus Calmette-Guerin; isoniazid; methotrexate, fluorouracil; leucovorin; methotrexate, rAd-p53, PV-10, Leukocyte interleukin, nimotuzumab, afatinib dimaleate, afatinib dimaleate; cisplatin, carboplatin; cetuximab; fluorouracil, cetuximab; cisplatin, nedaplatin, docetaxel; fluorouracil, nimorazole, gemcitabine hydrochloride, afatinib dimaleate, nedaplatin, ladenovec contusugen, Lactobacillus brevis CD2, cetuximab, nimotuzumab, E-10A, cisplatin; gemcitabine, cisplatin; lobaplatin, endostatin (recombinant)_dapsone; doxycycline; minocycline, carboplatin; cyclophosphamide; docetaxel; doxorubicin; paclitaxel, nivolumab, pelareorep, autologous stem cells; carboplatin; etoposide; ifosfamide, vinflunine ditartrate, gemcitabine, cisplatin; fluorouracil; mitomycin, porfiromycin, olimel, pembrolizumab, AminoPure (food supplement), nedaplatin, Liang Ge San (food supplement), eicosapentanoic acid, celecoxib; methotrexate, cisplatin; pembrolizumab (tegafur + uracil); cisplatin; epirubicin; mitomycin, durvalumab; tremelimumab, sodium hypochlorite, cetuximab; cisplatin, cisplatin; paclitaxel, amcasertib, capecitabine, R-TPR-033, VB-4847, gabapentin, raltitrexed, cisplatin; fluorouracil; leucovorin, cisplatin; docetaxel, celecoxib, durvalumab; durvalumab + tremelimumab, TT-10, (sodium alginate + sodium carbonate + propolis + aloe vera + calendula + honey + chamomile); cisplatin, pembrolizumab; talimogen lagerparepvec, avelumab, nimorazole, eicosapentanoic acid, lovastatin, dexamethasone; etoposide; gemcitabine; PEG-aspargas, ipilimumab; nivolumab, cetuximab; cisplatin; nivolumab, capecitabine; cisplatin; docetaxel, isotretinoin, carboplatin; cisplatin; gemcitabine; paclitaxel, erlotinib hydrochloride, VB-4847 (Proxy Plus Best Supportive Care), celecoxib; thalidomide, cisplatin; fluorouracil, curcumin, celecoxib, imiquimod, cisplatin; cyclophosphamide; etoposide, zotatercept, cisplatin; docetaxel; fluorouracil, cetuximab; cisplatin; docetaxel, human endostatin, melatonin, epigallocatechin gallate, cisplatin; gemcitabine, gemcitabine; paclitaxel, (gimeracil + oteracil + tegafur), eicosapentanoic acid; undeclared nutritional supplement, celecoxib; methotrexate, pembrolizumab (keytruda), afatinib dimaleate, cetuximab (erbitux), durvalumab, durvalumab + tremelimumab, E-10A, entrectinib, lycocytic interleukin (multikin), nimotuzumab, nivolumab (opdivo), pelareorep (reolizin), TT-10, vinflunine ditartrate (javlor), acalobrutinib, AlloVax vaccine, and alpelizib.

In the most preferred embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is typically used for the treatment and/or prevention of head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, where the compound is a PD- inhibitor 1, preferably an anti-PD-1 antagonist antibody, preferably selected from the group consisting of nivolumab (opdivo) and pembrolizumab (keytruda).

), карбоплатин; цисплатин; фторурацил; паклитаксел, биафин, метотрексат, цисплатин; фторурацил, альфа токоферол; изотретиноин; рекомбинантный интерферон альфа, панитумумаб, цисплатин, блеомицин; фторурацил; леуковорин; метотрексат; винкристин, нимотузумаб, панитумумаб, аминофостин; фторурацил, цисплатин; доцетаксел; фторурацил, капецитабин; цисплатин; фторурацил, пеметрексед динатрия, цисплатин; гемцитабин, транексамовая кислота, карбоплатин; фторурацил, цефазолин, эпоэтин альфа, тирапазамин, эрлотиниба гидрохлорид, цетуксимаб; доцетаксел; фторурацил, мегестрол, контусуген ладеновек, цевимелина гидрохлорид, цисплатин; фторурацил, цисплатин; фторурацил; паклитаксел, изотретиноин, порфиромицин, эскиталопрама оксалат, гимерацил + отерацил + тегафур, IntraDose (цисплатин плюс эпинефрин), мизонидазол, тирапазамин, карбоплатин; цисплатин; доцетаксел; фторурацил, гефитиниб, эпоэтин альфа, паклитаксел, гефитиниб, палифермин, пилокартин, лцелекоксиб, цисплатин; доцетаксел; филграстим; фторурацил; паклитаксел, цисплатин; фторурацил; леуковорин, цисплатин; гемцитабин; маннит, Lactobacillus brevis CD2, глутамин, карбоген; ниацинамид, цетуксимаб; цисплатин; доцетаксел; фторурацил, карбоген; диоксид углерода; ниацинамид, цисплатин; доцетаксел; фторурацил, растворимый бета-глюкан, контусуген ладеновек, залутумумаб, талимоген лагерпарепвек, сукралфат, доксепин, метотрексат, аминофостин, капсаицин, цисплатин; фторурацил; панитумумаб, алдеслейкин, транексамовая кислота, цинка сульфат, вакцина на основе бациллы Кальметта-Герена [connaught]; блеомицин; циклофосфамид; фторурацил; метотрексат, аминофостин, фторурацил; гидроксимочевина, бацитрацин; клотримазол; гентамицин, циклофосфамид; доксорубицин, пелареореп, филграстим, энтеральное питание, пентоксифиллин, эпирубицин; фторурацил; леуковорин; митомицин, порфиромицин, блеомицин; цисплатин; метотрексат; винкристин, вакцина на основе бациллы Кальметта-Герена; изониазид; метотрексат, фторурацил; леуковорин;метотрексат, rAd-p53, PV-10, лейкоцитарный интерлейкин, нимотузумаб, афатиниба дималеат, афатиниба дималеат; цисплатин, карбоплатин; цетуксимаб; фторурацил, цетуксимаб; цисплатин, недаплатин, доцетаксел; фторурацил, ниморазол, гемцитабина гидрохлорид, афатиниба дималеат, недаплатин, контусуген ладеновек, Lactobacillus brevis CD2, цетуксимаб, нимотузумаб, Е-10А, цисплатин; гемцитабин, цисплатин; лобаплатин, эндостатин (рекомбинантный)_дапсон; доксициклин; миноциклин, карбоплатин; циклофосфамид; доцетаксел; доксорубицин; паклитаксел, ниволумаб, пелареореп, аутологичные стволовые клетки; карбоплатин; этопозид; ифосфамид, винфлунина дитартрат, гемцитабин, цисплатин; фторурацил; митомицин, порфиромицин, олимел, пембролизумаб, пищевая добавка AminoPure, недаплатин, пищевая добавка Liang Ge San, эйкозапентаноевая кислота, целекоксиб;метотрексат, цисплатин; пембролизумаб, (тегафур + урацил); цисплатин; эпирубицин; митомицин, дурвалумаб; тремелимумаб, натрия гипохлорит, цетуксимаб; цисплатин, цисплатин; паклитаксел, амказертиб, капецитабин, R-TPR-033, VB-4847, габапентин, ралтитрексед, цисплатин; фторурацил; леуковорин, цисплатин; доцетаксел, лцелекоксиб, дурвалумаб; дурвалумаб + тремелимумаб, ТТ-10, (натрия альгинат + натрия карбонат + прополис + алоэ вера + календула + мед + ромашка); цисплатин, пембролизумаб; талимоген лагерпарепвек, авелумаб, ниморазол, эйкозапентаноевая кислота, ловастатин, дексаметазон; этопозид; гемцитабин; ПЭГ-аспаргаза, ипилимумаб; ниволумаб, цетуксимаб; цисплатин; ниволумаб, капецитабин; цисплатин; доцетаксел, изотретиноин, карбоплатин; цисплатин; гемцитабин; паклитаксел, эрлотиниба гидрохлорид, VB-4847 (проксиниум плюс наилучший поддерживающий уход), целекоксиб; талидомид, цисплатин; фторурацил, куркумин, целекоксиб, имиквимод, цисплатин; циклофосфамид; этопозид, зотатерцепт, цисплатин; доцетаксел; фторурацил, цетуксимаб; цисплатин; доцетаксел, человеческий эндостатин, мелатонин, эпигаллокатехина галлат, цисплатин; гемцитабин, гемцитабин; паклитаксел, (гимерацил + отерацил + тегафур), эйкозапентаноевая кислота; незаявленная питательная добавка, целекоксиб; метотрексат, пембролизумаб (кейтруда), афатиниба дималеат, цетуксимаб (эрбитукс), дурвалумаб, дурвалумаб + тремелимумаб, Е-10А, энтректиниб, лейкоцитарный интерлейкин (мультикин), нимотузумаб, ниволумаб (опдиво), пелареореп (реолизин), ТТ-10, винфлунина дитартрат (явлор), акалобрутиниб, вакцина AlloVax и алпелизиб.In some embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is typically used for the treatment and/or prevention of adenoid cystic carcinoma (ACC), preferably advanced by ACC, where the compound is preferably selected from the group consisting of the following compounds : nivolumab, cetuximab (erbitux), albumin-bound paclitaxel (abraksan), gimeracil + oteracil + tegafur (TS-1), docetaxel (docetaxel, doxel, taxotere, docetaxel An, nanoxel M, tautax, docetaxel-AS, docetaxel-M , Quidadotax, Relidoce, Taxelo, Oncodosel, Doxotel, Pacancer, Docetrust, Dodetax, Dodabur, Sulaxcin, Taxedol, Docefim, Ribodocel, Critidoc, Azodoc, Chemodoc, Docelibbs, Docenat, Dincilezan, Dostradixinol, Docephrez, Kamitotic, Oncotaxel, Somatixel, Belotaxel , quidadotax, takceus, cetadocur, docetaxel ST, tevaxter, dociren, eurotere, akstere, celotax, taxanite, drobanos, cetado, doxocad, tactseus, e hydrox, tedocad, docecad, docelex, docetax, docetere, dotax, taxuba, monotaxel, taceedo, detaxl, docet, ferdotax, vintaxel, kamidocon, naltoxater), tegafur + uracil (Uft, Uft E, tefudex, unitoral, luporal, tagracil) , fluorouracil (bn: 5-FU, fluorouracil, fluorouracil), gimeracil + oteracil + tegafur ODT (combination OD (bn TS-1), bleomycin sulfate (tecnomycin, cinaleo, bleomycin, bloicin-S, bonar, bleocin, bleo, bleomycin sulfate, bleocel, bleotex, oncobleo, bleonco, bleosol, lyoble, bleomycin sulfate, blenamax, blenoxan, bleomycin, Bellon bleomycin, bleoprim), carboplatin (carboplatin, platamin CS, carbaccord, carboplatin, carboplatino, paraplatin, carbosine, tecnocarb, carbomerc , paract, carboplatin CTRS, carboplatin from Intsel Chimos, carbochem, carbotinol, fouldcarbo, evocarbo, cytoplatin, platinum, carboplatin from Qualimed, carboplatin, carboplatino, carboplatin), ciprofloxacin (hypoflox, ufexil), ciprofloxacin hydrochloride (ciprofloxacin Pharma, prodine, c iproxin), cisplatin (cisplatin, stritin, ifapla, accocyt, unistin, carcinotin, cisplan, cytoplax, nuoxin, placis, cisplatino, displanor, cisplatin, randa, cisplatin, cispla, fauldcispla, briplatin, platinex, platinol, riboplatin, platinum CS, platosin, accocyt), cyclophosphamide (endoxan, cyclophosphamide), doxyuridine (doxyuridine, May Vladimir, doxyuridine), doxorubicin (doxorubicin hydrochloride, adriamycin RDF, doxorubicin, doxorubicin hydrochloride, doxorubicin PFS), epirubicin hydrochloride (brecila, Cloridrato De Epirrubicina, epirubicin, pharmarubicin, nuovodox, adnexa, 4-eppedo, flavicin), fluorouracil (agicyl, fluorouracil, fauldfluor, oncurcil, flocil, 5 flucel), folic acid + methotrexate (truxophore), human adenovirus type 5 (recombinant) (oncorin), hydroxyurea ( oxyurea, durea, myelostat, riborea, unidrea, ondrea, hydran, leucocel, hydroxyurea, hydrea), ifosfamide (goloxan, ifosfamide EG), levamisole (zirsol), methotrexate (tratoben, methotrexate, fresexa t, neometo, fouldmetro, sodium methotrexate, methocel, gytas, metachord, methophyll, methotrexato, traxocord, plastomet, tevatrex, metrex, cadytrex, cardiotrex, vibzy, imutrex, biotrexate, metorex, meksat, neotrexate, oncotrex, remtrex, tryxyl, Hi -Trex, metorex, track, unitrexate, ebetrexac, fouldexato, lantarel, maxtrex, myantrex CS, rheumatrex, folex, folex PFS, abitrexate, trxall, emtrexate, abitrexate, meadow, meksat Aq, biometrox, otaxem), mitomycin (mitomycin C, mitomycin, mitonco, lyomite), nedaplatin (jiebaishu, aoxanda, akupla), nimesulide (nimulide), nimotuzumab (EGFR biomab, ledemab), nitrofurantoin (furatsilin), ofloxacin (entof), paclitaxel (paclitaxel, taxol), peplomycin sulfate (pepleo ), picibanil (picibanil), pyrarubicin (pyrarubicin hydrochloride, terarubicin, pinorubin), sodium glycidazole (CMNa), tegafur (utephos, icarus, futrafur, tegafur, himeracil, oteracil potassium), temoporfin (foscan), topotecan hydrochloride (topotecan), ubenimex (ubenimex), vinblastine sulfate (vinblastine, vblastine, vincristine, vincristine sulfate, vincristine, sutuvin, vincrisan, eldizine), vincristine sulfate (oncovin), gefitinib, escitalopram oxalate, gene therapy for p53 activation in oncology, cevimeline hydrochloride, docetaxel; lenograstim, bortezomid; docetaxel; irinotecan, carboplatin; paclitaxel, cisplatin; docetaxel; fluorouracil, human papillomavirus vaccine (vaccination against human papillomavirus types 16 and 18 and unvaccinated controls), carboplatin; cisplatin; paclitaxel, an undeclared epidermal growth factor receptor inhibitor, cetuximab, sorafenib tosylate; sunitinib malate, aminophostin, cisplatin; dexamethasone; docetaxel; metoclopramide, platinum-based chemotherapy, cetuximab; nimotuzumab, nimotuzumab, dobutamine hydrochloride; dopexamine hydrochloride; epinephrine; norepinephrine bitartrate, cetuximab; cisplatin, cetuximab; cisplatin; docetaxel; fluorouracil, cisplatin; paclitaxel, gendicin, doce oncovis (docetaxel), picibanil, docetaxel; lobaplatin, oxytetracycline hydrochloride, cisplatin; mitomycin, bleomycin, nimotuzumab, cisplatin; fluorouracil; nimotuzumab, cetuximab; cisplatin; cyclophosphamide; dacarbazine; docetaxel; doxorubicin; etoposide; fluorouracil; gemcitabine hydrochloride; irinotecan hydrochloride; oxaliplatin; paclitaxel; pemetrexed disodium; temozolomide, varenicline, acetylcysteine, dopamine; norepinephrine, (gimeracil + oteracil + tegafur), nimotuzumab, icotinib hydrochloride, kushen (kuh-seng), carboxymethylpachymaran, BCM-95, lactofos, PEG-filgrastim, methadone, varanadi grita, cisplatin; palifermin, cetuximab, cisplatin; lapatinib ditosylate, gefitinib, zalutumumab, erlotinib hydrochloride, beta carotene; E-Tabs, bevacizumab, levothyroxine; liothyronine sodium; recombinant human thyroid-stimulating hormone, cisplatin; docetaxel; fluorouracil; hydroxyurea, fluorouracil, docetaxel; hypericum extract (

), carboplatin; cisplatin; fluorouracil; paclitaxel, biafine, methotrexate, cisplatin; fluorouracil, alpha tocopherol; isotretinoin; recombinant interferon alfa, panitumumab, cisplatin, bleomycin; fluorouracil; leucovorin; methotrexate; vincristine, nimotuzumab, panitumumab, aminofostin; fluorouracil, cisplatin; docetaxel; fluorouracil, capecitabine; cisplatin; fluorouracil, pemetrexed disodium, cisplatin; gemcitabine, tranexamic acid, carboplatin; fluorouracil, cefazolin, epoetin alfa, tirapazamine, erlotinib hydrochloride, cetuximab; docetaxel; fluorouracil, megestrol, ladenovec contusugen, cevimeline hydrochloride, cisplatin; fluorouracil, cisplatin; fluorouracil; paclitaxel, isotretinoin, porfiromycin, escitalopram oxalate, gimeracil + oteracil + tegafur, IntraDose (cisplatin plus epinephrine), misonidazole, tirapazamine, carboplatin; cisplatin; docetaxel; fluorouracil, gefitinib, epoetin alfa, paclitaxel, gefitinib, palifermin, pilocartin, celecoxib, cisplatin; docetaxel; filgrastim; fluorouracil; paclitaxel, cisplatin; fluorouracil; leucovorin, cisplatin; gemcitabine; mannitol, Lactobacillus brevis CD2, glutamine, carbogen; niacinamide, cetuximab; cisplatin; docetaxel; fluorouracil, carbogen; carbon dioxide; niacinamide, cisplatin; docetaxel; fluorouracil, soluble beta-glucan, ladenovec contusugen, zalutumumab, talimogen lagerparepvec, sucralfate, doxepin, methotrexate, aminophostin, capsaicin, cisplatin; fluorouracil; panitumumab, aldesleukin, tranexamic acid, zinc sulfate, Bacillus Calmette-Guerin vaccine [connaught]; bleomycin; cyclophosphamide; fluorouracil; methotrexate, aminophostin, fluorouracil; hydroxyurea, bacitracin; clotrimazole; gentamicin, cyclophosphamide; doxorubicin, pelareorep, filgrastim, enteral nutrition, pentoxifylline, epirubicin; fluorouracil; leucovorin; mitomycin, porfiromycin, bleomycin; cisplatin; methotrexate; vincristine, a vaccine based on the bacillus Calmette-Guerin; isoniazid; methotrexate, fluorouracil; leucovorin; methotrexate, rAd-p53, PV-10, leukocyte interleukin, nimotuzumab, afatinib dimaleate, afatinib dimaleate; cisplatin, carboplatin; cetuximab; fluorouracil, cetuximab; cisplatin, nedaplatin, docetaxel; fluorouracil, nimorazole, gemcitabine hydrochloride, afatinib dimaleate, nedaplatin, ladenovec contusugen, Lactobacillus brevis CD2, cetuximab, nimotuzumab, E-10A, cisplatin; gemcitabine, cisplatin; lobaplatin, endostatin (recombinant)_dapsone; doxycycline; minocycline, carboplatin; cyclophosphamide; docetaxel; doxorubicin; paclitaxel, nivolumab, pelareorep, autologous stem cells; carboplatin; etoposide; ifosfamide, vinflunine ditartrate, gemcitabine, cisplatin; fluorouracil; mitomycin, porfiromycin, olimel, pembrolizumab, AminoPure dietary supplement, nedaplatin, Liang Ge San dietary supplement, eicosapentanoic acid, celecoxib; methotrexate, cisplatin; pembrolizumab (tegafur + uracil); cisplatin; epirubicin; mitomycin, durvalumab; tremelimumab, sodium hypochlorite, cetuximab; cisplatin, cisplatin; paclitaxel, amcasertib, capecitabine, R-TPR-033, VB-4847, gabapentin, raltitrexed, cisplatin; fluorouracil; leucovorin, cisplatin; docetaxel, celecoxib, durvalumab; durvalumab + tremelimumab, TT-10, (sodium alginate + sodium carbonate + propolis + aloe vera + calendula + honey + chamomile); cisplatin, pembrolizumab; talimogen lagerparepvec, avelumab, nimorazole, eicosapentanoic acid, lovastatin, dexamethasone; etoposide; gemcitabine; PEG-aspargas, ipilimumab; nivolumab, cetuximab; cisplatin; nivolumab, capecitabine; cisplatin; docetaxel, isotretinoin, carboplatin; cisplatin; gemcitabine; paclitaxel, erlotinib hydrochloride, VB-4847 (Proxynium Plus Best Supportive Care), celecoxib; thalidomide, cisplatin; fluorouracil, curcumin, celecoxib, imiquimod, cisplatin; cyclophosphamide; etoposide, zotatercept, cisplatin; docetaxel; fluorouracil, cetuximab; cisplatin; docetaxel, human endostatin, melatonin, epigallocatechin gallate, cisplatin; gemcitabine, gemcitabine; paclitaxel, (gimeracil + oteracil + tegafur), eicosapentanoic acid; undeclared nutritional supplement, celecoxib; methotrexate, pembrolizumab (keytruda), afatinib dimaleate, cetuximab (erbitux), durvalumab, durvalumab + tremelimumab, E-10A, entrectinib, leukocyte interleukin (multikin), nimotuzumab, nivolumab (opdivo), pelareorep (reolizin), TT-10, vinflunine ditartrate (javlor), acalobrutinib, AlloVax vaccine, and alpelizib.

), карбоплатин; цисплатин; фторурацил; паклитаксел, биафин, метотрексат, цисплатин;фторурацил, альфа-токоферол; изотретиноин; рекомбинантный интерферон альфа, панитумумаб, цисплатин, блеомицин; фторурацил; леуковорин; метотрексат; винкристин, нимотузумаб, панитумумаб, аминофостин; фторурацил, цисплатин; доцетаксел; фторурацил, капецитабин; цисплатин; фторурацил, пеметрексед динатрия, цисплатин; гемцитабин, транексамовая кислота, карбоплатин; фторурацил, цефазолин, эпоэтин альфа, тирапазамин, эрлотиниба гидрохлорид, цетуксимаб; доцетаксел; фторурацил, мегестрол, контусуген ладеновек, цевимелин гидрохлорид, цисплатин; фторурацил, цисплатин; фторурацил; паклитаксел, изотретиноин, порфиромицин, эсуиталопрам оксалат, гимерацил + отерацил + тегафур, IntraDose (цисплатин плюс эпинефрин), мизонидазол, тирапазамин, карбоплатин; цисплатин; доцетаксел; фторурацил, гефитиниб, эпоэтин альфа, паклитаксел, гефитиниб, палифермин, пилокартин, целекоксиб, цисплатин; доцетаксел; филграстим; фторурацил; паклитаксел, цисплатин; фторурацил; леуковорин, цисплатин; гемцитабин; маннит, Lactobacillus brevis CD2, Глутамин, карбоген; ниацинамидем, цетуксимаб; цисплатин; доцетаксел; фторурацил, карбоген; диоксид углерода; ниацинамид, цисплатин; доцетаксел; фторурацил, растворимый бета-глюкан, контусуген ладеновек, залутумумаб, талимоген лагерпарепвек, сукралфат, доксепин, метотрексат, аминофостин, капсаицин, цисплатин; фторурацил; панитумумаб, алдеслейкин, транексамовая кислота, цинка сульфат, вакцина на основе бациллы Кальметта-Герена [connaught]; блеомицин; циклофосфамид; фторурацил; метотрексат, аминофостин, фторурацил; гидроксимочевина, бацитрацин; клотримазол; гентамицин, циклофосфамид; доксорубицин, пелареореп, филграстим, энтеральное питание, пентоксифиллин, эпирубицин; фторурацил; леуковорин; митомицин, порфиромицин, блеомицин; цисплатин; метотрексат; винкристин, вакцина на основе бациллы Кальметта-Герена; изониазид;метотрексат, фторурацил; леуковорин; метотрексат, rAd-p53, PV-10, лейкоцитарный интерлейкин, нимотузумаб, афатиниба дималеат, афатиниба дималеат; цисплатин, карбоплатин; цетуксимаб; фторурацил, цетуксимаб; цисплатин, недаплатин, доцетаксел;фторурацил, ниморазол, гемцитабина гидрохлорид, афатиниба дималеат, недаплатин, контусуген ладеновек, Lactobacillus brevis CD2, цетуксимаб, нимотузумаб, Е-10А, цисплатин; гемцитабин, цисплатин; лобаплатин, эндостатин (рекомбинантный)_дапсон; доксициклин; миноциклин, карбоплатин; циклофосфамид; доцетаксел; доксорубицин; паклитаксел, ниволумаб, пелареореп, аутологичные стволовые клетки; карбоплатин; этопозид; ифосфамид, винфлунина дитартрат, гемцитабин, цисплатин; фторурацил; митомицин, порфиромицин, олимел, пембролизумаб, пищевая добавка AminoPure, недаплатин, пищевая добавка Liang Ge San, эйкозапентаноевая кислота, целекоксиб; метотрексат, цисплатин; пембролизумаб, (тегафур + урацил); цисплатин; эпирубицин; митомицин, дурвалумаб; тремелимумаб, натрия гипохлорит, цетуксимаб; цисплатин, цисплатин; паклитаксел, амказертиб, капецитабин, R-TPR-033, VB-4847, габапентин, ралтитрексед, цисплатин; фторурацил; леуковорин, цисплатин; доцетаксел, целекоксиб, дурвалумаб; дурвалумаб + тремелимумаб, ТТ-10, (натрия альгинат + натрия карбонат + прополис + алоэ вера + календула + мед + ромашка); цисплатин, пембролизумаб; талимоген лагерпарепвек, авелумаб, ниморазол, эйкозапентаноевая кислота, ловастатин, дексаметазон; этопозид; гемцитабин; ПЭГ-аспаргаза, ипилимумаб; ниволумаб, цетуксимаб; цисплатин; ниволумаб, капецитабин; цисплатин; доцетаксел, изотретиноин, карбоплатин; цисплатин; гемцитабин; паклитаксел, эрлотиниба гидрохлорид, VB-4847 (проксиниум плюс наилучший поддерживающий уход), целекоксиб; талидомид, цисплатин; фторурацил, куркумин, целекоксиб, имиквимод, цисплатин; циклофосфамид; этопозид, зотатерцепт, цисплатин; доцетаксел; фторурацил, цетуксимаб; цисплатин; доцетаксел, человеческий эндостатин, мелатонин, эпигаллокатехина галлат, цисплатин; гемцитабин, гемцитабин; паклитаксел, (гимерацил + отерацил + тегафур), эйкозапентаноевая кислота; незаявленная питательная добавка, целекоксиб; метотрексат, пембролизумаб (кейтруда), афатиниба дималеат, цетуксимаб (эрбитукс), дурвалумаб, дурвалумаб + тремелимумаб, Е-10А, энтректиниб, лейкоцитарный интерлейкин (мультикин), нимотузумаб, ниволумаб (опдиво), пелареореп (реолизин), ТТ-10, винфлунина дитартрат (явлор), акалобрутиниб, вакцина AlloVax и алпелизиб.In some embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is generally used for the treatment and/or prevention of cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, where the compound is preferably selected from the group, consisting of the following compounds: nivolumab, cetuximab (erbitux), albumin-bound paclitaxel (abraksan), gimeracil + oteracil + tegafur (TS-1), docetaxel (docetaxel, doxel, taxotere, docetaxel An, nanoxel M, tautax, docetaxel-AS , docetaxel-M, quidadotax, relidoce, taxelo, oncodosel, doxotel, pacancer, docetrust, dodetax, dodabur, sulaxcin, taxedol, docefim, ribodocel, kritidok, azodok, hemodoc, docelibbs, docenat, dincilezan, dostradixinol, docefrez, kamitotic, oncotaxel , somatixel, belotaxel, quidadotax, takceus, cetadocur, docetaxel ST, tevaxter, dociren, eurotere, axtere, celotax, taxanite, drobanos, cetado, do xocad, tacceus, aegidox, tedocad, docecad, docelex, docetax, docetere, dotax, taxuba, monotaxel, taceedo, detaxl, docet, ferdotax, vintaxel, kamidocon, naltoxater), tegafur + uracil (Uft, Uft E, tefudex, unitoral, luporal, tagracil), fluorouracil (bn: 5-FU, fluorouracil, fluorouracil), gimeracil + oteracil + tegafur ODT (OD bn TS-1 combination), bleomycin sulfate (tecnomycin, cinaleo, bleomycin, bloicin-S, bonar, bleost, bleo, bleomycin sulfate, bleocel, bleotex, oncobleo, bleonco, bleozol, lyoble, bleomycin sulfate, blenamax, blenoxan, bleomycin, Bellon bleomycin bleoprim), carboplatin (carboplatin, platamin CS, carbaccord, carboplatin, carboplatino, paraplatin, carbosin, technocarb , Carbomerc, Paract, Carboplatin CTRS, Intsel Chimos Carboplatin, Carbochem, Carbotinol, Fauldcarbo, Evocarbo, Cytoplatin, Platinum, Qualimed Carboplatin, Carboplatin, Carboplatino, Carboplatin), Ciprofloxacin (Hypoflox, Ufexil), Ciprofloxacin Hydrochloride (Ciprofloxacin fi rma Pharma, prodin, cyproxin), cisplatin (cisplatin, stritin, ifapla, accocyt, unistin, carcinotin, cisplan, cytoplax, nuoxin, placis, cisplatino, displanor, cisplatin, randa, cisplatin, cispla, fauldcispla, briplatin, platinex, platinol, riboplatin, platistin CS, platosin, accocyt), cyclophosphamide (endoxan, cyclophosphamide), doxyuridine (May Vladimir's doxyuridine, doxyuridine), doxorubicin (doxorubicin hydrochloride, adriamycin RDF, doxorubicin, doxorubicin hydrochloride, doxorubicin PFS), epirubicin hydrochloride (brecila, Cloridrato De Epirubicin, epirubicin, farmorubicin, nuovodox, adnexa, 4-eppedo, flavicin), fluorouracil (agicyl, fluorouracil, fauldfluor, oncurcil, flocil, 5 flucel), folic acid + methotrexate (truxophore), human adenovirus type 5 (recombinant) ( oncorin), hydroxyurea (oxyurea, durea, myelostat, riborea, unidrea, ondrea, hydran, leukocel, hydroxyurea, hydrea), ifosfamide (goloxan, ifosfamide EG), levamisole (zirzol), methotrexate (trat oben, methotrexate, fresexate, neometo, fouldmetro, methotrexate sodium, methocel, gytas, metachord, metophyll, methotrexato, traxocord, plastomet, tevatrex, metrex, cadytrex, cardiotrex, vibzy, imutrex, biotrexate, metorex, mexate, neotrexate, ontrexotrex, remtrex , Trixylem, Hi-Trex, Metorex, Tracke, Unitrexate, Ebetrexac, Fouldexato, Lantarel, Maxtrex, Miantrex CS, Rheumatrex, Folex, Folex PFS, Abitrexate, Trxall, Emtrexate, Abitrexate, Meadow, Mexat Aq, Biometrox, Otaxem), Mitomycin (mitomycin C, mitomycin, mitonko, lyomite), nedaplatin (jiebaishu, aoxanda, akupla), nimesulide (nimulide), nimotuzumab (EGFR biomab, ledemab), nitrofurantoin (furatsilin), ofloxacin (entof), paclitaxel (paclitaxel, taxol), peplomycin sulfate (pepleo), picibanil (picibanil), pyrarubicin (pyrarubicin hydrochloride, terarubicin, pinorubine), glycididazole sodium (CMNa), tegafur (utefos, icarus, futraful, tegafur, gimeracil, oteracil potassium), temoporfin (foscan), toptecan hydrochloride (Toptekan ), ubinimex (ubinimex), vinblastine sulfate (vinblastine, vblastine, vincristine, vincristine sulfate, vincristine, sutuvin, vincrisane, eldizine), vincristine sulfate (oncovin), gefitinib, esuitalopram oxalate, gene therapy for p53 activation in oncology, cevimeline hydrochloride, docetaxel; lenograstim, bortezomid; docetaxel; irinotecan, carboplatin; paclitaxel, cisplatin; docetaxel; fluorouracil, human papillomavirus vaccine (vaccination against human papillomavirus types 16 and 18 and unvaccinated controls), carboplatin; cisplatin; paclitaxel, an undeclared epidermal growth factor receptor inhibitor, cetuximab, sorafenib tosylate; sunitinib malate, aminophostin, cisplatin; dexamethasone; docetaxel; metoclopramide, platinum-based chemotherapy, cetuximab; nimotuzumab, nimotuzumab, dobutamine hydrochloride; dopexamine hydrochloride; epinephrine; norepinephrine bitartrate, cetuximab; cisplatin, cetuximab; cisplatin; docetaxel; fluorouracil, cisplatin; paclitaxel, gendicin, doce oncovis (docetaxel), picibanil, docetaxel; lobaplatin, oxytetracycline hydrochloride, cisplatin; mitomycin, bleomycin, nimotuzumab, cisplatin; fluorouracil; nimotuzumab, cetuximab; cisplatin; cyclophosphamide; dacarbazine; docetaxel; doxorubicin; etoposide; fluorouracil; gemcitabine hydrochloride; irinotecan hydrochloride; oxaliplatin; paclitaxel; pemetrexed disodium; temozolomide, varenicline, acetylcysteine, dopamine; norepinephrine, (gimeracil + oteracil + tegafur), nimotuzumab, icotinib hydrochloride, kushen (kuh-seng), carboxymethylpachymaran, BCM-95, lactofos, PEG-filgrastim, methadone, Varanadi grita, cisplatin; palifermin, cetuximab, cisplatin; lapatinib ditosylate, gefitinib, zalutumumab, erlotinib hydrochloride, beta-carotene; food supplement E-Tabs, bevacizumab, levothyroxine; liothyronine sodium; recombinant human thyroid stimulating hormone, cisplatin; docetaxel; fluorouracil; hydroxyurea, fluorouracil, docetaxel; hypericum extract (

), carboplatin; cisplatin; fluorouracil; paclitaxel, biafine, methotrexate, cisplatin; fluorouracil, alpha-tocopherol; isotretinoin; recombinant interferon alfa, panitumumab, cisplatin, bleomycin; fluorouracil; leucovorin; methotrexate; vincristine, nimotuzumab, panitumumab, aminofostin; fluorouracil, cisplatin; docetaxel; fluorouracil, capecitabine; cisplatin; fluorouracil, pemetrexed disodium, cisplatin; gemcitabine, tranexamic acid, carboplatin; fluorouracil, cefazolin, epoetin alfa, tirapazamine, erlotinib hydrochloride, cetuximab; docetaxel; fluorouracil, megestrol, ladenovec contusugen, cevimeline hydrochloride, cisplatin; fluorouracil, cisplatin; fluorouracil; paclitaxel, isotretinoin, porfiromycin, esuitalopram oxalate, gimeracil + oteracil + tegafur, IntraDose (cisplatin plus epinephrine), misonidazole, tirapazamine, carboplatin; cisplatin; docetaxel; fluorouracil, gefitinib, epoetin alfa, paclitaxel, gefitinib, palifermin, pilocartin, celecoxib, cisplatin; docetaxel; filgrastim; fluorouracil; paclitaxel, cisplatin; fluorouracil; leucovorin, cisplatin; gemcitabine; mannitol, Lactobacillus brevis CD2, Glutamine, carbogen; niacinamide, cetuximab; cisplatin; docetaxel; fluorouracil, carbogen; carbon dioxide; niacinamide, cisplatin; docetaxel; fluorouracil, soluble beta-glucan, ladenovec contusugen, zalutumumab, talimogen lagerparepvec, sucralfate, doxepin, methotrexate, aminophostin, capsaicin, cisplatin; fluorouracil; panitumumab, aldesleukin, tranexamic acid, zinc sulfate, Bacillus Calmette-Guerin vaccine [connaught]; bleomycin; cyclophosphamide; fluorouracil; methotrexate, aminophostin, fluorouracil; hydroxyurea, bacitracin; clotrimazole; gentamicin, cyclophosphamide; doxorubicin, pelareorep, filgrastim, enteral nutrition, pentoxifylline, epirubicin; fluorouracil; leucovorin; mitomycin, porfiromycin, bleomycin; cisplatin; methotrexate; vincristine, a vaccine based on the bacillus Calmette-Guerin; isoniazid; methotrexate, fluorouracil; leucovorin; methotrexate, rAd-p53, PV-10, leukocyte interleukin, nimotuzumab, afatinib dimaleate, afatinib dimaleate; cisplatin, carboplatin; cetuximab; fluorouracil, cetuximab; cisplatin, nedaplatin, docetaxel; fluorouracil, nimorazole, gemcitabine hydrochloride, afatinib dimaleate, nedaplatin, ladenovec contusugen, Lactobacillus brevis CD2, cetuximab, nimotuzumab, E-10A, cisplatin; gemcitabine, cisplatin; lobaplatin, endostatin (recombinant)_dapsone; doxycycline; minocycline, carboplatin; cyclophosphamide; docetaxel; doxorubicin; paclitaxel, nivolumab, pelareorep, autologous stem cells; carboplatin; etoposide; ifosfamide, vinflunine ditartrate, gemcitabine, cisplatin; fluorouracil; mitomycin, porfiromycin, olimel, pembrolizumab, AminoPure supplement, nedaplatin, Liang Ge San supplement, eicosapentanoic acid, celecoxib; methotrexate, cisplatin; pembrolizumab (tegafur + uracil); cisplatin; epirubicin; mitomycin, durvalumab; tremelimumab, sodium hypochlorite, cetuximab; cisplatin, cisplatin; paclitaxel, amcasertib, capecitabine, R-TPR-033, VB-4847, gabapentin, raltitrexed, cisplatin; fluorouracil; leucovorin, cisplatin; docetaxel, celecoxib, durvalumab; durvalumab + tremelimumab, TT-10, (sodium alginate + sodium carbonate + propolis + aloe vera + calendula + honey + chamomile); cisplatin, pembrolizumab; talimogen lagerparepvec, avelumab, nimorazole, eicosapentanoic acid, lovastatin, dexamethasone; etoposide; gemcitabine; PEG-aspargas, ipilimumab; nivolumab, cetuximab; cisplatin; nivolumab, capecitabine; cisplatin; docetaxel, isotretinoin, carboplatin; cisplatin; gemcitabine; paclitaxel, erlotinib hydrochloride, VB-4847 (Proxynium Plus Best Supportive Care), celecoxib; thalidomide, cisplatin; fluorouracil, curcumin, celecoxib, imiquimod, cisplatin; cyclophosphamide; etoposide, zotatercept, cisplatin; docetaxel; fluorouracil, cetuximab; cisplatin; docetaxel, human endostatin, melatonin, epigallocatechin gallate, cisplatin; gemcitabine, gemcitabine; paclitaxel, (gimeracil + oteracil + tegafur), eicosapentanoic acid; undeclared nutritional supplement, celecoxib; methotrexate, pembrolizumab (keytruda), afatinib dimaleate, cetuximab (erbitux), durvalumab, durvalumab + tremelimumab, E-10A, entrectinib, leukocyte interleukin (multikin), nimotuzumab, nivolumab (opdivo), pelareorep (reolizin), TT-10, vinflunine ditartrate (javlor), acalobrutinib, AlloVax vaccine, and alpelizib.

In some embodiments of the invention, at least one additional pharmaceutically active ingredient is a compound that is generally used for the treatment and/or prevention of vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC, resistant to surgery or chemotherapy, most preferably advanced VSCC, resistant to surgery or chemotherapy, where the compound is preferably selected from the group consisting of the following compounds: mitomycin-C2, cisplatin, carboplatin, vinorelbine, paclitaxel, tyrosine kinase inhibitor (e.g., erlotinib ), nivolumab, bleomycin sulfate (eg, bleomycin, bleomycin sulfate, blenamax, tevableo, oncobleo, bleo, bloicin-S), 5-fluorouracil (5-FU), gardazil 9 (human papillomavirus vaccine (9-valent)) , omiganan pentahydrochloride, alisertib, ISA-101 (13 synthetic long peptides (25-35 amino acids long) derived from HPV 16 E6 and E7 oncogenic proteins), PDS-0101, Vicovirix (P16 vaccine 37-63), TA-CIN (fusion protein vaccine containing L2 capsid proteins, E6 and E7 from HPV16) and a human papillomavirus peptide vaccine based on 16 E6.

In some embodiments, at least one additional pharmaceutically active ingredient is a therapeutic peptide or protein (eg, an antibody, decoy receptor, or cytokine), or a fragment or variant thereof. Said therapeutic peptide or protein, or fragment or variant thereof, may be in the form of the indicated substances or in the form of a nucleic acid (eg, RNA as described herein) that encodes a therapeutic peptide or protein, or fragment or variant thereof. It is also preferred that the therapeutic peptide or protein (eg, antibody, decoy receptor, or cytokine) contains a signal peptide, eg, a secretory signal peptide. These signal sequences are, but not limited to, peptide segments that are typically about 15-30 amino acids in length and are preferably located at the N-terminus of the encoded peptide. The signal peptides described herein preferably provide localization of the therapeutic peptide or protein, or fragment or variant thereof, to a particular cell membrane or a particular cell compartment, preferably the cell surface, the cytoplasmic membrane, the endoplasmic reticulum (ER), or the endosomal-liposomal compartment. .

In some embodiments, the signal peptide can be selected from a list of amino acid sequences, which are designated as SEQ ID NO: 1-1115 and SEQ ID NO: 1728 in international patent application WO 2017/081082, or fragments or variants of any of these sequences. At the level of nucleic acids, you can choose any nucleotide sequence (eg, RNA sequence) that encodes these amino acid sequences. In this context, the description of WO 2017/081082 is incorporated herein by reference.

Examples of secretory signal sequences referred to herein include, but are not limited to, signal sequences (or fragments or variants thereof) of classical or non-classical MHC molecules (e.g., signal sequences of MHC I and MHC II molecules, e.g., HLA-A *0201 MHC class I), cytokines or immunoglobulins specified herein, signal sequences of the invariant chain of immunoglobulins or antibodies specified herein, signal sequences of Lamp1, tapazin, Erp57, calreticulin, calnexin and other membrane-associated proteins or proteins associated with the endoplasmic reticulum (ER), or proteins associated with the endosomal-lysosomal compartment. Most preferred in the context of the present invention are the signal sequences of the MHC class I HLA-A*0201 molecule, or a fragment or variant thereof.

According to a preferred embodiment of the invention, at least one additional pharmaceutically active ingredient is a therapeutic peptide or protein, or a fragment or variant thereof, containing a signal sequence (or a fragment or variant thereof) derived from HLA-A2, HsPLAT, HsEPO, HsALB, IgE , HsCD5, HsIL2, HsCTRB2, human immunoglobulin heavy chain, human immunoglobulin light chain, GpLuc, mouse immunoglobulin kappa chain, NrChit1, ClLp1.1, NgNep1, HsAzu1, HsCD33, VcCtxB, HsCST4, HsIns-iso1, HsSPARC, H1N1 (Netherlands2009 ), FV, MHCII or JEV.

It is also preferred that at least one additional pharmaceutically active ingredient is a therapeutic peptide or protein (for example, an antibody, decoy receptor or cytokine) or a fragment or variant thereof, containing or consisting of the amino acid sequence shown in one of SEQ ID NOs: 739-769, or a fragment or variant of one of the indicated amino acid sequences. Preferably, at least one additional pharmaceutically active ingredient is a therapeutic peptide or protein (for example, an antibody, decoy receptor or cytokine) or a fragment or variant thereof, containing or consisting of an amino acid sequence that is at least 50%, 60% identical to , 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94 %, 95%, 96%, 97%, 98%, 99% of one of SEQ ID NOs: 739-769.

According to a particularly preferred embodiment of the invention, the at least one additional pharmaceutically active ingredient is a checkpoint modulator or a cytokine.

Known surface molecules of negative regulation of T cells, which are characterized by up-regulation in activated T cells to reduce their activity, which leads to less effective destruction of tumor cells. These inhibitory molecules are referred to as negative co-stimulatory molecules because of their homology to the T-cell co-stimulatory molecule CD28. These proteins, also referred to as immune checkpoint proteins, function in many ways, including attenuating early activation signals, competing with positive costimulation, and directly inhibiting antigen-presenting cells (Bour-Jordan et al., Immunol Rev. 241(1), 2011, pp. 180-205).

In the context of the present invention, a checkpoint modulator is typically a molecule, such as a protein (e.g., an antibody), a dominant negative receptor, a decoy receptor, or a ligand or fragment thereof, or a variant that modulates the function of an immune checkpoint protein, e.g. , inhibits or reduces the activity of checkpoint inhibitors (or checkpoint inhibitory molecules) or stimulates the activity of checkpoint stimulators (or checkpoint stimulating molecules). Thus, the checkpoint modulators described herein affect the activity of checkpoint molecules.

In this context, checkpoint inhibitory molecules refer to checkpoint inhibitors and these terms can be used interchangeably. Also, checkpoint stimulating molecules refer to checkpoint stimulators and these terms can be used interchangeably.

Preferably, the checkpoint modulator is selected from agonist antibodies, antagonist antibodies, ligands, dominant negative receptors and decoy receptors, or combinations thereof.

Methods for creating and using mRNA-encoded antibodies are known in the art (see, for example, WO 2008/083949 or PCT/EP 2017/060226).

Preferred checkpoint inhibitory molecules that can be inhibited by a checkpoint modulator in the context of the present invention are PD-1, PD-L1, CTLA-4, PD-L2, LAG3, TIM3/HAVCR2, 2B4, A2aR, B7H3, B7H4, BTLA, CD30, CD160, CD155, GAL9, HVEM, IDO1, IDO2, KIR, LAIR1 and VISTA.

Preferred checkpoint stimulating molecules that can be stimulated by a checkpoint modulator in the context of the present invention are CD2, CD27, CD28, CD40, CD137, CD226, CD276, GITR, ICOS, OX40 and CD70.

According to a preferred embodiment of the invention, the isRNA is intended for the use described herein, the use comprising - as an additional pharmaceutically active ingredient - a checkpoint modulator selected from the group consisting of PD-1 inhibitor, PD-L1 inhibitor, PD inhibitor -L2, CTLA-4 inhibitor, LAG3 inhibitor, TIM3 inhibitor, TIGIT inhibitor, OX40 stimulator, 4-1BB stimulator, CD40L stimulator, CD28 stimulator and GITR stimulator.

According to a preferred embodiment of the invention, the target of the checkpoint modulator used in the context of the present description is a member of the PD-1 pathway. Representatives of the PD-1 pathway are typically proteins that are associated with PD-1 signaling. On the one hand, this group contains proteins that induce PD-1 signaling in the opposite direction to PD-1, such as PD-1, PD-L1 and PD-L2 ligands and the PD-1 receptor involved in signal transduction. On the other hand, this group contains proteins that transduce a signal in the forward direction relative to the PD-1 receptor. Particularly preferred representatives of the PD-1 pathway in the context of the present invention are PD-1, PD-L1 and PD-L2.

In the context of the present invention, a PD-1 pathway antagonist (or PD-1 inhibitor) preferably means a compound having the ability to disrupt the PD-1 signaling pathway, preferably PD-1 receptor-mediated signaling. Thus, a PD-1 pathway antagonist can be any antagonist directed against any member of the PD-1 pathway that has the ability to antagonize the PD-1 signaling pathway.

In a preferred embodiment, checkpoint modulator as used herein refers to a PD-1 inhibitor or a PD-L1 inhibitor, where the PD-1 inhibitor is preferably an anti-PD-1 antagonist antibody and the PD-L1 inhibitor is preferably is an antagonistic antibody directed against PD-L1.

In this context, an antagonist may be an antagonist antibody as defined herein that targets any member of the PD-1 pathway, preferably an antagonist antibody directed against the PD-1, PD-L1 or PD-L2 receptor. Said antagonistic antibody may also be encoded by a nucleic acid. In addition, the PD-1 pathway antagonist may be a fragment of the PD-1 receptor that blocks the activity of PD1 ligands. B7-1 or fragments thereof may also act as PD1 antagonist ligands. In addition, a PD-1 pathway antagonist may be a protein containing an amino acid sequence (or nucleic acid encoding it) that has the ability to bind to PD-1 but interferes with PD-1 signaling, for example, by inhibiting the interaction between PD-1 and B7-H1 or B7-DL (WO 2014/127917; WO 2012/062218).

Most preferred are PD1 antibodies nivolumab (MDX-1106/BMS-936558/ONO-4538), (Brahmer et al., J Clin Oncol. 28(19), 2010, pp. 3167-3175; PMID: 20516446); pidilizumab (CT-011), (Berger et al., Clin Cancer Res. 14(10), 2008, pp. 3044-3051; PMID: 18483370); pembrolizumab (MK-3475, SCH 900475); AMP-224 and MEDI0680 (AMP-514).

Particularly preferred are anti-PD-L1 antibodies MDX-1105/BMS-936559 (Brahmer et al., N Engl J Med. 366(26), 2012, pp. 2455-2465; PMID: 22658128); atezolizumab (MPDL3280A/RG7446); durvalumab (MEDI4736) and avelumab (MSB0010718).

In another preferred embodiment, the checkpoint modulator is a decoy receptor (eg, a soluble receptor). Preferably the decoy receptor is a soluble PD-1 receptor. More preferably, the decoy receptor is a soluble variant of the PD-1 receptor, or a fragment or variant thereof, wherein the PD-1 receptor is derived from a mammal, preferably selected from the group which includes, but is not limited to, for example, goats, cows, pigs, dogs, cats, donkeys, horses, monkeys, great apes, rodents (eg mice, hamsters, rabbits or rats), and most preferably humans. Even more preferably, the decoy receptor is a soluble variant of the PD-1 receptor, or a fragment or variant thereof, wherein the PD-1 receptor contains an amino acid sequence identical to or at least 50%, 60%, 70%, 75%, 80 %, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% of the amino acid sequence of SEQ ID NO: 1, or a fragment or variant thereof. In a particularly preferred embodiment, the decoy receptor used herein as a checkpoint modulator is a soluble PD-1 receptor that contains an amino acid sequence that is at least 50%, 60%, 70%, 75 %, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence of SEQ ID NO: 2, or a fragment or variant thereof.

According to another embodiment of the invention, the checkpoint modulator that is used according to the invention is an OX40 stimulator. OX40 is a member of the TNFR receptor superfamily and is expressed on the surface of antigen-activated mammalian CD4 ⁺ and CD8 ⁺ T lymphocytes. The OX40 ligand (OX40L, also referred to as gp34, ACT-4-L and CD252) is a protein that specifically interacts with the OX40 receptor. The term OX40L includes the full OX40 ligand, the soluble OX40 ligand, and fusion proteins containing a functionally active region of the OX40 ligand covalently linked to a second moiety, eg, a protein domain. Also included in the definition of OX40L are variants that differ in amino acid sequence from naturally occurring OX4L, but which retain the ability to specifically bind to the OX40 receptor. In addition, variants that increase the biological activity of OX40 fall under the definition of OX40L. An OX40 agonist is a molecule that induces or enhances the biological activity of OX40, such as signal transduction mediated by OX40. An OX40 agonist is preferably referred to herein as a binding molecule capable of specifically binding to OX40. Thus, an OX40 agonist can be any agonist that binds to OX40 and has the ability to stimulate OX40 signaling. In this context, an OX40 agonist may be an agonist antibody that binds to OX40.

OX40 agonists and anti-OX40 monoclonal antibodies are described in WO 1995/021251, WO 1995/012673 and WO 1995/21915. Particularly preferred is the anti-OX40 antibody 9B12, a mouse monoclonal anti-OX40 antibody directed against the extracellular domain of human OX40 (Weinberg et al., J. Immunother. 29(6), 2006, pp. 575-585).

According to another embodiment of the invention, the checkpoint modulator that is used according to the invention is an antagonist antibody selected from the group consisting of anti-CTLA4, anti-PD1, anti-PD-L1, anti-Vista, anti-Tim-3, anti-TIGIT, anti-LAG-3 and anti-BTLA.

Preferably, an anti-CTLA4 antibody that can be used as a checkpoint modulator is directed against cytotoxic T lymphocyte antigen-4 (CTLA-4). CTLA-4 is expressed primarily in the intracellular compartment of T cells. After an effective or prolonged stimulus is applied to a naive T cell, CTLA-4 is transported to the cell surface via the T cell receptor (TCR) and concentrated at the immunological synapse. CTLA-4 then competes with CD28 for CD80/CD86 and down-modulates TCR signaling, affecting Akt signaling. Thus, CTLA-4 functions physiologically as a signal quencher (Weber J., Semin. Oncol. 37(5), 2010, pp. 430-439).

In a preferred embodiment of the invention, the isRNA is for the use described herein, where the use includes, as an additional pharmaceutically active ingredient, a CTLA4 antagonist, which is preferably an anti-CTLA4 antagonist antibody (anti-CTLA4 antibody). The term "antagonist" CTLA4 in the context of the present description refers to any compound, such as an antibody, which is an antagonist of the physiological function of CTLA4. In the context of the present invention, the term “anti-CTLA4 antibody” may refer to an antagonist antibody directed against CTLA4 (or a functional fragment or variant of said antibody) or to a nucleic acid, preferably RNA, encoding said antagonistic antibody (or a functional fragment thereof). A functional fragment or variant of an anti-CTLA4 antibody preferably acts as a CTLA4 antagonist. More preferably, "anti-CTLA4 antibody" refers to a monoclonal antibody directed against CTLA4 (or a functional fragment or variant of said antibody) or a nucleic acid encoding a monoclonal antibody directed against CTLA4 (or a functional fragment or variant of said antibody). In the context of the present invention, the term "anti-CTLA4 antibody" may refer to the heavy or light chain of an antibody, respectively, or also refers to both antibody chains (heavy and light chains), or to a fragment or variant of one of these chains. Preferably, the fragment or variant of the anti-CTLA4 antibody used according to the present description is a functional fragment or variant, preferably specified in the present description.

The most preferred anti-CTLA-4 antibodies are ipilimumab (Yervoy®), tremelimumab and AGEN-1884. In addition, the preferred antibodies to CTLA4 used according to the present invention are BMS 734016; BMS-734016; BMS734016; MDX010; MDX 101; MDX-010; MDX-101; MDX-CTLA-4; MDX-CTLA4; MDX010; winglor; and Yervoy® or a functional fragment or variant of any of these antibodies.

In some embodiments, the checkpoint modulator used herein is a CTLA4 antagonist, preferably an anti-CTLA4 antibody. In this case, the antibody to CTLA4 preferably contains two polypeptide chains, as a rule, designated as "heavy chain" and "light chain", respectively. In a preferred embodiment, the heavy chain comprises or consists of the amino acid sequence shown in one of SEQ ID NO: 645, 832, 661, or 833, or a fragment or variant of one of the indicated amino acid sequences, preferably SEQ ID NO: 645, or a fragment thereof, or option. The heavy chain preferably contains or consists of an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to one of SEQ ID NO: 645, 832, 661 or 833, preferably SEQ ID NO: 645. The light chain preferably contains or consists of the amino acid sequence shown in any of SEQ ID NO: 677, 834, 693, or 706, or a fragment or variant of one of the indicated amino acid sequences, preferably SEQ ID NO: 677, or a fragment or variant thereof. More preferably, the light chain contains or consists of an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to one of SEQ ID NOs: 677, 834, 693 or 706, preferably SEQ ID NO: 677. Thus, in a preferred embodiment, the anti-CTLA4 antibody comprises a heavy chain and a light chain as defined herein, or a fragment or variant of each of said chains. Most preferably, the anti-CTLA4 antibody comprises a heavy chain and a light chain, or a fragment or variant thereof, wherein the heavy chain, or a fragment or variant thereof, comprises or consists of the amino acid sequence shown in SEQ ID NO: 645, or a fragment or variant thereof, and wherein the light chain or a fragment or variant thereof contains or consists of the amino acid sequence shown in SEQ ID NO: 677, or a fragment or variant thereof.

According to another embodiment of the invention, the checkpoint modulator used according to the present description is at least one antibody listed in Table 1, or a fragment or variant thereof.

According to a preferred embodiment of the invention, at least one additional pharmaceutically active ingredient is a cytokine.

More preferably, at least one additional pharmaceutically active ingredient is IL-12 or a fragment or variant thereof. Even more preferably, at least one additional pharmaceutically active ingredient is an IL-12 analog or a fragment or variant thereof. Most preferably, at least one additional pharmaceutically active ingredient is a compound, such as a peptide or protein, a mutant peptide or mutant protein, a cross-linked heterodimer, an antibody, preferably an RNA-encoded antibody, or artificial binding domains that bind to the IL-12 receptor and preferably result in activation of the JAK-STAT signaling pathway. In a preferred embodiment of the invention, at least one additional pharmaceutically active ingredient is an IL-12 receptor agonist.

Naturally occurring IL-12 is typically a heterodimeric cytokine encoded by two different genes, IL-12A (p35) and IL-12B (p40). The naturally occurring heterodimer is also referred to as p70. In the context of the present invention, the term "IL-12" refers to a protein consisting of or containing a naturally occurring form of heterodimeric IL-12, monomeric IL-12A, monomeric IL-12B, as well as fragments or variants of any of these proteins, such as merging IL-12A or a fragment or variant thereof with IL-12B or a fragment or variant thereof, wherein said protein may also contain an amino acid sequence not related to IL-12A or IL-12B. For example, the term "IL-12" as used herein also refers to a protein containing IL-12A or a fragment or variant thereof, IL-12B or a fragment or variant thereof, in which IL-12A or a fragment or variant thereof is covalently linked to IL-12B or a fragment or variant thereof via a linker, wherein the linker preferably has an amino acid sequence unrelated to IL-12A or IL-12B. More preferably, the linker is a peptide or protein linker, which preferably contains the amino acid sequence shown in SEQ ID NO: 9, or a fragment or variant thereof. In addition, the term "IL-12" also refers to a protein in which IL-12A or a fragment or variant thereof is directly linked to IL-12B or a fragment or variant thereof, preferably via a covalent bond, more preferably via a peptide bond. In addition, the terms "IL-12" or "IL-12 analog" when used in the context of the present description also refers to any compound, such as a peptide or protein, a mutant peptide or mutant protein, a cross-linked heterodimer, an antibody, preferably an antibody encoded by RNA, or artificial binding domains, that bind to the IL-12 receptor and preferentially result in activation of the JAK-STAT signaling pathway. Thus, the terms "IL-12" or "IL-12 analog" as used herein also refer to a compound, such as a peptide or protein, that functions as an IL-12 receptor agonist.

As used herein, an IL-12 fragment or variant preferably has the ability to specifically bind to the IL-12 receptor and more preferably functions as an IL-12 receptor agonist.

According to a preferred embodiment of the invention, the IL-12 that is used in the context of the present invention is derived from a mammal, preferably selected from the group that contains (but not limited to), for example, goats, cows, pigs, dogs, cats, donkeys, horses, monkeys, great apes, rodents (eg mice, hamsters, rabbits or rats), and most preferably humans. Even more preferably IL-12 used according to the present description contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85 %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to one of the amino acid sequences shown in SEQ ID NO: 3-8, or a fragment or variant of any of the indicated sequences. In an alternative or additional embodiment, IL-12 used according to the present description contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84% , 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence shown in SEQ ID NO: 9, or a fragment or variant thereof. In a particularly preferred embodiment of the invention, IL-12 used according to the present description contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84 %, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical amino acid sequence, presented in SEQ ID NO: 10, or a fragment or variant thereof.

In an alternative embodiment of the invention, at least one additional pharmaceutically active ingredient is CD40L or a fragment or variant thereof. CD40L (also referred to as "CD40 ligand", as "CD40LG", or as "CD154") is expressed primarily on activated T and B cells. CD40L binds to CD40, which is typically expressed by antigen-presenting cells (APCs). The interaction of CD40 and CD40L plays a major role in the development of humoral and cellular immune responses. As used herein, "CD40L" refers to a naturally occurring CD40L protein or fragment or variant thereof, where the fragment or variant preferably has the ability to specifically bind to CD40.

According to a preferred embodiment of the invention, the CD40L used in the context of the present invention is derived from a mammal, preferably selected from the group that contains (but not limited to), for example, goats, cows, pigs, dogs, cats, donkeys, horses, monkeys , great apes, rodents (eg mice, hamsters, rabbits or rats), and most preferably humans. Even more preferably CD40L used according to the present description contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence shown in SEQ ID NO :11, or a fragment or variant of it.

According to a particularly preferred embodiment of the invention, at least one additional pharmaceutically active ingredient is a tumor antigen, preferably selected from any tumor antigen, which contains an amino acid sequence selected from the group consisting of SEQ ID NO: 1-504; 4558-4560 specified in PCT/EP 2017/059525, or a fragment or variant of one of the specified amino acid sequences.

Thus, a preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises administering at least one coding RNA (as an additional pharmaceutically active ingredient) that encodes at least one tumor antigen, preferably at least one mRNA, where at least one coding sequence contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 505-4033; 4561-4591 specified in PCT/EP 2017/059525, or a fragment or variant of one of the specified sequences.

More preferably, the tumor antigen is selected from the following group: 1A01_HLA-A/m; 1A02; 5T4; ACRBP; AFP; AKAP4; alpha-actinin-4/m; alpha-methylacyl-coenzyme_A_-racemase; ANDR; ART-4; ARTC1/m; AURKB; B2MG; B3GN5; B4GN1; B7H4; BAGE-1; BASI; BCL-2; bcr/abl; beta-catenin/m; BING-4; BIRC7; BRCA1/m; BY55; calreticulin; CAMEL; CASP-8/m; CASPA; cathepsin_B; cathepsin_L; CD1A; CD1B; CD1C; CD1D; CD1E; CD20; CD22; CD276; CD33; CD3E; CD3Z; CD44_isoform_1; CD44_isoform_6; CD4; CD52; CD55; CD56; CD80; CD86; CD8A; CDC27/m; CDE30; CDK4/m; CDKN2A/m; CEA; CEAM6; CH3L2; CLCA2; CML28; CML66; COA-1/m; coactosin-like_protein; collagen_XXIII; COX-2; CP1B1; CSAG2; CT45A1; CT55; CT-9/BRD6; CTAG2_isoform_LAGE-1A; CTAG2_isoform_LAGE-1B; CTCFL; cten; cyclin_B1; cyclin_D1; cyp-B; DAM-10; DEP1A; E7; EF1A2; EFTUD2/m; EGFR; EGLN3; ELF2/m; EMMPRIN; Epcam; EphA2; EphA3; ErbB3; ERBB4; erg; ETV6; EWS; EZH2; FABP7; FCGR3A_version_1; FCGR3A_version_2; FGF5; FGFR2; fibronectin; FOS; FOXP3; FUT1; G250; GAGE-1; GAGE-2; GAGE-3; GAGE-4; GAGE-5; GAGE-6; GAGE7b; GAGE-8_(GAGE-2D); GASR; GnT-V; GPC3; GPNMB/m; GRM3; HAGE; hepsin; Her2/neu; HLA-A2/m; homeobox_NKX3.1; HOM-TES-85; HPG1; HS71A; HS71B; HST-2; hTERT; iCE; IF2B3; IL10; IL-13Ra2; IL2-RA; IL2-RB; IL2-RG; IL-5; IMP3; ITA5; ITB1; ITB6; kallikrein-2; kallikrein-3; kallikrein-4; KI20A; KIAA0205; KIF2C; KK-LC-1; LDLR; LGMN; LIRB2; LY6K; MAGA5; MAGA8; MAGAB; MAGE-A10; MAGE-A12; MAGE-A1; MAGE-A2; MAGE-A3; MAGE-A4; MAGE-A6; MAGE-A9; MAGE-B10; MAGE-B16; MAGE-B17; MAGE-B1; MAGE-B2; MAGE-B3; MAGE-B4; MAGE-B5; MAGE-B6; MAGE-C1; MAGE-C2; MAGE-C3; MAGE-D1; MAGE-D2; MAGE-D4; MAGE-E1; MAGE-E1 (MAGE 1); MAGE-E2; MAGE-F1; MAGE-H1; MAGEL2; mammaglobin _A; MART-1/melan-A; MART-2; MC1_R; M-CSF; mesothelin; MITF; MMP1_1; MMP7; MUC-1; MUM-1/m; MUM-2/m; MYCN; MYOIA; MYOIB; MYOIC; MYOID; MYOIE; MYOIF; MYOIG; MYO1H; NA17; NA88-A; Neo-PAP; NFYC/m; NGEP; NPM; NRCAM; NSE; NUF2; NY-ESO-1; OA1; OGT; OS-9; osteocalcin; osteopontin; p53; PAGE-4; PAI-1; PAI-2; PAP; PATE; PAX3; PAX5; PD1L1; PDCD1; PDEF; PECA1; PGCB; PGFRB; Pim-1_-kinase; Pin-1; PLAC1; PMEL; PML; POTEF; POTE; PRAME; PRDX5/m; PRM2; protein; proteinase-3; PSA; PSB9; PSCA; PSGR; PSM; PTPRC; RAB8A; RAGE-1; RARA; RASH; RASK; RASN; RGS5; RHAMM/CD168; RHOC; RSSA; RU1; RU2; RUNX1; S-100; SAGE; SART-1; SART-2; SART-3; SEPR; serpinB5; SIA7F; SIA8A; SIAT9; SIRT2/m; SOX10; SP17; SPNXA; SPXN3; SSX-1; SSX-2; SSX3; SSX-4; ST1A1; STAG2; STAMP-1; STEAP-1; survivin-2B; survivin; SYCP1; SYT-SSX-1; SYT-SSX-2; TARP; TCRg; TF2AA; TGFB1; TGFR2; TGM-4; TIE2; TKTL1; TPI/m; TRGV11; TRGV9; TRPC1; TRP-p8; TSG10; TSPY1; TVC_(TRGV3); TX101; tyrosinase; TYRP1; TYRP2; UPA; VEGFR1; WT1 and XAGE1.

In preferred embodiments of the invention, the tumor antigen, preferably specified herein, is in the form of at least one coding RNA, preferably specified herein, which contains at least one coding sequence that encodes a peptide or protein containing the tumor antigen or its fragment or variant. Said at least one coding RNA, which contains at least one coding sequence which encodes a peptide or protein containing a tumor antigen or fragment or variant thereof, can preferably be introduced into the tumor. Alternatively, said at least one coding RNA may be administered intradermally, intramuscularly or subcutaneously.

In a preferred embodiment of the invention, at least one additional pharmaceutically active ingredient used according to the present description is a coding RNA, preferably mRNA. Thus, a particular embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer as described herein, wherein the treatment also includes the administration of at least one coding RNA, preferably at least one mRNA, where the isRNA is preferably administered within a tumor ( e.g. locoregional). In a particularly preferred embodiment of the invention, the coding RNA, preferably mRNA, is administered within the tumor (eg, locoregional). More preferably, the isRNA, as well as at least one coding RNA, is administered intratumorally (eg, locoregional).

In a preferred embodiment of the invention, at least one additional pharmaceutically active ingredient used according to the present description is a coding RNA, preferably mRNA. Thus, a specific embodiment of the invention is an isRNA for use in treating a tumor or cancer as described herein, wherein the treatment comprises further administration of at least one coding RNA, preferably at least one mRNA, where the isRNA is preferably administered within a tumor. In a particularly preferred embodiment of the invention, the coding RNA, preferably mRNA, is introduced into the tumor. More preferably, the isRNA, as well as at least one coding RNA, is introduced into the tumor.

In some embodiments of the invention, at least one coding RNA is included in the preparative form in combination with an isRNA intended for use specified in the present description. In a particularly preferred embodiment of the invention, the at least one coding RNA is included in the formulation separately from the isRNA, with the at least one coding RNA as well as the isRNA being preferably introduced into the tumor (eg, locoregional).

According to a preferred embodiment of the invention, the isRNA is formulated in combination with at least one coding RNA, with the combined formulation being preferably administered intratumorally (eg, locoregional).

In some embodiments of the invention, at least one coding RNA is included in the preparative form in combination with isRNA intended for use specified in the present description. In a particularly preferred embodiment of the invention, the at least one coding RNA is included in the formulation separately from the isRNA, with the at least one coding RNA as well as the isRNA being preferably introduced into the tumor.

According to a preferred embodiment of the invention, the isRNA is formulated in combination with at least one coding RNA, with the combined formulation being preferably administered intratumorally.

According to a preferred embodiment of the invention, at least one coding RNA encodes at least one peptide or protein containing at least one of the peptides or proteins mentioned in the present description, as an additional pharmaceutically active ingredient. More preferably, at least one coding RNA encodes at least one peptide or protein which contains at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L and

- PD-1 decoy receptor, preferably soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L or PD-1 receptor decoy, or a fragment or variant of any of these compounds is preferably a compound specified in the present description. Even more preferably, at least one coding RNA encodes at least one peptide or protein that contains at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L,

a PD-1 decoy receptor, preferably a soluble PD-1 receptor, and

- antibodies to CTLA4,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, PD-1 decoy receptor or anti-CTLA4 antibody, or a fragment or variant of any of these compounds is preferably a compound as defined herein.

Alternatively, at least one coding RNA encodes at least one peptide or protein which contains at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L and

- antibodies to CTLA4,

or a fragment or variant of any of these compounds,

where IL-12, CD40L or an antibody to CTLA4, or a fragment or variant of any of these compounds is preferably a compound specified in the present description.

A preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isRNA contains a nucleotide sequence, which is described by formula (I) (G ₁ X _m G _n ), formula (II) (C ₁ X _m C _n ), formula (III) (N _u G ₁ X _m G _n N _v ) _a or formula (IV) (N _u C ₁ X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in one of SEQ ID NOs: 433-434, 1014-1016, or a fragment or variant of any of specified sequences,

where isRNA is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI), more preferably at least one of the disulfide crosslinked cationic peptides Cys-Arg ₁₂ , Cys-Arg ₁₂ -Cys or Trp-Arg ₁₂ -Cys,

where isRNA is preferably injected into the tumor,

where the treatment of a tumor or cancerous disease includes the introduction of at least one coding RNA, preferably at least one mRNA that encodes at least one peptide or protein containing at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L and

PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant of any of these compounds,

where IL-12, CD40L or PD-1 receptor decoy, or a fragment or variant of any of these compounds is preferably a compound specified in the present description.

A particularly preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isRNA contains a nucleotide sequence, which is described by formula (I) (G ₁ X _m G _n ), formula (II) (C ₁ X _m C _n ), formula (III) (N _u G ₁ X _m G _n N _v ) _a or formula (IV) (N _u C ₁ X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in any of SEQ ID NOs: 433-437, 1014-1016, 1055 or 1056, or a fragment or a variant of any of the above sequences,

where isRNA is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI), more preferably at least one of the disulfide crosslinked cationic peptides Cys-Arg ₁₂ , Cys-Arg ₁₂ -Cys or Trp-Arg ₁₂ -Cys,

where isRNA is preferably injected into the tumor,

where the neoplastic or cancerous disease is preferably selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC, most preferably cutaneous squamous cell carcinoma (cSCC), or other malignant skin cancers, adenoid cystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably advanced HNSCC ;

where the treatment of a tumor or cancerous disease includes the introduction of at least one coding RNA, preferably at least one mRNA that encodes at least one peptide or protein containing at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L and

- PD-1 decoy receptor, preferably soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L or PD-1 receptor decoy, or a fragment or variant of any of these compounds is preferably a compound specified in the present description.

Another preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isRNA contains a nucleotide sequence that is described by formula (I) (GiXmGn), formula (II) (C ₁ X _m C _n ), formula (III) (N _u G ₁ X _m G _n N _v ) _a or formula (IV ) (N _u C ₁ X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in any of SEQ ID NOs: 433-437, 1014-1016 or 1055 or 1056, or a fragment or variant of any of these sequences

where isRNA is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI), more preferably at least one of the disulfide crosslinked cationic peptides Cys-Arg ₁₂ , Cys-Arg ₁₂ -Cys or Trp-Arg ₁₂ -Cys,

where isRNA is preferably injected into the tumor, including peritumoral or locoregional administration,

where the treatment of a tumor or cancerous disease includes the introduction of at least one coding RNA, preferably at least one mRNA that encodes at least one peptide or protein containing at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L,

- antibodies to CTLA4 and

optionally a PD-1 decoy receptor, preferably a soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, PD-1 decoy receptor or anti-CTLA4 antibody, or a fragment or variant of any of these compounds, is preferably a compound as defined herein.

A particularly preferred embodiment of the invention is an isRNA for use in the treatment of a tumor or cancer,

where isRNA contains a nucleotide sequence, which is described by formula (I) (G ₁ X _m G _n ), formula (II) (C ₁ X _m C _n ), formula (III) (N _u G ₁ X _m G _n N _v ) _a or formula (IV) (N _u C ₁ X _m C _n N _v ) _a , preferably at least one nucleotide sequence as shown in one of SEQ ID NOs: SEQ ID NOs: 433-437, 1014-1016, preferably as shown in one of SEQ ID NOs: 433, 434 or 1014-1016, or a fragment or variant of any of these sequences,

where isRNA is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI), more preferably at least one of the disulfide crosslinked cationic peptides Cys-Arg ₁₂ , Cys-Arg ₁₂ -Cys or Trp-Arg ₁₂ -Cys,

where isRNA is preferably injected into the tumor, including peritumoral or locoregional administration,

where the neoplastic or cancerous disease is preferably selected from the group which consists of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably the cutaneous T-cell lymphoma subtype mycotic fungoid, and vulvar squamous cell carcinoma (VSCC);

where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

where the treatment of a tumor or cancerous disease includes the introduction of at least one coding RNA, preferably at least one mRNA that encodes at least one peptide or protein containing at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L,

- antibodies to CTLA4 and

optionally a PD-1 decoy receptor, preferably a soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, PD-1 decoy receptor or anti-CTLA4 antibody, or a fragment or variant of any of these compounds is preferably a compound as defined herein.

According to preferred embodiments of the invention, the treatment or prevention of a cancerous or neoplastic disease as described herein comprises administering a PD-1 decoy receptor as described herein when the subject is not or has not been treated with a PD-1 antagonist and/ or a PD-L1 antagonist. In cases where the patient is not or has not been treated with an anti-PD-1 and/or anti-PD-L1 agent (e.g., an anti-PD-1 antibody or an anti-PD-L1 antibody), it is most preferred if at least one mRNA encodes the PD-1 decoy receptor.

In other cases where the subject is or has been treated with a PD-1 or PD-L1 antagonist, the treatment or prevention of a cancerous or neoplastic disease preferably does not include administration of the PD-1 decoy receptor as defined herein or a nucleic acid. , which encodes a PD-1 decoy receptor, or a fragment or variant thereof.

According to a preferred embodiment of the invention, the treatment or prevention of a cancerous or neoplastic disease in an individual who is or has been treated with a PD-1 or PD-L1 antagonist comprises administering at least one coding RNA, preferably at least one mRNA that encodes at least one peptide or protein containing at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L and

- antibodies to CTLA4,

or a fragment or variant of any of these compounds,

where IL-12, CD40L or an antibody to CTLA4, or a fragment or variant of any of these compounds is preferably a compound specified in the present description.

According to other preferred embodiments of the invention, the treatment or prevention of a cancerous or neoplastic disease in an individual who is not or has not been treated with a PD-1 or PD-L1 antagonist comprises administering at least one coding RNA, preferably at least one mRNA that encodes at least one peptide or protein containing at least one peptide or protein selected from the group consisting of

- IL-12,

- CD40L and

- antibodies to CTLA4, and

optionally a PD-1 decoy receptor, preferably a soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, anti-CTLA4 antibody or PD-1 decoy receptor, or a fragment or variant of any of these compounds is preferably a compound specified in the present description.

According to a preferred embodiment of the invention, at least one coding RNA encodes a peptide or protein containing IL-12, or a fragment or variant thereof, specified in the present description. In some embodiments of the invention, at least one coding RNA encodes a peptide or protein, a mutant peptide or mutant protein, a cross-linked heterodimer, an antibody, preferably an RNA-encoded antibody, or artificial binding domains containing an IL-12 analog or fragment or variant thereof specified in this description. Preferably, the encoded peptide or protein contains the amino acid sequence shown in one of SEQ ID NOs: 3-8, or a fragment or variant of any of these sequences. The encoded peptide or protein may preferably also contain the amino acid sequence shown in SEQ ID NO: 9, or a fragment or variant thereof. More preferably, the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 10, or a fragment or variant thereof. Most preferably, the encoded peptide or protein contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to one of the amino acid sequences shown in SEQ ID NO: 3 -8, or a fragment or variant of any of the indicated sequences. In the most preferred embodiment of the invention, the encoded peptide or protein contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence shown in SEQ ID NO : 10, or a fragment or variant of it.

In another preferred embodiment of the invention, at least one coding RNA encodes a peptide or protein containing IL-12 or a fragment or variant thereof, specified in the present description, where at least one coding RNA contains the nucleotide sequence shown in one of SEQ ID NO : 14-19 or 21 or SEQ ID NOs: 440-445 or 447, preferably in one of SEQ ID NOs: 440-445 or 447, or a fragment or variant of any of these sequences. More preferably, at least one coding RNA encodes a peptide or protein containing IL-12 or a fragment or variant thereof, specified in the present description, where at least one coding RNA contains a nucleotide sequence identical or at least 50%, 60% , 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94 %, 95%, 96%, 97%, 98%, 99% identical to one of the nucleotide sequences shown in SEQ ID NO: 14-19 or 21 or SEQ ID NO: 440-445 or 447, preferably in one of SEQ ID NO: 440-445 or 447, or a fragment or variant of any of these sequences.

In an alternative or additional embodiment, at least one coding RNA encodes a peptide or protein containing IL-12 or a fragment or variant thereof, specified in the present description, where at least one coding RNA contains the nucleotide sequence shown in SEQ ID NO: 20 or 446, preferably in SEQ ID NO: 446, or a fragment or variant of any of these sequences. More preferably, at least one coding RNA encodes a peptide or protein containing IL-12 or a fragment or variant specified in the present description, where at least one coding RNA contains a nucleotide sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% , 95%, 96%, 97%, 98%, 99% identical to the nucleotide sequence shown in SEQ ID NO: 20 or 446, preferably in SEQ ID NO: 446, or a fragment or variant of any of these sequences.

In a particularly preferred embodiment of the invention, at least one coding RNA encodes a peptide or protein containing IL-12 or a fragment or variant thereof, specified in the present description, where at least one coding RNA contains the nucleotide sequence shown in SEQ ID NO: 21 or 447, preferably in SEQ ID NO: 447, or a fragment or variant of any of these sequences. More preferably, at least one coding RNA encodes a peptide or protein containing IL-12 or a fragment or variant specified in the present description, where at least one coding RNA contains a nucleotide sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% , 95%, 96%, 97%, 98%, 99% identical to the nucleotide sequence shown in SEQ ID NO: 21 or 447, preferably in SEQ ID NO: 447, or a fragment or variant of any of these sequences.

According to another embodiment of the invention, at least one coding RNA encodes a peptide or protein containing CD40L or a fragment or variant specified in the present description. Preferably, the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 11, or a fragment or variant thereof. More preferably, the encoded peptide or protein contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence shown in SEQ ID NO: 11, or its fragment or variant.

In a further preferred embodiment of the invention, at least one coding RNA encodes a peptide or protein containing CD40L or a fragment or variant thereof as described herein, wherein at least one coding RNA contains the nucleotide sequence shown in SEQ ID NO: 22 or SEQ ID NO: 448, preferably in SEQ ID NO: 448, or a fragment or variant thereof. More preferably, at least one coding RNA encodes a peptide or protein containing CD40L, or a fragment or variant thereof, as described herein, wherein the at least one coding RNA contains a nucleotide sequence identical or at least 50%, 60%, 70 %, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the nucleotide sequence shown in SEQ ID NO: 22 or SEQ ID NO: 448, preferably in SEQ ID NO: 448, or a fragment or variant of any of these sequences.

According to an alternative embodiment of the invention, at least one coding RNA encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof, as specified herein, more preferably a soluble PD-1 receptor, or a fragment or variant thereof, as specified in this description. Preferably, the encoded peptide or protein contains the amino acid sequence shown in one of SEQ ID NO: 2 or SEQ ID NO: 1042, or a fragment or variant thereof. More preferably, the encoded peptide or protein contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 1042, or a fragment or variant thereof.

In another preferred embodiment of the invention, at least one coding RNA encodes a peptide or protein containing a PD-1 decoy receptor, more preferably a soluble PD-1 receptor, or a fragment or variant thereof, specified in the present description, where at least one coding RNA contains the nucleotide sequence shown in SEQ ID NO: 13 or SEQ ID NO: 439, preferably in SEQ ID NO: 439, or a fragment or variant thereof. More preferably, at least one coding RNA encodes a PD-1 decoy receptor-containing peptide or protein, more preferably a soluble PD-1 receptor, or fragment or variant thereof, as defined herein, wherein at least one coding RNA contains nucleotide sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89% , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the nucleotide sequence shown in SEQ ID NO: 13 or SEQ ID NO: 439, preferably in SEQ ID NO: 439, or a fragment or variant of any of the indicated sequences.

According to an alternative embodiment of the invention, at least one coding RNA encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof, as specified herein, more preferably a soluble PD-1 receptor, or a fragment or variant thereof, as specified in this description. Preferably, the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 1, or a fragment or variant thereof. More preferably, the encoded peptide or protein contains an amino acid sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87 %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the amino acid sequence shown in SEQ ID NO: 1, or its fragment or variant.

In a further preferred embodiment of the invention, at least one coding RNA encodes a PD-1 decoy receptor-containing peptide or protein, more preferably a soluble PD-1 receptor, or a fragment or variant thereof, as defined herein, wherein at least one the coding RNA contains the nucleotide sequence shown in SEQ ID NO: 12 or SEQ ID NO: 438, preferably in SEQ ID NO: 438, or a fragment or variant thereof. More preferably, at least one coding RNA encodes a PD-1 decoy receptor-containing peptide or protein, more preferably a soluble PD-1 receptor, or fragment or variant thereof, as defined herein, wherein at least one coding RNA contains nucleotide sequence identical or at least 50%, 60%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89% , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the nucleotide sequence shown in SEQ ID NO: 12 or SEQ ID NO: 438, preferably in SEQ ID NO: 438, or a fragment or variant of any of the indicated sequences.

According to a preferred embodiment of the invention, at least one coding RNA encodes a peptide or protein containing a CTLA4 antagonist as defined herein. Preferably, at least one coding RNA encodes a peptide or protein comprising an anti-CTLA4 antibody as defined herein, or a fragment or variant thereof as defined herein, wherein the fragment or variant is preferably a functional fragment or functional variant. More preferably, at least one coding RNA encodes a peptide or protein comprising an anti-CTLA4 antibody as defined herein, or a fragment or variant thereof as defined herein, wherein at least one coding RNA comprises a nucleotide sequence as set forth in one of the SEQs. ID NOs: 646-660, 662-676, 678-692, 694-705, or 707-715, preferably as shown in one of SEQ ID NOs: 646-660, 679-692, or 710-715, or a fragment or variant of any of the indicated nucleotide sequences. Even more preferably, at least one coding RNA encodes a peptide or protein containing an anti-CTLA4 antibody, or fragment or variant thereof, as described herein, wherein the at least one coding RNA contains a nucleotide sequence that is at least 50% identical, 60 %, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical to the nucleotide sequence shown in SEQ ID NO: 646-660, 662-676, 678-692, 694-705 or 707-715, preferably in one from SEQ ID NO: 646-660, 679-692, or 710-715.

Preferably, at least one coding RNA also encodes a peptide or protein comprising an anti-CTLA4 antibody heavy chain, or fragment or variant thereof, and an anti-CTLA4 antibody light chain, or fragment or variant thereof, wherein the heavy chain and light chain or fragment or variant thereof are preferably indicated. in this description.

Preferably, at least one coding RNA encodes a peptide or protein comprising an anti-CTLA4 antibody heavy chain or fragment or variant and an anti-CTLA4 antibody light chain or fragment or variant,

where the heavy chain or a fragment or variant thereof is encoded by a nucleotide sequence selected from one of SEQ ID NOs: 646-660, 662-676 or 710-715, preferably from one of SEQ ID NOs: 646-660, or a fragment or variant of any of specified nucleotide sequences, and where the light chain or its fragment or variant is encoded by a nucleotide sequence selected from one of SEQ ID NO: 678-692, 694-705, 707-709 or 710-715, preferably from one of SEQ ID NO: 678 -692, or a fragment or variant of any of the indicated nucleotide sequences.

Wherein, the heavy chain and the light chain, or a fragment or variant of any of them, respectively, are preferably encoded either by the same coding RNA or by different coding RNAs.

A preferred embodiment of the invention is an isRNA for the use described herein, where the use includes - use as an additional pharmaceutically active ingredient - an anti-CTLA4 antibody or fragment or variant thereof, specified in the present description, where the anti-CTLA4 antibody is in the form of two different RNAs (which come in different or the same preparative form),

where the heavy chain of the antibody to CTLA4 or its fragment or variant is encoded by a nucleotide sequence selected from one of SEQ ID NO: 646-660, 662-676, or 710-715, preferably from one of SEQ ID NO: 646-660, or a fragment or a variant of any of the indicated nucleotide sequences, and where the light chain or a fragment or variant thereof is encoded by a nucleotide sequence selected from one of SEQ ID NOs: 678-692, 694-705, 707-709 or 710-715, preferably from one of SEQ ID NO: 678-692, or a fragment or variant of any of the indicated nucleotide sequences.

An alternative embodiment of the invention is an isRNA for use as described herein, where the use includes - use as an additional pharmaceutically active ingredient - an anti-CTLA4 antibody or fragment or variant thereof, as described herein, where the anti-CTLA4 antibody or fragment or variant are in the form of an RNA, where one RNA encodes both the heavy chain of an anti-CTLA4 antibody, or fragment or variant thereof, and the light chain of an antibody to CTLA4, or a fragment or variant thereof, and where the RNA preferably contains or consists of the nucleotide sequence shown in one of the SEQ ID NO: 710-712, 713-715, or a fragment or variant of one of the indicated nucleotide sequences.

The present invention also provides an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein at least one coding RNA codes for at least two peptides or proteins selected from the group consisting of

- IL-12,

- CD40L,

- antibodies to CTLA4 and

optionally a PD-1 decoy receptor, preferably a soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, PD-1 decoy receptor or anti-CTLA4 antibody, or a fragment or variant of any of these compounds is preferably a compound as defined herein.

In the context of the present invention, the term “anti-CTLA4 antibody”, as used herein, may refer to “(one) peptide or protein” (singular), even if the (mature) anti-CTLA4 antibody or fragment or variant preferably contains at least two peptides or proteins, namely a heavy chain or fragment or variant thereof and a light chain or fragment or variant thereof.

Thus, in some embodiments of the invention, the treatment of a tumor or cancer involves the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least two, three, four or five coding RNAs that encode at least two , preferably two, three or four peptides or proteins or a fragment or variant of any of them, which preferably results in the expression of said at least two peptides or proteins, or fragments or variants of any of them after administration of at least one coding RNA to the individual.

According to a particularly preferred embodiment of the invention, the treatment of a tumor or cancer involves the administration of at least two or three coding RNAs (as additional pharmaceutically active ingredients), where each of the coding RNAs encodes one different peptide or protein selected from the group which consists of

- IL-12,

- CD40L,

- antibodies to CTLA4 and

optionally a PD-1 decoy receptor, preferably a soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, PD-1 decoy receptor or anti-CTLA4 antibody, or a fragment or variant of any of these compounds is preferably a compound as defined herein.

According to another embodiment of the invention, the treatment of a tumor or cancer comprises administering at least one coding RNA (as additional pharmaceutically active ingredient(s)), where at least one coding RNA is a bi- or polycistronic RNA , which encodes at least one peptide or protein, preferably two, three or four peptides or proteins selected from the group consisting of

- IL-12,

- CD40L,

- antibodies to CTLA4 and

optionally a PD-1 decoy receptor, preferably a soluble PD-1 receptor,

or a fragment or variant of any of these compounds,

where IL-12, CD40L, PD-1 decoy receptor or anti-CTLA4 antibody, or a fragment or variant of any of these compounds, is preferably a compound as defined herein.

In this context, the invention has surprisingly found that the expression of a combination of two, preferably three or four of the peptides or proteins described herein is particularly advantageous for the treatment of a neoplastic or cancerous disease, in particular when combined with the isRNA described herein. description.

A preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12 or fragment or variant thereof.

Another preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA,

where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein, containing a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof.

Another preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof.

A preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant.

A preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant.

A preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant.

A particularly preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof.

In this embodiment of the invention, a coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, a coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof, and a coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, may preferably be on different coding RNAs, preferably different mRNAs. Alternatively, at least two of their coding sequences that encode a peptide or protein containing IL-12, or a fragment or variant thereof, encode a peptide or protein containing a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or its fragment or variant and encode the peptide or protein containing CD40L or its fragment or variant are on the same coding RNA, which is preferably a bi- or polycistronic RNA.

Some embodiments of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof, the same or another coding RNA contains at least one coding sequence that encodes a peptide or a protein containing or consisting of CD40L or a fragment or variant thereof, and the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of a CTLA4 antibody, preferably specified herein, or fragment or variant.

This embodiment is particularly preferred if the patient is or has been treated with a PD-1 antagonist or PD-L1 antagonist, such as an anti-PD-1 antibody or an anti-PD-L1 antibody.

Some embodiments of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof, the same or another coding RNA contains at least one coding sequence that encodes a peptide or a protein containing or consisting of a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof,

the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of CD40L or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of a CTLA4 antibody, preferably as defined herein, or a fragment or variant thereof.

This embodiment is particularly preferred if the patient is not or has not been treated with a PD-1 antagonist or PDL-1 antagonist, such as an anti-PD-1 antibody or an anti-PD-L1 antibody.

In these embodiments, a coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof, optionally a coding sequence that encodes a peptide or protein containing or consisting of a PD-1 decoy receptor, is preferably soluble PD-1 receptor, or fragment or variant thereof, coding sequence encoding a peptide or protein containing or consisting of CD40L or a fragment or variant thereof, and coding sequence encoding a peptide or protein containing or consisting of an anti-CTLA4 antibody or a fragment or variant thereof, may preferably be on different coding RNAs, preferably on different mRNAs. Alternatively, at least two of the following coding sequences: a coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof, a coding sequence that encodes a peptide or protein containing or consisting of PD-1 decoy receptor, preferably a soluble PD-1 receptor, or fragment or variant thereof, a coding sequence encoding a peptide or protein containing or consisting of CD40L or a fragment or variant thereof, and a coding sequence encoding a peptide or protein containing or consisting of an anti-CTLA4 antibody or fragment or variant thereof, may preferably be on the same coding RNA, which is preferably a bi- or polycistronic RNA.

Some embodiments of the present invention is an isRNA for use in the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein

at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof,

the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of CD40L or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing or consisting of an anti-CTLA4 antibody, preferably as defined herein, or a fragment or variant thereof.

In these embodiments, a coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof, a coding sequence that encodes a peptide or protein containing or consisting of CD40L or a fragment or variant thereof, and a coding sequence that encodes a peptide or protein containing or consisting of an anti-CTLA4 antibody or fragment or variant thereof may preferably be on different coding RNAs, preferably on different mRNAs. Alternatively, at least two of the following coding sequences: a coding sequence that encodes a peptide or protein containing or consisting of IL-12 or a fragment or variant thereof, a coding sequence that encodes a peptide or protein containing or consisting of CD40L or its fragment or variant and a coding sequence that encodes a peptide or protein containing or consisting of an anti-CTLA4 antibody or fragment or variant may preferably be on the same coding RNA, which is preferably a bi- or polycistronic RNA.

A preferred embodiment of the present invention is an isRNA for the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein at least at least one coding sequence encodes at least one tumor antigen or fragment or variant thereof. Preferably the coding sequence contains at least one nucleotide sequence, preferably selected from the group which consists of SEQ ID NO: 505-4033; 4561-4591 specified in PCT/EP 2017/059525, or a fragment or variant of any of the specified sequences.

A preferred embodiment of the present invention is an isRNA for the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, wherein at least at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 14-19 or SEQ ID NO: 440-445 or 447, preferably from the group consisting of SEQ ID NO: 440-445 or 447, or a fragment or variant any of these sequences, preferably the nucleotide sequence shown in SEQ ID NO: 21 or SEQ ID NO: 447, preferably in SEQ ID NO: 447, or a fragment or variant of any of these sequences;

b) the nucleotide sequence shown in SEQ ID NO: 22 or SEQ ID NO: 448, preferably in SEQ ID NO: 448, or a fragment or variant thereof,

c) a nucleotide sequence as shown in one of SEQ ID NOs: 646-660 or 662-676, preferably in one of SEQ ID NOs: 646-660, or a fragment or variant of any of the said nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NOs: 678-692, 694-705 or 707-709, preferably as shown in one of SEQ ID NOs: 678-692, or a fragment or variant of any of the indicated nucleotide sequences

or

the nucleotide sequence shown in one of SEQ ID NOs: 710-712 or 713-715, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally the nucleotide sequence shown in SEQ ID NO: 13 or SEQ ID NO: 439, preferably in SEQ ID NO: 439, or a fragment or variant thereof.

According to one embodiment of the invention, at least one coding RNA or isRNA specified in the present description may be in the form of a modified RNA, while any modification specified in the present description may be introduced into at least one RNA or isRNA specified in this description. According to a preferred embodiment of the invention, at least one coding RNA specified in the present description contains at least one coding sequence that contains a nucleotide sequence modified in comparison with the nucleotide sequence of the coding sequence of the corresponding wild-type RNA, and the amino acid sequence encoded said coding sequence, preferably not modified from the amino acid sequence encoded by the corresponding wild-type RNA coding sequence. Specified in the present description of the modification preferably lead to the stabilization of at least one coding RNA used according to the present description.

Thus, another preferred embodiment of the present invention is an isRNA for the treatment of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NOs: 14-19; 440-445; 447; 25-30; 36-41; 47-52; 58-63; 69-74; 80-85; 91-96; 102-107; 113-118; 124-129; 135-140; 601-606; 612-617; 623-628; 716-725; 727; 1018-1021 and 1059-1062, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 21; 447; 32; 43; 54; 65; 76; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632-644; 726 and 1058, or a fragment or variant of any of these sequences;

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 22; 448; 33; 44; 55; 66; 77; 88; 99; ON; 121; 132; 143; 609; 620; 631; 728-738 and 1025-1028, or a fragment or variant of any of these sequences;

c) the nucleotide sequence shown in one of SEQ ID NOs: 646-660; 662-676 or 1029-1036, preferably as shown in one of SEQ ID NOs: 646-660, or a fragment or variant of any of the indicated nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NOs: 678-692, 694-705 ; 707-709 or 1037-1041, preferably represented in one of SEQ ID NOs: 678-692, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in one of SEQ ID NOs: 710-712 or 713-715, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 12; 438; 23; 34; 45; 56; 67; 78; 89; 100; 111; 122; 133; 599; 610; 621 and 1022-1024, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 13, 439; 24; 439; 35; 46; 57; 68; 79; 90; 101; 112; 123; 134; 600; 611; 622 and 1043-1054, or a fragment or variant of any of these sequences.

Thus, another preferred embodiment of the present invention is an isPHK for the treatment of a tumor or cancer described herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA , where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 25-30; 36-41; 47-52; 58-63; 69-74; 80-85; 91-96; 102-107; 113-118; 124-129; 135-140; 601-606; 612-617; 623-628; 716-725; 727; 1018-1021 and 1059-1062, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 32; 43; 54; 65; 76; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632-644; 726 and 1058, or a fragment or variant of any of these sequences;

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 44; 55; 66; 77; 88; 99; 110; 121; 132; 143; 609; 620; 631; 728-738; 1025-1028 and 1025-1028, or a fragment or variant of any of these sequences;

c) the nucleotide sequence shown in one of SEQ ID NOs: 646-660; 662-676 or 1029-1036, preferably as shown in one of SEQ ID NOs: 646-660, or a fragment or variant of any of the indicated nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NOs: 678-692, 694-705 ; 707-709 or 1037-1041, preferably represented in one of SEQ ID NOs: 678-692, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in one of SEQ ID NOs: 710-712 or 713-715, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 23; 34; 45; 56; 67; 78; 89; 100; 111; 122; 133; 599; 610; 621; 1022-1024, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 24; 35; 46; 57; 68; 79; 90; 101; 112; 123; 134; 600; 611; 622 and 1043-1054, or a fragment or variant of any of these sequences.

In this context, a coding RNA used according to the present description, containing at least one coding sequence that contains a (wild-type or modified) nucleotide sequence that encodes IL-12 or a fragment or variant thereof, specified in the present description, may preferably contain a nucleotide the sequence shown in any of SEQ ID NO: 20; 31; 42; 53; 64; 75; 86; 97; 108; 119; 130; 141; 446; 607; 618 or 629, or a fragment or variant of any of these sequences.

According to one embodiment of the invention, at least one coding RNA specified in the present description, can be obtained in the form of "stabilized RNA", i. as RNA that is substantially resistant to in vivo cleavage (eg, exo- or endonuclease). Said stabilization can be accomplished, for example, by modifying the phosphate backbone of at least one coding RNA as described herein. Framework modification in the context of the present invention is a modification in which the phosphates of the framework of the nucleotides included in the RNA are chemically modified. Nucleotides which can preferably be used in this connection comprise, for example, a phosphorothioate-modified phosphate backbone, preferably at least one of the oxygen atoms of the phosphate included in the phosphate backbone is replaced by a sulfur atom. Stabilized RNAs may further include, for example: non-ionic phosphate analogs, such as, for example, alkyl and aryl phosphonates, in which the charged oxygen of the phosphonate is replaced by an alkyl or aryl group, or phosphodiesters and alkyl phosphotriesters, in which the charged oxygen-containing residue is present in the alkylated form . Said backbone modifications typically include, but are not limited to, modifications selected from the group consisting of methylphosphonates, phosphoramidates, and phosphorothioates (eg, cytidine-5'-O-(1-thiophosphate)).

Described below are specific modifications that can preferably "stabilize" at least one coding RNA as defined herein.

Chemical modifications:

As used herein, "RNA modification" may refer to chemical modifications, including backbone modifications, as well as sugar or base modifications.

In this context, the modified RNA described herein may contain nucleotide analogs/modifications, such as backbone modifications, sugar modifications, or base modifications. Framework modification in the context of the present invention is a modification in which the phosphates of the framework of the nucleotides included in the RNA specified in the present description are chemically modified. Modification of sugars in the context of the present invention is a chemical modification of sugar in the nucleotides of the RNA specified in the present description. In addition, the modification of the bases in the context of the present invention is a chemical modification of the main fragment in the RNA nucleotides. In this context, nucleotide analogs or modifications are preferably selected from nucleotide analogs that can be used for transcription and/or translation.

Sugar modifications:

Modified nucleosides and nucleotides that can be included in the modified RNA described herein can be modified in the sugar moiety. For example, the 2'-hydroxyl group (OH) may be modified or replaced with a number of different "oxy" or "deoxy" substituents. Examples of "oxy" modifications of the 2'-hydroxyl group include, but are not limited to, an alkoxy group or an aryloxy group (-OR, for example, R is H, alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or sugar); polyethylene glycols (PEG), -O(CH ₂ CH ₂ O) _n CH ₂ CH ₂ OR; "closed" nucleic acids (LNA), in which the 2'-hydroxyl is connected, for example, with a methylene bridge, to the 4'-carbon of the same ribose sugar; and amino groups (-O-amino, in which the amino group, for example, NRR, may be an alkylamino group, a dialkylamino group, a heterocyclyl, an arylamino group, a diarylamino group, a heteroarylamino group or a diheteroarylamino group, an ethylenediamine, a polyamino group) or an aminoalkoxy group.

"Deoxy" modifications include hydrogen, an amino group (eg, NH ₂ ; an alkylamino group, a dialkylamino group, a heterocyclyl, an arylamino group, a diarylamino group, a heteroarylamino group, a diheteroarylamino group, or an amino acid); or the amino group may be attached to the sugar via a linker, where the linker contains one or more C, N and O atoms.

The sugar moiety may also contain one or more carbon atoms in the opposite stereochemical configuration to that in which the corresponding carbon atom is found in the ribose. Thus, the modified RNA may include nucleotides containing, for example, arabinose as a sugar.

Frame mods:

You can also modify the phosphate backbone in the modified nucleosides and nucleotides, which can be included in the modified RNA specified in the present description. The backbone phosphate groups can be modified by replacing one or more oxygen atoms with another substituent. In addition, modified nucleosides and nucleotides may include the complete replacement of an unmodified phosphate moiety with a modified phosphate as defined herein. Examples of modified phosphate groups include, but are not limited to, phosphorothioate, phosphoroselenates, boranophosphates, boranophosphate esters, acid phosphonates, phosphoramidates, alkyl or aryl phosphonates, and phosphotriesters. In phosphorodithioates, both unbound oxygens are replaced by sulfur. The phosphate bond can be modified by replacing the bound oxygen with nitrogen (bridged phosphoroamidates), sulfur (bridged phosphorothioates), and carbon (bridged methylenephosphonates).

Base modifications:

Modified nucleosides and nucleotides, which can be included in the modified RNA described in the present description, can also be modified to include a nucleotide base fragment. Examples of nucleotide bases found in RNA are (but not limited to) adenine, guanine, cytosine and uracil. For example, the nucleosides and nucleotides described herein can be chemically modified on the surface of the major groove. In some embodiments, chemical modifications of the major groove may include an amino group, a thiol group, an alkyl group, or a halo group.

In the most preferred embodiments of the present invention, the nucleotide analogs/modifications are selected from base modifications, which are preferably selected from 2-amino-6-chloropurine riboside-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-methylinosine-5'-triphosphate , 4-thiouridine-5'-triphosphate, 5-aminoallylcytidine-5'-triphosphate, 5-aminoallyluridine-5'-triphosphate, 5-bromocytidine-5'-triphosphate, 5-bromouridine-5'-triphosphate, 5-bromo- 2'-deoxycytidine-5'-triphosphate, 5-bromo-2'-deoxyuridine-5'-triphosphate, 5-iodocytidine-5'-triphosphate, 5-iodine-2'-deoxycytidine-5'-triphosphate, 5-ioduridine -5'-triphosphate, 5-iodine-2'-deoxyuridine-5'-triphosphate, 5-methylcytidine-5'-triphosphate, 5-methyluridine-5'-triphosphate, 5-propynyl-2'-deoxycytidine-5'- triphosphate, 5-propynyl-2'-deoxyuridine-5'-triphosphate, 6-azacytidine-5'-triphosphate, 6-azauridine-5'-tripho sphate, 6-chloropurine riboside-5'-triphosphate, 7-deazaadenosine-5'-triphosphate, 7-deazaguanosine-5'-triphosphate, 8-azaadenosine-5'-triphosphate, 8-azidoadenosine-5'-triphosphate, benzimidazole riboside-5 '-triphosphate, N1-methyladenosine-5'-triphosphate, N1-methylguanosine-5'-triphosphate, N6-methyladenosine-5'-triphosphate, O6-methylguanosine-5'-triphosphate, pseudouridine-5'-triphosphate or puromycin-5 '-triphosphate, xanthosine-5'-triphosphate. The most preferred nucleotides for base modifications are selected from the group of base-modified nucleotides including 5-methylcytidine-5'-triphosphate, 7-deazaguanosine-5'-triphosphate, 5-bromocytidine-5'-triphosphate, and pseudouridine-5'-triphosphate.

In some embodiments, the modified nucleosides include pyridine-4-oneribonucleoside, 5-azauridine, 2-thio-5-aza-uridine, 2-thiouridine, 4-thiopseudouridine, 2-thiopseudouridine, 5-hydroxyuridine, 3-methyluridine, 5- carboxymethyluridine, 1-carboxymethylpseudouridine, 5-propynyluridine, 1-propynylpseudouridine, 5-taurinomethyluridine, 1-taurinomethylpseudouridine, 5-taurinomethyl-2-thiouridine, 1-taurinomethyl-4-thiouridine, 5-methyluridine, 1-methylpseudouridine, 4-thio- 1-methylpseudouridine, 2-thio-1-methylpseudouridine, 1-methyl-1-deazapseudouridine, 2-thio-1-methyl-1-deazapseudouridine, dihydrouridine, dihydropseudouridine, 2-thiodihydrouridine, 2-thiodihydropseudouridine, 2-methoxyuridine, 2- methoxy-4-thiouridine, 4-methoxypseudouridine and 4-methoxy-2-thiopseudouridine.

In some embodiments, the modified nucleosides include 5-azacytidine, pseudoisocytidine, 3-methylcytidine, N4-acetylcytidine, 5-formylcytidine, N4-methylcytidine, 5-hydroxymethylcytidine, 1-methyl-pseudoisocytidine, pyrrolocytidine, pyrrolopseudoisocytidine, 2-thiocytidine, 2-thio -5-methylcytidine, 4-thiopseudisocytidine, 4-thio-1-methylpseudoisocytidine, 4-thio-1-methyl-1-deazapseudoisocytidine, 1-methyl-1-deazapseudoisocytidine, zebularine, 5-azazebularine, 5-methylzebularine, 5-aza -2-thiozebularine, 2-thiosebularine, 2-methoxycytidine, 2-methoxy-5-methylcytidine, 4-methoxypseudoisocytidine and 4-methoxy-1-methylpseudoisocytidine.

In other embodiments, the modified nucleosides include 2-aminopurine, 2,6-diaminopurine, 7-deazaadenin, 7-deaza-8-azaadenine, 7-deaza-2-aminopurine, 7-deaza-8-aza-2-aminopurine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyladenosine, N6-methyladenosine, N6-isopentenyladenosine, N6-(cis-hydroxyisopentenyl)adenosine, 2-methylthio-N6 -(cis-hydroxyisopentenyl)adenosine, N6-glycinylcarbamoyladenosine, N6-threonylcarbamoyladenosine, 2-methylthio-N6-threonylcarbamoyladenosine, N6,N6-dimethyladenosine, 7-methyladenine, 2-methylthioadenine and 2-methoxyadenine.

In other embodiments, the modified nucleosides include inosine, 1-methylinosine, viosin, vibutosin, 7-deazaguanosine, 7-deaza-8-azaguanosine, 6-thioguanosine, 6-thio-7-deazaguanosine, 6-thio-7-deaza- 8-azaguanosine, 7-methylguanosine, 6-thio-7-methylguanosine, 7-methylinosine, 6-methoxyguanosine, 1-methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, 8-oxoguanosine, 7-methyl-8-oxoguanosine, 1-methyl-6-thioguanosine, N2-methyl-6-thioguanosine and N2,N2-dimethyl-6-thioguanosine.

In some embodiments, the nucleotide may be modified at the surface of the major groove and may include replacing the hydrogen on the C-5 of uracil with a methyl group or a halogen group.

In specific embodiments, the modified nucleoside is 5'-O-(1-thiophosphate)adenosine, 5'-O-(1-thiophosphate)cytidine, 5'-O-(1-thiophosphate)guanosine, 5'-O- (1-thiophosphate)uridine or 5'-O-(1-thiophosphate)pseudouridine.

In other specific embodiments, the modified RNA described herein may contain nucleoside modifications selected from 6-azacytidine, 2-thiocytidine, α-thiocytidine, pseudoisocytidine, 5-aminoallyluridine, 5-yoduridine, N1-methylpseudouridine, 5,6- dihydrouridine, α-thiouridine, 4-thiouridine, 6-azauridine, 5-hydroxyuridine, deoxythymidine, 5-methyluridine, pyrrolocytidine, inosine, α-thioguanosine, 6-methylguanosine, 5-methylcytidine, 8-oxoguanosine, 7-deazaguanosine, N1- methyladenosine, 2-amino-6-chloropurine, N6-methyl-2-aminopurine, pseudoisocytidine, 6-chloropurine, N6-methyladenosine, α-thioadenosine, 8-azidoadenosine, 7-deazaadenosine.

Lipid modification:

According to another embodiment of the invention, the modified RNA described herein may contain a lipid modification. Such lipid-modified RNA typically contains the RNA as defined herein, preferably the coding RNA as described herein. Such a lipid-modified RNA as described herein typically further comprises at least one linker covalently linked to said RNA and at least one lipid covalently linked to the corresponding linker. Alternatively, the lipid-modified RNA comprises at least one RNA as defined herein, preferably encoding an RNA as described herein, and at least one (bifunctional) lipid covalently linked (without a linker) to said RNA. According to a third alternative, the lipid-modified RNA comprises an RNA molecule as defined herein, preferably encoding an RNA as defined herein, at least one linker covalently linked to said RNA, and at least one lipid covalently linked to an appropriate linker, and also at least one (bifunctional) lipid covalently linked (without a linker) to said RNA. In this context, it is most preferred that the lipid modification be present at the ends of the linear RNA sequence.

G/C content modification:

According to a particularly preferred embodiment of the invention, at least one coding RNA specified in the present description is modified. Preferably, the RNA is stabilized by modifying and preferably increasing the content of G (guanosine)/C (cytosine) in at least one of its coding regions. Thus, the content of G/C in the coding region of the RNA is increased compared to the content of G/C in the coding region of its particular wild-type coding sequence, i.e. corresponding unmodified RNA. However, the amino acid sequence encoded by the RNA is preferably unmodified as compared to the amino acid sequence encoded by the particular wild-type/unmodified RNA.

The modification of the G/C content of at least one coding RNA referred to herein is based on the fact that RNA sequences having an increased content of G (guanosine)/C (cytosine) are more stable than sequences having an increased content of A (adenosine) / U (uracil). Thus, the codons of the coding sequence or the total RNA can be changed compared to the wild-type coding sequence or RNA so that they contain more G/C nucleotides while maintaining the translated amino acid sequence. Considering the fact that several codons code for the same amino acid (the so-called degeneracy of the genetic code), it is possible to determine the codons most preferable in terms of stability (the so-called alternative most frequent codons). Depending on the amino acid to be encoded by at least one RNA, there are different possibilities for modifying the RNA sequence compared to the corresponding wild-type coding sequence. In the case of amino acids that are encoded by codons containing exclusively G or C nucleotides, no modification of the codon is necessary. Thus, codons Pro (CCC or CCG), Arg (CGC or CGG), Ala (GCC or GCG) and Gly (GGC or GGG) do not need to be modified because they do not contain A or U. In contrast, codons which contain A and/or U nucleotides can be modified by substitution with other codons that code for the same amino acids but do not contain A and/or U. Examples of these are: CCU or CCA codons encoding Pro can be replaced with CCC or CCG ; codons CGU or CGA or AGA or AGG encoding Arg can be changed to CGC or CGG; GCU or GCA codons encoding Ala can be changed to GCC or GCG; The codons GGU or GGA encoding Gly can be changed to GGC or GGG. In other cases where A or U nucleotides cannot be eliminated from codons, A and U content can be reduced by using codons that contain A and/or U nucleotides in a lower amount. Examples of said colons are: the UUU codon encoding Phe can be replaced with UUC; UUA, UUG, CUU or CUA codons encoding Leu can be replaced with CUC or CUG; the UCU or UCA or AGU codons encoding Ser can be changed to UCC, UCG or AGC; the codon UAU encoding Tyr can be changed to UAC; the UGU codon encoding Cys can be changed to UGC; the CAU codon encoding His can be changed to CAC; the CAA codon encoding Gin can be changed to CAG; AUU or AUA codons encoding Ile can be replaced with AUC; ACU or ACA codons encoding Thr can be replaced with ACC or ACG; the AAU codon encoding Asn can be changed to AAC; the AAA codon encoding Lys can be changed to AAG; codons GUU or GUA encoding Val can be replaced by GUC or GUG; the GAU codon encoding Asp can be changed to GAC; the GAA codon encoding Glu can be changed to GAG; the stop codon UAA can be changed to UAG or UGA. On the other hand, in the case of Met (AUG) and Trp (UGG) codons, there is no possibility of sequence modification. The substitutions listed above can be used either alone or in any possible combination to increase the G/C content of at least one mRNA in a composition of the present invention compared to a particular wild-type mRNA (i.e., parent sequence). Thus, for example, all Thr codons occurring in the wild-type sequence can be modified to ACC (or ACG). However, it is preferable, for example, to use combinations of the above possible substitutions:

replacement of all codons encoding Thr in the original sequence (wild-type mRNA) with ACC (or ACG) and

changing all codons encoding in the original Ser sequence to UCC (or UCG or AGC); changing all codons encoding in the original Ile sequence to AUC, and

changing all codons coding in the original Lys sequence to AAG, and

replacement of all codons encoding in the original Tyr sequence with UAC; changing all codons encoding in the original Val sequence to GUC (or GUG), and

replacing all codons encoding in the original Glu sequence with GAG, and

changing all codons encoding in the original Ala sequence to GCC (or GCG), and

replacing all codons encoding in the original Arg sequence with CGC (or CGG); and

replacing all codons encoding in the original Gly sequence with GGC (or GGG); and

replacement of all codons encoding in the original Asn sequence with AAC; and

replacing all codons encoding in the original Phe sequence with UUC; and

replacement of all codons encoding in the original Cys sequence with UGC; and

changing all codons encoding in the original Leu sequence to CUG (or CUC); and

replacement of all codons encoding in the original Gln sequence with CAG; and

replacement of all codons encoding in the original Pro sequence with CCC (or CCG); and

replacement of all codons encoding in the original His sequence with CAC; and

replacement of all codons encoding in the original Asp sequence with GAC; and

replacement of all codons encoding a stop codon in the original sequence with UGA (or UAG), etc.

Preferably, the content of G/C in the coding region of at least one coding RNA specified in the present description is increased by at least 7%, more preferably at least 15%, most preferably at least 20%, compared with the content G/C in the wild-type RNA coding region. In a particular embodiment of the invention, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, more preferably at least 70%, even more preferably at least 80%, and most preferably at least at least 90%, 95%, or even 100% of codon substitutions in the region encoding the protein or peptide specified in the present description, or a fragment or variant thereof, or the entire wild-type RNA sequence or coding sequence, thereby increasing the content of G/ C in that order. In this context, it is most preferable to increase the content of G/C in at least one RNA in the composition of the invention to a maximum (i.e. up to 100% suitable for substitution of codons), primarily in the coding region, compared with the sequence of the wild type.

According to the invention, a further preferred modification of the coding sequence of at least one coding RNA is based on the discovery that the efficiency of translation is also determined by the different frequency of occurrence of tRNAs in cells. Thus, if in at least one coding region of at least one coding RNA specified in the present description, the so-called "rare codons" are present in an increased number, then the level of translation of the corresponding modified at least one coding RNA is significantly lower, than when there are codons encoding relatively "frequent" tRNAs. According to the invention, in the modified at least one coding RNA specified in the present description, the region that encodes at least one of the specified peptides or proteins is modified in comparison with the corresponding region of the wild-type RNA so that at least one codon of the wild-type sequence , which codes for a tRNA that is relatively rare in the cell, is replaced with a codon that codes for a tRNA that is relatively common in the cell and carries the same amino acid as the relatively rare tRNA. Through such modification, the sequence of at least one coding region of at least one coding RNA specified in the present description is modified in such a way as to insert codons for which frequently occurring tRNAs are available. In other words, according to the invention, with such a modification, all codons of the wild-type sequence that encode a tRNA that is relatively rare in the cell can in each case be replaced by a codon that encodes a tRNA that is relatively common in the cell, and which in each case carries such the same amino acid as the relatively rare tRNA. tRNAs that are relatively common in a cell, and vice versa, that are relatively rare, are known to those skilled in the art, see, for example, Akashi, Curr. Opin. Genet. Dev., 11(6), 2001, pp. 660-666. Particularly preferred are codons that are used for the most frequently occurring tRNA of a particular amino acid, for example the Gly codon, which uses the tRNA most frequently found in the (human) cell. According to the invention, it is most preferred to combine an increase, preferably to a maximum, in the content of G/C in a sequence modified in at least one coding RNA specified in the present description with "frequently occurring" codons without amino acid modification of the protein sequence encoded by the coding region of the RNA. This preferred embodiment of the invention allows the most efficient translation and stabilization of the (modified) at least one coding RNA specified in the present description. Detection of modified at least one coding RNA as defined herein (increased G/C; tRNA substitution) can be performed using the computer program described in WO 02/098443, the entire content of which is incorporated into the present invention. Using said computer program, the nucleotide sequence of any desired coding RNA can be modified by the genetic code or its degenerate nature so as to obtain the maximum G/C content in combination with the use of codons that code for the most common tRNA possible in the cell, while the amino acid sequence encoded by the modified at least one coding RNA is preferably not modified compared to the unmodified sequence. Alternatively, only the G/C content or only the frequently occurring codons can be modified from the original sequence. The source code in Visual Basic 6.0 (Operative Development Environment used: Microsoft Visual Studio Enterprise 6.0 with Servicepack 3) is also described in WO 02/098443. In another preferred embodiment of the present invention, the A/U content surrounding the ribosome binding site of at least one coding RNA described herein is increased relative to the A/U content surrounding the ribosome binding site of its corresponding wild-type RNA. This modification (increased A/U content around the ribosome binding site) increases the efficiency of ribosome binding to at least one RNA. The efficiency of ribosome binding to the ribosome binding site (Kozak sequence: GCCGCCACCAUGG (SEQ ID NO: 429), AUG forms the start codon) in turn affects the translation efficiency of at least one coding RNA. According to the following variant of implementation of the present invention, at least one coding RNA specified in the present description, you can modify in relation to potentially destabilizing elements of the sequence. In particular, the coding region and/or the 5'- and/or 3'-untranslated region of said RNA can be modified in comparison with the specific wild-type RNA so that it does not contain destabilizing sequence elements, while the encoded amino acid sequence is modified by at least one the coding RNA is preferably not altered from the corresponding wild-type RNA sequence. It is known that, for example, in the RNA sequences of eukaryotic organisms, there are destabilizing sequence elements (DEPs), to which signal proteins bind and regulate the enzymatic cleavage of RNA in vivo. For additional stabilization of at least one coding RNA, optionally in the region that encodes the protein or peptide specified in the present description, one or more of these modifications can be carried out in comparison with the corresponding region of the wild-type RNA in such a way as to completely or substantially remove destabilizing sequence elements. According to the invention, using these modifications in at least one coding RNA specified in the present description, it is also possible to remove DEPs present in untranslated regions (3'-UTR and/or 5'-UTR). Said destabilizing sequences are, for example, AU rich sequences (AURES), which are present in the 3'-UTR regions of numerous unstable RNAs (Caput et al., Proc. Natl. Acad. Sci. USA, 83, 1986, cc. 1670- 1674). Thus, at least one coding RNA as defined herein is preferably modified from wild-type RNA such that at least one coding RNA does not contain said destabilizing sequences. This also applies to those sequence motifs that are recognized by possible endonucleases, for example, the GAACAAG sequence, which is present in the 3'-UTR segment of the gene that encodes the transferrin receptor (Binder et al., EMBO J., 13, 1994, pp. 1969 -1980). Said sequence motifs are also preferably removed from at least one coding RNA as described herein.

Thus, a preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 25-30; 80-85; 91-96; 102-107; 113-118; 601-606; 124-129; 135-140; 612-617; 623-628; 716-725; 727; 1018-1021 and 1059-1062, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 32; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632; 636-644; 726 and 1058, or a fragment or variant of any of these sequences;

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 88; 99; 110; 121; 132; 143; 609; 620; 631; 728-738 and 1025-1028, or a fragment or variant of any of these sequences;

c) a nucleotide sequence as shown in one of SEQ ID NOs: 646, 650-658, 662, 666-674 or 1029-1036, preferably as shown in one of SEQ ID NOs: 646 or 650-658, or a fragment or variant of any of of the indicated nucleotide sequences, and the nucleotide sequence shown in one of SEQ ID NOs: 678, 682-690, 694, 698-705, 707, or 1037-1041, preferably shown in one of SEQ ID NOs: 678 or 682-690, or a fragment or variant of any of the specified nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 710 or 713, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 23; 78; 89; 100; 111; 122; 133; 599; 610; 621 and 1022-1024, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 24; 79; 90; 101; 112; 123; 134; 600; 611; 622; 1043 and 1047-1054, or a fragment or variant of any of these sequences.

Adaptation to human common codons:

According to the invention, a further preferred modification of at least one coding RNA as described herein is based on the discovery that codons encoding the same amino acid occur at different frequencies. According to the invention, in the modified at least one coding RNA specified in the present description, the region that encodes one of the above peptides or proteins (coding sequence) is preferably modified in comparison with the corresponding region of the wild-type RNA so that the frequency of codons encoding one and the same amino acid corresponded to the naturally occurring frequency of a codon frequently found in the human coding region, which are presented in Table 2.

This means, for example, that in the case of the amino acid alanine (Ala) present in the amino acid sequence of the encoded protein of the invention, the wild-type coding sequence is adapted so that the codon "GCC" is used at a frequency of 0.40, the codon "GCT" is used at a frequency of 0.28, a "GCA" codon is used at a frequency of 0.22, and a "GCG" codon is used at a frequency of 0.10, and so on. (see table 2).

Thus, a preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NOs: 47-52 and 58-63, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 54; 65 and 634, or a fragment or variant of any of these sequences;

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 55-66, or a fragment or variant of any of these sequences;

c) a nucleotide sequence as shown in one of SEQ ID NOs: 648, 659, 664 or 675, preferably as shown in SEQ ID NOs: 648 or 659, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NO: 680, 691, 696 or 708, preferably as shown in SEQ ID NO: 680 or 691, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 711 or 714, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NOs: 45 and 56, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NOs: 46-57 and 1045, or a fragment or a variant of any of these sequences.

Codon optimization:

According to a particularly preferred embodiment of the invention, preferably all codons of the wild-type sequence of the coding region of at least one coding RNA specified in the present description, which encode tRNAs that are relatively rare in the cell, in each case were replaced with a codon encoding a tRNA that is often in the cell and which in each case carries the same amino acid as the relatively rare tRNA. Thus, it is particularly preferred to use the most frequently occurring codons for each encoded amino acid (see Table 2, in which the most frequently occurring codons are indicated by an asterisk).

This means, for example, that in the case of the amino acid alanine (Ala) present in the amino acid sequence of the encoded peptide or protein of the invention, the wild-type coding sequence is adapted such that the most frequently occurring human codon "GCC" is always used for said amino acid. or in the case of the amino acid cysteine (Cys), the wild-type sequence is adapted such that the most commonly occurring human codon "TGC" is always used for said amino acid, and so on.

Thus, a preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NOs: 69-74, or a fragment or variant of any of these sequences, preferably a nucleotide sequence shown in SEQ ID NOs: 76 and 635, or a fragment or variant thereof;

b) the nucleotide sequence of SEQ ID NO: 77 or a fragment or variant thereof;

c) a nucleotide sequence as shown in one of SEQ ID NOs: 649, 659, 660, 665 or 676, preferably as shown in SEQ ID NOs: 649 or 660, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NOs: 681, 692, 697 or 709, preferably as shown in SEQ ID NOs: 681 or 692, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 712 or 715, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally the nucleotide sequence of SEQ ID NO: 67 or a fragment or variant thereof, more preferably the nucleotide sequence shown in SEQ ID NO: 68 or 1046 or a fragment or variant thereof.

C-enrichment:

According to another embodiment of the invention, at least one coding RNA, specified in the present description, can be modified by increasing the content of C in the RNA, preferably in the coding region of at least one coding RNA.

In a particularly preferred embodiment of the present invention, the C content in the coding region of at least one RNA specified herein is modified, preferably increased, compared to the C content in the coding region of the specific wild-type RNA, i.e. unmodified mRNA. The amino acid sequence encoded by the at least one coding RNA is preferably not modified from the amino acid sequence encoded by the particular wild-type RNA.

In a preferred embodiment of the present invention, the modified RNA is modified to achieve at least 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% or at least 90% of the theoretical maximum cytosine content. or even maximum cytosine content.

In other preferred embodiments of the invention, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or even 100% of the codons of the wild-type RNA sequence in which "can be optimized "cytosine content" is replaced by codons with a higher cytosine content than those present in the wild-type sequence.

In a further preferred embodiment, some of the codons of the wild-type coding sequence can be further modified so that the codons of a relatively rare tRNA in the cell are replaced by a codon of a relatively common tRNA in the cell, provided that the replaced codon of the relatively common tRNA carries the same amino acid, as the original codon corresponding to the relatively rare wild-type tRNA. Preferably, all codons corresponding to a relatively rare tRNA are replaced by codons corresponding to a relatively common tRNA in the cell, with the exception of codons encoding amino acids, which are exclusively encoded by codons that do not contain cytosine, or with the exception of glutamine (Gln), which is encoded by two codons, each of which contains the same amount of cytosine.

In another preferred embodiment of the present invention, the modified RNA is modified to achieve at least 80% or at least 90% of the theoretical maximum cytosine content, or even the maximum cytosine content, using codons that code for the relatively common tRNAs in the cell, when this amino acid sequence remains unchanged.

Due to the naturally occurring degeneracy of the genetic code, multiple codons can code for a particular amino acid. Thus, 18 of the 20 naturally occurring amino acids are encoded by more than 1 codon (except Tryp and Met), e.g. 2 codons (e.g. Cys, Asp, Glu), 3 codons (e.g. Ile), 4 codons (e.g. Al , Gly, Pro) or 6 codons (eg Leu, Arg, Ser). However, not all codons encoding the same amino acid are used with the same frequency in vivo. Depending on each individual organism, as a rule, a profile of typical frequently occurring codons is established.

The term "codon in which the content of cytosine can be optimized (optimized codon)" in the context of the present description refers to codons in which a lower amount of cytosines is present than in other codons encoding the same amino acid. Thus, any wild-type codon that can be replaced with another codon encoding the same amino acid and having a higher number of cytosines within the codon is considered to be a codon that can be optimized for cytosine content (C-optimized codon). Any such substitution of a C-optimized wild-type codon with a specific C-optimized codon in the wild-type coding region increases the total C content and corresponds to a C-enriched modified RNA sequence. The C-maximized RNA sequence contains C-optimized codons in all potentially C-optimized codons. Thus, 100% or all of the theoretically replaceable C-optimized codons under these conditions are actually replaced by C-optimized codons along the entire length of the coding region.

In this context, codons optimized for cytosine content are codons that contain less cytosine than other codons encoding the same amino acid.

Any of the GCG, GCA, GCU codons that code for the amino acid Ala can be replaced with a GCC codon that codes for the same amino acid, and/or

a UGU codon that codes for Cys can be replaced with a UGC codon that codes for the same amino acid, and/or

the GAU codon that codes for Asp can be replaced with a GAC codon that codes for the same amino acid, and/or

the UUU codon that codes for Phe can be replaced with a UUC codon that codes for the same amino acid, and/or

any of the GGG, GGA, GGU codons that code for Gly can be replaced with a GGC codon that codes for the same amino acid, and/or

the CAU codon that codes for His can be replaced with a CAC codon that codes for the same amino acid, and/or

any of the AUA, AUU codons that code for Ile can be replaced with an AUC codon, and/or

any of the UUG, UUA, CUG, CUA, CUU codons that code for Leu can be replaced with a CUC codon that codes for the same amino acid, and/or

an AAU codon that codes for Asn can be replaced with an AAC codon that codes for the same amino acid, and/or

any of the CCG, CCA, CCU codons that encode Pro can be replaced with a CCC codon encoding the same amino acid, and/or

any of the AGG, AGA, CGG, CGA, CGU codons that code for Arg can be replaced with a CGC codon that codes for the same amino acid, and/or

any of the AGU, AGC, UCG, UCA, UCU codons that code for Ser can be replaced with a UCC codon that codes for the same amino acid, and/or

any of the ACG, ACA, ACU codons that code for Thr can be replaced with an ACC codon that codes for the same amino acid, and/or

any of the GUG, GUA, GUU codons that code for Val can be replaced with a GUC codon that codes for the same amino acid, and/or

The UAU codon that codes for Tyr can be replaced with a UAC codon that codes for the same amino acid.

In any of the above cases, the number of cytosines is increased by 1 at each replacement codon. Replacing all codons with non-optimized C content (which correspond to codons that can be optimized for C content) in the coding region results in a coding sequence with C content maximized. In the context of the invention, at least 70% of the codons in the coding region, preferably at least at least 80%, more preferably at least 90% of the non-C-optimized codons are replaced with C-optimized codons in the wild-type sequence.

It may be preferable that, for some amino acids, the percentage of C-optimized codons changed to C-optimized codons is less than 70%, while for other amino acids, the percentage of codons changed is greater than 70%, so that the total the percentage of C content optimization was at least 70% of all wild-type coding region codons in which C content could be optimized.

Preferably, in the C-optimized RNAs of the invention, at least 50% of the C-optimized wild-type codons for any particular amino acid are replaced with C-optimized codons, e.g., any modified C-enriched RNA preferably contains at least 50%, preferably at least 60% C-optimized codons at wild-type codon positions that can optimize C content encoding any one of the above amino acids Ala, Cys, Asp, Phe, Gly, His, Ile, Leu, Asn, Pro, Arg, Ser, Thr, Val and Tyr.

In this context, codons encoding amino acids in which cytosine content cannot be optimized, and which are encoded by at least two codons, can be used without any additional selection process. However, a wild-type sequence codon that codes for a relatively rare tRNA in a cell, such as a human cell, can be replaced with a codon that codes for a relatively common tRNA in the cell, as long as both code for the same amino acid. Thus, a relatively rare GAA codon encoding Glu can be replaced by a relatively common GAG codon encoding the same amino acid, and/or

the relatively rare AAA codon encoding Lys can be replaced by the relatively common AAG codon encoding the same amino acid, and/or

the relatively rare CAA codon encoding Gln is replaced by the relatively common CAG codon encoding the same amino acid.

In this context, the amino acids Met (AUG) and Trp (UGG), each encoded by only one codon, remain unchanged. Stop codons cannot be optimized for cytosine content, however, the relatively rare stop codon amber-codon, ocher-codon (UAA, UAG) can be replaced by the relatively common stop codon opal (UGA).

Obviously, the above substitutions can be used individually, but all possible combinations of them can also be used to optimize the content of cytosine in the modified RNA compared to the wild-type RNA sequence.

Thus, the region of the modified RNA that codes for a peptide or protein can be changed compared to the coding region of the wild-type RNA so that for an amino acid encoded by at least two or more codons, of which one contains one additional cytosine, the specified codon could be changed to a C-optimized codon that contains at least one additional cytosine without changing the amino acid from the wild-type sequence.

Thus, a preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, wherein the treatment comprises the administration of at least one coding RNA (as an additional pharmaceutically active ingredient), preferably at least one mRNA, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NOs: 36-41, or a fragment or variant of any of these sequences, preferably a nucleotide sequence shown in SEQ ID NOs: 43 and 633, or a fragment or variant thereof;

b) the nucleotide sequence of SEQ ID NO: 44 or a fragment or variant thereof;

c) the nucleotide sequence shown in SEQ ID NO: 647 or 663, preferably as shown in SEQ ID NO: 647, or a fragment or variant of any of the said nucleotide sequences, and the nucleotide sequence as shown in SEQ ID NO: 679 or 695, preferably as shown in SEQ ID NO: 679, or a fragment or variant of any of the specified nucleotide sequences;

and/or

d) optionally the nucleotide sequence of SEQ ID NO: 34 or a fragment or variant thereof, more preferably the nucleotide sequence shown in SEQ ID NO: 35 and 1044 or a fragment or variant thereof.

According to another embodiment of the invention, at least one coding RNA specified in the present description preferably contains at least one of the following structural elements: an element representing a 5' - and / or 3' - untranslated region (UTR element), before a total 5'-UTR element that contains or consists of a nucleotide sequence derived from the 5'-UTR of the TOP gene or a fragment, homologue or variant thereof, or a 5'- and/or 3'-UTR element that can be derived from the gene from which the stable mRNA is derived, or from a homologue, fragment or variant thereof; a histone stem-loop structure, preferably a stem-loop histone structure in its 3'-untranslated region; 5' cap structure; poly-A-tail (poly(A)-sequence) or poly(C)-sequence.

In a preferred embodiment of the invention, at least one coding RNA contains at least one 5' or 3' UTR element. In this context, a UTR element contains or consists of a nucleotide sequence that is derived from the 5' or 3' UTR of any naturally occurring gene, or that is derived from a fragment, homologue or variant of the 5' or 3'UTR of a gene. Preferably the 5' or 3'UTR element used in accordance with the present invention is heterologous with respect to the coding region of at least one coding RNA as defined herein. While 5' or 3' UTR elements derived from naturally occurring genes are preferred, synthetic UTR elements can also be used in the context of the present invention.

In a particularly preferred embodiment of the invention, at least one coding RNA contains at least one element, which is a 5'-untranslated region (5'-UTR element), which contains or consists of a nucleotide sequence that is derived from the 5'-UTR of the TOP gene, or which is derived from a fragment, homologue or variant of the 5'UTR of the TOP gene.

Most preferably, the 5'UTR element does not contain the TOP motif or 5'TOP as defined above.

In some embodiments, the nucleotide sequence of the 5'UTR element that is derived from the 5'UTR of the TOP gene terminates at its 3' end with a nucleotide located at positions 1, 2, 3, 4, 5, 6, 7 , 8, 9, or 10 upstream from the start codon (eg, A(U/T)G) of the gene or mRNA derived from it. Thus, the 5'UTR element does not contain any portion of the protein coding region. Thus, preferably only the protein-coding portion of at least one coding RNA referred to herein is a coding region.

The nucleotide sequence derived from the 5'UTR of the TOP gene is preferably derived from a eukaryotic TOP gene, preferably a plant or animal TOP gene, more preferably a chordate TOP gene, even more preferably a vertebrate TOP gene, most preferably a TOP gene. a mammalian gene, such as the human TOP gene.

For example, the 5'UTR element is preferably selected from 5'UTR elements containing or consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of patent application WO 2013/143700, the description of which is incorporated herein by reference in its entirety, from the homologues of SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of patent application WO 2013/143700, from their variants, or preferably from the corresponding RNA sequence. The term "homologs of SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421, and SEQ ID NO: 1422 as set forth in patent application WO 2013/143700" refers to sequences from non-human species (Homo sapiens) that are homologues of the sequences SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of patent application WO 2013/143700.

In a preferred embodiment of the invention, the 5'-UTR element contains or consists of a nucleotide sequence that is derived from a nucleotide sequence extending from nucleotide position 5 (i.e., the nucleotide located at position 5 in the sequence) to the nucleotide position immediately adjacent to 5' side to the start codon (located at the 3' end of the sequences), for example, to the nucleotide position immediately adjacent on the 5' side to the ATG sequence of the nucleotide sequence selected from SEQ ID NO: 1-1363, SEQ ID NO : 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of patent application WO 2013/143700 from homologues of SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO : 1422 specified in patent application WO 2013/143700, from their variants or the corresponding RNA sequence. Most preferably, the 5'-UTR element is derived from a nucleotide sequence extending from the nucleotide position immediately 3'-side of the 5'-TOP to the nucleotide position immediately 5'-side of the start codon (localized at the 3' end of the sequences), for example, up to the nucleotide position immediately adjacent on the 5' side to the ATG sequence of the nucleotide sequence selected from SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of WO 2013/143700 homologues of SEQ ID NO: 1-1363, SEQ ID NO: 1395, SEQ ID NO: 1421 and SEQ ID NO: 1422 of WO patent application 2013/143700, from their variants or the corresponding RNA sequence.

In some embodiments, the 5'UTR element may be the 5'UTR element described in WO 2016/107877. In this context, the description of WO 2016/107877 relating to 5'-UTR elements/sequences is incorporated herein by reference. Particularly preferred 5'-UTR elements have the nucleotide sequences shown in SEQ ID NOs: 25-30 and SEQ ID NOs: 319-382 in patent application WO 2016/107877, or fragments or variants of these sequences. In this context, it is particularly preferred if the 5'UTR element contains or consists of the corresponding RNA sequences of the nucleotide sequence shown in SEQ ID NO: 25-30 and SEQ ID NO: 319-382 in patent application WO 2016/107877 .

In some embodiments, the 5'UTR element may be any of the 5'UTR elements described in WO 2017/036580. In this context, the description of WO 2017/036580 relating to 5'-UTR elements/sequences is incorporated herein by reference. Particularly preferred 5'-UTR elements have the nucleotide sequences shown in SEQ ID NO: 1-151 in patent application WO 2017/036580, or fragments or variants of these sequences. In this context, it is particularly preferred if the 5'UTR element contains or consists of the corresponding RNA sequences of the nucleotide sequence shown in SEQ ID NO: 1-151 in patent application WO 2017/036580.

In a particularly preferred embodiment, the 5'UTR element comprises or consists of a nucleotide sequence that is derived from the 5'UTR of a TOP gene encoding a ribosomal protein or from a variant of the 5'UTR of a TOP gene encoding a ribosomal protein. For example, the 5'-UTR element contains or consists of a nucleotide sequence that is derived from the 5'-UTR nucleotide sequence shown in any of SEQ ID NOs: 67, 170, 193, 244, 259, 554, 650, 675, 700 , 721, 913, 1016, 1063, 1120, 1138, and 1284-1360 of patent application WO 2013/143700, the corresponding RNA sequence, homologue or variant thereof, as described herein, preferably lacking the 5'TOP motif. As described above, the sequence extending from position 5 to the nucleotide immediately adjacent 5' to the ATG (located at the 3' end of the sequences) corresponds to the 5' UTR of the indicated sequences.

Preferably the 5'-UTR element comprises or consists of a nucleotide sequence derived from the 5'-UTR of the TOP gene encoding the ribosome large subunit protein (RPL) or from a homologue or variant of the 5'-UTR of the TOP gene encoding the large subunit protein ribosomes (RPL). For example, the 5'-UTR element contains or consists of a nucleotide sequence derived from the 5'-UTR nucleotide sequence shown in any of SEQ ID NOs: 67, 259, 1284-1318, 1344, 1346, 1348-1354, 1357, 1358, 1421 and 1422, specified in patent application WO 2013/143700, the corresponding RNA sequence, its homologue or variant, specified in the present description, preferably without the 5'TOP motif.

In a particularly preferred embodiment, the 5'-UTR element comprises or consists of a nucleotide sequence derived from a 5'-UTR derived from the 5'-UTR of the 32 ribosome large subunit protein gene, preferably from the 32 ribosome large subunit protein gene (L32) vertebrate, more preferably from a mammalian ribosome 32 large subunit protein (L32) protein gene, most preferably from a human ribosome 32 large subunit protein (L32) protein gene, or from a 5'-UTR variant of the ribosome 32 large subunit protein gene, preferably a large subunit protein gene ribosome 32 (L32) vertebrate, more preferably mammalian ribosome 32 (L32) large subunit protein gene, most preferably human ribosome 32 large subunit protein (L32), preferably the 5'-UTR element does not contain the 5'TOP of said gene .

The preferred sequence of the 5'UTR element corresponds to SEQ ID NO: 1368 of patent application WO 2013/143700.

Thus, according to a particularly preferred embodiment of the invention, the 5'UTR element contains or consists of a nucleotide sequence that is at least about 20% identical, preferably at least about 40%, preferably at least about 50% identical, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, still more preferably at least about 99% of the above nucleotide sequence (SEQ ID NO: 408 (5'-UTR of the human ribosome large subunit 32 protein without the 5'-terminal oligoprimidine tract:

GGCGCTGCCTACGGAGGTGGCAGCCATCTCCTTCTCGGCATC;

which corresponds to SEQ ID NO: 1368 in patent application WO 2013/143700) or preferably the corresponding RNA sequence, or in which at least one 5'-UTR element contains or consists of a fragment of a nucleotide sequence that is at least about 40%, preferably at least about 50%, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90% , even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence of SEQ ID NO: 409, or more preferably the corresponding RNA sequence, while preferably the fragment described above is a continuous segment of nucleotides, which accounts for at least 20%, etc. full-length 5'-UTR.

Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably the fragment is a functional fragment, as specified in the present description.

In some embodiments of the invention, at least one coding RNA specified in the present description contains a 5'-UTR element that contains or consists of a nucleotide sequence derived from the 5'-UTR of the TOP gene of vertebrates, such as mammals, for example, human TOP gene selected from RPSA, RPS2, RPS3, RPS3A, RPS4, RPS5, RPS6, RPS7, RPS8, RPS9, RPS10, RPS11, RPS12, RPS13, RPS14, RPS15, RPS15A, RPS16, RPS17, RPS18, RPS19, RPS20 , RPS21, RPS23, RPS24, RPS25, RPS26, RPS27, RPS27A, RPS28, RPS29, RPS30, RPL3, RPL4, RPL5, RPL6, RPL7, RPL7A, RPL8, RPL9, RPL10, RPL10A, RPL11, RPL12, RPL13, RPL13A, RPL14 . , RPL38, RPL39, RPL40, RPL41, RPLP0, RPLP1, RPLP2, RPLP3, RPLP0, RPLP1, RPLP2, EEF1A1, EEF1B2, EEF1D, EEF1G, EEF2, EIF3E, EIF3F, EIF3H, EIF2S3, EIF3C, EIF3K, EIF3EIP, EIF4A2, EIF4A2 , HNRNPA1, TPT1, TUBB1, UBA52, NPM1, ATP5G2, GNB2L1, NME2, UQCRB, or from a homologue or variant thereof, wherein preferably the 5'-UTR element does not contain the TOP motif or 5'-TOP of the indicated genes, and in which optionally, the 5' end of the 5' UTR element starts at the nucleotide located at position 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 downstream of the 5' oligoprimidine tract (TOP) , and in which also optionally the 5'-UTR element derived from the 5'-UTR of the TOP gene terminates at its 3' end with a nucleotide located at position 1, 2, 3, 4, 5, 6, 7, 8 , 9 or 10 in the opposite direction relative to the start code (A(U/T)G) of the gene from which it is derived.

In some embodiments of the invention, at least one coding RNA specified in the present description contains a 5'-UTR element that contains or consists of a nucleotide sequence that is derived from the 5'-UTR of a gene selected from the group that consists of MP68 (6.8 kDa mitochondrial proteolipid), Nosip (nitric oxide synthase interacting protein), HSD17B4 (hydroxysteroid (17-beta) dehydrogenase 4), Rpl31 (60S ribosomal protein L31), TUBB4B (beta-4B tubulin chain ), ATP5A1 (ATP synthase alpha subunit (mitochondrial)) and Ndufa4.1 (NDUFA4 cytochrome c oxidase subunit), or from a variant of any of these genes, wherein the gene or variant is preferably a vertebrate gene, more preferably a mammalian gene, and even more preferably a human gene.

According to another preferred embodiment of the invention, at least one coding RNA specified in the present description contains a 5'-UTR element that contains or consists of a nucleotide sequence that is derived from the 5'-UTR of a gene selected from the group consisting of MP68 (6.8 kDa mitochondrial proteolipid), Nosip (nitric oxide synthase interacting protein), HSD17B4 (hydroxysteroid (17-beta) dehydrogenase 4), Rpl31 (60S ribosomal protein L31), TUBB4B (beta-4B chain tubulin), ATP5A1 (ATP synthase alpha subunit (mitochondrial)) and Ndufa4.1 (NDUFA4 cytochrome c oxidase subunit), ribosome large subunit protein 32 gene (RPL32), ribosome large subunit protein 35 gene (RPL35), ribosome large subunit protein 21 (RPL21), gene for ATP synthase, H ⁺ -transporting, mitochondrial complex F1, alpha subunit 1, cardiac muscle (ATP5A1), androgen inducible gene 1 (AIG1), gene for subunit VIc oxidase cyte ochrome c (COX6C) and the N-acylsphingosine amidohydrolase (acid ceramidase) 1 (ASAH1) gene, or from a variant of any of these genes, wherein the gene or variant is preferably a vertebrate gene, more preferably a mammalian gene, and even more preferably a gene person.

According to the following particularly preferred embodiments of the invention, the 5'-UTR element comprises or consists of a nucleotide sequence that is derived from the 5'-UTR of the ribosome large subunit 32 protein gene (RPL32), the ribosome large subunit 35 protein gene (RPL35), the large protein ribosome 21 subunit (RPL21), ATP synthase gene, H ⁺ transporter, mitochondrial complex F1, alpha subunit 1, heart muscle (ATP5A1), hydroxysteroid (17-beta) dehydrogenase 4 gene (HSD17B4), androgen-induced gene 1 ( AIG1), the cytochrome c oxidase VIc subunit gene (COX6C) or the N-acylsphingosine amidohydrolase (acid ceramidase) 1 (ASAH1) gene, or a variant thereof, preferably from the vertebrate ribosome large subunit 32 protein gene (RPL32), large protein gene subunit of ribosome 35 (RPL35) of vertebrates, protein gene of large subunit of ribosome 21 (RPL21) of vertebrates, gene of ATP synthase, H ⁺ -transporting, mitochondrial complex F1, vertebrate cardiac muscle (ATP5A1) alpha subunit, vertebrate hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) gene, vertebrate androgen inducible gene 1 (AIG1), vertebrate cytochrome c oxidase VIc subunit (COX6C) gene, or from a vertebrate N-acylsphingosine amidohydrolase (acid ceramidase) 1 (ASAH1) gene, or from a variant thereof, more preferably from a mammalian ribosome large subunit 32 (RPL32) protein gene, a mammalian ribosome large subunit 35 (RPL35) protein gene, a large protein gene mammalian ribosome 21 (RPL21) subunit, mammalian ATP synthase gene, H ⁺ -transporting gene, mitochondrial complex F1, alpha subunit 1, mammalian heart muscle (ATP5A1), mammalian androgen-induced hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) gene mammalian cytochrome c oxidase subunit VIc (COX6C) gene 1 (AIG1), or the N-acylsphingosine amidohydrolase (acid ceramidase) 1 (ASA H1) mammalian, most preferably from the human ribosome large subunit 32 (RPL32) protein gene, the mammalian mammalian ribosome large subunit 35 (RPL35) protein gene, the human ribosome large subunit 21 (RPL21) protein gene, the ATP synthase, H ⁺ -transporting gene, mitochondrial complex F1, alpha subunit 1, human heart muscle (ATP5A1), human hydroxysteroid (17beta) dehydrogenase 4 (HSD17B4) gene, human androgen inducible gene 1 (AIG1), human cytochrome c oxidase subunit VIc (COX6C) gene, or the human N-acylsphingosine amidohydrolase (acid ceramidase) 1 (ASAH1) gene, or a variant thereof, wherein preferably the 5'-UTR element does not contain the 5'-TOP of said gene.

According to a particularly preferred embodiment of the invention, the 5'-UTR element contains or consists of a nucleotide sequence that is at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence of SEQ ID NO: 1368 or SEQ ID NO: 1412-1420, which are specified in patent application WO 2013/143700, or the corresponding RNA sequence, or in which at least one 5'-UTR element contains or consists of a fragment of the nucleotide sequence , which is at least about 20%, preferably at least about 40%, preferably at least about 50% identical %, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95% , even more preferably at least about 99% of the nucleotide sequence of SEQ ID NO: 1368 or SEQ ID NO: 1412-1420, which are specified in patent application WO 2013/143700, while preferably the fragment is the fragment described above, i.e. e. is a continuous segment consisting of nucleotides, which accounts for at least 20%, etc. from the full-length 5'-UTR. Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably the fragment is a functional fragment, as specified in the present description.

According to a particularly preferred embodiment of the invention, the 5'-UTR element contains or consists of a nucleotide sequence that is at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence, shown in one of SEQ ID NOs: 838, 840, 842, 844, 846, 848, 850, or 1004-1013, or the corresponding RNA sequence, or where at least one 5'-UTR element contains or consists of a fragment of the nucleotide sequence , which is at least about 20% identical, preferably at least about 40% identical, preferably at least about 50% identical, preferably preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, still more preferably at least about 99% of the nucleotide sequence shown in one of SEQ ID NOs: 838, 840, 842, 844, 846, 848, 850 or 1004-1013, where preferably the fragment is the fragment described above, i.e. . is a continuous segment consisting of nucleotides, which accounts for at least 20%, etc. from the full-length 5'-UTR. Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably the fragment is a functional fragment, as specified in the present description.

In another preferred embodiment of the invention, the 5'-UTR element contains or consists of a nucleotide sequence that is at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence, represented in one of SEQ ID NOs: 838, 840, 842, 844, 846, 848, or 850, or the corresponding RNA sequence, preferably selected from SEQ ID NOs: 839, 841, 843, 845, 847, 849, and 851, or where at least one 5'-UTR element contains or consists of a fragment of a nucleotide sequence that is at least about 20%, preferably at least about 40%, identical, preferably at least about 50%, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence shown in one of SEQ ID NOs: 838, 840, 842, 844, 846, 848, or 850, where preferably the fragment is as described above fragment, i.e. is a continuous segment consisting of nucleotides, which accounts for at least 20%, etc. from the full-length 5'-UTR. Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably the fragment is a functional fragment, as specified in the present description.

Thus, in a particularly preferred embodiment, the 5'UTR element contains or consists of a nucleotide sequence that is at least about 20% identical, preferably at least about 40%, preferably at least about 50% identical, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, still more preferably at least about 99% of the nucleotide sequence of SEQ ID NO: 410 (ATP5A1 5'-UTR lacking the 5'-oligopyrimidine tract:

GCGGCTCGGCCATTTTGTCCCAGTCAGTCCGGAGGCTGCGGCTGCAGAA GTACCGCCTGCGGAGTAACTGCAAAG; corresponds to SEQ ID NO: 1414 in patent application WO 2013/143700 (ATP5A1 5'-UTR lacking a 5'-oligopyrimidine tract) or preferably the corresponding RNA sequence (SEQ ID NO: 411), or where at least one 5 the '-UTR element contains or consists of a fragment of a nucleotide sequence that is at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least about 70% identical, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence of SEQ ID NO: 26 (specified in patent application WO 2013/143700) or more preferably the corresponding RNA sequence, in which preferably the fragment is the fragment described above, i.e. is a continuous segment consisting of nucleotides, which accounts for at least 20%, etc. from the full-length 5'-UTR. Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably the fragment is a functional fragment, as specified in the present description.

In another preferred embodiment of the invention, at least one RNA specified in the present description also contains at least one 3'-UTR element, which contains or consists of a nucleotide sequence derived from the 3'-UTR of the gene of chordates, preferably the gene a vertebrate, more preferably a mammalian gene, most preferably a human gene, or from a 3'UTR variant of a chordate gene, preferably a vertebrate gene, more preferably a mammalian gene, most preferably a human gene.

The term "3'-UTR element" refers to a nucleotide sequence that contains or consists of a nucleotide sequence derived from a 3'-UTR or from a 3'-UTR variant. The 3'UTR element in the context of the present invention may be the 3'UTR of an mRNA. Thus, in the context of the present invention, preferably the 3'-UTR element may be the 3'-UTR of an mRNA, preferably an artificial mRNA, or may be a template for transcription of the 3'-UTR of an mRNA. Thus, the 3'UTR element is preferably a nucleotide sequence that corresponds to the 3'UTR of an mRNA, preferably the 3'UTR of an artificial mRNA, such as an mRNA obtained by transcription of a genetically engineered vector construct. Preferably, the 3'UTR element performs the function of a 3'UTR or encodes a sequence that performs the function of a 3'UTR.

Preferably, the inventive mRNA contains a 3'UTR element that can be derived from a gene that corresponds to an mRNA with an extended half-life (which is a stable mRNA), such as the 3'UTR element indicated and described below. Preferably the 3'UTR element is a nucleotide sequence derived from the 3'UTR of a gene that preferably encodes a stable mRNA, or from a homologue, fragment or variant of said gene.

In a particularly preferred embodiment, the 3'-UTR element comprises or consists of a nucleotide sequence that is derived from the 3'-UTR of a gene selected from the group consisting of an albumin gene, an α-globin gene, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene and a collagen alpha chain gene, such as a type (I) collagen alpha 1 chain gene, or from a 3'-UTR variant of a gene selected from the group consisting of an albumin gene, an α-globin gene, a β-globin gene , a tyrosine hydroxylase gene, a lipoxygenase gene and a collagen alpha chain gene, such as the type (I) collagen alpha 1 chain gene, the sequences of which are shown in SEQ ID NO: 1369-1390 in patent application WO 2013/143700, the contents of which included in the present description by reference. In a most preferred embodiment, the 3'UTR element comprises or consists of a nucleotide sequence that is derived from the 3'UTR of an albumin gene, preferably a vertebrate albumin gene, more preferably a mammalian albumin gene, most preferably a human albumin gene, which has the SEQ ID NO: 420 (corresponds to SEQ ID NO: 1369 in patent application WO 2013/143700). The mRNA sequence may contain or consist of a nucleotide sequence that is derived from the 3'-UTR of the human albumin gene having GenBank access code NM_000477.5, or from a fragment or variant thereof.

In this context, it is particularly preferred that at least one coding RNA specified in the present description contains a 3'-UTR element that contains the corresponding RNA sequence derived from nucleic acids having SEQ ID NO: 1369-1390, which are specified in the application for patent WO 2013/143700, or a fragment, homologue or variant thereof.

Most preferably, the 3'-UTR element contains a nucleotide sequence derived from the human albumin gene fragment (albumin7 3'-UTR) shown in SEQ ID NO: 422 or 424 (corresponding to SEQ ID NO: 1376 in patent application WO 2013/143700 ).

In this context, it is particularly preferred that the 3'UTR element of at least one RNA in the composition according to the invention comprises or consists of the corresponding RNA sequence, the nucleotide sequence of which corresponds to SEQ ID NO: 423 or 425.

In another particularly preferred embodiment, the 3'UTR element comprises or consists of a nucleotide sequence derived from the 3'UTR of an α-globin gene, preferably a vertebrate α- or β-globin gene, more preferably an α- or β-globin gene. mammalian α-globin, most preferably the human α- or β-globin gene shown in SEQ ID NO: 412 (corresponding to SEQ ID NO: 1370 in patent application WO 2013/143700 (3'-UTR of hemoglobin alpha chain 1 (HBA1) Homo sapiens)), or as shown in SEQ ID NO: 414 (corresponding to SEQ ID NO: 1371 in patent application WO 2013/143700 (3'-UTR of hemoglobin 2 alpha chain (HBA2) Homo sapiens)), and/or as shown in SEQ ID NO: 416 (corresponding to SEQ ID NO: 1372 in patent application WO 2013/143700 (3'-UTR of the beta chain of hemoglobin (HBB) Homo sapiens).

For example, the 3'-UTR element may contain or consist of the central α-complex-binding region of the 3'-UTR of the α-globin gene having SEQ ID NO: 418 (corresponding to SEQ ID NO: 1393 in patent application WO 2013/143700 ).

In this context, it is particularly preferred that the 3'UTR element of at least one RNA in the composition according to the invention contains or consists of the corresponding RNA sequence, the nucleotide sequence of which corresponds to SEQ ID NO: 419 above, or its homologue, fragment or variant.

The term "nucleotide sequence derived from the 3'-UTR […] of a gene" preferably refers to a nucleotide sequence based on the 3'-UTR sequence of the […] gene or a portion thereof, e.g., the 3'-UTR of the albumin gene, α gene -globin, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene, and a collagen alpha chain gene such as a type (I) collagen alpha 1 chain gene, preferably an albumin gene or a portion thereof. This concept includes sequences corresponding to the complete 3'-UTR sequence, i.e. the full-length 3'-UTR sequence of the gene, and sequences corresponding to a fragment of the 3'-UTR sequence of the gene, for example, the albumin gene, the α-globin gene, the β-globin gene, the tyrosine hydroxylase gene, the lipoxygenase gene, and the collagen alpha chain gene, such as a collagen type (I) alpha 1 chain gene, preferably an albumin gene.

The term “nucleotide sequence derived from the 3'-UTR […] gene variant” preferably refers to a nucleotide sequence based on the 3'-UTR sequence variant of a gene, e.g. , a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene, and a collagen alpha chain gene such as the type (I) collagen alpha 1 chain gene, or a portion thereof as above. This term includes sequences corresponding to the complete sequence of the 3'-UTR variant of the gene, i.e. full-length 3'-UTR sequence of the gene variant, and sequences corresponding to a fragment of the variant 3'-UTR sequence of the gene. The fragment in this context preferably consists of a contiguous nucleotide segment corresponding to the contiguous nucleotide segment of the full-length variant 3'-UTR, which accounts for at least 20%, preferably at least 30%, more preferably at least 40%, more preferably at least at least 50%, even more preferably at least 60%, even more preferably at least 70%, even more preferably at least 80% and most preferably at least 90% of the full length 3'-UTR variant. The specified fragment of the variant in the context of the present invention is preferably a functional fragment of the variant indicated in the present description.

In some embodiments, the 3'UTR element may be any of the 3'UTR elements described in WO 2016/107877. In this context, the description of WO 2016/107877 regarding 3'-UTR elements/sequences is incorporated herein by reference. Particularly preferred 3'-UTR elements have SEQ ID NOs: 1-24 and SEQ ID NOs: 49-318 of WO 2016/107877, or fragments or variants of these sequences. In this context, it is particularly preferred that the 3'UTR element contains or consists of the corresponding RNA sequence, the nucleotide sequence of which corresponds to SEQ ID NOs: 1-24 and SEQ ID NOs: 49-318 as set forth in patent application WO 2016/107877.

In some embodiments, the 3'UTR element may be any 3'UTR described in WO 2017/036580. In this context, the description of WO 2017/036580 relating to 3'-UTR elements/sequences is incorporated herein by reference. Particularly preferred 3'-UTR elements have SEQ ID NOs: 152-204 as set forth in patent application WO 2017/036580, or fragments or variants of said sequences. In this context, it is particularly preferred that the 3'-UTR element contains or consists of the corresponding RNA sequence, the nucleotide sequence of which corresponds to SEQ ID NO: 152-204 as set forth in patent application WO 2017/036580.

According to one of the embodiments of the invention, at least one coding RNA specified in the present description also contains at least one 3'-UTR element, which contains or consists of a nucleotide sequence derived from the 3'-UTR of a gene selected from the group , which consists of the 40S subunit ribosomal protein S9 gene (RPS9), proteasome beta 3 subunit (PSMB3), caspase 1 (CASP1), and cytochrome c oxidase subunit 6B1 (COX6B1), or a variant of any of these genes, where the gene or variant thereof is preferred is a vertebrate gene, more preferably a mammalian gene, and most preferably a human gene.

In a particularly preferred embodiment, the 3'UTR element comprises or consists of a nucleotide sequence that is derived from the 3'UTR of a gene selected from the group consisting of an albumin gene, an α-globin gene, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene and a collagen alpha chain gene, such as the collagen alpha 1 chain type (I) gene, preferably as described herein, the 40S subunit ribosomal protein S9 gene (RPS9), the proteasome beta 3 subunit (PSMB3), caspase 1 ( CASP1) and cytochrome c oxidase subunit 6B1 (COX6B1), or a variant of any of these genes, wherein the gene or variant is preferably a vertebrate gene, more preferably a mammalian gene, and most preferably a human gene.

In another preferred embodiment, the 3'-UTR element contains or consists of a nucleotide sequence that is at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence represented by in one of SEQ ID NOs: 852, 854, 856, or 858, or the corresponding RNA sequence, preferably selected from SEQ ID NOs: 853, 855, 857, or 859, or where at least one 3'-UTR element contains or consists of a fragment of a nucleotide sequence that is at least about 20%, at least about 40%, preferably at least about 50% identical, respectfully at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, still more preferably at least about 99% of the nucleotide sequence shown in one of SEQ ID NOs: 852, 854, 856 or 858, where preferably the fragment is the fragment described above, i.e. is a continuous segment consisting of nucleotides, which accounts for at least 20%, etc. from the full-length 3'-UTR. Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably, the fragment is a functional fragment as specified in the present description.

In a particularly preferred embodiment, the 3'-UTR element contains or consists of a nucleotide sequence that is at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence represented by in one of SEQ ID NOs: 852, 854, 856, 858, 412, 414, 416, 418, 420, 422 or 424, or the corresponding RNA sequence, preferably selected from SEQ ID NOs: 853, 855, 857 or 859, or where at least one 3'-UTR element contains or consists of a fragment of a nucleotide sequence that is at least about 20% identical, at least about 40% identical, preferably at least about 50%, preferably at least about 60%, preferably at least about 70%, more preferably at least about 80%, more preferably at least about 90%, even more preferably at least about 95%, even more preferably at least about 99% of the nucleotide sequence shown in one of SEQ ID NOs: 852, 854, 856, 858, 412, 414, 416, 418, 420, 422, or 424, where preferably the fragment is the fragment described above, i.e. is a continuous segment consisting of nucleotides, which accounts for at least 20%, etc. from the full-length 3'-UTR. Preferably, the fragment is at least about 20 nucleotides or more, preferably at least about 30 nucleotides or more, more preferably at least about 40 nucleotides or more. Preferably, the fragment is a functional fragment as specified in the present description.

Preferably, at least one 5'UTR element and at least one 3'UTR element act synergistically to increase protein production with at least one coding RNA as defined herein.

Thus, in a preferred embodiment of the invention, at least one coding RNA specified in the present description contains at least one 5'-UTR element, preferably specified in the present description, and at least one 3'-UTR element, preferably specified in the present description. Particularly preferred 5'-UTR elements, 3'-UTR elements, and their respective combinations are summarized in Table A below. The 5'-UTR elements and 3'-UTR elements shown are preferably indicated herein.

According to preferred embodiments of the invention, the 5'-UTR element listed in column 1 ("5'-UTR element") in Table A, and which is listed in the present description, is combined in at least one coding RNA used according to the present description , with the 3'-UTR element listed in the same row in column 4 ("3-UTR element") in table A, and which is listed in the present description. For example, a 5'UTR element derived from the MP68 gene or a variant thereof as described herein can preferably be combined with a 3'UTR element derived from the RPS9 gene or a variant thereof as described herein. More preferably, a 5'UTR element that contains the RNA sequence listed under SEQ ID NO: in column 2 ("SEQ ID NO: RNA) in Table A, or the DNA sequence listed under SEQ ID NO: in column 3" SEQ ID NO: DNA") in Table A, or a fragment or variant of said RNA or DNA sequence can be combined with a 3'-UTR element which is listed in the same row in Table A, i.e. preferably with a 3'-UTR element that contains the RNA sequence listed under SEQ ID NO: in column 5 ("SEQ ID NO: RNA) in the same row in Table A, or the DNA sequence listed under SEQ ID NO: in column 6 ("SEQ ID NO: DNA) in the same row in table A, or a fragment or variant of the specified RNA or DNA sequence. For example, at least one coding RNA used according to the present description may contain a 5'-UTR element containing or consisting of the nucleotide sequence shown in SEQ ID NO: 841, or a fragment or variant thereof, specified in the present description, and 3'-UTR element containing or consisting of the nucleotide sequence shown in SEQ ID NO: 853, or a fragment or variant specified in the present description.

According to another preferred embodiment of the invention, the isRNA or at least one coding RNA as defined herein can be modified by adding a so-called "5'-cap" structure that preferably stabilizes the RNA as described herein. A 5'-cap is a structure, typically a modified nucleotide structure, that typically "caps" the 5' end of a mature mRNA. The 5' cap can generally be formed by a modified nucleotide, primarily a derivative of a guanine nucleotide. Preferably the 5' cap is linked to the 5' end via a 5'-5' triphosphate bond. The 5' cap may be methylated, eg m7GpppN, where N is the 5' terminal nucleotide of the nucleic acid carrying the 5' cap, typically the 5' end of the mRNA. m7GpppN is a 5' cap structure that occurs naturally in mRNA that is transcribed by polymerase II and is therefore preferably not considered in this context as a modification that is contained in the modified RNA. This means that the modified RNA of the present invention may contain m7GpppN as the 5' cap, but in addition the modified RNA will typically contain at least one additional modification as described herein.

Other examples of 5'-cap structures are glyceryl, inverted deoxy group (fragment) devoid of a nitrogenous base, 4',5'-methylene nucleotide, 1-(beta-D-erythrofuranosyl) nucleotide, 4'-thionucleotide, carbocyclic nucleotide, 1, 5-anhydrohexitol nucleotide, L-nucleotides, alpha-nucleotide, base-modified nucleotide, treopentofuranosyl nucleotide, acyclic 3',4'-seconucleotide, acyclic 3,4-dihydroxybutyl nucleotide, acyclic 3,5-dihydroxypentyl nucleotide, 3'-3 '-Inverted Nucleotide Fragment, 3'-3'-Inverted Nucleotide Fragment, 3'-2'-Inverted Nucleotide Fragment, 3'-2'-Inverted Nucleotide Fragment, 1,4-Butanediol Phosphate, 3'-Phosphoramidate , hexylphosphate, aminohexylphosphate, 3'-phosphate, 3'-phosphorothioate, phosphorodithioate, or a bridged or unbridged methylphosphonate moiety. In this context, these modified 5'-cap structures are considered to be at least one modification.

Particularly preferred modified 5'-cap structures are CAP1 (ribose methylation of the nucleotide adjacent to m7G), CAP2 (methylation of the 2nd nucleotide ribose upstream of m7G), CAP3 (methylation of the 3rd nucleotide ribose downstream of m7G). relative to m7G), CAP4 (methylation of the ribose of the 4th nucleotide located in the forward direction relative to m7G), ARCA (correctly oriented cap analog), modified ARCA (for example, modified ARCA phosphorothioate), inosine, N1-methylguanosine, 2' -fluoroguanosine, 7-deazaguanosine, 8-oxoguanosine, 2-aminoguanosine, LNA-guanosine and 2-azidoguanosine.

In some embodiments of the invention, at least one coding RNA specified in the present description, preferably contains a poly(A) - and/or poly(C)-sequence.

In a particularly preferred embodiment of the invention, at least one coding RNA as defined herein contains, in addition to a coding region that encodes at least one peptide or protein as defined above, or a fragment or variant thereof, a poly(A) sequence , the so-called poly-A tail, preferably at the 3' end of the RNA. When present, said poly(A) sequence comprises a sequence of about 25 to about 400 adenosine nucleotides, preferably a sequence of about 50 to about 400 adenosine nucleotides, more preferably a sequence of about 50 to about 300 adenosine nucleotides. nucleotides, even more preferably a sequence containing from about 50 to about 250 adenosine nucleotides, most preferably a sequence containing from about 60 to about 250 adenosine nucleotides. In this context, "about" refers to a deviation of ±10% of the value(s) to which it refers. Specified poly(A)-sequence is preferably located at the 3'-end of the coding region, which is contained in at least one coding RNA specified in the present description.

Preferably, the poly(A) sequence in at least one coding RNA as defined herein is obtained from a DNA template by in vitro transcription of the RNA. Alternatively, the poly(A) sequence can also be obtained in vitro by combining chemical synthesis methods without the need for its transcription from the precursor DNA. In addition, poly(A) sequences or poly(A) tails can be generated by enzymatic polyadenylation of at least one RNA using commercially available polyadenylation kits and appropriate protocols known in the art.

Alternatively, at least one coding RNA as defined herein optionally contains a polyadenylation signal as defined herein, which is a signal that causes polyadenylation of (transcribed) mRNA by specific protein factors (such as, for example, a specific cleavage factor and polyadenylation (CPSF), cleavage-stimulating factor (CstF), cleavage factors I and II (CF I and CF II), poly(A) polymerase (PAP)). In this context, the polyadenylation consensus signal preferably contains the NN(U/T)ANA consensus sequence. In the most preferred aspect of the invention, the polyadenylation signal contains one of the following sequences: AA(U/T)AAA or A(U/T)(U/T)AAA (in which uridine is typically present in the RNA and thymidine is typically present in DNA).

According to another preferred embodiment of the invention, at least one coding RNA specified in the present description can be modified with a sequence consisting of at least 10 cytosines, preferably at least 20 cytosines, more preferably at least 30 cytosines ( the so-called "poly(C)-sequence"). In particular, the RNA may comprise a poly(C) sequence that typically contains about 10 to 200 cytosine nucleotides, preferably about 10 to 100 cytosine nucleotides, more preferably about 10 to 70 cytosine nucleotides, or even more preferably about 20 to 50 or even 20 to 30 cytosine nucleotides. Said poly(C) sequence is preferably located 3' to the coding region, more preferably 3' to the optional poly(A) sequence contained in at least one coding RNA as defined herein.

In a particularly preferred embodiment of the invention, at least one coding RNA specified in the present description contains a histone sequence/stem-loop structure. Said stem-loop histone sequences are preferably selected from the stem-loop histone sequences as set forth in WO 2012/019780, the contents of which are incorporated herein by reference.

The stem-loop histone sequence that can be used in the present invention is preferably selected from at least one of the following formulas (VII) or (VIII):

formula (VII) (sequence of a stem-loop structure without stem boundary elements):

formula (VIII) (sequence of a stem-loop structure with stem boundary elements):

in which:

stem1 or stem2 boundary elements N _1-6 denote a contiguous sequence consisting of 1-6, preferably 2-6, more preferably 2-5, even more preferably 3-5, most preferably 4-5 or 5 N, where N is each independently selected from each other from a nucleotide selected from A, U, T, G, and C, or a nucleotide analogue thereof;

stem1 [N _0-2 GN _3-5 ] denotes a sequence reversely complementary or partially reversely complementary to stem2 element, and is a contiguous sequence of 5-7 nucleotides;

in which N _0-2 denotes a contiguous sequence consisting of 0-2, preferably 0-1, more preferably 1 N, where N is each independently selected from a nucleotide selected from A, U, T, G and C or its nucleotide analog;

in which N _3-5 denotes a continuous sequence consisting of 3-5, preferably 4-5, more preferably 4 N, where N is each independently selected from a nucleotide selected from A, U, T, G and C or its nucleotide analog, and

in which G denotes guanosine or its analogue and optionally can be replaced by cytidine or its analogue, provided that its complementary nucleotide cytidine in stem2 is replaced by guanosine;

the loop sequence [N _0-4 (U/T)N _0-4 ] is located between stem1 and stem2 elements and denotes a contiguous sequence of 3-5 nucleotides, more preferably 4 nucleotides;

in which N _0-4 each independently of the other denotes a continuous sequence consisting of 0-4, preferably 1-3, more preferably 1-2 N, where N is each independently selected from a nucleotide selected from A, U, T, G and C or its nucleotide analogue; and

wherein U/T is uridine or optionally thymidine;

stem2 [N _3-5 CN _0-2 ] denotes a sequence reversely complementary or partially reversely complementary to stem1 element, and is a contiguous sequence of 5-7 nucleotides;

in which N _3-5 denotes a continuous sequence consisting of 3-5, preferably 4-5, more preferably 4 N, where N is each independently selected from a nucleotide selected from A, U, T, G and C or its nucleotide analog;

in which N _0-2 denotes a contiguous sequence consisting of 0-2, preferably 0-1, more preferably 1 N, where N is each independently selected from a nucleotide selected from A, U, T, G or C or its nucleotide analog; and

wherein C is cytidine or an analog thereof and may optionally be replaced by guanosine or an analog thereof, provided that its complementary nucleoside guanosine in stem1 is replaced by cytidine;

where

stem1 and stem2 elements can base-pair with each other to form a reverse complementary sequence, where base-pairing can take place between stem1 and stem2, such as through Watson-Crick base-pairing of nucleotides A and U/T or G and C, or by non-Watson-Crick base-pairing, e.g., by "swinging" base-pairing ("swinging" base-pairing), the reverse of Watson-Crick base-pairing, by Hoogsteen base-pairing, by the reverse of Hoogsteen base-pairing, or they may be pairing bases with each other to form a partially reverse complementary sequence, while incomplete base pairing can occur between stem1 and stem2, due to the fact that one or more bases in one stem do not have a complementary base in the reverse complementary sequence of the other stem.

According to another preferred embodiment of the invention of the first object of the invention, the sequence of at least one mRNA in the composition proposed in the invention may contain at least one sequence of histone stem-loop structure corresponding to at least one of the following specific formulas (VIIa) or (VIIIa):

formula (VIIa) (stem-loop structure sequence without stem boundary elements):

formula (VIIa) (sequence of a stem-loop structure with stem boundary elements):

wherein:

N, C, G, T and U are as defined above.

According to another more preferred embodiment of the invention of the first object of the invention, the sequence of at least one mRNA in the composition proposed in the invention may contain at least one sequence of histone stem-loop structure corresponding to at least one of the following specific formulas (VIIb ) or (VIIIb):

formula (VIIb) (stem-loop structure sequence without stem boundary elements):

formula (VIIIb) (stem-loop structure sequence with stem boundary elements):

wherein:

N, C, G, T and U are as defined above.

A particularly preferred stem-loop histone structure has the sequence of SEQ ID NO: 426.

More preferably, the histone stem-loop sequence corresponds to an RNA sequence having the nucleotide sequence shown in SEQ ID NO: 427.

According to another particularly preferred embodiment of the invention, at least one coding RNA specified in the present description, in an additional or alternative embodiment, may encode a secretory signal peptide. Said secretory signal sequences are, but not limited to, peptide segments that are typically about 15-30 amino acids in length and are preferably located at the N-terminus of the encoded peptide. The signal peptides described herein preferably provide for the transfer of an antigen, antigenic protein or antigenic peptide encoded by at least one coding RNA described herein to a specific cell compartment, preferably the cell surface, the endoplasmic reticulum (ER) or endosomal-lysosomal compartment. Examples of secretory signal sequences referred to herein include, but are not limited to, classical or non-classical MHC signal sequences (e.g., MHC I and MHC II signal sequences, e.g., HLA-A*0201 MHC class I ), secretory signal sequences for cytokines or immunoglobulins as defined herein, secretory signal sequences for an invariant chain of immunoglobulins or antibodies as described herein, signal sequences for Lamp1, tapazin, Erp57, calreticulin, calnexin, and other membrane-associated proteins or proteins associated with endoplasmic reticulum (ER) or endosomal-lysosomal compartment. Most preferably, according to the present invention, the signal sequences of the MHC class I HLA-A*0201 molecule can be used.

In some embodiments of the invention, at least one coding RNA specified in the present description, preferably mRNA, contains, preferably in the direction from the 5' end to the 3' end, the following elements:

a) 5'-cap structure, preferably m7GpppN,

b) at least one coding sequence that encodes at least one peptide or protein containing IL-12, a PD-1 decoy receptor, preferably a soluble PD-1 receptor as defined herein, CD40L, an anti-CTLA4 antibody and/or a tumor antigen or a fragment or variant of any of these proteins,

c) a 3'-UTR element containing a nucleotide sequence derived from the α-globin gene, preferably containing the corresponding RNA sequence of the nucleotide sequence as shown in SEQ ID NO: 418, or a homologue, fragment or variant thereof,

d) a poly(A) tail, preferably consisting of 10-200, 10-100, 40-80 or 50-70 adenosine nucleotides,

e) a poly(C) tail, preferably consisting of 10-200, 10-100, 20-70, 20-60 or 10-40 cytosine nucleotides, and

e) a histone stem-loop structure, preferably containing the RNA sequence shown in SEQ ID NO: 427.

According to a preferred embodiment of the invention, at least one coding RNA specified in the present description contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO0: 146-151; 157-162; 168-173; 179-184; 190-195; 201-206; 212-217; 223-228; 234-239; 245-250; 256-261 and 267-272, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263, 274; 992 and 598, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264, 275 and 596, or a fragment or variant of any of the indicated sequences,

c) a nucleotide sequence as set forth in one of SEQ ID NOs: 860-874, 875-889, or 594, preferably as set forth in SEQ ID NO: 594, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as set forth in one of SEQ ID NO: 890-904, 905-919 or 595, preferably as shown in SEQ ID NO: 595, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 920-922 or 923-925, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 144; 155; 166; 177; 188; 199; 210; 221; 232; 243; 254 and 265, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences.

According to another embodiment of the invention, at least one coding RNA specified in the present description contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 146-151; 451-456; 157-162; 168-173; 179-184; 190-195; 201-206; 212-217; 223-228; 234-239; 245-250; 256-261 and 267-272, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 153; 458; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263, 274; 992 and 598, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 459; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264, 275 and 596, or a fragment or variant of any of the indicated sequences,

c) a nucleotide sequence as set forth in one of SEQ ID NOs: 860-874, 875-889, or 594, preferably as set forth in SEQ ID NO: 594, or a fragment or variant of any of these sequences, and a nucleotide sequence as set forth in one of SEQ ID NO: 890-904, 905-919 or 595, preferably as shown in SEQ ID NO: 595, or a fragment or variant of any of these sequences;

or

the nucleotide sequence shown in SEQ ID NO: 920-922 or 923-925, or a fragment or variant of any of these sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 144; 449; 155; 166; 177; 188; 199; 210; 221; 232; 243; 254 and 265, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 145; 450; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences.

In a preferred embodiment of the invention, at least one coding RNA specified in the present description contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NOs: 451-456; 157-162; 168-173; 179-184; 190-195; 201-206; 212-217; 223-228; 234-239; 245-250; 256-261 and 267-272, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 164; 175; 186; 197; 208; 219; 230; 241; 252; 263, 274; 992 and 598, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 459; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264, 275 and 596, or a fragment or variant of any of the indicated sequences,

c) a nucleotide sequence as set forth in one of SEQ ID NOs: 860-874, 875-889, or 594, preferably as set forth in SEQ ID NO: 594, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as set forth in one of SEQ ID NO: 890-904, 905-919 or 595, preferably as shown in SEQ ID NO: 595, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 920-922 or 923-925, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 144; 449; 166; 177; 188; 199; 210; 221; 232; 243; 254 and 265, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 145; 450; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences.

A particularly preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, preferably comprising the intratumoral administration of isRNA, wherein the treatment comprises the administration of at least three, preferably at least four or five, coding RNAs as indicated in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five mRNAs in which

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992 and 598, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275 and 596, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NO: 860-874 or 594, preferably shown in SEQ ID NO: 594, or a fragment or variant of any of these nucleotide sequences, and a nucleotide sequence as set forth in one of SEQ ID NOs: 890-904 or 595, preferably as set forth in SEQ ID NO: 595, or a fragment or variant of any of said nucleotide sequences, and/or

optionally the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences,

where the first, second, third and fourth coding RNA is preferably introduced into the tumor.

A particularly preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, preferably comprising the intratumoral administration of isRNA, wherein the treatment comprises the administration of at least three, preferably at least four or five, coding RNAs as indicated in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five mRNAs in which

a) the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992 and 598, or a fragment or variant of any of these sequences,

b) the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275 and 596, or a fragment or variant of any of these sequences,

c) the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NO: 860-874 or 594, preferably shown in SEQ ID NO: 594, or a fragment or variant of any of the specified nucleotide sequences, and

the fourth coding RNA contains the nucleotide sequence shown in one of SEQ ID NO: 890-904 or 595, preferably shown in SEQ ID NO: 595, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences,

where the first, second, third, fourth and fifth coding RNAs are preferably introduced into the tumor.

A particularly preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, preferably comprising the intratumoral administration of isRNA, wherein the treatment comprises the administration of at least three, preferably at least four or five, coding RNAs as indicated in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five mRNAs in which

a) the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992 and 598, or a fragment or variant of any of these sequences,

b) the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275 and 596, or a fragment or variant of any of these sequences,

c) the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NO: 860-874 or 594, preferably shown in SEQ ID NO: 594, or a fragment or variant of any of the specified nucleotide sequences, and

the fourth coding RNA contains the nucleotide sequence shown in one of SEQ ID NO: 890-904 or 595, preferably shown in SEQ ID NO: 595, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences,

where the first, second, third, fourth and fifth coding RNAs are preferably introduced into the tumor.

In some embodiments of the invention, at least one coding RNA specified in the present description, preferably mRNA, contains, preferably in the direction from the 5' end to the 3' end, the following elements:

a) 5'-cap structure, preferably m7GpppN,

b) a 5'-UTR element that contains or consists of a nucleotide sequence derived from the 5'-UTR of the TOP gene, preferably containing an RNA sequence that corresponds to the nucleotide sequence shown in SEQ ID NO: 408, or a homologue, fragment, or option,

c) at least one coding sequence that encodes at least one peptide or protein containing IL-12, a PD-1 decoy receptor, preferably a soluble PD-1 receptor as defined herein, CD40L, an anti-CTLA4 antibody and/or a tumor antigen or a fragment or variant of any of these proteins,

d) a 3'-UTR element containing a nucleotide sequence derived from the α-globin gene, preferably containing the corresponding RNA sequence of the nucleotide sequence as represented by SEQ ID NO: 418, or a homologue, fragment or variant thereof, and/or

a 3'-UTR element containing a nucleotide sequence derived from the albumin gene, preferably containing the corresponding RNA sequence of the nucleotide sequence as shown in SEQ ID NO: 422 or 424, or a homologue, fragment or variant of any of these sequences,

e) a poly(A) tail, preferably consisting of 10-200, 10-100, 40-80 or 50-70 adenosine nucleotides,

f) a poly(C) tail, preferably consisting of 10-200, 10-100, 20-70, 20-60 or 10-40 cytosine nucleotides, and

g) a histone stem-loop structure, preferably containing the RNA sequence shown in SEQ ID NO: 427.

In a preferred embodiment of the invention, at least one coding RNA specified in the present description contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 278-283; 289-294; 300-305; 311-316; 322-327; 333-338; 344-349; 355-360; 366-371; 377-382; 388-393; 399-404 and 462-467, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

c) a nucleotide sequence as shown in one of SEQ ID NOs: 926-940 or 941-955, preferably as shown in SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NO: 956-970 or 971-985, preferably as shown in SEQ ID NO: 956-970, or a fragment or variant of any of the indicated nucleotide sequences; or

the nucleotide sequence shown in SEQ ID NO: 986-988 or 989-991, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 276; 287; 298; 309; 320; 331; 342; 353; 364; 375; 386; 460 and 397, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 461; 387 and 398, or a fragment or variant of any of these sequences.

In another embodiment of the invention, at least one coding RNA specified in the present description contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 289-294; 300-305; 311-316; 322-327; 333-338; 344-349; 355-360; 366-371; 377-382; 388-393 and 399-404, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396 and 407, or a fragment or variant of any of these sequences,

c) a nucleotide sequence as shown in one of SEQ ID NOs: 926-940 or 941-955, preferably as shown in SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NO: 956-970 or 971-985, preferably as shown in SEQ ID NO: 956-970, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 986-988 or 989-991, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430 and 992, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387 and 398, or a fragment or variant of any of these sequences.

In a preferred embodiment of the invention, at least one coding RNA specified in the present description contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 278-283; 289-294; 300-305; 311-316; 322-327; 333-338; 344-349; 355-360; 366-371; 377-382; 388-393; 399-404 and 462-467, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396 and 407, or a fragment or variant of any of these sequences,

c) a nucleotide sequence as shown in one of SEQ ID NOs: 926-940 or 941-955, preferably as shown in SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and a nucleotide sequence as shown in one of SEQ ID NO: 956-970 or 971-985, preferably as shown in SEQ ID NO: 956-970, or a fragment or variant of any of the indicated nucleotide sequences;

or

the nucleotide sequence shown in SEQ ID NO: 986-988 or 989-991, or a fragment or variant of any of the indicated nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 276; 287; 298; 309; 320; 331; 342; 353; 364; 375; 386; 460 and 397, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 461; 387 and 398, or a fragment or variant of any of these sequences.

A particularly preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, preferably comprising the intratumoral administration of isRNA, wherein the treatment comprises the administration of at least three, preferably at least four or five, coding RNAs as indicated in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five mRNAs in which

a) the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

c) the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and

the fourth coding RNA contains the nucleotide sequence shown in one of SEQ ID NOs: 956-970, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences;

where the first, second, third, fourth and fifth coding RNAs are preferably introduced into the tumor.

Another preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, preferably comprising the intratumoral administration of isRNA, wherein the treatment comprises the administration of at least three, preferably at least four or five, of the coding RNAs indicated in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five mRNAs in which

a) the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

c) the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and

the fourth coding RNA contains the nucleotide sequence shown in one of SEQ ID NOs: 956-970, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences,

where the first, second, third, fourth and fifth coding RNAs are preferably introduced into the tumor.

Another particularly preferred embodiment of the present invention is an isRNA for use in the treatment of a neoplastic or cancerous disease as defined herein, preferably comprising the intratumoral administration of isRNA, wherein the treatment comprises the administration of at least three, preferably at least four or five, coding RNAs. specified in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five mRNA, in which

a) the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

c) the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and

the fourth coding RNA contains the nucleotide sequence shown in one of SEQ ID NOs: 956-970, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences;

where the first, second, third, fourth and fifth coding RNAs are preferably introduced into the tumor.

A preferred embodiment of the present invention is an isRNA for use in the treatment of a tumor or cancer disease as defined herein, wherein the treatment comprises the administration of at least one coding RNA as defined herein (as an additional pharmaceutically active ingredient), where isRNA is administered in the form of RNA in complex with one or more cationic or polycationic compounds, preferably a polymeric carrier, specified in the present description, and at least one coding RNA, more preferably mRNA, is administered in the form of free RNA.

Another preferred embodiment of the invention is isRNA for use in the treatment of a tumor or cancer,

where isPHK contains a nucleotide sequence, which is described by formula (I) (G _l X _m G _n ), formula (II) (C _l X _m C _n ), formula (III) (N _u G _l X _m G _n N _v ) _a or formula (IV) (N _u C _l X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in one of SEQ ID NO: SEQ ID NO: 433-437, 1014-1016, 1055 or 1056, or a fragment or variant of any of the indicated sequences, more preferably represented in one of SEQ ID NOs: 433, 434, 1014-1016, or a fragment or variant thereof,

where isPHK is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, more preferably with a polymeric carrier, which is formed using a disulfide cross-linked cationic component, which preferably contains a peptide of formula (V), (Va) and/or (Vb ), and/or a compound of formula (VI), more preferably at least one of the disulfide crosslinked cationic peptides Cys-Arg ₁₂ , Cys-Arg ₁₂ -Cys or Trp-Arg ₁₂ -Cys,

where isRNA is preferably injected into the tumor,

where the neoplastic or cancerous disease is preferably selected from the group which consists of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably the cutaneous T-cell lymphoma subtype mycotic fungoid, and vulvar squamous cell carcinoma (VSCC);

where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

where the treatment of a neoplastic or cancerous disease comprises the administration of at least three, preferably at least four or five coding RNAs specified in the present description (as additional pharmaceutically active ingredients), preferably at least three, more preferably at least four or five , mRNA, in which

a) the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

c) the third coding RNA contains a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in one of SEQ ID NOs: 926-940, or a fragment or variant of any of said nucleotide sequences, and

the fourth coding RNA contains the nucleotide sequence shown in one of SEQ ID NOs: 956-970, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences,

where the first, second, third, fourth and fifth coding RNAs are preferably introduced into the tumor.

Another object of the present invention is the combination of isRNA and at least one coding RNA, where at least one coding RNA encodes at least one peptide or protein containing IL-12, CD40L, PD-1 decoy receptor, preferably soluble PD- 1 receptor, and an anti-CTLA4 antibody, or a fragment or variant of any of these proteins.

the isRNA in the combination of the invention is preferably the isRNA as defined herein for isRNA for use in the treatment of a tumor or cancer. The at least one coding RNA in the combination of the invention is preferably the coding RNA as defined herein, more preferably the coding RNA as defined herein for the at least one coding RNA that is used as an additional pharmaceutically active ingredient. In an additional or alternative embodiment, at least one coding RNA may encode at least one tumor antigen, preferably specified in the present description, or a fragment or variant.

In a preferred embodiment of the invention, the combination contains isPHK and at least one coding RNA, which are included in one or different preparative forms, preferably specified in the present description.

Regardless of their preparative form, isRNA and at least one coding RNA can preferably be administered simultaneously. Alternatively, isRNA and at least one coding RNA in combination can be administered alternately.

The terms "administration in combination (in combination)", "co-administration" or "simultaneous administration" in the context of the present description refers to a situation where a pharmaceutically active ingredient, such as isPHK, specified in the present description, is administered to an individual before, simultaneously or after administration at least one additional pharmaceutically active ingredient, such as at least one coding RNA specified in the present description, to the same individual. The time interval between the administration of pharmaceutically active ingredients depends on the nature and biological effect of the particular pharmaceutically active ingredient and can be determined by the attending physician. Preferably, the time interval is less than about 48 hours, more preferably less than about 24, 12, 6, 4, 2, 1 hours, most preferably less than about 30, 15, or 5 minutes. In a particularly preferred embodiment of the invention, the term "administration in combination" refers to the concomitant administration of pharmaceutically active ingredients, i. simultaneous administration of at least two compounds; or administration of at least two compounds in a time frame that is typically less than 5 minutes. The concept of "administration in combination" does not only refer to the situation where the pharmaceutically active ingredients are in physical contact with each other or come in the same formulation. The concept of "introduction in combination" in the context of the present description also refers to the separate introduction of pharmaceutically active ingredients (for example, by two different injections). Alternatively, one pharmaceutically active ingredient, such as isPHK as defined herein, can be combined by mixing the ingredient with at least one additional pharmaceutically active ingredient, such as at least one coding RNA, prior to administration and administering the mixture to an individual.

The terms "administration in combination", "co-administration" or "simultaneous administration" in the context of the present description also refers to a situation where a pharmaceutically active ingredient, such as isPHK, specified in the present description, is administered to an individual before, simultaneously or after administration of at least one additional pharmaceutically active ingredient, such as at least one coding RNA specified in the present description, to the same individual. In some embodiments, the time interval between administration of the pharmaceutically active ingredients is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 30 minutes. In some embodiments, isRNA is administered at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 30 minutes after administration of at least one coding RNA specified herein. description.

isRNA and at least one coding RNA in the combination according to the invention are preferably administered at the same site or at different sites, preferably by injection. Most preferably, at least one isRNA and at least one coding RNA in combination, preferably both RNAs, is administered into the tumor, preferably as described herein.

Another object of the invention is the combination of isPHK and at least one coding RNA specified in the present description, intended for use as a drug. The invention also provides a combination of isRNA and at least one coding RNA for use in the preparation of a medicament.

One embodiment of the invention is a combination as described herein for use in the treatment or prevention of a disease selected from the group consisting of neoplastic and cancerous diseases, infectious diseases, allergies, and autoimmune diseases. A preferred embodiment of the invention is a combination as described herein for use in the treatment or prevention of neoplastic or cancerous diseases, preferably as described herein. A particularly preferred embodiment of the invention is a combination for use in the treatment or prevention of melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL), squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC of the skin, more preferably cutaneous squamous cell carcinoma (cSCC), or other forms of malignant skin cancer, adenoid cystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably running HNSCC. Alternatively, the combination is intended for use in the treatment or prophylaxis

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the tumor or cancer is preferably at an advanced stage and/or is resistant to standard therapy.

Preferably, the combination as described herein is for use in the treatment or prevention of a disease as described herein, wherein the treatment or prevention comprises the administration of at least one additional pharmaceutically active ingredient, preferably as described herein. In a preferred embodiment, the combination is for use in the treatment or prevention of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

where the treatment or prevention includes the administration of at least one additional pharmaceutically active ingredient, where at least one additional pharmaceutically active ingredient is a compound that is usually used for the treatment or prevention of any of these diseases, preferably the compound specified in this context in the present description .

In a particularly preferred embodiment of the invention, the combination described herein is for use in the treatment or prevention of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

wherein the treatment or prophylaxis comprises administering a PD-1 inhibitor or inhibitor or PD-L1, preferably as defined herein, more preferably an antagonist antibody directed against PD-1 or PD-L1.

In another preferred embodiment of the invention, the combination described herein is for use in the treatment or prevention of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or

for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma , preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

where treatment or prevention includes the introduction of antibodies to CTLA4, preferably specified in the present description.

The next object of the present invention is the coding RNA specified in the present description. The coding RNA according to the invention is generally characterized by one of the features mentioned herein in the context of at least one coding RNA that can be used as an additional pharmaceutically active ingredient mentioned in the present description regarding the isRNA to be used, proposed in the invention. In particular, the coding RNA of the invention encodes a peptide or protein comprising at least one peptide or protein selected from the group consisting of IL-12, CD40L, PD-1 decoy receptor, preferably soluble PD-1 a receptor, an anti-CTLA4 antibody, and a tumor antigen, or a fragment or variant of any of these proteins.

In a preferred embodiment, the coding RNA of the invention encodes a peptide or protein comprising IL-12, CD40L and a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant of any of these proteins. For example, a coding RNA that encodes said peptide or protein may be a polycistronic RNA containing three open reading frames, where each open reading frame encodes a different peptide or protein selected from the group consisting of IL-2, CD40L, A decoy PD-1 receptor, preferably a soluble PD-1 receptor, an anti-CTLA4 antibody and a tumor antigen, or a fragment or variant of any of these proteins.

Another object of the present invention is a coding RNA according to the invention, intended for the treatment or prevention of a disease selected from the group consisting of neoplastic and cancerous diseases, infectious diseases, allergies and autoimmune diseases. A preferred embodiment of the invention is a coding RNA as defined herein for use in the treatment or prevention of neoplastic or cancerous diseases, preferably as described herein. A particularly preferred embodiment of the invention is a coding RNA as defined herein for use in the treatment or prevention of melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL), squamous cell carcinoma (SCC) of the skin, preferably unresectable and /or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), or other malignant skin cancers, adenoid cystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head squamous cell carcinoma and neck (HNSCC), preferably triggered by HNSCC. In a preferred embodiment, the coding RNA is for use in the treatment or prevention of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the tumor or cancer is preferably at an advanced stage and/or is resistant to standard therapy.

The coding RNA of the invention is preferably for use in the treatment or prevention of the diseases described herein, preferably in the treatment or prevention of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), squamous cell carcinoma (SCC ) skin, preferably unresectable and/or advanced SCC, most preferably cutaneous squamous cell carcinoma (cSCC) or other forms of malignant skin cancer, adenoid cystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably advanced by HNSCC;

where the coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, CD40L or PD-1 decoy receptor, preferably a soluble PD-1 receptor, or a fragment or variant thereof, and where treatment or prophylaxis includes the introduction of a second coding RNA and/or third coding RNA, where the second or third coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a PD-1 decoy receptor, preferably a soluble PD-1- the receptor, or fragment or variant thereof, resulting in the peptide(s) or protein(s) encoded by the co-coding RNAs, contains(at) IL-12, CD40L or PD-1 decoy receptor, preferably soluble PD- 1-receptor, or a fragment or variant thereof. In this case, the coding RNA as well as the second and/or third coding RNAs are preferably the coding RNAs mentioned in the present description.

The coding RNA of the invention is preferably for use in the treatment or prevention of a disease as defined herein, preferably in the treatment or prevention of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

where the coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, CD40L, a PD-1 decoy receptor, preferably a soluble PD-1 receptor, or an anti-CTLA4 antibody, or a fragment or variant of any of these peptides or proteins, and where treatment or prevention includes the introduction of a second coding RNA, a third coding RNA and/or a fourth coding RNA, where the second, third or fourth coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, CD40L, PD-1 decoy receptor, preferably soluble PD-1 receptor, or anti-CTLA4 antibody, or fragment or variant thereof, resulting in peptide(s) or protein(s) encoded(s) co-coding RNA, contains (at) IL-12, CD40L, PD-1 decoy receptor, preferably soluble PD-1 receptor, and anti-CTLA4 antibody, or fragments or variants thereof. When this coding RNA as well as the second, third or fourth coding RNA preferably represent the coding RNA specified in the present description.

In some embodiments, the invention is a coding RNA for use in the treatment or prevention of a disease described herein, where the treatment or prevention also includes chemotherapy, radiation therapy, and/or surgery. According to a preferred embodiment of the invention, treatment or prophylaxis comprises the administration of at least one additional pharmaceutically active ingredient. In another preferred embodiment of the invention, treatment or prophylaxis comprises administering a compound that is commonly used to treat

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy;

preferably the compound specified in this context in the present description. More preferably, treatment or prophylaxis comprises administering a PD-1 inhibitor or PD-L1 inhibitor, preferably an antagonist antibody directed against PD-1 or PD-L1. In a particularly preferred embodiment of the invention, treatment or prophylaxis comprises administering, preferably intratumorally, an isRNA, preferably an isRNA, as defined herein.

In some embodiments, treatment or prophylaxis comprises administering a compound that is commonly used to treat

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphomas, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the neoplastic or cancerous disease is preferably at an advanced stage and/or is resistant to standard therapy; preferably the compound specified in this context in the present description. More preferably, treatment or prophylaxis comprises administering an anti-CTLA4 antibody. In a particularly preferred embodiment of the invention, treatment or prophylaxis comprises administering, preferably intratumorally, an isRNA, preferably an isRNA, as defined herein.

The coding RNA for the use described herein is preferably introduced into the tumor. In a particularly preferred embodiment of the invention, the coding RNA for the use described herein is introduced into the tumor.

Another object of the present invention is a pharmaceutical composition containing isRNA, preferably specified in the present description, at least one coding RNA, preferably specified in the present description, or a combination thereof, where the pharmaceutical composition contains a pharmaceutically acceptable carrier and/or excipient.

Preferably, the pharmaceutical composition is formulated for intratumoral administration, preferably by injection into tumor tissue. Sterile injectable forms of the pharmaceutical composition according to the invention may be an aqueous or oily suspension. Such suspensions may be prepared by methods known in the art using suitable dispersing or wetting agents and suspending agents.

A pharmaceutically acceptable carrier typically includes a liquid or non-liquid base composition that contains isRNA, preferably specified in the present description, at least one coding RNA, preferably specified in the present description, or a combination thereof, specified in the present description. If the composition is in liquid form, then the carrier can generally be pyrogen-free water; isotonic saline or buffered (aqueous) solutions, such as solutions buffered with phosphate, citrate, etc. The buffer to be injected may be hypertonic, isotonic, or hypotonic with respect to the particular reference medium, i.e. the salt content of the buffer may be greater than, identical to, or less than that of the particular reference medium, and it is preferable to use concentrations of the aforementioned salts that do not result in cell damage due to osmosis or other concentration-related influences. Reference media can be, for example, fluids used in in vivo methods, such as blood, lymph, cytosolic fluids, or other body fluids, or, for example, fluids that can be used as reference media in in vivo methods. vitro" such as conventional buffers or liquids. These conventional buffers or liquids are known to the person skilled in the art. The most preferred liquid base is lactated Ringer's solution.

However, one or more compatible solid or liquid excipients or diluents or encapsulating compounds that can be used for administration to the patient to be treated can also be used in the pharmaceutical composition of the invention. The term "compatible" in the context of the present description means that these components of the pharmaceutical composition according to the invention can be mixed with the components of the pharmaceutical composition according to the invention in such a way that there is no interaction that could significantly reduce the pharmaceutical effectiveness of the pharmaceutical composition under normal conditions of use.

Proposed in the invention, the pharmaceutical composition may contain additional components that accelerate the introduction and absorption of the components of the pharmaceutical composition. These additional components may be an appropriate carrier or excipient, additional adjuvants supporting any immune response, antibacterial and/or antiviral agents.

An additional component of the pharmaceutical composition according to the invention may be an immunotherapeutic agent, which can be selected from immunoglobulins, preferably of the IgG type, monoclonal or polyclonal antibodies, polyclonal serum or sera, etc. Preferably, said additional immunotherapeutic agent may be in the form of a peptide/protein or may be encoded by a nucleic acid, preferably DNA or RNA, most preferably mRNA.

The pharmaceutical composition of the invention typically contains, in a "safe and effective amount", the components of the pharmaceutical composition of the invention, primarily the isRNA encoding the RNAs described herein, or a combination thereof, as described herein. As used herein, "safe and effective amount" means the amount of RNA molecule(s) referred to herein that is sufficient to significantly induce a positive modification of a disease, preferably a tumor or cancer disease. However, at the same time, the "safe and effective amount" is small enough to avoid serious side effects and provide a reasonable balance between benefit and risk. The determination of these limits, as a rule, is within the competence of the treating physician.

The pharmaceutical composition according to the invention can be used for human treatment as well as for veterinary medicine, preferably in human medicine in general as a pharmaceutical composition.

According to another particularly preferred object of the invention, the pharmaceutical composition specified in the present description can be obtained or used as a vaccine. As a rule, the specified vaccine is the vaccine specified above in the description of pharmaceutical compositions. Preferably, said vaccine typically contains an isRNA as described herein, at least one coding RNA as described herein, or a combination thereof as described herein. The vaccine may also contain a pharmaceutically acceptable carrier, adjuvant and/or excipient specified in the present description for the pharmaceutical composition according to the invention. In a particular embodiment of a vaccine, the choice of a pharmaceutically acceptable carrier determines in principle the route by which the vaccine according to the invention is administered. The vaccine according to the invention can be injected into the tumor tissue.

The vaccine may additionally contain one or more auxiliary substances designed to increase, if necessary, immunogenicity or immunostimulatory ability. Particularly preferred as excipients are the adjuvants or additives indicated for the pharmaceutical composition.

The following object of the invention is a set or set of components containing the isRNA specified in the present description, at least one coding RNA specified in the present description, their combination specified in the present description, which contains isRNA and at least one coding RNA specified in the present description, or containing the pharmaceutical composition or vaccine specified in the present description, or their components and optionally technical instructions with information on the introduction and dosage of the components.

In addition to isRNA and/or at least one coding RNA, the kit may additionally contain a pharmaceutically acceptable excipient, an adjuvant and at least one additional component, for example, an additional pharmaceutically active component / active compound specified in the present description, as well as means for its administration and technical instructions. The components of the composition, in particular the isRNA or at least one coding RNA specified in the present description, and possible additional components may be in lyophilized form. In a preferred embodiment of the invention, prior to using the kit, a predetermined amount of excipient is added to the lyophilized components, which is prescribed, for example, in the attached technical instructions.

In a particularly preferred embodiment of the invention, the kit may contain isRNA, preferably as part of a complex with a polymer carrier specified in the present description, in lyophilized form and at least one coding RNA specified in the present description, in lyophilized form and additionally a pharmaceutically acceptable excipient, adjuvant and at least one additional component, for example, additional pharmaceutically active component/active compounds specified in the present description, as well as means of administration and technical instructions. Preferably, the kit contains isRNA, preferably as part of a complex with a polymer carrier specified in the present description, in lyophilized form and at least three, preferably at least four or five coding RNAs that encode IL-12, CD40L, PD-1 receptor a decoy, preferably a soluble PD-1 receptor, an anti-CTLA4 antibody and/or a tumor antigen as described herein, or a fragment or variant of any of them, in lyophilized form, and a reconstitution liquid, eg lactated Ringer's solution or water.

The present invention also relates to some variants of the introduction and use of isRNA, specified in the present description, at least one coding RNA, specified in the present description, a combination thereof, specified in the present description, or, respectively, a pharmaceutical composition or vaccine, or kit or kit of components, specified in the present description. According to the main object of the invention isRNA specified in the present description, at least one coding RNA specified in the present description, their combination specified in the present description, or respectively a pharmaceutical composition or kit or kit of components can be used as a drug, preferably for treatment or prevention of a disease as defined herein, more preferably for the treatment of a neoplastic or cancerous disease, most preferably for the treatment of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or for the treatment of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC); where the tumor or cancer is preferably at an advanced stage and/or is resistant to standard therapy.

Thus, the present invention provides the use of an isRNA as defined herein, at least one coding RNA as defined herein, a combination thereof as defined herein, or a pharmaceutical composition or vaccine, respectively, or a kit or kit of components as defined in the present description, for the preparation of a medicinal product. In this context, treatment is preferably carried out by intratumoral administration, in particular by injection into the tumor tissue. Another object of the present invention is the second medical use of the isRNA specified in the present description, at least one coding RNA specified in the present description, a combination thereof, specified in the present description, or, respectively, a pharmaceutical composition or vaccine, or a set or set of components specified above , the essence of which is the use for the preparation of a medicinal product, primarily for intratumoral administration (use) for the treatment of neoplastic or cancerous diseases, preferably indicated in the present description.

One aspect of the present invention is a method for treating or preventing a disorder, wherein the method comprises administering, preferably intratumorally, to an individual in need thereof, an effective amount of a drug as defined herein, preferably an isRNA as defined herein, at least one coding RNA, specified in the present description, their combination, specified in the present description, or, respectively, a pharmaceutical composition or vaccine. More preferably, the method is for the treatment or prevention of a neoplastic or cancerous disease as defined herein, most preferably a disorder selected from the group consisting of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy;

or selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably the cutaneous T-cell lymphoma subtype mycotic fungoid, and vulvar squamous cell carcinoma (VSCC); where the disorder is preferably at an advanced stage and/or is resistant to standard therapy.

Thus, the present invention provides an isRNA as defined herein, at least one coding RNA as defined herein, a combination thereof as defined herein, or a pharmaceutical composition or vaccine, respectively, or a kit or kit of components as defined herein. description as a medicinal product. Thus, the term "drug" when used in the present description, as a rule, refers to isRNA, specified in the present description, at least one coding RNA, specified in the present description, their combination, specified in the present description (preferably in the form, suitable for administration, for example, in a liquid formulation), or, respectively, a pharmaceutical composition or vaccine, or a set or set of components specified in the present description. In this context, it is preferred that the isRNA and/or at least one coding RNA referred to herein be in lyophilized form and re-solubilized prior to administration, for example by adding an acceptable excipient known in the art or specified herein, such as lactated Ringer's solution or water.

The drug described in the present description, you can enter using conventional needle injection or needleless jet injection into the tumor tissue. In a preferred embodiment of the invention, the drug is administered by bolus injection. The term "jet injection" refers to a needleless injection technique in which a liquid containing a composition and optionally additional acceptable excipients is forced through an orifice, thereby creating an ultra-fine, high-pressure liquid jet that is capable of penetrating the skin of a mammal. In principle, the liquid jet forms an opening in the skin through which the liquid jet passes into the target tissue, namely the tumor tissue. According to the invention, jet injection can be used for intratumoral administration of the drug specified in the present description.

The drug can be administered by conventional needle injection or needleless jet injection adjacent and/or in close proximity to the tumor tissue. In a preferred embodiment of the invention, the drug is administered by jet injection adjacent to and/or in close proximity to the tumor tissue. According to the invention, jet injection can be used for intratumoral administration (in the vicinity and/or in close proximity to the tumor tissue), especially for the injection of a drug.

In some embodiments, the drug may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implantable reservoir. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intraarticular, intranodal, intrasynovial, epigastric, intrathecal, intrahepatic, intralesional, intracranial, transdermal, intradermal, intrapulmonary, intraperitoneal, intracardiac, intraarterial and sublingual injection or infusion. In addition, particularly preferred routes of administration are intradermal and intramuscular injection. Preferably the introduction involves the use of an imaging method, preferably specified in the present description. More preferably, the drug is administered locoregional, preferably as described herein. Even more preferably, the drug is administered locoregional, wherein the administration involves the use of an imaging technique, preferably as described herein.

According to another embodiment of the invention, the treatment or prevention of a disease, preferably a neoplastic or cancerous disease, described in the present description, includes the introduction of at least one pharmaceutical composition that contains the isRNA specified in the present description, and the introduction of at least one additional pharmaceutical composition, which contains at least one coding RNA specified in the present description, where the pharmaceutical compositions can be entered in the same way or in different ways. More preferably, the pharmaceutical compositions are administered using the same route, preferably intratumorally, for example by intratumoral or peritumoral injection.

According to a specific embodiment of the invention, the drug can be administered to the patient as a single dose or as multiple doses. In some embodiments, the drug may be administered to a patient as a single (single) dose followed by a second dose and optionally even a third, fourth (or more) subsequent doses, etc.

Preferably, the drug contains at least 25 μg of isRNA and/or coding RNA per dose. Alternatively, a unit dose of the drug may contain at least 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 µg of isRNA and /or coding RNA specified in the present description. More specifically, the amount of isRNA and/or coding RNA included in a single dose is typically at least 100 or 200 µg, preferably 200 to 1000 µg, more preferably 300 to 850 µg, even more preferably 300 to 700 mcg. When a medicinal product contains more than one type of RNA, the above values refer to each type of RNA.

A particularly preferred embodiment of the present invention is an isRNA as defined herein for use in the treatment of a neoplastic or cancerous disease, preferably a disease selected from the group consisting of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably the cutaneous T-cell lymphoma subtype mycotic fungoid, and vulvar squamous cell carcinoma (VSCC); where the disorder is preferably at an advanced stage and/or is resistant to standard therapy.

Preferably, the treatment comprises administering, preferably intratumorally, an isRNA as defined herein complexed with a cationic or polycationic compound. In a preferred embodiment, the isRNA contains a nucleotide sequence which is described by formula (I) (G _l X _m G _n ), formula (II) (C _l X _m C _n ), formula (III) (N _u G _l X _m G _n N _v ) _a or formula (IV) (N _u C _l X _m C _n N _v ) _a , preferably at least one nucleotide sequence shown in one of SEQ ID NOs: SEQ ID NOs: 433-437, 1014- 1016, preferably represented in one of SEQ ID NOs: 433, 434, or 1014-1016, 1055, or 1056, or a fragment or variant of any of these sequences, where the isRNA is present in a complex with a cationic or polycationic compound, preferably with a polymeric carrier, which is formed by a disulfide crosslinked cationic component which preferably contains a peptide of formula (V), (Va) and/or (Vb) and/or a compound of formula (VI), more preferably at least one of the disulfide crosslinked cationic peptides Cys- Arg ₁₂ , Cys-Arg ₁₂ -Cys or Trp-Arg ₁₂ -Cys. More preferably, the isRNA comprises a nucleotide sequence as set forth in SEQ ID NO: 433-437, 1014-016, or a fragment or variant of any of these sequences, preferably as shown in SEQ ID NO: 433, or a fragment or variant thereof which forms a complex with a cationic or a polycationic compound as defined herein, preferably with a disulfide cross-linked Cys-Arg ₁₂ -Cys peptide. Most preferably, the isRNA consists of the RNA sequence shown in SEQ ID NO: 433, or a fragment or variant thereof, and is present in a complex formed by a disulfide cross-linked Cys-Arg ₁₂ -Cys peptide.

The treatment preferably comprises intratumoral administration of the isRNA indicated above (or a pharmaceutical composition which contains said isRNA, respectively) to an individual who is suffering from a disease selected from the group consisting of

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably the cutaneous T-cell lymphoma subtype mycotic fungoid, and vulvar squamous cell carcinoma (VSCC); where the disease is preferably at an advanced stage and/or is resistant to standard therapy.

In a preferred embodiment of the invention, the individual being treated suffers from advanced and/or metastatic melanoma, unresectable and/or advanced SCC, unresectable and/or advanced adenocystic carcinoma (ACC), unresectable and/or advanced or cutaneous T-cell lymphoma, or advanced and /or platinum-resistant HNSCC. Preferably, the subject has tumor sites available for injection. More preferably, the individual is not undergoing other treatment options.

More preferably, the treatment comprises intratumoral administration of an isRNA as defined above (or a pharmaceutical composition which contains said isRNA, respectively) to an individual who is suffering from advanced melanoma, preferably advanced cutaneous melanoma, who is being treated with a checkpoint inhibitor, preferably as defined herein. Most preferably, the subject is treated with a PD-1 or PD-L1 inhibitor, preferably as described herein, more preferably an anti-PD-1 antagonist antibody or an anti-PD-L1 antagonist antibody.

The treatment preferably comprises intratumoral administration of the isRNA indicated above (or a pharmaceutical composition which contains said isRNA, respectively) to the individual, either once or multiple times. In this context, a single dose preferably contains 20 to 500 μg, more preferably 50 to 350 μg of the isRNA mentioned above. In preferred embodiments, the unit dose contains at least 25, 50, 75, 100, 125, 150, 175, 200, 225, or at least 250 μg of the isRNA listed above. Most preferably, a single dose contains about 25 µg, about 50 µg, about 100 µg, or about 150 µg of the isRNA mentioned above.

The treatment may include repeated intratumoral administration to the individual of a single dose of the isRNA indicated above (or a pharmaceutical composition that contains the indicated isRNA, respectively), while the individual is preferably administered at least 2, 3, 4, 5, 6, 7, 8, 9, 10 , 11, 12 or more single doses and the interval between two single doses is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days. The interval between two single doses may be constant or may vary during treatment. For example, treatment may include intratumoral administration of a single dose once a week for 4 weeks, followed by the introduction of additional single doses, preferably 3-8 additional single doses, which are administered every 2 weeks.

According to another embodiment of the invention, the treatment comprises intratumoral administration of an isRNA as defined above (or a pharmaceutical composition which contains said isRNA, respectively) to an individual suffering from a neoplastic or cancerous disease, preferably selected from the group consisting of breast cancer (positive for hormone receptors (hormone -positive) or hormone-negative forms); melanoma, preferably advanced and/or metastatic melanoma; squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC, or other forms of malignant skin cancer; adenocystic carcinoma (ACC), preferably advanced ACC; cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma; head and neck squamous cell carcinoma (HNSCC), preferably advanced by HNSCC; salivary gland cancer; cancers of the nasopharynx; lung cancer or lung metastases from other malignant diseases; mesothelioma; bladder cancer; thyroid cancer; cancer of the esophagus and stomach; liver cancer; malignant diseases with liver metastases; ovarian cancer; cervical cancer; kidney cancer; adrenal malignancies, soft tissue sarcomas, hematologic malignancies with injectable lesions such as cutaneous T-cell lymphoma; solitary or multiple myeloma; Hodgkin's disease; non-Hodgkin's lymphoma with injectable lesions; sarcoma, including its various subtypes; glioma degree I-IV; colorectal, rectal and anal cancer,

preferably selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced SCC, most preferably cutaneous squamous cell carcinoma (cSCC), or others forms of malignant skin cancer, adenocystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably advanced HNSCC, where the treatment also includes administration, preferably intratumoral administration of at least one coding RNA specified in the present description. In this embodiment of the invention, said treatment preferably comprises administering the combination of the present invention, as described herein.

In this embodiment, the isRNA is preferably the above isRNA and the at least one coding RNA is preferably an mRNA as defined herein that encodes at least one IL-12, PD-1 receptor-containing peptide or protein. decoy, preferably a soluble PD-1 receptor, CD40L, or an anti-CTLA4 antibody, or a fragment or variant of any of the proteins mentioned herein.

More preferably, the treatment comprises intratumoral administration of the isRNA as defined above (or a pharmaceutical composition that contains said isRNA, respectively) and further comprises administration, preferably intratumorally, of at least three, preferably at least four or five, coding RNAs as defined herein, preferably at least three, more preferably at least four or five mRNAs in which

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences, while the first, second, third, fourth and fifth coding RNAs are preferably in different formulations and are administered simultaneously.

Even more preferably, the treatment comprises intratumoral administration of the isRNA as defined above (or a pharmaceutical composition that contains said isRNA, respectively) and further comprises administration, preferably intratumorally, of at least three, preferably at least four or five, coding RNAs as defined herein. , preferably at least three, more preferably at least four or five mRNAs in which

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences, while the first, second, third, fourth and fifth coding RNAs are preferably in different formulations and are administered simultaneously.

Most preferably, the treatment comprises intratumoral administration of the isRNA as defined above (or a pharmaceutical composition that contains said isRNA, respectively) and further comprises administration, preferably intratumorally, of at least three, preferably at least four or five, coding RNAs as defined herein, preferably at least three, more preferably at least four or five mRNAs in which

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences, while the first, second, third, fourth and fifth coding RNAs are preferably in different formulations and are administered simultaneously.

Thus, the treatment preferably comprises the intratumoral administration of an isRNA which contains the nucleotide sequence shown in SEQ ID NO: 433-437, 1014-1016, or a fragment or variant of any of these sequences, preferably shown in SEQ ID NO: 433, or a fragment thereof. or a variant which is complexed with a cationic or polycationic compound as defined herein, preferably formed with a disulfide cross-linked Cys-Arg ₁₂ -Cys peptide, and

intratumoral, peritumoral, or locoregional administration of at least five coding RNAs, preferably mRNAs, where

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 297; 308; 319; 330; 341; 352; 363; 374; 385; 396 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 288; 299; 310; 321; 332; 343; 354; 365; 376; 387 and 398, or a fragment or variant of any of these sequences,

wherein the first, second, third, fourth and fifth coding RNA are preferably in different formulations and administered simultaneously.

In an alternative embodiment of the invention, the treatment comprises intratumoral administration of an isRNA that contains the nucleotide sequence shown in SEQ ID NO: 433-437, 1014-016, 10555, or 1056, or a fragment or variant of any of these sequences, preferably shown in SEQ ID NO: 433, or a fragment or variant thereof, which is complexed with a cationic or polycationic compound as defined herein, preferably formed with a disulfide cross-linked Cys-Arg ₁₂ -Cys peptide, and

intratumoral, peritumoral, or locoregional administration of at least five coding RNAs, preferably mRNAs, in which

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences,

wherein the first, second, third, fourth and fifth coding RNA are preferably in different formulations and administered simultaneously.

Most preferably, the treatment comprises intratumoral, peritumoral, or locoregional administration of an isRNA that contains the nucleotide sequence set forth in SEQ ID NO: 433-437, 1014-1016, 1055, or 1056, or a fragment or variant of any of these sequences, preferably as shown in SEQ ID NO. :433, or a fragment or variant thereof, which is complexed with a cationic or polycationic compound as defined herein, preferably formed with a disulfide cross-linked Cys-Arg ₁₂ -Cys peptide, and

intratumoral, peritumoral, or locoregional administration of at least five coding RNAs, preferably mRNAs, in which

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 297; 308; 319; 330; 341; 352; 363; 374; 385; 396 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 288; 299; 310; 321; 332; 343; 354; 365; 376; 387 and 398, or a fragment or variant of any of these sequences,

wherein the first, second, third, fourth and fifth coding RNA are preferably in different formulations and administered simultaneously.

In this isRNA embodiment, the isRNA dosing regimen and isRNA administration are preferably those described above for isRNA for use in the treatment of a tumor or cancer.

The dosing regimen and administration of the at least one coding RNA administered simultaneously with the above isRNA is preferably identical to the dosing regimen and administration described above for isRNA for use in the treatment of a tumor or cancer. Thus, treatment preferably comprises intratumoral administration of a single dose of at least one coding RNA as defined herein (or a pharmaceutical composition that contains said RNA, respectively) to an individual, either once or multiple times. In this context, a unit dose preferably contains 20 to 500 μg, more preferably 50 to 350 μg of at least one coding RNA as defined above. In preferred embodiments, the unit dose contains at least 25, 50, 75, 100, 125, 150, 175, 200, 225, or at least 250 μg of at least one coding RNA as defined above. Most preferably, a single dose contains about 25 µg, about 50 µg, about 100 µg, or about 150 µg of at least one coding RNA as defined herein. More preferably, the treatment comprises administering at least three of the coding RNAs listed above, wherein the unit dose contains the amounts of each of the coding RNAs listed above. Treatment preferably includes multiple administration of the single dose indicated above. Preferably, doses of at least one coding RNA are administered simultaneously with the isRNA mentioned above, preferably according to the administration scheme described in this context.

In a particularly preferred embodiment of the invention, the individual receiving the isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) may be a patient suffering from a cancer or tumor who is undergoing or has undergone standard treatment options. cancer. Preferably, the patient has achieved a partial response or stabilization of the disease after receiving standard treatment.

Conventional cancer treatments include chemotherapy, radiation therapy, chemoradiation, and surgery, depending on the particular type of cancer or tumor being/are being treated, these treatments being used alone or in combination.

In some embodiments of the invention, the individual receiving isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing the specified RNA(s), may be a patient with a tumor or cancer, preferably specified in the present description, more preferably a disease selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced SCC, most preferably cutaneous squamous cell carcinoma (cSCC ), or other forms of malignant skin cancer, adenocystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably advanced HNSCC, which has been subjected to or subjected to chemo therapy (eg, first-line or second-line chemotherapy), radiation therapy, chemoradiation (a combination of chemotherapy and radiation therapy), treatment with kinase inhibitors, antibodies, and/or checkpoint modulators (eg, CTLA4 inhibitors, PD1 pathway inhibitors), or a patient who who achieved a partial response or stabilization of the disease after receiving one or more of the treatment options listed above.

According to some embodiments of the invention, an individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing the specified RNA(s) may be an individual who suffers from a disease selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC, most preferably cutaneous squamous cell carcinoma (cSCC), or other forms of malignant skin cancer, adenoid cystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably advanced HNSCC, which has been or is being treated, preferably by intratumoral administration, with a compound, usually P applicable to any of these diseases specified in the present description.

More preferably, the individual receiving the isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) suffers from a disease selected from the group consisting of melanoma, preferably advanced and/or metastatic melanoma, most preferably advanced cutaneous melanoma (cMEL), skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced SCC, most preferably cutaneous squamous cell carcinoma (cSCC), or other forms of malignant skin cancer, adenoid cystic carcinoma (ACC), preferably advanced ACC, cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma, and head and neck squamous cell carcinoma (HNSCC), preferably advanced HNSCC, which has been or is being treated with a checkpoint modulator.

According to some embodiments of the invention, an individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing the specified RNA(s) may be a patient having a tumor or cancer disease selected from

melanoma, preferably advanced and/or metastatic melanoma, more preferably advanced cutaneous melanoma (cMEL);

skin squamous cell carcinoma (SCC), preferably unresectable and/or advanced skin SCC, more preferably cutaneous squamous cell carcinoma (cSCC), even more preferably unresectable and/or advanced cSCC;

head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, more preferably immunotherapy-resistant or platinum-resistant HNSCC, even more preferably immunotherapy-resistant triggered HNSCC, or platinum-resistant triggered HNSCC;

- adenoid cystic carcinoma (ACC), preferably advanced ACC;

- cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic fungoid subtype, more preferably cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, even more preferably advanced cutaneous T-cell lymphoma resistant to topical treatment or chemotherapy, or cutaneous T-cell lymphoma of the mycotic fungoid subtype resistant to topical treatment or chemotherapy, and

- vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC resistant to surgery or chemotherapy, most preferably advanced VSCC resistant to surgery or chemotherapy; or selected from cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and squamous vulvar cancer (VSCC); where the tumor or cancer is preferably at an advanced stage and/or is resistant to standard therapy.

More preferably, the individual receiving the isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) may be a patient suffering from a tumor or cancer described herein who has been or is undergoing chemotherapy. (eg, first-line or second-line chemotherapy), radiation therapy, chemoradiation (a combination of chemotherapy and radiation therapy), treatment with kinase inhibitors, antibodies, and/or checkpoint modulators (eg, CTLA4 inhibitors, PD1 pathway inhibitors), or a patient who a partial response or stabilization of the disease has been achieved after receiving one or more of the treatments listed above. More preferably, the subject is a patient suffering from a tumor or cancer as described herein and who has been or is being treated, preferably via intratumoral administration, with a compound commonly used for any of these diseases as described herein, more preferably a patient who is or has been treated, preferably by intratumoral administration, with a checkpoint modulator.

An individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) preferably suffers from melanoma, preferably advanced and/or metastatic melanoma, and has been or is being exposed, preferably by intratumoral administration, at least one of the following treatment options:

- monotherapy using a checkpoint modulator such as pembrolizumab, nivolumab or ipilimumab;

- combination therapy including a checkpoint modulator such as nivolumab and ipilimumab;

- combination therapy including dabrafenib and trametinib or vemurafenib and cobimetinib, or therapy using a single agent such as vemurafenib or dabrafenib;

- treatment with a high dose of IL-2;

- treatment with imatinib;

- treatment with cytotoxic agents using compounds such as dacarbazine, temozolomide, paclitaxel, albumin-bound paclitaxel, carboplatin/paclitaxel;

- biochemotherapy using compounds such as dacarbazine and/or temozolomide and/or carboplatin with/without vinblastine and/or nitrosourea and/or IL-2 and/or interferon alfa2b.

An individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) preferably suffers from head and neck squamous cell carcinoma (HNSCC), preferably triggered by HNSCC, and has been or is being exposed, preferably by intratumoral administration, at least one of the following treatment options:

- single agent treatment options such as cisplatin, carboplatin, paclitaxel, docetaxel, 5-FU, methotrexate, cetuximab, gemcitabine, capecitabine, vinorelbine, afatinib;

- treatment options using a combination of agents; such as carboplatin and infused 5-FU;

- 5-FU and hydroxyurea;

- cisplatin and paclitaxel;

- cisplatin and infused 5-FU;

- cisplatin and 5-FU;

- carboplatin and paclitaxel;

- cisplatin followed by treatment with cisplatin and 5-FU;

- docetaxel and cisplatin and 5-FU;

- paclitaxel and cisplatin, and 5-FU administered by infusion;

- docetaxel and cisplatin;

- cisplatin and epirubicin, paclitaxel;

- cisplatin or carboplatin and 5-FU, and cetuximab;

- cisplatin or carboplatin and docetaxel or paclitaxel;

- cisplatin and cetuximab;

- cisplatin and decetaxel, cetuximab;

- cisplatin and paclitaxel, and cetuximab;

- carboplatin and cetuximab;

- cisplatin and gemcitabine;

- gemcitabine and vinorelbine.

An individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) preferably suffers from squamous cell carcinoma (SCC) of the skin, preferably unresectable and/or advanced SCC, and has been or is being subjected to, preferably by intratumoral administration, at least one of the following treatment options, which use:

- 5-FU;

- cisplatin;

- cisplatin and 5-FU;

- interferon alpha;

- cis-retinoic acid;

- interferon alpha and cis-retinoic acid, and cisplatin;

- cetuximab;

- vismodegib;

- cisplatin and 5-FU, and cetuximab;

- imiquimod;

- photodynamic therapy (aminolevulinic acid, sodium porfimer);

- intensive cryotherapy;

- electrodessication;

- diclofenac;

- chemical peeling (trichloroacetic acid);

- cryotherapy and 5-FU, and imiquimod;

- retinoids (acitretin, isotretinoin);

- calcineurin inhibitors and / or mTOR inhibitors (rapamycin, temsirolimus, sirolimus, everolimus, ridaforolimus, deforolimus);

- cisplatin and/or carboplatin and/or 5-FU and/or paclitaxel and/or docetaxel.

An individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) preferably suffers from adenocystic carcinoma (ACC), preferably advanced by ACC, and has been or is being exposed, preferably by intratumoral administration, at least one of the following treatment options, including treatments used alone or in combination:

- radiation therapy;

- cisplatin;

- paclitaxel;

- mitoxantrone;

- doxo-/epirubicin;

- methotrexate;

- vinorelbine;

- remote radiation therapy.

An individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) preferably suffers from cutaneous T-cell lymphoma, preferably advanced cutaneous T-cell lymphoma or cutaneous T-cell lymphoma of the mycotic subtype. fungoid, and it has been or is being subjected, preferably by intratumoral administration, to at least one of the following treatment options, including treatments that are used alone or in combination:

- corticosteroids;

- carmustine;

- nitrogenous analogue of mustard gas (mechloethamine hydrochloride);

- bexarotene;

- Taxarotene gel;

- imiquimod;

- phototherapy;

- electronic therapy (TSEBT);

- alemtuzumab;

- retinoids;

- interferon;

- vorinostat;

- romidepsin;

- extracorporeal photopheresis (ECP);

- methotrexate;

- liposomal doxorubicin;

- gemcitabine;

- pentostatin;

- temozolomide;

- pralatrexate;

- allogeneic cell graft.

An individual receiving an isRNA, at least one coding RNA, a combination thereof, or a pharmaceutical composition or vaccine containing said RNA(s) preferably suffers from vulvar cancer, preferably vulvar squamous cell carcinoma (VSCC), more preferably advanced VSCC, even more preferably VSCC, resistant to surgery or chemotherapy, most preferably triggered VSCC resistant to surgery or chemotherapy, and has been or is being subjected, preferably via intratumoral administration, to at least one of the following treatment options, including treatments that are used alone or in combination:

- mitomycin-C2;

- cisplatin;

- carboplatin;

- vinorelbine;

- paclitaxel;

- a tyrosine kinase inhibitor (eg erlotinib);

- nivolumab;

- bleomycin sulfate (eg bleomycin, bleomycin sulfate, blenamax, tevableo, oncobleo, bleo, bloicin-S);

- 5-fluorouracil (5-FU);

- Gardasil 9 (vaccine (9-valent) against human papillomavirus);

- omiganan pentahydrochloride;

- alisertib;

- ISA-101 (13 synthetic long peptides (consisting of 25-35 amino acids) derived from oncogenic proteins E6 and E7 of the HPV 16 virus);

- PDS-0101;

- Vicorix (vaccine P16_37-63);

- TA-CIN (fusion protein vaccine containing capsid protein L2, E6 and E7 from HPV16); and

- a vaccine based on the 16 E6 peptide of the human papillomavirus.

The present invention and preferred embodiments of the invention are further described in the following paragraphs:

1. An immunostimulatory RNA (isRNA) for use in the treatment or prevention of a tumor or cancer, preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the tumor or cancer is preferably advanced and/or resistant to standard therapy.

2. isRNA for use according to claim 1, where isRNA is administered into the tumor, including peritumoral or locoregional administration.

3. isRNA for use according to claim 2, wherein the isRNA is administered by injection.

4. isRNA for use according to one of the preceding claims, where isRNA is a non-coding RNA.

5. isRNA intended for use according to one of the previous paragraphs, where isRNA contains

the nucleotide sequence shown in formula (I)

(G _l X _m G _n ),

wherein:

G is guanosine (guanine), uridine (uracil), or an analogue of guanosine (guanine) or uridine (uracil);

X is guanosine (guanine), (uridine) uracil, adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of the above nucleotides (nucleosides);

l denotes an integer from 1 to 40,

where,

when l=1, then G denotes guanosine (guanine) or its analogue,

when l>1, then at least 50% of the nucleotides (nuclesides) are guanosine (guanine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X denotes uridine (uracil) or its analogue,

when m>3, then at least 3 consecutive nucleotides are present, representing uridine (uracil) or an analogue of uridine (uracil);

n is an integer from 1 to 40,

where,

when n=1, then G denotes guanosine (guanine) or its analogue,

when n>1, then at least 50% of the nucleotides (nucleosides) are guanosine (guanine) or its analogue;

the nucleotide sequence shown in formula (II)

(C _l X _m C _n ),

wherein:

C is cytidine (cytosine), uridine (uracil), or an analog of cytidine (cytosine) or uridine (uracil);

X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of the above nucleotides (nucleosides);

l denotes an integer from 1 to 40,

where,

when l=1, then C denotes cytidine (cytosine) or its analogue,

when l>1, then at least 50% of the nucleotides are cytidine (cytosine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X denotes uridine (uracil) or its analogue,

when m>3, then at least 3 consecutive nucleotides are present, representing uridine (uracil) or an analogue of uridine (uracil);

n is an integer from 1 to 40,

where,

when n=1, then C denotes cytidine (cytosine) or its analogue, when n>1, then at least 50% of nucleotides (nucleosides)

are cytidine (cytosine) or its analogue;

the nucleotide sequence shown in formula (III)

(N _u G _l X _m G _n N _v ) _a ,

wherein:

G is guanosine (guanine), uridine (uracil) or an analogue of guanosine (guanine) or uridine (uracil), preferably guanosine (guanine) or an analogue thereof;

X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or analogs of said nucleotides (nucleosides), preferably uridine (uracil) or an analog thereof;

N denotes a nucleotide sequence consisting of about 4-50, preferably about 4-40, more preferably about 4-30 or 4-20 nucleic acids, with each N independently selected from guanosine (guanine), uridine ( uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of these nucleotides (nucleosides);

a is an integer from 1 to 20, preferably from 1 to 15, most preferably from 1 to 10;

l denotes an integer from 1 to 40, where,

when l=1, then G denotes guanosine (guanine) or its analogue,

when l>1, then at least 50% of these nucleotides (nucleosides) are guanosine (guanine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X is uridine (uracil) or an analogue thereof, and

when m>3, then at least 3 consecutive nucleotides are present, representing uridine (uracil) or an analogue of uridine (uracil);

n is an integer from 1 to 40,

where,

when n=1, then G denotes guanosine (guanine) or its analogue,

when n>1, then at least 50% of these nucleotides (nucleosides) are guanosine (guanine) or its analogue;

u, v can independently represent an integer from 0 to 50, preferably when u=0, then v≥1 or

when v=0, then u≥1;

wherein the nucleic acid molecule of formula (III) consists of at least 50 nucleotides, preferably at least 100 nucleotides, more preferably at least 150 nucleotides, even more preferably at least 200 nucleotides, and most preferably at least 250 nucleotides; and/or

the nucleotide sequence shown in formula (IV)

(N _u C _l X _m C _n N _v ) _a ,

wherein:

C is cytidine (cytosine), uridine (uracil) or an analog of cytidine (cytosine) or uridine (uracil), preferably cytidine (cytosine) or an analog thereof;

X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analog of the above nucleotides (nucleosides), preferably uridine (uracil) or an analog thereof;

N denotes a nucleotide sequence consisting of about 4-50, preferably about 4-40, more preferably about 4-30 or 4-20 nucleic acids, with N each independently selected from guanosine (guanine), uridine ( uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of these nucleotides (nucleosides);

a is an integer from 1 to 20, preferably from 1 to 15, most preferably from 1 to 10;

l denotes an integer from 1 to 40,

where,

when l=1, then C denotes cytidine (cytosine) or its analogue,

when l>1, then at least 50% of these nucleotides (nucleosides) are cytidine (cytosine) or its analogue;

m is an integer and is at least 3;

where,

when m=3, then X denotes uridine (uracil) or its analogue,

when m>3, then at least 3 consecutive uridine (uracil) or uridine analogs (uracil) are present;

n is an integer from 1 to 40,

where,

when n=1, then C denotes cytidine (cytosine) or its analogue,

when n>1, then at least 50% of these nucleotides (nucleosides) are cytidine (cytosine) or its analogue;

u, v can independently denote an integer from 0 to 50,

preferably, when u=0, then v≥1 or

when v=0, then u≥1;

wherein the nucleic acid molecule of formula (IV) consists of at least 50 nucleotides, preferably at least 100 nucleotides, more preferably at least 150 nucleotides, even more preferably at least 200 nucleotides, and most preferably at least 250 nucleotides.

6. isRNA for use according to one of the preceding paragraphs, where isRNA contains at least one nucleotide sequence presented in one of SEQ ID NO: 433-437, 1014-1016, preferably in one of SEQ ID NO: 433, 434 or 1014-1016, or a fragment or variant of any of the indicated nucleotide sequences.

7. isRNA for use according to one of the preceding claims, wherein the isRNA forms a complex with a cationic or polycationic compound, preferably with a cationic or polycationic polymer, a cationic or polycationic peptide or protein, for example protamine, a cationic or polycationic polysaccharide and/or a cationic or polycationic lipid.

8. isRNA for use according to claim 7, wherein the cationic or polycationic compound is a polymeric carrier.

9. isRNA for use according to claim 8, wherein the polymeric carrier is formed by a disulfide crosslinked cationic component, preferably a disulfide crosslinked cationic peptide, where the disulfide crosslinked cationic peptide preferably comprises

peptide having the formula V

in which l+m+n+o+x are 8-15 and l, m, n or o each independently of each other can be any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provided that the total content of Arg, Lys, His and Orn is at least 50% of the total amino acid content of the oligopeptide; and Xaa can be any amino acid selected from native (ie, naturally occurring) or non-naturally occurring amino acids with the exception of Arg, Lys, His, or Orn; and x may be any number selected from 0, 1, 2, 3, or 4, provided that the total Xaa content does not exceed 50% of the total amino acid content of the oligopeptide;

a peptide having the formula Va

in which (Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o and x have the meanings indicated for formula V, Xaa' denotes any amino acid selected from native (i.e. occurring naturally) or non-naturally occurring amino acids other than Arg, Lys, His, Orn, or Cys, and y is any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-90, provided that the total content of Arg (arginine), Lys (lysine), His (histidine) and Orn (ornithine) is at least 10% of all amino acids of the oligopeptide;

peptide having the formula Vb

falling under the empirical formula {(Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x } specified for formula (V) and forms the core of the amino acid sequence corresponding to the (semi-empirical) formula ( V), and in which Cys ₁ and Cys ₂ are cysteine residues located proximal or terminal relative to (Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x ; and/or

compound having formula VI

wherein

P ¹ and P ³ are different or identical to each other and represent a linear or branched hydrophilic polymer chain, each P ¹ and P ³ carries at least one -SH-group capable of forming a disulfide bond when condensed with the P ² component, or alternatively to this with (AA) (amino acid component), (AA) _x or [(AA) _x ] _z if these components are used as a linker between P ¹ and P ² or P ³ and P ² ) and / or with other components ( e.g. (AA), (AA) _x , [(AA) _x ] _z or L), a linear or branched hydrophilic polymer chain independently selected from polyethylene glycol (PEG), poly-N-(2-hydroxypropyl)methacrylamide , poly-2-(methacryloyloxy)ethylphosphorylcholines, poly(hydroxyalkyl-L-asparagine), poly(2-(methacryloyloxy)ethylphosphorylcholine), hydroxyethyl starch or poly(hydroxyalkyd-L-glutamine), where the hydrophilic polymer chain has a molecular weight of from about 1 up to about 100 kDa, preferably from about 2 to about 25 kDa and or more preferably from about 2 to about 10 kDa, for example, from about 5 to about 25 kDa or from 5 to about 10 kDa;

P ² is a cationic or polycationic peptide or protein, for example as defined above for a polymeric carrier formed by disulfide crosslinked cationic moieties, and preferably about 3 to about 100 amino acids in length, more preferably about 3 to about 50 amino acids in length, still more preferably about 3 to about 25 amino acids in length, e.g., about 3 to 10, 5 to 15, 10 to 20, or 15 to 25 amino acids in length, more preferably about 5 to about 20 amino acids in length, and more more preferably having a length of from about 10 to about 20 amino acids; or

denotes a cationic or polycationic polymer, for example, as defined above for a polymer carrier formed by cross-linked disulfides of cationic components, typically having a molecular weight of from about 0.5 to about 30 kDa, including a molecular weight of from about 1 to about 20 kDa, even more preferably from about 1.5 to about 10 kDa, or having a molecular weight from about 0.5 to about 100 kDa, including a molecular weight from about 10 to about 50 kDa, even more preferably from about 10 to about 30 kDa;

each P ² carries at least two —SH-groups capable of forming a disulfide bond when condensed with other components of P ² or with component (s) P ¹ and / or P ³ , or alternatively with other components (for example, (AA) , (AA) _x or [(AA) _x ] _z );

-SS- denotes a (reversible) disulfide bond (brackets omitted for readability), in which S is preferably sulfur or a bearing -SH group which forms a (reversible) disulfide bond. The (reversible) disulfide bond is preferably obtained by condensation of the -SH groups of either the components P ¹ and P ² or P ² and P ³ or P ² and P ³ , or optionally other components specified in the present description (for example, L, ( AA), (AA) _x , [(AA) _x ] _z etc.); -SH-group may be part of the structure of these components or may be added by modification, as indicated below;

L is an optional ligand which may or may not be present and can be selected independently from RGD, transferrin, folate, signal peptide or signal sequence, localization signal or sequence, nuclear localization signal or sequence (NLS), antibody penetrating into peptide cell (eg, TAT or KALA), receptor ligand (eg, cytokines, hormones, growth factors, etc.), small molecules (eg, carbohydrates such as mannose or galactose, or synthetic ligands), small molecule agonists, inhibitors, or antagonists receptors (eg, analogues of RGD-peptidomimetics) or any other proteins mentioned in the present description, etc.;

n is an integer, typically selected from the range of about 1 to 50, preferably from the range of about 1, 2, or 3 to 30, more preferably from the range of about 1, 2, 3, 4, or 5 to 25, or the range of about 1, 2, 3, 4, or 5 to 20, or a range of about 1, 2, 3, 4, or 5 to 15, or a range of about 1, 2, 3, 4, or 5 to 10, including, for example, the range about 4 to 9, 4 to 10, 3 to 20, 4 to 20, 5 to 20, or 10 to 20, or a range of about 3 to 15, 4 to 15, 5 to 15, or 10 to 15, or a range of about 6 to 11 or 7 to 10. Most preferably, n is in the range of about 1, 2, 3, 4, or 5 to 10, more preferably in the range of about 1, 2, 3, or 4 to 9, in the range from about 1, 2, 3, or 4 to 8, or in the range from about 1, 2, or 3 to 7.

10. isRNA for use according to claim 8 or claim 9, wherein the polymeric carrier contains at least one of the disulfide cross-linked cationic peptides Cys-Arg ₁₂ or Cys-Arg ₁₂ -Cys.

11. isRNA intended for use according to one of paragraphs. 7-10, wherein the N/P ratio of isRNA and cationic or polycationic compound, preferably a cationic or polycationic peptide or protein, is in the range of about 0.1-10, including a range of about 0.3-4, about 0 .5-2, about 0.7-2 and about 0.7-1.5.

12. isRNA for use according to one of the preceding claims, wherein the isRNA is present in a complex with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.

13. isRNA for use according to one of the preceding claims, wherein the treatment comprises the administration of at least one additional pharmaceutically active ingredient.

14. isRNA for use according to claim 13, wherein at least one additional pharmaceutically active ingredient is a compound that is used to treat a neoplastic or cancerous disease, preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous carcinomas (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC) where the tumor or cancer is preferably is advanced and/or resistant to standard therapy.

15. isRNA for use according to claim 13 or claim 14, wherein at least one additional pharmaceutically active ingredient is a checkpoint modulator or a fragment or variant thereof.

16. isRNA for use according to claim 15, wherein the checkpoint modulator is selected from the group consisting of PD-1 inhibitor, PD-L1 inhibitor, CTLA-4 inhibitor, LAG3 inhibitor, TIM3 inhibitor, TIGIT inhibitor, OX40 stimulator, stimulator 4-1BB, a CD40L stimulator, a CD28 stimulator, and a GITR stimulator, or a fragment or variant of one of these checkpoint modulators.

17. isRNA for use according to claim 16, wherein the checkpoint modulator is a PD-1 inhibitor or a PD-L1 inhibitor, wherein the PD-1 inhibitor is preferably an anti-PD-1 antagonist antibody and the PD-L1 inhibitor is an antagonist an anti-PD-L1 antibody, or a fragment or variant of said antibody.

18. isRNA for use according to claim 16, wherein the checkpoint modulator is a CTLA-4 inhibitor, preferably an anti-CTLA4 antagonist antibody or fragment or variant thereof.

19. isRNA for use according to claim 13 or claim 14, wherein at least one additional pharmaceutically active ingredient is an interleukin, preferably IL-12, or a fragment or variant thereof.

20. isRNA intended for use according to one of paragraphs. 1-19, where the treatment includes the introduction of at least one coding RNA, preferably at least one mRNA.

21. isRNA for use according to claim 20, where at least one coding RNA contains at least one coding region that encodes at least one peptide or protein, which is at least one peptide or protein selected from the group , which consists of

- IL-12,

- CD40L,

- PD-1 decoy receptor, and

- antagonistic antibody against CTLA4

or a fragment or variant of any of these compounds.

22. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, or an IL analog -12 or its fragment or variant.

23. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a CD40L-containing peptide or protein, or fragment or variant thereof.

24. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof .

25. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant.

26. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12, or a fragment or variant thereof.

27. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof.

28. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof.

28a. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing at least one tumor antigen or fragment or variant thereof.

29. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant thereof.

30. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant thereof.

31. isRNA for use according to claim 20 or claim 21, wherein at least one coding RNA contains at least one coding region that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof , and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant thereof.

32. isRNA intended for use according to claim 20 or claim 21, where at least one coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12 or a fragment or variant thereof,

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant.

33. isRNA intended for use according to claim 20 or claim 21, where at least one coding RNA contains at least one coding region that encodes a peptide or protein containing IL-12 or a fragment or variant thereof,

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing CD40L or a fragment or variant,

the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant thereof, and

optionally, the same or another coding RNA contains at least one coding region that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof.

34. isRNA intended for use according to one of paragraphs. 1-33, wherein the subject is not or has not been treated with a PD-1 or PD-L1 antagonist, and wherein the use comprises administering at least one peptide or protein comprising a PD-1 decoy receptor, or fragment or variant thereof, or introducing a nucleic acid, preferably an coding RNA, more preferably an mRNA containing a nucleotide sequence that encodes at least one peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof.

35. isRNA intended for use according to one of paragraphs. 1-34, wherein the subject is or has been treated with a PD-1 or PD-L1 antagonist, and wherein the use does not include administering at least one peptide or protein containing a PD-1 decoy receptor, or fragment or variant thereof, or administering nucleic acid, preferably encoding RNA, more preferably mRNA, containing a nucleotide sequence that encodes at least one peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof.

36. isRNA for use according to claim 33, wherein the coding sequence that codes for the peptide or protein is located on a separate coding RNA, preferably on a separate mRNA.

37. isRNA for use according to claim 33, wherein at least two of the coding sequences that encode the peptide or protein are located on the same coding RNA, which is preferably a bi- or polycistronic RNA.

38. isRNA intended for use according to one of paragraphs. 20-37, where at least one coding RNA is introduced into the tumor.

39. isRNA intended for use according to one of paragraphs. 20-38, wherein at least one coding RNA is administered intradermally, intramuscularly, or subcutaneously.

40. isRNA for use according to claim 36, wherein different coding RNAs are included in one formulation and injected into the tumor.

41. isRNA intended for use according to one of paragraphs. 20-40, where isRNA is included in the formulation in combination with at least one coding RNA.

42. isRNA for use according to claim 37, wherein the combined formulation is administered into the tumor.

43. isRNA intended for use according to one of paragraphs. 20-42, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, preferably at least one of IL-12A or IL-12B, or a fragment or variant of any of the indicated proteins.

44. isRNA for use according to claim 43, wherein the encoded peptide or protein contains an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-8, or a fragment or variant of any of these sequences.

45. isRNA for use according to claim 43 or claim 44, wherein at least one coding sequence contains a nucleotide sequence selected from the group consisting of SEQ ID NOs: 440-445, or a fragment or variant of any of these sequences .

46. isRNA intended for use according to one of paragraphs. 43-45, where the encoded peptide or protein contains IL-12A and IL-12B, or a fragment or variant of each of these proteins.

47. isRNA for use according to 46, wherein the encoded peptide or protein comprises the amino acid sequence shown in SEQ ID NO: 10, or a fragment or variant thereof.

48. isRNA intended for use according to one of paragraphs. 43-47, where at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 447, or a fragment or variant thereof.

49. isRNA intended for use according to one of paragraphs. 20-48, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, where the encoded peptide or protein preferably contains the amino acid sequence shown in SEQ ID NO: 11 , or a fragment or variant of it.

50. isRNA for use according to claim 49, wherein at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 448, or a fragment or variant thereof.

51. isRNA intended for use according to one of paragraphs. 20-50, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor or fragment or variant, preferably the extracellular part of the PD-1 receptor or fragment thereof or option.

52. isRNA for use according to claim 51, wherein the decoy PD-1 receptor is a peptide or protein containing soluble PD-1, or a fragment or variant thereof.

53. isRNA for use according to claim 51 or claim 52, wherein the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 2 or 1042, or a fragment or variant thereof.

54. isRNA intended for use according to one of paragraphs. 51-53, where at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 439, or a fragment or variant.

55. isRNA intended for use according to one of paragraphs. 20-54, wherein at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody, or fragment or variant thereof.

56. isRNA for use according to claim 55, wherein the encoded peptide or protein comprises the amino acid sequence shown in SEQ ID NOs: 645 and/or 677, or a fragment or variant of any of said amino acid sequences.

57. isRNA for use according to claim 55 or claim 56, wherein at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 646 and/or 678, or a fragment or variant of any of said nucleotide sequences.

58. isRNA intended for use according to p.p. 20-57, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing at least one tumor antigen or tumor antigen fragment or variant.

59. isRNA for use according to 58, wherein the tumor antigen is preferably selected from the following group: 1 A01_HLA-A/m; 1A02; 5T4; ACRBP; AFP; ACAR4; alpha-actinin-4/m; alpha-methylacyl-coenzyme_A_-racemase; ANDR; ART-4; ARTC1/m; AURKB; B2MG; B3GN5; B4GN1; B7H4; BAGE-1; BASI; BCL-2; bcr/ab1; beta-catenin/m; BING-4; BIRC7; BRCA1/m; BY55; calreticulin; CAMEL; CASP-8/m; CASPA; cathepsin_B; cathepsin_L; CD1A; CD1B; CD1C; CD1D; CD1E; CD20; CD22; CD276; CD33; CD3E; CD3Z; ST_44_isoform_1; ST_44_isoform_6; CD4; CD52; CD55; CD56; CD80; CD86; CD8A; CDC27/m; CDE30; CDK4/m; CDKN2A/m; CEA; CEAM6; CH3L2; CLCA2; CML28; CML66; SOA-1/m; coactosin-like_protein; collagen_XXIII; COX-2; SR1B1; CSAG2; ST45A1; ST55; CT-_9/BRD6; CTAG2_isoform_LAGE-1A; CTAG2_isoform_LAGE-1B; CTCFL; cten; cyclin_B1; cyclin_D1; sur-B; DAM-10; DEP1A; E7; EF1A2; EFTUD2/m; EGFR; EGLN3; ELF2/m; EMMPRIN; Epcam; EphA2; EphA3; ErbB3; ERBB4; erg; ETV6; EWS; EZH2; FABP7; FCGR3A_version_1; FCGR3A_version_2; FGF5; FGFR2; fibronectin; FOS; FOXP3; FUT1; G250; GAGE-1; GAGE-2; GAGE-3; GAGE-4; GAGE-5; GAGE-6; GAGE7b; GAGE-8_(GAGE-2D); GASR; GnT-V; GPC3; GPNMB/m; GRM3; HAGE; hepsin; Her2/neu; HLA-A2/m; homeobox_NKX3.1; HOM-TES-85; HPG1; HS71A; HS71B; HST-2; hTERT; iCE; IF2B3; IL10; IL-13Ra2; IL2-RA; IL2-RB; IL2-RG; IL-5; IMP3; ITA5; ITB1; ITB6; kallikrein-2; kallikrein-3; kallikrein-4; KI20A; KIAA0205; KIF2C; KK-LC-1; LDLR; LGMN; LIRB2; LY6K; MAGA5; MAGA8; MAGAB; MAGE-A10; MAGE-A12; MAGE-A1; MAGE-A2; MAGE-A3; MAGE-A4; MAGE-A6; MAGE-A9; MAGE-B10; MAGE-B16; MAGE-B17; MAGE-B1; MAGE-B2; MAGE-B3; MAGE-B4; MAGE-B5; MAGE-B6; MAGE-C1; MAGE-C2; MAGE-C3; MAGE-D1; MAGE-D2; MAGE-D4; MAGE-E1; MAGE-E1 (MAGE 1); MAGE-E2; MAGE-F1; MAGE-H1; MAGEL2; mammaglobin _A; MART-1/melan-A; MART-2; MC1_R; M-CSF; mesothelin; MITF; MMP1_1; MMP7; MUC-1; MUM-1/m; MUM-2/m; MYCN; MYO1A; MYO1B; MYO1C; MYO1D; MYO1E; MYO1F; MYO1G; MYO1H; NA17; NA88-A; Neo-PAP; NFYC/m; NGEP; NPM; NRCAM; NSE; NUF2; NY-ESO-1; OA1; OGT; OS-9; osteocalcin; osteopontin; p53; PAGE-4; PAI-1; PAI-2; PAP; PATE; PAX3; PAX5; PD1L1; PDCD1; PDEF; PECA1; PGCB; PGFRB; Pim-1_-kinase; Pin-1; PLAC1; PMEL; PML; POTEF; POTE; PRAME; PRDX5/m; PRM2; protein; proteinase-3; PSA; PSB9; PSCA; PSGR; PSM; PTPRC; RAB8A; RAGE-1; RARA; RASH; RASK; RASN; RGS5; RHAMM/CD168; RHOC; RSSA; RU1; RU2; RUNX1; S-100; SAGE; SART-_1; SART-2; SART-3; SEPR; serpinB5; SIA7F; SIA8A; SIAT9; SIRT2/m; SOX10; SP17; SPNXA; SPXN3; SSX-1; SSX-2; SSX3; SSX-4; ST1A1; STAG2; STAMP-1; STEAP-1; survivin-2 B; survivin; SYCP1; SYT-SSX-1; SYT-SSX-2; TARP; TCRg; TF2AA; TGFB1; TGFR2; TGM-4; TIE2; TKTL1; TPI/m; TRGV11; TRGV9; TRPC1; TRP-p8; TSG10; TSPY1; TVC_(TRGV3); TX101; tyrosinase; TYRP1; TYRP2; UPA; VEGFR1; WT1 and XAGE1.

60. isRNA intended for use according to claim 58 or claim 59, where the encoded peptide or protein contains an amino acid sequence selected from the group consisting of SEQ ID NO: 1-504; 4558-4560, which are presented in PCT/EP 2017/059525, or a fragment or variant of any of these sequences.

61. isRNA intended for use according to one of paragraphs. 58-60, where at least one coding sequence of at least one coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 505-4033; 4561-4591, which are presented in PCT/EP 2017/059525, or a fragment or variant of any of these sequences.

62. isRNA intended for use according to one of paragraphs. 58-61, where at least one coding RNA is not injected into the tumor.

63. isRNA intended for use according to one of paragraphs. 58-62, wherein at least one coding RNA is administered intradermally, intramuscularly, or subcutaneously.

64. isRNA intended for use according to one of paragraphs. 20-63, where at least one coding RNA contains at least one coding sequence containing a nucleotide sequence that is modified compared to the nucleotide sequence of the coding sequence corresponding to the wild-type RNA, and where the amino acid sequence encoded by said coding sequence is preferably is not modified from the amino acid sequence encoded by the corresponding wild-type RNA coding sequence.

65. isRNA intended for use according to claim 64, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 25-30; 36-41; 47-52; 58-63; 69-74; 80-85; 91-96; 102-107; 113-118; 124-129; 135-140; 601-606; 612-617; 623-628; 716-725; 727; 1018-1021 and 1059-1062, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 32; 43; 54; 65; 76; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632-644; 726 and 1058, or a fragment or variant of any of these sequences;

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 44; 55; 66; 77; 88; 99; 110; 121; 132; 143; 609; 620; 631; 728-738 and 1025-1028, or a fragment or variant of any of these sequences;

c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 646-660; 662-676; 678-692; 694-705; 707-715 or 1029-1041, or a fragment or variant of any of these sequences; and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 23; 34; 45; 56; 67; 78; 89; 100; 111; 122; 133; 599; 610; 621; 1022-1024, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 24; 35; 46; 57; 68; 79; 90; 101; 112; 123; 134; 600; 611; 622 and 1043-1054, or a fragment or variant of any of these sequences.

66. isRNA intended for use according to one of paragraphs. 20-65, where at least one coding RNA contains at least one coding sequence having a modified, preferably increased, content of G / C compared to the content of G / C in the coding sequence corresponding to the wild-type RNA, and where the amino acid sequence, encoded by said coding sequence is preferably not modified from the amino acid sequence encoded by the coding sequence corresponding to the wild-type RNA.

67. isRNA for use according to claim 66, where at least one coding sequence contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 25-30; 80-85; 91-96; 102-107; 113-118; 601-606; 124-129; 135-140; 612-617; 623-628; 716-725 and 727 and 1018-1021 and 1059-1062, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 32; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632; 636-644 and 726, and 1058, or a fragment or variant of any of these sequences;

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 88; 99; 110; 121; 132; 143; 609; 620; 631, 728-738 and 1025-1028, or a fragment or variant of any of these sequences; and/or

c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 646; 650-658; 662; 666-674; SEQ ID NO: 678; 682-690; 694; 698-705; 707; 710, 713 and 1029-1041, or a fragment or variant of any of these sequences; and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 23; 78; 89; 100; 111; 122; 133; 599; 610; 621 and 1022-1024, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 24; 79; 90; 101; 112; 123; 134; 600; 611; 622 and 1043-1054, or a fragment or variant of any of these sequences.

68. isRNA intended for use according to one of paragraphs. 20-67, where at least one coding RNA contains a 5'-cap structure.

69. isRNA intended for use according to one of paragraphs. 20-68, wherein at least one coding RNA contains a 5'UTR element and/or a 3'UTR element.

70. isRNA intended for use according to one of paragraphs. 20-69, wherein at least one coding RNA contains a poly(A) sequence and/or a poly(C) sequence.

71. isRNA intended for use according to one of paragraphs. 20-70, wherein at least one coding RNA contains a stem-loop histone structure sequence.

72. isRNA intended for use according to one of paragraphs. 20-71, where at least one coding RNA contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 146-151; 451-456; 157-162; 168-173; 179-184; 190-195; 201-206; 212-217; 223-228; 234-239; 245-250; 256-261 and 267-272, or a fragment or variant of any of the sequences, preferably selected from the group which consists of SEQ ID NO: 153; 458; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263, 274; 992 and 598, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 459; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264, 275 and 596, or a fragment or variant of any of the sequences

c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 594; 595; 860-925, or a fragment or variant of any of the indicated sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 144; 449; 155; 166; 177; 188; 199; 210; 221; 232; 243; 254 and 265, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 145; 450; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences.

73. isRNA intended for use according to one of paragraphs. 20-72, where the treatment comprises the administration, preferably intratumoral administration, of at least three coding RNAs, where

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992; 458; 598; 32; 43; 54; 65; 76; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632-644; 726 and 1058, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 44; 55; 66; 77; 88; 99; 110; 121; 132; 143; 609; 620; 631; 728-738; 1025-1028; 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275; 459 and 596, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 920-922; 923-925; 646-660; 662-676; 678-692; 694-705; 707-715 or 1029-1041, or a fragment or variant of any of the specified sequences, and

optionally, the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266; 450; 597; 24; 35; 46; 57; 68; 79; 90; 101; 112; 123; 134; 600; 611; 622 and 1043-1054, or a fragment or variant of any of these sequences.

74. isRNA intended for use according to one of paragraphs. 20-73, where the treatment comprises the administration, preferably intratumoral administration, of at least four coding RNAs, where

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992; 458 and 598, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275; 459 and 596, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NOs: 594 and 860-874, or a fragment or variant of any of these sequences,

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NOs: 595 and 890-904, or a fragment or variant of any of these sequences, and

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266; 450 and 597, or a fragment or variant of any of these sequences.

75. isRNA intended for use according to one of paragraphs. 20-74, where at least one coding RNA contains

a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 278-283; 289-294; 300-305; 311-316; 322-327; 333-338; 344-349; 355-360; 366-371; 377-382; 388-393; 399-404 and 462-467, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences, and/or

c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-955; or a fragment or variant of any of the specified nucleotide sequences and a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-985, or a fragment or variant of any of the specified nucleotide sequences; or a nucleotide sequence selected from the group consisting of SEQ ID NO: 986-991, or a fragment or variant of any of the specified nucleotide sequences, and/or

d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 276; 287; 298; 309; 320; 331; 342; 353; 364; 375; 386; 460 and 397, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 461; 387 and 398, or a fragment or variant of any of these sequences.

76. isRNA intended for use according to one of paragraphs. 20-65, where the treatment comprises the administration, preferably intratumoral administration, of at least four coding RNAs, where

the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of these sequences,

the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment or variant of any of these sequences,

the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of these sequences, and/or

the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and/or

optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences.

77. isRNA intended for use according to one of paragraphs. 20-76, where isRNA is administered as RNA in complex with one or more cationic or polycationic compounds, and at least one coding RNA, preferably mRNA, is administered as free RNA or administered as RNA in complex with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.

78. isRNA intended for use according to one of paragraphs. 1-77, where the treatment includes chemotherapy, radiation therapy and/or surgery.

79. Pharmaceutical composition containing immunostimulatory RNA (isRNA) and a pharmaceutically acceptable carrier and / or excipient, intended for use in the treatment of a tumor or cancer selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the tumor or cancer is preferably at an advanced stage and/or is resistant to standard therapy, where the pharmaceutical composition is injected into the tumor.

80. A pharmaceutical composition intended for use according to claim 79, in which is isRNA specified in p. 1-12.

81. A pharmaceutical composition intended for use according to claim 79 or 80, where the treatment includes the introduction of at least one additional pharmaceutically active ingredient, preferably specified in one of the paragraphs. 13-68.

82. A set or set of components containing immunostimulatory RNA (isRNA), preferably isRNA, specified in p. 1-12, or a pharmaceutical composition specified in one of paragraphs. 79-81, and optionally technical instructions with administration and dosage information,

for use in the treatment of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma , preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the neoplastic or cancerous disease is preferably advanced and/or resistant to standard therapy,

where the pharmaceutical composition is injected into the tumor.

83. The use of isRNA, preferably isRNA according to one of paragraphs. 1-12, a pharmaceutical composition according to one of paragraphs. 79-81 or the kit or kit of components of claim 82, for use in the preparation of a medicament for the treatment of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), squamous cell carcinoma head and neck (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the tumor or cancer is preferably at an advanced stage and/ or is resistant to standard therapy, for intratumoral, peritumoral or locoregional administration, preferably for intratumoral administration.

84. A method of treating or preventing a disorder selected from the group consisting of a tumor or cancer selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the disorder is preferably advanced and/or resistant to standard therapy, where the method comprises administering , preferably inside the tumor, the individual who needs it, in an effective amount of isRNA, preferably isRNA according to one of paragraphs. 1-12, a pharmaceutical composition according to one of paragraphs. 79-81 or the set or set of components of claim 82.

85. A combination of isRNA and at least one coding RNA, in which at least one coding RNA encodes at least one peptide or protein containing IL-12, CD40L, PD-1 decoy receptor, anti-CTLA4 antibody and/or a tumor antigen; or a fragment or variant of each of said proteins.

86. The combination according to claim 85, where the isRNA is an isRNA according to one of the paragraphs. 4-12.

87. The combination according to p. 85 or p. 86, in which at least one coding RNA is a coding RNA according to one of p. 13-78.

88. Combination according to one of paragraphs. 85-87, in which isRNA and at least one coding RNA are in one or different formulations.

89. Combination according to one of paragraphs. 85-88, in which isRNA and at least one coding RNA are administered simultaneously.

90. Combination according to one of paragraphs. 85-89, in which the isRNA and at least one coding RNA are introduced at the same site.

91. Combination according to one of paragraphs. 85-90 for use in the treatment or prevention of a disease selected from the group consisting of neoplastic and cancerous disease, infectious diseases, allergies, and autoimmune diseases.

92. The combination of claim 91, wherein the combination is for use in the treatment or prevention of a tumor or cancer.

93. The combination of claim 92, wherein the combination is for use in the treatment or prevention of a tumor or cancer selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC) , adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the cancer or neoplastic disease is preferably advanced and/or resistant to standard therapy .

94. The combination of claim 93, wherein the combination is administered intratumorally.

95. The combination of claim 93 or claim 94, wherein the treatment or prophylaxis comprises the administration of at least one additional pharmaceutically active ingredient.

96. The combination according to p. 95, where at least one additional pharmaceutically active ingredient is a compound according to p. 14-18.

97. The combination of claim 96, wherein at least one additional pharmaceutically active ingredient is a PD-1 inhibitor or PD-L1 inhibitor, preferably an antagonist antibody directed against PD-1 or PD-L1, or a fragment or variant thereof.

98. The combination of claim 96 wherein at least one additional pharmaceutically active ingredient is an anti-CTLA4 antibody or fragment or variant thereof.

99. Coding RNA that encodes a protein containing at least one peptide or protein containing IL-12, CD40L, a PD-1 decoy receptor, an anti-CTLA4 antibody, and/or a tumor antigen, or a fragment or variant of any of these proteins .

100. The coding RNA according to claim 99, which is the coding RNA according to one of the paragraphs. 13-78.

101. Coding RNA according to claim 99 or 100, intended for use in the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), squamous cell carcinoma of the head and neck (HNSCC ), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the cancer or neoplastic disease is preferably advanced and/or resistant to standard therapy.

102. A coding RNA for use according to claim 101, wherein the coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, or a fragment or variant thereof.

103. Coding RNA intended for use according to one of paragraphs. 99-102, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

at least one coding sequence that encodes a peptide or protein containing IL-12, or a fragment or variant thereof.

104. Coding RNA intended for use according to one of paragraphs. 99-103, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

at least one coding sequence that encodes a PD-1 decoy receptor-containing peptide or protein, or a fragment or variant thereof.

105. Coding RNA intended for use according to one of paragraphs. 99-104, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and

at least one coding sequence that encodes a PD-1 decoy receptor-containing peptide or protein, or a fragment or variant thereof.

106. Coding RNA intended for use according to one of paragraphs. 99-105, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and

at least one coding sequence that encodes at least one tumor antigen or fragment or variant thereof.

107. Coding RNA intended for use according to one of paragraphs. 99-106, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody, or fragment or variant thereof.

108. Coding RNA intended for use according to one of paragraphs. 99-107, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof, and

at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody, or fragment or variant thereof.

109. Coding RNA intended for use according to one of paragraphs. 99-108, where at least one coding RNA contains

at least one coding sequence that encodes a PD-1 decoy receptor-containing peptide or protein, or a fragment or variant thereof, and

at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody, or fragment or variant thereof.

110. Coding RNA intended for use according to one of paragraphs. 99-109, where at least one coding RNA contains

at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof,

at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof, and

at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody, or fragment or variant thereof.

111. Coding RNA intended for use according to one of paragraphs. 99-110, where the treatment or prevention includes the introduction of a second coding RNA and/or a third coding RNA, where

the coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12 or a fragment or variant thereof,

the second coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a fragment or variant thereof,

the third coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antibody or fragment or variant thereof.

112. A coding RNA for use according to claim 111, wherein the treatment or prophylaxis further comprises administering a fourth coding RNA, wherein the fourth coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor or a fragment or variant of it.

113. Coding RNA intended for use according to claim 111 or claim 112, where the second RNA, third RNA and/or fourth RNA is a coding RNA according to one of the paragraphs. 13-78.

114. Coding RNA intended for use according to one of paragraphs. 101-113, where the treatment or prophylaxis comprises the administration of an isRNA.

115. Coding RNA for use according to claim 114, where isRNA is isRNA according to one of the paragraphs. 4-12.

116. Coding RNA intended for use according to one of paragraphs. 101-115, where at least one coding RNA is introduced into the tumor.

117. Coding RNA intended for use according to one of paragraphs. 101-116, wherein the treatment or prophylaxis comprises administering at least one additional pharmaceutically active ingredient, preferably a compound that is commonly used to treat a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC ), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the cancerous or neoplastic disease is preferably located on advanced stage and/or resistant to standard therapy.

118. Coding RNA for use according to claim 117, where at least one additional pharmaceutically active ingredient is a compound according to one of paragraphs. 14-33.

119. A coding RNA for use according to claim 117 or claim 118, wherein at least one additional pharmaceutically active ingredient is a PD-1 inhibitor or a PD-L1 inhibitor, preferably an antagonist antibody directed against PD-1 or PD- L1, or a fragment or variant thereof.

120. Coding RNA intended for use according to one of paragraphs. 117-119, wherein at least one additional pharmaceutically active ingredient is an anti-CTLA4 antibody or fragment or variant thereof.

Brief description of the drawings

The following examples and drawings are given only for the purpose of illustrating and further describing the present invention. These drawings and examples should not be construed as limiting the present invention.

The drawings show

in fig. 1 - panel (A) - results of analysis of median tumor growth in Balb/C mice bearing CT26 tumors after intratumoral treatment with RNAdjuvant® (non-coding immunostimulatory RNA), mRNA encoding IL-12, and mRNA encoding soluble PD-1. Tested appropriate combinations of these compounds, including control groups, as indicated in the drawing. The experiment was carried out according to the method described in example 1.

Panel (B) shows survival ratios of mice bearing CT26 tumors after intratumoral treatment with mRNA encoding IL-12, RNAadjuvant, and mRNA encoding soluble PD-1. Tested appropriate combinations of these compounds, including control groups, as indicated in the drawing. The experiment was carried out according to the method described in Example 1. Kaplan-Meier survival curves are shown;

in fig. 2 - survival rates of Balb/C mice bearing CT26 tumors after intratumoral treatment with RNAdjuvant (non-coding immunostimulatory RNA) and intraperitoneal treatment with anti-PD-1 antibody. Tested appropriate combinations of these compounds, including control groups, as indicated in the drawing. The experiment was carried out according to the method described in Example 2. Kaplan-Meier survival curves are shown;

in fig. 3: Survival rates of Balb/C mice bearing CT26 tumors after intratumoral treatment with RNAadjuvant, mRNA encoding IL-12, mRNA encoding CD40L, compared with intratumoral treatment with mRNA encoding IL-12 alone. Tested appropriate combinations of these compounds, including control groups, as indicated in the drawing. The experiment was carried out according to the method described in Example 3. Kaplan-Meier survival curves are shown;

in fig. 4 shows the results of analysis of median tumor growth after rechallenge Balb/C mice with syngeneic CT26 colon carcinoma cells on day 113 after the first tumor challenge. Mice were pretreated intratumorally with RNAadjuvant alone or in combination with anti-PD1 antibody treatment. Tested appropriate combinations of these compounds, including control groups, as indicated in the drawing. The experiment was carried out according to the method described in example 4;

in fig. 5: Analysis of median tumor growth after rechallenge Balb/C mice with syngeneic CT26 colon carcinoma cells on day 113 after the first tumor challenge. Mice were pretreated intratumorally with RNAdjuvant alone or in combination with mRNA encoding CD40L, mRNA encoding IL-12. Tested appropriate combinations of these compounds, including control groups, as indicated in the drawing. The experiment was carried out according to the method described in example 5;

in fig. 6 - Results of analysis of median tumor growth in Balb/C mice bearing CT26 tumors after intratumoral treatment with immunostimulatory RNA (RNAdjuvant), mRNA encoding soluble PD1 (solPD1) and CD40 ligand (CD40L), in combination with anti-CTLA4 antibody as an inhibitor control points. The experiment was carried out according to the method described in example 7;

in fig. 7 - Analysis of median tumor growth in untreated lesions in Balb/C mice bearing CT26 tumors introduced into both flanks after intratumoral treatment of a single lesion with immunostimulatory RNA (RNAdjuvant), mRNA encoding soluble PD1 (solPD1) and CD40 ligand (CD40L), in combination with an anti-CTLA4 antibody as a checkpoint inhibitor. The experiment was carried out according to the method described in example 8;

in fig. 8 - panel (A) - results of analysis of median tumor growth in Balb/C mice bearing E.G7-OVA tumors after intratumoral treatment with immunostimulatory RNAadjuvant and vaccinated (i.d.) with OVA (RNAActive®) (vaccine preparation) or in combination with anti-PD1 antibody as checkpoint inhibitor (which was administered i.p.) and PpLuc RNActive or buffer as a non-specific control. The experiment was carried out according to the method described in example 10;

Panel (B) shows survival rates of Balb/C mice bearing E.G7-OVA tumors after intratumoral treatment with immunostimulatory RNAadjuvant and vaccinated (i.d.) with OVA (RNAActive) or in combination with anti-PD1 antibody as a checkpoint inhibitor (which was administered i.p.) and PpLuc RNActive or buffer as a non-specific control. The experiment was carried out according to the method described in Example 10. Kaplan-Meier survival curves are shown;

in fig. 9 - panel (A) - results of analysis of median tumor growth in Balb/C mice carrying E.G7-OVA tumors after intratumoral treatment with immunostimulatory RNAadjuvant and mRNA encoding IL12 vaccinated with (i.d.) OVA (RNActive) and PpLuc RNActive or buffer as a non-specific control. The experiment was carried out according to the method described in example 11.

Panel (B) shows survival rates of Balb/C mice harboring E.G7-OVA tumors after intratumoral treatment with immunostimulatory RNAadjuvant and mRNA encoding IL12, vaccinated with (i.d.) OVA (RNAactive) or in combination with anti-PD1 antibody as an inhibitor control points (which was administered i.p.) and PpLuc RNAActive or buffer as a non-specific control. The experiment was carried out according to the method described in Example 11. Kaplan-Meier survival curves are shown;

in fig. 10 - panel (A) - data on the level of resulting mRNA products in the form of IL12 in the supernatants of transfected RNA A375 cells after 5 hours. The experiment was carried out according to the method described in example 13.

Panel (B) - data on the level of resulting translation of mRNA products in the form of IL12 in the supernatants of transfected RNA A375 cells after 24 h. The experiment was carried out according to the method described in example 13;

in fig. 11 - panel (A) - data on the level of resulting mRNA products in the form of solPD1 in the supernatants of transfected RNA A375 cells after 5 hours. The experiment was carried out according to the method described in example 13.

Panel (B) - data on the level of products resulting from the translation of mRNA in the form of solPD1 in the supernatants of transfected RNA A375 cells after 24 hours. The experiment was carried out according to the method described in example 13;

in fig. 12 - panel (A) - data on the level of the resulting mRNA products in the form of antibodies to CTLA4 in the supernatants of transfected RNA A375 cells after 5 hours. The experiment was carried out according to the method described in example 13.

Panel (B) shows data on the level of anti-CTLA4 antibody-derived mRNA products in supernatants of transfected A375 cell RNA after 24 hours. The experiment was carried out according to the method described in Example 13;

in fig. 13 shows the level of membrane-bound, translated CD40LG mRNA product on transfected A375 cells after 24 hours by FACS analysis. The experiment was carried out according to the method described in example 13.

Examples

The following examples are given only for the purpose of illustrating and further describing the present invention. These examples are not intended to limit the present invention.

Preparation of DNA, mRNA and immunostimulatory RNA constructs (RNAdjuvant)

1. Preparation of DNA and RNA constructs

The constructs IL-12 (GC), soluble PD-1 (GC) (solPD1), CD40L (GC), and two anti-CTLA4 antibody chains were generated using a stabilizing sequence derived from the 3'-UTR of albumin, a segment consisting of 64 adenosines ( poly(A)-sequence), a segment consisting of 30 cytosines (poly(C)-sequence), and a histone stem-loop structure. Most of the DNA sequences were obtained by modifying the wild-type DNA coding sequence by introducing a GC-optimized sequence for stabilization, using an in silico algorithm to increase the GC content of the corresponding coding sequence compared to the wild-type coding sequence (referred to as "GC"). mRNA expressing human IL-12, soluble PD-1 receptor, CD40L and anti-CTLA4 antibody was prepared in a similar manner using the corresponding human coding sequences.

In the present example, a DNA sequence was obtained that encodes a non-coding immunostimulatory RNA (isRNA) R2025 and then used for in vitro RNA transcription reactions.

2. Transcription of RNA in vitro

The corresponding DNA plasmids, the preparation of which is described above in section 1, were transcribed in vitro using T7 polymerase. In vitro RNA transcription reactions of constructs encoding IL-12, CD40L, soluble PD-1, and anti-CTLA4 antibody were performed in the presence of a cap analog (m ⁷ GpppG). isRNA R2025 was obtained without the cap analog. The RNA was then purified with PureMessenger® (Cure Vac, Tübingen, Germany; WO ^2008/077592 ).

3. Obtaining a complex polymer carrier : cargo-molecule ("RNAdiuvant")

The following cationic peptide was used as the cationic component of the polymer carrier (Cys-Arg ₁₂ -Cys or CR ₁₂ C) having SEQ ID NO: 579 or SEQ ID NO: 580.

For the synthesis of complexes containing a polymeric carrier and a cargo molecule, an RNA molecule having the R2025 RNA sequence indicated in section 1 above was mixed with the CR12C cationic peptide component indicated above. The required amount of RNA was mixed with the appropriate cationic component in the following mass ratios, obtaining a complex. If, according to the present invention, polymerizable cationic components were used, the polymerization of the cationic components occurred simultaneously with the complexation of the nucleic acid as a cargo molecule. Then the volume of the resulting solution was adjusted with water to a final volume of 50 µl and incubated for 30 min at room temperature. Additional details are described in WO 2012/013326.

The mass ratio of peptide : RNA was 1:3.7. A complex containing a polymeric carrier and a cargo molecule was formed using a disulfide-crosslinked cationic CR ₁₂ C peptide as a carrier and an immunostimulatory nucleic acid R2025 as a cargo molecule. This complex containing a polymeric carrier and a R2025/CR ₁₂ C cargo molecule (designated R2391) was used as an adjuvant in the following examples (designated "RNAdjuvant").

4. Obtaining RNA for administration

mRNA IL-12 (R1328), mRNA soluble PD-1 (R3971) and mRNA CD40L mRNA (R3571) was administered in lactated Ringer's solution (RiLa). Co-prepared forms of "naked" (i.e., not included in the preparation) mRNA and a complex containing a polymeric carrier and a cargo molecule "RNAdjuvant" (R2391) were also administered in lactated Ringer's solution (RiLa) after mixing both components immediately before injection .

Example 1 Intratumoral Treatment of Immunostimulatory RNA ("RNAdjuvant") and mRNA Encoding Soluble PD-1 and mRNA Encoding IL-12

Balb/c mice (see Table 4) were injected subcutaneously (sc) with 1×10 ⁶ CT26 cells (colon carcinoma cell line) per mouse (in a volume of 100 μl of PBS) in the right lateral region on day 0 of the experiment. On day 9 after challenge with tumors, mice were sorted according to tumor size, obtaining groups with an average tumor volume of approximately 50 mm ³ . Intratumoral (it) therapy was started on day 9 and continued with treatment twice a week for three weeks. Mice were injected with a combination of RNAadjuvant (25 μg R2391), mRNA encoding IL-12 (25 μg R2763) and mRNA encoding soluble PD-1 (R3971) (group A in Table 4), or mRNA encoding IL-12 (25 μg R2763) (group B in table 4), individually or individually RNAdjuvant (25 μg R2391) (group C in table 4). To control the antitumor effect due to the injection procedure, mice were injected with buffer (RiLa, group D in Table 4), respectively.

Monitoring of tumor growth was performed by measuring the size of tumors in three directions using calipers. Tumor volume was calculated using the following formula:

On days 9, 11, 14, 17, and 21 of the experiment, mice were injected intratumorally (i.t.) with the RNA indicated in Table 4 below. The intratumoral injection volume was 50 μl.

Table 4 summarizes the processing options used in this example. RNAadjuvant and mRNA constructs encoding IL-12 and soluble PD-1 were injected into the tumor (i.t.). In CT26 control treated mice, survival rates and median tumor growth were analyzed.

Tumor challenge and administration of the composition according to the invention:

Mice were treated by injection according to the scheme presented in Table 4. Median tumor growth was determined using the above formula. The results of the experiment are shown in Fig. 1, with 1A showing the effect of a composition according to the invention on tumor growth, and FIG. 1B shows the effect of the composition according to the invention on survival.

Results:

The results shown in FIG. 1A demonstrate that the inventive composition, which contains mRNA encoding IL-12 and mRNA encoding soluble PD-1, in combination with RNAadjuvant (group A in Table 4) significantly reduced the median volume of tumors compared to other treatments. (groups B-D in table 4). In addition, the results presented in Fig. 1B demonstrate that the inventive composition, which contains mRNA encoding IL-12 and mRNA encoding soluble PD-1, in combination with RNAadjuvant (group "A" in Table 4), significantly increased the survival of tumor-bearing mice compared to with other treatment options (groups B-G in table 4).

Example 2 Treatment with Immunostimulatory RNA ("RNAdjuvant") in Combination with Anti-PD-1 Checkpoint Inhibitor Antibody

Table 5 summarizes the processing options that were used in this example. In addition to RNAdjuvant (i.t. administration), i.p. anti-PD-1 antibody (BioXCell) as a checkpoint inhibitor. Mice challenged with CT26 tumor cells were analyzed for survival rates.

Tumor challenge and administration of the composition according to the invention:

Control tumor infection was carried out according to the experiment described above (see example 1). Mice were treated by injection according to the schedule shown in Table 5. The results of the experiment are shown in FIG. 2.

Results:

In FIG. 2 demonstrates that intratumoral (i.t.) treatment with RNAdjuvant® (R2391) in combination with i.p. treatment with anti-PD-1 antibody (group "B" in Table 5) resulted in increased survival compared to the relevant control group, which was treated with the checkpoint inhibitor alone, ie. anti-PD-1 antibody (Group "D" in Table 5), and increased survival rates compared to RNAdjuvant treatment and control antibody (anti-hamster IgG, BioXCell) (Group "B" in Table 5).

Example 3 Intratumoral Treatment of Immunostimulatory RNA ("RNAdjuvant") and mRNA Encoding CD40 Ligand (CD40L) and mRNA Encoding IL-12

Table 6 summarizes the processing options that were used in this example. RNAadjuvant and mRNA constructs encoding IL-12 and mouse CD40L were injected into tumors (i.t.). Mice challenged with CT26 tumor cells were analyzed for survival rates.

Tumor challenge and administration of the composition according to the invention:

Tumor challenge was carried out according to the experiment described above (see example 1). Mice were treated by injection according to the schedule shown in Table 6. The results of the experiment are shown in FIG. 3.

Results:

The results shown in FIG. 3 demonstrate that the inventive composition, which contains mRNA encoding IL-12 and mRNA encoding CD40L, in combination with RNAdjuvant (Group A in Table 6) resulted in a significant increase in median survival in tumor-challenged mice compared to with other treatment options (groups B-C in table 6).

Example 4 Induction of a Systemic Secondary Immune Response (T-Cell Memory Response) by Combining Intratumoral Treatment with Immunostimulatory RNA ("RNAdjuvant") and Systemic Treatment with cPP-1 Antibody

Table 7 summarizes the processing options used in this example. The effect of RNAdjuvant (i.t. injection) and systemic treatment with anti-PD-1 antibody (BioXCell) as a checkpoint inhibitor was evaluated after rechallenge mice with completely eradicated primary tumors of the CT-26 line after the first cycle of treatment, analyzing the survival rates.

Tumor re-infection after administration of the composition according to the invention:

The first tumor challenge was performed by sc-injection of CT-26 tumor cells into the right flank of Balb/C mice, while re-challenge using 1×10 ⁶ CT26 syngeneic colon carcinoma cells was performed in left lateral region on day 113 after the first tumor challenge. As a control, naive animals subjected to control infection were used. Eradication of primary tumors was found in a lower percentage of animals treated intratumorally with RNAdjuvant alone (3 of 10 mice) compared with the combination of systemic anti-PD-1 antibody and intratumoral RNAdjuvant treatment (7 of 9 mice). The results of the experiment are shown in Fig. four.

Results:

The results shown in FIG. 4 demonstrate that all mice that had completely eradicated primary tumors were completely protected from a second tumor challenge, indicating the induction of a systemic secondary immune response. A systemic secondary immune response was also induced by intratumoral treatment with RNAadjuvant alone. The induction of a systemic secondary immune response is unexpected since no adaptive immune response-inducing vaccine has been administered. Thus, the introduction of the isRNA according to the invention, especially in combination with systemic treatment with an anti-PD-1 antibody, was sufficient to induce a systemic secondary immune response, which could not be predicted.

Example 5: Induction of a systemic secondary immune response (T-cell memory response) by combining intratumoral processing of mRNA encoding CD40 ligand (CD40L) and mRNA encoding IL-12

Table 8 summarizes the processing options used in this example. The effect of RNAadjuvant and mRNA constructs encoding IL-12 and murine CD40L (i.t.-administration) was assessed after re-challenging mice with completely eradicated primary tumors of the CT-26 line after the first cycle of treatment, analyzing the survival rates.

Tumor re-infection after administration of the composition according to the invention:

The first tumor challenge was performed by sc injection of CT-26 tumor cells into the right lateral region of Balb/C mice. After intratumoral treatment with RNAdjuvant alone or in combination with mRNA encoding CD40 ligand (CD40L) and mRNA encoding IL-12, a left flank challenge was performed on day 113 after the first tumor challenge, for which 1×10 ⁶ was used. syngeneic cells of colon carcinoma line CT26,. As a control, naive animals subjected to control infection were used. Eradication of primary tumors was found in a lower percentage of animals treated intratumorally with RNAdjuvant alone (3 out of 10 mice) compared to treatment with a combination of mRNA encoding CD40 ligand (CD40L) and mRNA encoding IL-12 combined with intratumoral treatment with RNAdjuvant (5 out of 10 mice). The results of the experiment are shown in Fig. 5.

Results:

The results shown in FIG. 5 demonstrate that all mice that had eradicated primary tumors were completely protected from a second tumor challenge, indicating the induction of a systemic secondary immune response. A systemic secondary immune response was also induced by intratumoral treatment with RNAadjuvant alone.

Example 6: Phase I/II Study of Intratumoral Administration of RNAdjuvant (CV8102) to Patients with Advanced Cutaneous Melanoma (cMEL), Cutaneous Squamous Cell Carcinoma (cSCC), Head and Neck Squamous Cell Carcinoma (HNSCC), or Adenoid Cystic Carcinoma (ACC)

Part 1:

A phase I, open-label, dose-escalation-expansion cohort study of intratumoral administration of RNAdjuvant with or without systemic anti-PD-1 antibody treatment was performed in patients with advanced cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), squamous cell carcinoma head and neck (HNSCC) or adenoid cystic carcinoma (ACC).

Intratumoral Injection RNAdjuvant: CV8102 was administered via the dermal, subcutaneous, or easily accessible lymph node lesions, which can be injected using clinically accepted direct imaging or under imaging (ultrasound) guidance.

Treatment regimen: Patients were subjected to a maximum of 8 intratumoral injections of CV8102 unless due to disease progression, the next line of therapy was required or unless unacceptable toxicity occurred:

The first 5 injections were carried out at weekly intervals (days 1, 8, 15, 22, 29). When patients were treated with anti-PD-1 antibody (cohorts C and D), treatment with CV8102 was started on the day of anti-PD-1 antibody treatment and continued according to the anti-PD-1 antibody regimen after day 29.

Three subsequent treatments with CV8102 were performed at 2-week intervals (cohorts A and B). When patients were treated with anti-PD-1 antibody (study cohorts C and D), CV8102 treatments after day 29 were performed according to the anti-PD-1 antibody treatment schedule and performed on the day of anti-PD-1 antibody administration; those. patients receiving nivolumab were treated with CV8102 every other week; patients receiving pembrolizumab were treated with CV8102 every third week.

Part A: Dose escalation when using RNAdjuvant as a single agent

In part A of the dose escalation study, a 2-parameter Bayesian logarithmic regression model with overdose control was used. Cohorts consisting of at least 1 (baseline dose level) or 2 patients (any other dose level) running cMEL, cSCC, HNSCC, or ACC were treated with escalating doses by intratumoral RNAadjuvant until the maximum tolerated dose (MTD) was determined and recommended dose (RD). A minimum of 7 patients must be included in part A of the study.

In part A, the initial dose of RNAadjuvant was 25 µg. Other dosage levels are shown in Table 9 below.

Inclusion Criteria: Cohort A:

Patients with histologically confirmed advanced (unresectable or metastatic) cMEL or cSCC who do not respond to standard therapy or who are not indicated for standard therapy;

not subject to surgical resection or locoregional radiation therapy for therapeutic purposes;

disease progression with/after at least one line of therapy; or

patients with histologically confirmed recurrent or metastatic HNSCC;

not subject to surgical resection or locoregional radiation therapy for therapeutic purposes;

progression of the disease, which is confirmed by radiological examination (confirmed the presence of new or progressive lesions during/after at least one line of therapy); or

patients with histologically or cytologically confirmed ACC,

not subject to surgical resection or locoregional radiation therapy for therapeutic purposes;

progression of the disease, which is confirmed by radiological examination; during/after at least one line of therapy.

Part B: Expanded Cohort

Following the completion of the Part A study, patients with advanced cSCC or ACC were included in separate extended cohorts that were treated with a previously determined recommended dose to further characterize the tolerability and safety profile of injectable RNAadjuvant in these patient populations and to provide preliminary data on antitumor activity. Up to 10 patients per extended cohort should be included in Part B of the study.

Inclusion Criteria:

Cohort B:

Expanded cohorts B1 and B2:

Patients with histologically confirmed advanced (unresectable/metastatic) cSCC (B1) or ACC (B2) who do not respond to standard therapy or who are not indicated for standard therapy;

not subject to therapeutic locoregional treatments;

disease progression with/after at least one line of therapy (radiological confirmation required in case of ACC).

Part B: Dose escalation of RNAadjuvant in combination with anti-PD-1 antibody therapy in patients with advanced cMEL or HNSCC

Part B of the study included patients with advanced cMEL or HNSCC undergoing anti-PD-1 antibody therapy at the time of the study. Patients must have stable disease or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment prior to initiation of RNAjuvant. Cohorts of at least 2 patients were treated with sequentially increasing doses of RNAadjuvant. Dose escalation studies and determination of MTD and RCD ("recommended combination dose") were performed using a 5-parameter Bayesian logarithmic regression model with overdose control.

Dose escalation in part B of the study was started after at least 3 doses of RNAadjuvant had been evaluated in part A. The baseline dose in part B was the dose lower than the highest dose considered to be tolerated in part A of the study at the start of the study. part B of the study (see Table 9).

Inclusion Criteria:

Cohorts C and D:

Patients with histologically confirmed advanced (unresectable or metastatic) cMEL in cohorts B and G1;

undergoing standard anti-PD-1 antibody therapy at the time of the study as described in the Summary of Product Characteristics (Supplementation Information) (SPC);

having stable or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment as assessed by the investigator;

intending to continue existing anti-PD-1 antibody therapy as a result of the perceived clinical benefit of continuing anti-PD-1 antibody therapy as assessed by the investigator.

Patients with histologically confirmed recurrent or metastatic hnSCC in cohorts C and D2;

currently undergoing standard anti-PD-1 antibody therapy provided in the SPC;

having stable or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment as defined as follows:

stable disease according to irRECIST (imaging-determined criteria for tumor response to therapy);

intending to continue existing anti-PD-1 antibody therapy as a result of the perceived clinical benefit of continuing anti-PD-1 antibody therapy as assessed by the investigator.

Part D: Expanded cohort to study RNAadjuvant in combination with anti-PD-1 antibody therapy in patients with advanced cMEL or HNSCC

After determining the RCD (“recommended combination dose”) in part B of the study, part D of the study was expanded to include additional patients with advanced cMEL or HNSCC to evaluate treatment with a PD-1 antagonist (using the acceptable requirements specified for part B of the study) in order to additional characterization of the tolerability and safety profile and evaluation of the antitumor activity of combination therapy. Approximately 21 patients should be included in Part D of the study.

Part 2 (alternatively may be carried out as a separate clinical trial)

A phase I, open-label, dose-escalation-expansion cohort study of intratumoral administration of RNAdjuvant and RNArt with or without systemic anti-PD-1 antibody treatment was performed in patients with advanced cutaneous melanoma, squamous cell carcinoma of the skin (SCCs), adenoid cystic carcinoma ( ACC), cutaneous T-cell lymphoma, or head and neck squamous cell carcinoma (HNSCC).

Part 2 of the Phase I clinical trial repeated the studies in Part 1, but studied a fixed dose combination of RNArt and RNAdjuvant. The methodology for dose escalation and cohort definition, including clinical indications, was the same as that used in Part 1. For a better understanding, the previous section should be studied in detail.

However, part 2 of the study considered information from part 1 that could lead to changes in the design of part 1 and/or 2. RNArt contains 3 compounds derived from an optimized RNA that encodes IL-12, PD-1 decoy receptor and CD-40L.

Example 7: Intratumoral treatment of immunostimulatory RNA ("RNAdjuvant") and mRNA encoding CD40 ligand (CD40L) and mRNA encoding soluble PD1 (solPD1) in combination with anti-CTLA-4 antibody as checkpoint inhibitor

Table 10 summarizes the processing options that were used in this example. RNAadjuvant and mRNA encoding soluble PD1 and CD40L, in combination with an anti-CTLA4 antibody (BioXcell, clone 9H10) used as a checkpoint inhibitor, were administered intratumorally (i.t.) to mice challenged with CT26 tumor cells and median tumor growth was analyzed.

Tumor challenge and administration of the composition according to the invention:

Control tumor infection was carried out according to the experiments described above (see example 1). Mice were treated by injection according to the schedule shown in Table 10. The results of the experiment are shown in FIG. 6.

Results:

In FIG. 6 demonstrates that the inventive composition containing RNAadjuvant and mRNA encoding soluble PD1 and CD40L, in combination with an anti-CTLA4 checkpoint inhibitor (group A in Table 10), significantly reduced the median tumor volume.

Example 8: Abscopal effect of intratumoral treatment of immunostimulatory RNA ("RNAdjuvant") and mRNA encoding CD40 ligand (CD40L) and mRNA encoding soluble PD1 (solPD1) in combination with anti-CTLA-4 antibody as checkpoint inhibitor

Tumor challenge and composition according to the invention: Balb/c mice were injected subcutaneously (sc) with 1×10 ⁶ CT26 cells (colon carcinoma cell line) per mouse (in a volume of 100 μl of PBS) in the right flank on day 0 of the experiment . On day 5 of the experiment, mice were injected subcutaneously (sc) with 1×10 ⁶ CT26 cells (in a volume of 100 μl of PBS) in the left lateral region to evaluate the abscopal effect (therapeutic effect occurring in an untreated tumor) of the composition of the invention. Table 10 in example 7 summarizes the processing options used in this example. RNAadjuvant and mRNA encoding soluble PD1 and CD40L, in combination with anti-CTLA4 antibody as a checkpoint inhibitor, were administered intratumorally (it) to CT26 bearing mice (right lateral region), median tumor growth in untreated tumor was analyzed (left lateral region) .

Mice were treated by injection according to the scheme presented in table 10 in example 7. Analyzed the median growth of the untreated tumor (left side area). The results of the experiment are shown in Fig. 7.

Results:

Intratumoral treatment of a single lesion with anti-CTLA4 antibody in combination with RNAdjuvant, mRNA encoding soluble PD1, and mRNA encoding CD40 ligand, induced a systemic effect and inhibited the growth of untreated tumor.

Example 9: Intratumoral treatment of immunostimulatory RNA (RNAadjuvant) and mRNA encoding CD40 ligand (CD40L), mRNA encoding IL-12, mRNA encoding soluble PD1 (solPD1) and anti-CTLA4 antibody in combination with anti-PD1 antibody (i.p. - introduction)

Tumor challenge and administration of the composition according to the invention:

Tumor challenge was carried out according to the experiment described above (see example 1). Mice were treated by injection according to the scheme presented in table 11.

Table 11 summarizes the processing options that were used in this example. RNAadjuvant and mRNA encoding soluble CD40L, mRNA encoding soluble PD1, mRNA encoding IL-12, and mRNA encoding anti-CTLA4 antibody as checkpoint inhibitor were administered intratumorally (i.t.) in combination with anti-PD1 antibody as checkpoint inhibitor. points to mice challenged with CT26 tumor cells and analyzed median tumor growth and survival rates.

Example 10: Intratumoral Treatment of Immunostimulatory RNA (RNAdjuvant) and mRNA Encoding Antigen (RNAActive) Intradermally (i.d.) in Combination with Anti-PD1 Antibody (i.p. - Administration)

C57BL/6 mice were inoculated with sc 3×10 ⁵ E.G7-OVA tumor cells in the right lateral region. Treatment was started at an average tumor size of 30 mm ³ . Mice were treated with it immunostimulatory RNAadjuvant and vaccinated with id OVA RNActive (mRNA encoding ovalbumin) in combination with an anti-PD1 antibody (which was administered i.p.). mRNA encoding firefly (Photinus pyralis) luciferase (PpLuc) or buffer was used as a non-specific control. On days 7, 11, 14, 17 and 20 of the experiment, mice were treated with the options shown in Table 12 below. Median tumor growth and survival rates were analyzed.

Tumor challenge and administration of the composition according to the invention:

Mice were treated by injection according to the schedule shown in Table 12. The results of the experiment are shown in FIG. eight.

Results:

The results shown in FIG. 8 demonstrate that immunostimulatory RNA (RNAadjuvant) when administered i.t. in combination with mRNA encoding the tumor antigen ovalbumin (OVA), and in combination with an antibody to PD1, significantly reduced tumor growth compared to other treatments (groups B-D in table 12). It is important to note that the results presented in Fig. 8 demonstrate that immunostimulatory RNAadjuvant in combination with anti-PD1 checkpoint inhibitor antibody and mRNA vaccinations (OVA, i.d.-administration) induced complete remission of tumors and significantly increased survival in tumor challenged mice compared to other treatments (Group B -D in table 12).

Example 11: Intratumoral treatment of immunostimulatory RNA (RNAadjuvant) and mRNA encoding IL-12 administered i.t. in combination with mRNA encoding the antigen (RNAactive), which was administered i.d.

C57BL/6 mice were inoculated with sc 3×10 ⁵ E.G7-OVA tumor cells in the right lateral region. Treatment was started at an average tumor size of 30 mm ³ . Mice were treated with it immunostimulatory RNAadjuvant and vaccinated with id mRNA encoding the tumor antigen ovalbumin (OVA RNAactive) in combination with mRNA encoding IL-2 (which was injected with it). mRNA encoding firefly (Photinus pyralis) luciferase (PpLuc) or buffer was used as a non-specific control. On days 7, 11, 14, 17 and 20 of the experiment, mice were treated with the options shown in Table 13 below. Median tumor growth and survival rates were analyzed.

Tumor challenge and administration of the composition according to the invention:

Mice were treated by injection according to the schedule shown in Table 13. The results of the experiment are shown in FIG. 9.

Results:

The results shown in FIG. 9 demonstrate that intratumoral treatment with immunostimulatory RNA (RNAdjuvant) and mRNA encoding IL-12, in combination with intradermal vaccination with OVA RNActive, significantly reduced the median volume of tumors compared to other treatments (groups B-D in Table 13). In addition, the results presented in Fig. 9 demonstrate that the inventive composition comprising immunostimulatory RNA (RNAdjuvant) and mRNA encoding IL-12, in combination with intradermal mRNA vaccination (OVA RNAActive), significantly increased the survival rate of tumor challenged mice compared to other treatment options (groups B-D in table 13).

Example 12: Phase I/II Study of Intratumoral Administration of RNAdjuvant (CV8102) to Patients with Advanced Cutaneous Melanoma (cMEL), Cutaneous Squamous Cell Carcinoma (cSCC), Head and Neck Squamous Cell Carcinoma (HNSCC), Adenoid Cystic Carcinoma (ACC), Vulvar Squamous Cell Carcinoma ( VSCC) or cutaneous T-cell lymphoma of the mycotic fungoid subtype (CTCL-MF)

Part 1:

Phase I open-label dose escalation and expansion phase studies of intratumoral administration of RNAadjuvant with or without systemic anti-PD-1 antibody treatment were performed in patients with advanced cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), squamous cell carcinoma head and neck (hnSCC), adenoid cystic carcinoma (ACC), vulvar squamous cell carcinoma (VSCC), or cutaneous T-cell lymphoma of the mycotic fungoid subtype (CTCL-MF).

Intratumoral Injection RNAdjuvant: CV8102 was administered via the dermal, subcutaneous, or easily accessible lymph node lesions, which can be injected using clinically accepted direct imaging or under imaging (ultrasound) guidance.

Treatment regimen: Patients were subjected to a maximum of 8 intratumoral injections of CV8102 unless due to disease progression, the next line of therapy was required or unless unacceptable toxicity occurred:

The first 5 injections were carried out at weekly intervals (days 1, 8, 15, 22, 29). For patients treated with anti-PD-1 antibody (cohorts C and D), treatment with CV8102 was initiated on the day of anti-PD-1 antibody treatment and continued according to the anti-PD-1 antibody regimen after day 29.

Three subsequent treatments with CV8102 were performed at 2-week intervals (cohorts A and B). In the case where patients treated with anti-PD-1 antibody (cohorts C and D), treatment with CV8102 after day 29 was performed according to the anti-PD-1 treatment schedule and performed on the day of administration of anti-PD-1 antibody; those. patients receiving nivolumab were treated with CV8102 every other week; patients receiving pembrolizumab were treated with CV8102 every third week.

Part A: Dose escalation when using RNAdjuvant as a single agent

In part A of the dose escalation study, a 2-parameter Bayesian logarithmic regression model with overdose control was used. Cohorts consisting of at least 1 (baseline dose level) or 2 patients (any other dose level) running cMEL, cSCC, hnSCC, or ACC were treated with escalating doses by intratumoral RNAadjuvant until the maximum tolerated dose (MTD) was determined and recommended dose (RD). A minimum of 7 patients must be included in part A of the study.

In part A, the initial dose of RNAadjuvant was 25 µg. Other dosage levels are shown in Table 14 below.

Inclusion Criteria:

Cohort A:

Patients with histologically confirmed advanced (unresectable or metastatic) cMEL or cSCC who do not respond to standard therapy or who are not indicated for standard therapy;

not subject to surgical resection or locoregional radiation therapy for therapeutic purposes;

disease progression with/after at least one line of therapy; or

patients with histologically confirmed recurrent or metastatic hnSCC;

not subject to surgical resection or locoregional radiation therapy for therapeutic purposes;

progression of the disease is confirmed by radiological examination (confirmed the presence of new or progressive lesions during / after at least one line of therapy);

or

patients with histologically or cytologically confirmed ACC,

not subject to surgical resection or locoregional radiation therapy for therapeutic purposes;

progression of the disease, which is confirmed by radiological examination; during/after at least one line of therapy;

or

patients with histologically confirmed recurrent or metastatic VSCC;

not subject to surgery, radiation therapy or radiochemistry for therapeutic purposes;

not candidates for standard systemic therapies;

or

patients with recurrent or resistant CTCL of the mycotic fungoid (MF) subtype;

diagnosed based on the standard staging system;

the presence of MF without transformation of large CD30 ⁺ cells and without signs of affecting the internal organs;

relapsing, persistent or progressive after at least one previous treatment form.

Part B: Expanded Cohort

Following the completion of the Part A study, patients with advanced cSCC, ACC, VSCC, or CTCL-MF were included in separate extended cohorts that were treated with a previously determined recommended dose to further characterize the tolerability and safety profile of orally administered RNAadjuvant in these patient populations and to provide preliminary antitumor data. activity. Part B studies should include up to 10 patients per expanded cohort.

Inclusion Criteria:

Cohort B:

Expanded cohorts B1 and B2

Patients with histologically confirmed advanced (unresectable/metastatic) cSCC (B1) or ACC (B2) who do not respond to standard therapy or who are not indicated for standard therapy;

not subject to therapeutic locoregional treatments;

disease progression with/after at least one line of therapy (radiological confirmation required in case of ACC).

Expanded cohort B3

Patients with confirmed recurrent or metastatic VSCC;

not subject to surgery, radiation therapy or radiochemistry for therapeutic purposes;

not candidates for standard systemic therapies.

Expanded cohort B4

Patients with recurrent or resistant CTCL of the mycotic fungoid (MF) subtype;

diagnosed based on the standard staging system;

the presence of MF without transformation of large CD30 ⁺ cells and without signs of affecting the internal organs;

relapsing, stable or progressive after at least one previous treatment form.

Part B: Dose Escalation of RNAadjuvant in Combination with Anti-PD-1 Antibody Therapy in Patients with Advanced cMEL or HNSCC

Part B of the study included patients with advanced cMEL or HNSCC undergoing anti-PD-1 antibody therapy at the time of the study. Patients must have stable disease or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment prior to initiation of RNAjuvant. Cohorts of at least 2 patients were treated with sequentially increasing doses of RNAdjuvant. Dose escalation studies and determination of MTD and RCD ("recommended combination dose") were performed using a 5-parameter Bayesian logarithmic regression model with overdose control.

Dose escalation in Part B of the study was initiated after at least 3 doses of RNAadjuvant had been evaluated in Part A. The starting dose in Part B was 25 µg (see Table 14).

Inclusion Criteria:

Cohorts C and D:

Patients with histologically confirmed advanced (unresectable or metastatic) cMEL in cohorts B and G1;

undergoing standard anti-PD-1 antibody therapy at the time of the study as described in the Summary of Product Characteristics (Supplementation Information) (SPC);

having stable or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment as assessed by the investigator;

intending to continue existing anti-PD-1 antibody therapy as a result of the perceived clinical benefit of continuing anti-PD-1 antibody therapy as assessed by the investigator.

Patients with histologically confirmed recurrent or metastatic HNSCC in cohorts C and D2;

currently undergoing standard anti-PD-1 antibody therapy provided in the SPC;

having stable or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment, as defined as:

stable disease according to irRECIST;

disease is considered stable if there is a decrease in disease severity of less than 5% or 5% (defined as ≤ 5% decrease in measurable disease parameter) over a time interval of at least 12 weeks to day 1;

intending to continue existing anti-PD-1 antibody therapy as a result of the perceived clinical benefit of continuing anti-PD-1 antibody therapy as assessed by the investigator.

Part D: Expanded cohort to study RNAadjuvant in combination with anti-PD-1 antibody therapy in patients with advanced cMEL or HNSCC

After determining the RCD (“recommended combination dose”) in part B of the study, part D of the study was expanded to include additional patients with advanced cMEL or HNSCC to evaluate treatment with a PD-1 antagonist (using the acceptable requirements specified for part B of the study) in order to additional characterization of the tolerability and safety profile and evaluation of the antitumor activity of combination therapy. Approximately 21 patients should be included in Part D of the study.

Part 2 (may be carried out as a separate clinical trial)

A phase I, open-label, dose-escalation-expansion cohort study of intratumoral administration of RNAdjuvant and RNArt with or without systemic anti-PD-1 antibody treatment was performed in patients with percutaneously detectable solid tumors or lymphoma.

Overall, the phase I design of the RNArt + RNadjuvnat clinical trial was consistent with the phase I design of the RNAdjuvant trial (Part 1). The tolerable dose range of the combinations should first be studied using a dose escalation procedure (Cohort A). The dose of RNArt, containing 5 RNA constructs encoding IL-12, CD40L, soluble PD-1, and two anti-CTLA-4 antibody chains, should be increased in increments while RNadjuvnat was administered at a fixed dose of 25 μg. RNArt and RNadjuvnat should be injected simultaneously into the same tumor-associated lesion. The dose escalation methodology is similar to that described in Part 1, Cohort A (Bayesian approach to dose escalation). The dosing schedule was as described above for RNAadjuvant (ie, 5 x weekly followed by 3 additional Q2W injections).

The dose escalation portion of the study (Cohort A) included patients who met the criteria listed in Part 1 plus additional criteria:

Patients

with human papillomavirus-associated advanced tumors, including advanced recurrent or metastatic vulvar squamous cell carcinoma, cervical cancer, or vaginal cancer;

not subject to surgery, radiation therapy or radiochemistry for therapeutic purposes;

not candidates for standard systemic therapies;

or

with low-grade follicular non-Hodgkin's lymphoma;

either previously untreated or with recurrent or persistent disease after at least one prior treatment;

not requiring active therapy (asymptomatic patients in the watchful waiting phase);

or

with nodal B-cell lymphoma marginal zone lymphoma;

either previously untreated or with recurrent or persistent disease after at least one prior treatment;

not requiring active therapy (asymptomatic patients in the watchful waiting phase);

or

with primary cutaneous anaplastic large cell lymphoma;

with relapsing, persistent or progressive disease after at least one previous treatment or for which no other therapy options are applicable;

or

with histologically confirmed advanced, recurrent or metastatic soft tissue sarcoma in adults;

not subject to surgery or other treatment options for therapeutic purposes;

who have undergone at least one line of previous systemic therapy or have sarcoma of histological subtypes for which there is currently no standard systemic therapy;

or

with histologically confirmed advanced (unresectable or metastatic) basal cell carcinoma of the skin;

not subject to surgery or other treatment options for therapeutic purposes;

not candidates for standard systemic therapies.

Cohort B: Expanded cohort

The criteria are as specified in Part 1, Extended Cohort B.

Cohort B: Dose escalation of RNart+RNAadjuvant in combination with anti-PD-1 antibody therapy in patients with advanced cMEL, HNSCC, or cSCC

As with the Phase I trial investigating RNAadjuvant, Part B included patients with advanced cMEL or HNSCC. Depending on whether an anti-PD-1 antibody is approved for the treatment of advanced cSCC at the start of cohort B trials, patients with cSCC may also be included in this cohort. Patients must have stable disease or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment before starting RNArt+RNAjuvant. The dose of RNArt, containing 4 RNA constructs encoding IL-12, CD40L, and two anti-CTLA-4 antibody chains, should be increased stepwise, while RNadjuvnat was used at a fixed dose of 25 µg. Dose escalation methodology is similar to that described in Part 1, Cohort B.

Inclusion Criteria:

Cohorts C and D:

Indications (criteria) include those listed in Part 1, cohorts C and D. Depending on the status of anti-PD-1 antibody approval, the following patients may be included in these cohorts:

with histologically confirmed advanced (inoperable or metastatic) cSCC;

undergoing standard anti-PD-1 antibody therapy at the time of the study as described in the Summary of Product Characteristics (Supplementation Information) (SPC);

having stable or slowly progressive disease after at least 12 weeks of anti-PD-1 antibody treatment as assessed by the investigator;

intending to continue existing anti-PD-1 antibody therapy as a result of the perceived clinical benefit of continuing anti-PD-1 antibody therapy as assessed by the investigator.

Example 13: Expression of individual RNArt constructs in A375 human melanoma cells

A375 cells were seeded in 24-well plates at a density of 50,000 cells/well. After 24 hours, the cells were transfected using the indicated amounts of RNA and Lipofectamine 2000 (Invitrogen) at a constant ratio of RNA : Lipofectamine 1:2. After 5 hours, the supernatants were collected and 1 ml of fresh medium was added. After incubation for another 24 h, the supernatants were collected again. The level of translation products of IL-12 mRNA, solPD1, and anti-CTLA4 antibodies was measured in the supernatant.

The content of human IL-12 in the supernatants was measured using the human IL-12p70 DuoSet, R&D Systems, catalog no. DY1270 according to the manufacturer's protocol, using dilutions of the supernatants 1:10, 1:100 and 1:1000 (see Fig. 10) .

The human PD1 ELISA was run in duplicate with the Human PD1 DuoSet, R&D Systems, Cat No: DY1086, according to the manufacturer's protocol using 1:10, 1:100 and 1:1000 dilutions of the supernatants (see FIG. 11). .

An ELISA for the evaluation of human anti-CTLA4 IgG1 was performed in duplicate using the antibody rituximab as standard (goat anti-human IgG (SouthernBiotech, cat. no. 2044-01, c=1 mg/mL, 1:1000) and goat anti-human IgG conjugated with biotin (Dianova, catalog No. 109065088-01, 1:20000) using dilutions of the supernatants 1:10, 1:100 and 1:1000 (see Fig. 12).

For detection of the membrane-bound CD40LG protein, A375 cells were seeded in 6-well plates at a density of 130,000 cells/well. After 24 hours, the cells were transfected using the indicated amounts of RNA and Lipofectamine 2000 (Invitrogen) at a constant ratio of RNA : Lipofectamine 1:2. After incubation for 24 hours, cells were harvested and cell surface stained with an anti-human CD154 antibody conjugated to APC (BD Pharmingen). Finally, cell surface expression of CD40LG was analyzed by flow cytometry (see FIG. 13).

--->

SEQUENCE LIST

<110> KUREVAK AG

<120> RNA FOR CANCER THERAPY

<130> CU01P232WO1

<160> 1062

<170>PatentIn version 3.5

<210> 1

<211>

<212>

<213> 288

PRT

Artificial Sequence

<220>

<223>

PDCD1

<400> 1

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln

1 5 10 15

Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp

20 25 30

Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp

35 40 45

Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val

50 55 60

Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala

65 70 75 80

Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg

85 90 95

Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg

100 105 110

Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu

115 120 125

Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val

130 135 140

Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro

145 150 155 160

Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly

165 170 175

Leu Leu Gly Ser Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys

180 185 190

Ser Arg Ala Ala Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro

195 200 205

Leu Lys Glu Asp Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly

210 215 220

Glu Leu Asp Phe Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro

225 230 235 240

Cys Val Pro Glu Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly

245 250 255

Met Gly Thr Ser Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg

260 265 270

Ser Ala Gln Pro Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu

275 280 285

<210> 2

<211> 149

<212> PRT

<213> Artificial Sequence

<220>

<223> PDCD1(1-149)

<400> 2

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln

1 5 10 15

Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp

20 25 30

Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp

35 40 45

Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val

50 55 60

Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala

65 70 75 80

Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg

85 90 95

Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg

100 105 110

Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu

115 120 125

Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val

130 135 140

Thr Glu Arg Arg Ala

145

<210> 3

<211> 219

<212> PRT

<213> Artificial Sequence

<220>

<223>IL12A

<400> 3

Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu

1 5 10 15

Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro

20 25 30

Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val

35 40 45

Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys

50 55 60

Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser

65 70 75 80

Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys

85 90 95

Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala

100 105 110

Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr

115 120 125

Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys

130 135 140

Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu

145 150 155 160

Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr

165 170 175

Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys

180 185 190

Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr

195 200 205

Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser

210 215

<210> 4

<211> 219

<212> PRT

<213> Artificial Sequence

<220>

<223> IL12A(1-219)

<400> 4

Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu

1 5 10 15

Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro

20 25 30

Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val

35 40 45

Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys

50 55 60

Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser

65 70 75 80

Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys

85 90 95

Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala

100 105 110

Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr

115 120 125

Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys

130 135 140

Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu

145 150 155 160

Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr

165 170 175

Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys

180 185 190

Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr

195 200 205

Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser

210 215

<210> 5

<211> 197

<212> PRT

<213> Artificial Sequence

<220>

<223> IL12A(23-219)

<400> 5

Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu

1 5 10 15

His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys

20 25 30

Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp

35 40 45

His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu

50 55 60

Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr

65 70 75 80

Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe

85 90 95

Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr

100 105 110

Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys

115 120 125

Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu

130 135 140

Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser

145 150 155 160

Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu

165 170 175

Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser

180 185 190

Tyr Leu Asn Ala Ser

195

<210> 6

<211> 328

<212> PRT

<213> Artificial Sequence

<220>

<223>IL12B

<400> 6

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu

1 5 10 15

Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val

20 25 30

Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu

35 40 45

Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln

50 55 60

Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys

65 70 75 80

Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val

85 90 95

Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp

100 105 110

Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe

115 120 125

Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp

130 135 140

Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg

145 150 155 160

Gly Ser Ser Asp Pro Glyn Gly Val Thr Cys Gly Ala Ala Thr Leu Ser

165 170 175

Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu

180 185 190

Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile

195 200 205

Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr

210 215 220

Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn

225 230 235 240

Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp

245 250 255

Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr

260 265 270

Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg

275 280 285

Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala

290 295 300

Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Ser Trp Ser

305 310 315 320

Glu Trp Ala Ser Val Pro Cys Ser

325

<210> 7

<211> 328

<212> PRT

<213> Artificial Sequence

<220>

<223> IL12B(1-328)

<400> 7

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu

1 5 10 15

Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val

20 25 30

Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu

35 40 45

Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln

50 55 60

Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys

65 70 75 80

Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val

85 90 95

Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp

100 105 110

Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe

115 120 125

Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp

130 135 140

Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg

145 150 155 160

Gly Ser Ser Asp Pro Glyn Gly Val Thr Cys Gly Ala Ala Thr Leu Ser

165 170 175

Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu

180 185 190

Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile

195 200 205

Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr

210 215 220

Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn

225 230 235 240

Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp

245 250 255

Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr

260 265 270

Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg

275 280 285

Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala

290 295 300

Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Ser Trp Ser

305 310 315 320

Glu Trp Ala Ser Val Pro Cys Ser

325

<210> 8

<211> 306

<212> PRT

<213> Artificial Sequence

<220>

<223> IL12B(23-328)

<400> 8

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr

1 5 10 15

Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu

20 25 30

Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly

35 40 45

Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly

50 55 60

Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu

65 70 75 80

Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys

85 90 95

Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys

100 105 110

Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr

115 120 125

Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln

130 135 140

Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly

145 150 155 160

Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala

165 170 175

Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala

180 185 190

Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg

195 200 205

Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu

210 215 220

Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp

225 230 235 240

Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln

245 250 255

Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr

260 265 270

Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala

275 280 285

Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro

290 295 300

Cys Ser

305

<210> 9

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218

<400> 9

Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr

1 5 10 15

Lys Gly

<210> 10

<211> 543

<212> PRT

<213> Artificial Sequence

<220>

<223>IL12

<400> 10

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu

1 5 10 15

Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val

20 25 30

Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu

35 40 45

Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln

50 55 60

Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys

65 70 75 80

Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val

85 90 95

Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp

100 105 110

Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe

115 120 125

Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp

130 135 140

Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg

145 150 155 160

Gly Ser Ser Asp Pro Glyn Gly Val Thr Cys Gly Ala Ala Thr Leu Ser

165 170 175

Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu

180 185 190

Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile

195 200 205

Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr

210 215 220

Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn

225 230 235 240

Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp

245 250 255

Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr

260 265 270

Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg

275 280 285

Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala

290 295 300

Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Ser Trp Ser

305 310 315 320

Glu Trp Ala Ser Val Pro Cys Ser Gly Ser Thr Ser Gly Ser Gly Lys

325 330 335

Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Arg Asn Leu Pro Val Ala

340 345 350

Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu

355 360 365

Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu

370 375 380

Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys

385 390 395 400

Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys

405 410 415

Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly

420 425 430

Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu

435 440 445

Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr

450 455 460

Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp

465 470 475 480

Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe

485 490 495

Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe

500 505 510

Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile

515 520 525

Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser

530 535 540

<210> 11

<211> 261

<212> PRT

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 11

Met Ile Glu Thr Tyr Asn Gln Thr Ser Pro Arg Ser Ala Ala Thr Gly

1 5 10 15

Leu Pro Ile Ser Met Lys Ile Phe Met Tyr Leu Leu Thr Val Phe Leu

20 25 30

Ile Thr Gln Met Ile Gly Ser Ala Leu Phe Ala Val Tyr Leu His Arg

35 40 45

Arg Leu Asp Lys Ile Glu Asp Glu Arg Asn Leu His Glu Asp Phe Val

50 55 60

Phe Met Lys Thr Ile Gln Arg Cys Asn Thr Gly Glu Arg Ser Leu Ser

65 70 75 80

Leu Leu Asn Cys Glu Glu Ile Lys Ser Gln Phe Glu Gly Phe Val Lys

85 90 95

Asp Ile Met Leu Asn Lys Glu Glu Thr Lys Lys Glu Asn Ser Phe Glu

100 105 110

Met Gln Lys Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser

115 120 125

Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly

130 135 140

Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln

145 150 155 160

Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr

165 170 175

Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser

180 185 190

Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala

195 200 205

Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His

210 215 220

Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn

225 230 235 240

Val Thr Asp Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe

245 250 255

Gly Leu Leu Lys Leu

260

<210> 12

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA wild type

<400> 12

augcagaucc cacaggcgcc cuggccaguc gucugggcgg ugcuacaacu gggcuggcgg 60

cgggauggu ucuuagacuc cccagacagg ccuggaacc cccccaccuu cuccccagcc 120

cugcucgugg ugaccgaagg ggacaacgcc accuucaccu gcagcuucuc caacacaucg 180

gagagcuucg ugcuaaacug guaccgcaug agccccagca accagacggga caagcuggcc 240

300

360

uaccucugug gggccaucuc ccuggccccc aaggcgcaga ucaaagagag ccugcgggca 420

gagcucaggg ugacagagag aagggcagaa gugcccacag cccaccccag ccccucaccc 480

aggccagccg gccaguucca aacccuggug guuggugucg ugggcggccu gcugggcagc 540

cuggugcugc uagucugggu ccuggccguc aucugcuccc gggccgcacg agggacaaua 600

ggagccaggc gcaccggcca gccccugaag gaggaccccu cagccgugcc uguguucucu 660

guggacuaug gggagcugga uuuccagugg cgagagaaga ccccggagcc ccccgugccc 720

ugugucccug agcagacgga guaugccacc auugucuuuc cuagcggaau gggcaccuca 780

ucccccgccc gcaggggcuc agccgacggc ccucggagug cccagccacu gaggccugag 840

gauggacacu gcucuuggcc ccucuga 867

<210> 13

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA wild type

<400> 13

augcagaucc cacaggcgcc cuggccaguc gucugggcgg ugcuacaacu gggcuggcgg 60

cgggauggu ucuuagacuc cccagacagg ccuggaacc cccccaccuu cuccccagcc 120

cugcucgugg ugaccgaagg ggacaacgcc accuucaccu gcagcuucuc caacacaucg 180

gagagcuucg ugcuaaacug guaccgcaug agccccagca accagacggga caagcuggcc 240

300

360

uaccucugug gggccaucuc ccuggccccc aaggcgcaga ucaaagagag ccugcgggca 420

gagcucaggg ugacagagag aagggcauga 450

<210> 14

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA wild type

<400> 14

60

uuggccagaa accuccccgu ggccacucca gaccaggaa uguucccaug ccuucaccac 120

ucccaaaacc ugcugagggc cgucagcaac augcuccaga aggccagaca aacucuagaa 180

uuuuacccuu gcacuucuga agagauugau caugaagaua ucacaaaaga uaaaaccagc 240

acagugggagg ccuguuuacc auuggaauua accaagaaug agaguugccu aaauuccaga 300

gagaccucuu ucauaacuaa ugggaguugc cuggccucca gaaagaccuc uuuuaugaug 360

gcccugugcc uuaguaguau uuaugaagac uugaagaugu accaggugga guucaagacc 420

augaaugcaa agcuucugau ggaucuaag aggcagaucu uucuagauca aaacaugcug 480

gcaguuauug augagcugau gcaggcccug aauuucaaca gugagacugu gccacaaaaa 540

uccucccuug aagaaccgga uuuuuauaaa acuaaaauca agcuucugcau acuucuucau 600

660

<210> 15

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA wild type

<400> 15

60

uuggccagaa accuccccgu ggccacucca gaccaggaa uguucccaug ccuucaccac 120

ucccaaaacc ugcugagggc cgucagcaac augcuccaga aggccagaca aacucuagaa 180

uuuuacccuu gcacuucuga agagauugau caugaagaua ucacaaaaga uaaaaccagc 240

acagugggagg ccuguuuacc auuggaauua accaagaaug agaguugccu aaauuccaga 300

gagaccucuu ucauaacuaa ugggaguugc cuggccucca gaaagaccuc uuuuaugaug 360

gcccugugcc uuaguaguau uuaugaagac uugaagaugu accaggugga guucaagacc 420

augaaugcaa agcuucugau ggaucuaag aggcagaucu uucuagauca aaacaugcug 480

gcaguuauug augagcugau gcaggcccug aauuucaaca gugagacugu gccacaaaaa 540

uccucccuug aagaaccgga uuuuuauaaa acuaaaauca agcuucugcau acuucuucau 600

gcuuucagaa uucgggcagu gacuauugau agagugauga gcuauucugaa ugcuucc 657

<210> 16

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA wild type

<400> 16

agaaaccucc ccguggccac uccagaccca ggaauguucc caugccuuca ccacucccaa 60

aaccugcuga gggccgucag caacaugcuc cagaaggcca gacaaacucu agaauuuuac 120

ccuugcacuu cugaagagau ugaucaugaa gauaucacaa aagauaaaac cagcacagug 180

gaggccuguu uaccauugga auuaaccaag aaugagaguu gccuaaauuc cagagagacc 240

ucuuucauaa cuaaugggag uugccuggcc uccagaaaga ccucuuuuau gauggcccug 300

ugccuuagua guauuuauga agacuugaag auguaccagg uggaguucaa gaccaugaau 360

gcaaagcuuc ugauggaucc uaagaggcag aucuuucuag aucaaaacau gcuggcaguu 420

auugaugagc ugaugcaggc ccugaauuuc aacagugaga cugugccaca aaaauccucc 480

cuugaagaac cggauuuuua uaaaacuaaa aucaagcucu gcauacuucu ucaugcuuuc 540

agaauucggg cagugacuau ugauagagug augagcuauc ugaaugcuuc cuaa 594

<210> 17

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA wild type

<400> 17

augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc 60

guggccaauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau 120

gccccuggag aaauggggu ccucaccugu gacaccccug aagaagaugg uaucaccugg 180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa 240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg 300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag 360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc 420

accugcuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga 480

ggcucuucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc 540

aggggacag acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca 600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau 660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac 720

uugcagcuga agccauuaaa gaauucucgg cagguggagg ucagcuggga guacccugac 780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag 840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc 900

960

gaaugggcau cugugcccug caguuag 987

<210> 18

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA wild type

<400> 18

augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc 60

guggccaauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau 120

gccccuggag aaauggggu ccucaccugu gacaccccug aagaagaugg uaucaccugg 180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa 240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg 300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag 360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc 420

accugcuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga 480

ggcucuucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc 540

aggggacag acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca 600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau 660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac 720

uugcagcuga agccauuaaa gaauucucgg cagguggagg ucagcuggga guacccugac 780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag 840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc 900

960

gaaugggcau cugugcccug cagu 984

<210> 19

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA wild type

<400> 19

auaugggaac ugaagaaaga uguuuauguc guagaauugg auugguaucc ggaugccccu 60

ggagaaaugg ugguccucac cugugacacc ccugaagaag augguaucac cuggaccuug 120

gaccagagca gugaggucuu aggcucuggc aaaacccuga ccauccaagu caaagaguuu 180

ggagaugcug gccaguacac cugucacaaa ggaggcgagg uucuaagcca uucgcuccug 240

cugcuucaca aaaaggaaga uggaauuugg uccacugaua uuuuaaagga ccagaaagaa 300

360

ugguggcuga cgacaaucag uacugauuug acauucagug ucaaaagcag cagaggcucu 420

ucugaccccc aaggggugac gugcggagcu gcuacacucu cugcagagag agucagaggg 480

gacaacaagg aguaugagua cucaguggag ugccagggagg acagugccug cccagcugcu 540

gaggagaguc ugcccauuga ggucauggug gaugccguuc acaagcucaa guaugaaaac 600

uacaccagca gcuucuucau cagggacauc aucaaaccug acccacccaa gaacuugcag 660

cugaagccau uaaagaauuc ucggcaggug gaggucagcu gggaguaccc ugacaccugg 720

aguacuccac auuccuacuu cucccugaca uucugcguuc agguccaggg caagagcaag 780

agagaaaaga aagauagagu cuucacggac aagaccucag ccacggucau cugccgcaaa 840

aaugccagca uuagcgugcg ggcccaggac cgcuacuaua gcucaucuug gagcgaaugg 900

gcaucugugc ccugcaguua g 921

<210> 20

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA wild type

<400> 20

ggcaguacuu cgggcagugg uaagccuggu agggugagg guaguacuaa gggu 54

<210> 21

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA wild type

<400> 21

augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc 60

guggccaauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau 120

gccccuggag aaauggggu ccucaccugu gacaccccug aagaagaugg uaucaccugg 180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa 240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg 300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag 360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc 420

accugcuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga 480

ggcucuucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc 540

aggggacag acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca 600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau 660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac 720

uugcagcuga agccauuaaa gaauucucgg cagguggagg ucagcuggga guacccugac 780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag 840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc 900

960

1020

gaggguagua cuaaggguag aaaccucccc guggccacuc cagacccagg aauguuccca 1080

ugccuucacc acucccaaaa ccugcugagg gccgucagca acaugcucca gaaggccaga 1140

1200

gauaaaacca gcacagugga ggccuguuua ccauuggaau uaaccaagaa ugagaguugc 1260

cuaaauucca gagagaccuc uuucauaacu aaugggaguu gccuggccuc cagaaagacc 1320

ucuuuuauga uggccugug ccuuaguagu auuuaugaag acuugaagau guaccaggug 1380

1440

caaaacaugc uggcaguuau ugaugagcug augcaggccc ugaauuucaa cagugagacu 1500

gugccacaaa aauccucccu ugaagaaccg gauuuuuaua aaacuaaaau caagcucugc 1560

1620

aaugcuuccu aa 1632

<210> 22

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA wild type

<400> 22

augaucgaaa cauacaacca aacuucuccc cgaucugcgg ccacuggacu gcccaucagc 60

augaaaauuu uuauguauuu acuuacuguu uuucuuauca cccagaugau ugggucagca 120

cuuuuugcug uguaucuuca uagaagguug gacaagauag aagaugaaag gaaucuucau 180

gaagauuuug uauucauga aacgauacag agaugcaaca caggagaaag auccuuaucc 240

uuacugaacu gugaggagau uaaaagccag uuugaaggcu uugugaagga uauaauguua 300

360

caaauugcgg cacaugucau aagugaggcc agcaguaaaa caacaucugu guuacagugg 420

gcugaaaaag gauacuacac caugagcaac aacuugguaa cccuggaaaa ugggaaacag 480

cugaccguua aaagacaagg acucuauuau aucuaugccc aagucaccuu cuguuccaau 540

cgggaagcuu cgagucaagc uccauuuaua gccagccucu gccuaaaguc cccgguaga 600

660

caauccauuc acuugggagg aguauuugaa uugcaaccag gugcuucggu guuugucaau 720

gugacugauc caagccaagu gagccauggc acuggcuuca cguccuuugg cuuacucaaa 780

cucuga 786

<210> 23

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt1

<400> 23

augcagaucc cccaggcccc guggcccgug gucugggccg ugcugcagcu cggcuggcgc 60

cccggguggu uccuggacag ccccgaccgg ccguggaacc cgcccccuu cucccccgcg 120

cugcucgugg ucaccgaggg cgacaacgcc acguucacgu gcagcuucuc caacaccagc 180

gaguccuucg ugcugaacug guaccgcaug agccccucca accagaccga caagcuggcc 240

gccuuccccg aggaccggag ccagcccggg caggacugcc gcuuccgggu gacccagcuc 300

cccaacggcc gcgacuucca cauguccguc gugcgggccc gcgggaacga cagcgggacc 360

uaccugucg gcgcgaucuc ccuggccccg aaggcccaga ucaagggag ccuccgcgcc 420

gagcugcggg ugaccgagcg ccgggcggag guccccaccg cccaccccuc ccccagcccg 480

cgccccgccg gccaguucca gacgcuggug gugggggucg ugggcgggcu ccugggcucc 540

cuggugcucc uggucugggu gcuggccgug aucugcagcc gggccgcgcg cgggaccauc 600

ggcgcccggc gcaccggcca gccccucaag gaggaccccu ccgccguccc gguguucagc 660

guggacuacg gggagcugga cuuccagugg cgggagaaga cccccgagcc gcccgucccc 720

ugcgugcccg agcagacgga guacgccacc aucguguucc ccuccggcau ggggaccagc 780

agccccgccc gccggggcuc cgcggacggc ccgcgcagcg cccagccccu gcgccccgag 840

gacgggcacu gcuccuggcc gcucuga 867

<210> 24

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt1

<400> 24

augcagaucc cccaggcccc guggcccgug gucugggccg ugcugcagcu cggcuggcgc 60

cccggguggu uccuggacag ccccgaccgg ccguggaacc cgcccccuu cucccccgcg 120

cugcucgugg ucaccgaggg cgacaacgcc acguucacgu gcagcuucuc caacaccagc 180

gaguccuucg ugcugaacug guaccgcaug agccccucca accagaccga caagcuggcc 240

gccuuccccg aggaccggag ccagcccggg caggacugcc gcuuccgggu gacccagcuc 300

cccaacggcc gcgacuucca cauguccguc gugcgggccc gcgggaacga cagcgggacc 360

uaccugucg gcgcgaucuc ccuggccccg aaggcccaga ucaagggag ccuccgcgcc 420

gagcugcggg ugaccgagcg ccgggcguga 450

<210> 25

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt1

<400> 25

augugccccg cccgcagccu gcuccuggug gccacccugg uccuccuggga ccaccugucc 60

cucgcgcgga accugccggu ggccaccccc gaccccggca uguuccccug ccugcaccac 120

agccagaacc uccugcgcgc cguguccaac augcugcaga aggcccggca gacgcucgag 180

uucuacccgu gcaccagcga ggagaucgac cacgaggaca ucaccaagga caagaccucc 240

acggucgagg ccugccugcc ccuggagcuc accaagaacg agagcugccu gaacucccgc 300

gagaccagcu ucaucaccaa cggguccugc cuggcgagcc ggaagacguc cuucaugaug 360

gcccucugcc ugagcuccau cuacgaggac cugaagaugu accaggugga guucaagacc 420

augaacgcca agcuccugau ggaccccaag cgccagaucu uccuggacca gaacaugcuc 480

gccgugaucg acgagcugau gcaggcgcug aacuucaaca gcgagaccgu cccccagaag 540

uccagccucg aggagccgga cuucuacaag accaagauca agcugugcau ccugcuccac 600

660

<210> 26

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt1

<400> 26

augugccccg cccgcagccu gcuccuggug gccacccugg uccuccuggga ccaccugucc 60

cucgcgcgga accugccggu ggccaccccc gaccccggca uguuccccug ccugcaccac 120

agccagaacc uccugcgcgc cguguccaac augcugcaga aggcccggca gacgcucgag 180

uucuacccgu gcaccagcga ggagaucgac cacgaggaca ucaccaagga caagaccucc 240

acggucgagg ccugccugcc ccuggagcuc accaagaacg agagcugccu gaacucccgc 300

gagaccagcu ucaucaccaa cggguccugc cuggcgagcc ggaagacguc cuucaugaug 360

gcccucugcc ugagcuccau cuacgaggac cugaagaugu accaggugga guucaagacc 420

augaacgcca agcuccugau ggaccccaag cgccagaucu uccuggacca gaacaugcuc 480

gccgugaucg acgagcugau gcaggcgcug aacuucaaca gcgagaccgu cccccagaag 540

uccagccucg aggagccgga cuucuacaag accaagauca agcugugcau ccugcuccac 600

gccuuccgga uccgcgccgu gacgaucgac cgggugaugu ccuaccua cgccagc 657

<210> 27

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt1

<400> 27

cggaaccugc cgguggccac ccccgacccc ggcauguucc ccugccugca ccacagccag 60

aaccuccugc gcgccguguc caacaugcug cagaaggccc ggcagacgcu cgaguucuac 120

ccgugcacca gcgaggagau cgaccacgag gacaucacca aggacaagac cuccacgguc 180

gaggccugcc ugcccugga gcucaccaag aacgagagcu gccugaacuc ccgcgagacc 240

agcuucauca ccaacggguc cugccuggcg agccggaaga cguccuucau gauggcccuc 300

ugccuagcu ccaucuacga ggaccugaag auguaccagg uggaguucaa gaccaugaac 360

gccaagcucc ugauggaccc caagcgccag aucuuccugg accagaacau gcucgccgug 420

aucgacgagc ugaugcaggc gcugaacuuc aacagcgaga ccguccccca gaaguccagc 480

cucgaggagc cggacuucua caagaccaag aucaagcugu gcauccugcu ccacgccuuc 540

cggauccgcg ccgugacgau cgaccgggug auguccuacc ugaacgccag cuga 594

<210> 28

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt1

<400> 28

augugccacc agcagcuggu gaucagcugg uucucccucg ucuuccuggc cagcccccug 60

guggccaucu gggagcucaa gaaggacgug uacgucgugg agcuggacug guacccggac 120

gcgcccggcg agaugguggu ccugaccugc gacacccccg aggaggacgg gaucacgugg 180

acccucgacc aguccagcga ggugcugggc uccgggaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggggca guacacgugc cacaagggcg gcgagguccu cagccacucc 300

cugcugcucc ugcacaagaa ggaggacggg aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgguuc 420

acgugcuggu ggcugaccac caucagcacc gaccugaccu ucuccgucaa gagcucccgc 480

gggagcuccg acccgcaggg cgugacgugc ggggccgcca cccucagcgc ggagcgggug 540

cgcggcgaca acaaggagua cgaguacucc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agucccugcc caucgaggug auggucgacg cggugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucauccgg gacaucauca agcccgaccc gcccaagaac 720

cuccagcuga agccccugaa gaacucccgc cagguggagg ucagcuggga guaccccgac 780

accuggucca cgccgcacag cuacuucucc cucaccuucu gcguccaggu gcagggcaag 840

agcaagcggg agaagaagga ccgcguguuc accgacaaga ccuccgccac ggugaucugc 900

cggaagaacg cggcaucuc cgugcgcgcc caggaccggu acuacagcuc cagcuggucc 960

gagugggcca gcguccccug cuccuga 987

<210> 29

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt1

<400> 29

augugccacc agcagcuggu gaucagcugg uucucccucg ucuuccuggc cagcccccug 60

guggccaucu gggagcucaa gaaggacgug uacgucgugg agcuggacug guacccggac 120

gcgcccggcg agaugguggu ccugaccugc gacacccccg aggaggacgg gaucacgugg 180

acccucgacc aguccagcga ggugcugggc uccgggaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggggca guacacgugc cacaagggcg gcgagguccu cagccacucc 300

cugcugcucc ugcacaagaa ggaggacggg aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgguuc 420

acgugcuggu ggcugaccac caucagcacc gaccugaccu ucuccgucaa gagcucccgc 480

gggagcuccg acccgcaggg cgugacgugc ggggccgcca cccucagcgc ggagcgggug 540

cgcggcgaca acaaggagua cgaguacucc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agucccugcc caucgaggug auggucgacg cggugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucauccgg gacaucauca agcccgaccc gcccaagaac 720

cuccagcuga agccccugaa gaacucccgc cagguggagg ucagcuggga guaccccgac 780

accuggucca cgccgcacag cuacuucucc cucaccuucu gcguccaggu gcagggcaag 840

agcaagcggg agaagaagga ccgcguguuc accgacaaga ccuccgccac ggugaucugc 900

cggaagaacg cggcaucuc cgugcgcgcc caggaccggu acuacagcuc cagcuggucc 960

gagugggcca gcguccccug cucc 984

<210> 30

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt1

<400> 30

aucgggagc ucaagaagga cguguacguc guggagcugg acugguaccc ggacgcgccc 60

ggcgagaugg ugguccugac cugcgacacc cccgaggagg acgggaucac guggacccuc 120

gaccagucca gcgaggugcu gggcuccggg aagacccuga ccauccaggu gaaggaguuc 180

ggcgacgccg ggcaguacac gugccacaag ggcggcgagg uccucagcca cucccugcug 240

cuccugcaca agaaggagga cgggaucugg agcaccgaca uccugaagga ccagaaggag 300

cccaagaaca agaccuuccu ccgcugcgag gccaagaacu acuccggccg guucacgugc 360

ugguggcuga ccaccaucag caccgaccug accuucuccg ucaagagcuc ccgcgggagc 420

uccgacccgc agggcgugac gugcggggcc gccacccuca gcgcggagcg ggugcgcggc 480

acagcgccug ccccgccgcc 540

gaggaguccc ugcccaucga ggugaugguc gacgcggugc acaagcugaa guacgagaac 600

uacaccagca gcuucuucau ccgggacauc aucaagcccg acccgcccaa gaaccuccag 660

cugaagcccc ugaagaacuc ccgccaggug gaggucagcu gggaguaccc cgacaccugg 720

uccacgccgc acagcuacuu cucccucacc uucugcgucc aggugcaggg caagagcaag 780

cgggagaaga aggaccgcgu guucaccgac aagaccuccg ccacggugau cugccggaag 840

aacgccagca ucuccgugcg cgcccaggac cgguacuaca gcuccagcug guccgagugg 900

gccagcgucc ccugcuccug a 921

<210> 31

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt1

<400> 31

ggcagcaccu ccgggagcgg caagcccggg uccggcgagg ggagcaccaa gggc 54

<210> 32

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt1

<400> 32

augugccacc agcagcuggu gaucagcugg uucucccucg ucuuccuggc cagcccccug 60

guggccaucu gggagcucaa gaaggacgug uacgucgugg agcuggacug guacccggac 120

gcgcccggcg agaugguggu ccugaccugc gacacccccg aggaggacgg gaucacgugg 180

acccucgacc aguccagcga ggugcugggc uccgggaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggggca guacacgugc cacaagggcg gcgagguccu cagccacucc 300

cugcugcucc ugcacaagaa ggaggacggg aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgguuc 420

acgugcuggu ggcugaccac caucagcacc gaccugaccu ucuccgucaa gagcucccgc 480

gggagcuccg acccgcaggg cgugacgugc ggggccgcca cccucagcgc ggagcgggug 540

cgcggcgaca acaaggagua cgaguacucc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agucccugcc caucgaggug auggucgacg cggugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucauccgg gacaucauca agcccgaccc gcccaagaac 720

cuccagcuga agccccugaa gaacucccgc cagguggagg ucagcuggga guaccccgac 780

accuggucca cgccgcacag cuacuucucc cucaccuucu gcguccaggu gcagggcaag 840

agcaagcggg agaagaagga ccgcguguuc accgacaaga ccuccgccac ggugaucugc 900

cggaagaacg cggcaucuc cgugcgcgcc caggaccggu acuacagcuc cagcuggucc 960

gagugggcca gcguccccug cuccggcagc accuccggga gcggcaagcc cggguccggc 1020

gaggggagca ccaagggccg gaaccugccg guggccaccc ccgaccccgg cauguucccc 1080

ugccugcacc acagccagaa ccuccugcgc gccgugucca acaugcugca gaaggcccgg 1140

cagacgcucg aguucuaccc gugcaccagc gaggagaucg accacgagga caucaccaag 1200

gacaagaccu ccacggucga ggccugccug ccccuggagc ucaccaagaa cgagagcugc 1260

1320

uccuucauga uggccucug ccugagcucc aucuacgagg accugaagau guaccaggug 1380

gaguucaaga ccaugaacgc caagcuccug auggaccca agcgccagau cuuccuggac 1440

1500

gucccccaga aguccagccu cgaggagccg gacuucuaca agaccaagau caagcugugc 1560

1620

aacgccagcu ga 1632

<210> 33

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt1

<400> 33

augaucgaga ccuacacca gaccagcccc cgcuccgccg ccacgggccu gccgaucagc 60

augaagaucu ucauguaccu ccugaccgug uuccugauca cccagaugau cggguccgcg 120

cuguucgccg ucuaccugca ccggcgccug gacaagaucg aggacgagcg gaaccuccac 180

gaggacuucg uguucaugaa gaccauccag cgcugcaaca cgggcgagcg gagccugucc 240

cugcucaacu gcgaggagau caagagccag uucgaggggu ucgugaagga caucaugcug 300

aacaaggagg agaccaagaa ggagaacucc uucgagaugc agaagggcga ccagaacccc 360

cagaucgccg cccacgucau cagcgaggcc uccagcaaga ccaccuccgu gcugcagugg 420

gcggagaagg gguacuacac gaugagcaac aaccucguga cccuggagaa cggcaagcag 480

cugaccguca agcgccaggg ccucuacuac aucuacgccc agguaccuu cugcuccaac 540

cgggaggcca gcucccaggc ccccuucauc gcgagccugu gccugaaguc cccggggcgc 600

uucgagcgga uccuccugcg cgccgccaac acgcacagcu ccgccaagcc gugcggccag 660

cagagcaucc accucggggg cguguucgag cuccagcccg gggccagcgu cuucgugaac 720

gugaccgacc ccucccaggu cagccacggc accggcuuca ccuccuucgg gcugcugaag 780

cucuga 786

<210> 34

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt2

<400> 34

augcagaucc cccaggcccc cuggcccguc gucugggccg uccuccagcu cggcuggcgc 60

cccggcuggu uccucgacuc ccccgaccgc ccuggaacc cccccaccuu cucccccgcc 120

cuccucgucg ucaccgagg cgacaacgcc accuucaccu guuccuucuc caacaccucc 180

gaguccuucg uccucaacug guaccgcaug uccccccucca accagaccga caagcucgcc 240

gccuuccccg aggaccgcuc ccagcccggc caggacugcc gcuuccgcgu cacccagcuc 300

cccaacggcc gcgacuucca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc ccucgccccc aaggcccaga ucaaggaguc ccuccgcgcc 420

gagcuccgcg ucaccgagcg ccgcgccgag guccccaccg cccaccccuc ccccuccccc 480

cgccccgccg gccaguucca gacccucguc gucggcgucg ucggcggccu ccucggcucc 540

cucguccucc ucgucugggu ccucgccguc aucugcuccc gcgccgcccg cggcaccauc 600

ggcgcccgcc gcaccggcca gccccucaag gaggaccccu ccgccguccc cgucuucucc 660

gucgacuacg gcgagcucga cuuccagugg cgcgagaaga cccccgagcc ccccgucccc 720

ugcguccccg agcagaccga guacgccacc aucgucuucc ccuccggcau gggcaccucc 780

ucccccgccc gccgcggcuc cgccgacggc ccccgcuccg cccagccccu ccgccccgag 840

gacggccacu gcuccuggcc ccucuga 867

<210> 35

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt2

<400> 35

augcagaucc cccaggcccc cuggcccguc gucugggccg uccuccagcu cggcuggcgc 60

cccggcuggu uccucgacuc ccccgaccgc ccuggaacc cccccaccuu cucccccgcc 120

cuccucgucg ucaccgagg cgacaacgcc accuucaccu guuccuucuc caacaccucc 180

gaguccuucg uccucaacug guaccgcaug uccccccucca accagaccga caagcucgcc 240

gccuuccccg aggaccgcuc ccagcccggc caggacugcc gcuuccgcgu cacccagcuc 300

cccaacggcc gcgacuucca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc ccucgccccc aaggcccaga ucaaggaguc ccuccgcgcc 420

gagcuccgcg ucaccgagcg ccgcgccuga 450

<210> 36

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt2

<400> 36

augugccccg cccgcucccu ccuccucguc gccacccucg uccuccucga ccaccucucc 60

cucgcccgca accuccccgu cgccaccccc gaccccggca uguuccccug ccuccaccac 120

ucccagaacc uccuccgcgc cgucuccaac augcuccaga aggcccgcca gacccucgag 180

uucuaccccu gcaccuccga ggagaucgac cacgaggaca ucaccaagga caagaccucc 240

accgucgagg ccugccuccc ccucgagcuc accaagaacg aguccugccu caacucccgc 300

gagaccuccu ucaucaccaa cggcuccugc cucgccuccc gcaagaccuc cuucaugaug 360

gcccucugcc ucuccuccau cuacgaggac cucaagaugu accaggucga guucaagacc 420

augaacgcca agcuccucau ggaccccaag cgccagaucu uccucgacca gaacaugcuc 480

gccgucaucg acgagcucau gcaggcccuc aacuucaacu ccgagaccgu cccccagaag 540

uccuccucg aggagcccga cuucuacaag accaagauca agcucugcau ccuccuccac 600

gccuuccgca uccgcgccgu caccaucgac cgcgucaugu ccuaccucaa cgccuccuga 660

<210> 37

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt2

<400> 37

augugccccg cccgcucccu ccuccucguc gccacccucg uccuccucga ccaccucucc 60

cucgcccgca accuccccgu cgccaccccc gaccccggca uguuccccug ccuccaccac 120

ucccagaacc uccuccgcgc cgucuccaac augcuccaga aggcccgcca gacccucgag 180

uucuaccccu gcaccuccga ggagaucgac cacgaggaca ucaccaagga caagaccucc 240

accgucgagg ccugccuccc ccucgagcuc accaagaacg aguccugccu caacucccgc 300

gagaccuccu ucaucaccaa cggcuccugc cucgccuccc gcaagaccuc cuucaugaug 360

gcccucugcc ucuccuccau cuacgaggac cucaagaugu accaggucga guucaagacc 420

augaacgcca agcuccucau ggaccccaag cgccagaucu uccucgacca gaacaugcuc 480

gccgucaucg acgagcucau gcaggcccuc aacuucaacu ccgagaccgu cccccagaag 540

uccuccucg aggagcccga cuucuacaag accaagauca agcucugcau ccuccuccac 600

gccuuccgca uccgcgccgu caccaucgac cgcgucaugu ccuaccucaa cgccucc 657

<210> 38

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt2

<400> 38

cgcaaccucc ccgucgccac ccccgacccc ggcauguucc ccugccucca ccacucccag 60

aaccuccucc gcgccgucuc caacaugcuc cagaaggccc gccagacccu cgaguucuac 120

cccugcaccu ccgaggagau cgaccacgag gacaucacca aggacaagac cuccaccguc 180

gaggccugcc ucccccucga gcucaccaag aacgaguccu gccucaacuc ccgcgagacc 240

uccuucauca ccaacggcuc cugccucgcc ucccgcaaga ccuccuucau gauggcccuc 300

ugccucuccu ccaucuacga ggaccucaag auguaccagg ucgaguucaa gaccaugaac 360

gccaagcucc ucauggaccc caagcgccag aucuuccucg accagaacau gcucgccguc 420

aucgacgagc ucaugcaggc ccucaacuuc aacuccgaga ccguccccca gaaguccucc 480

cucgaggagc ccgacuucua caagaccaag aucaagcucu gcauccuccu ccacgccuuc 540

cgcauccgcg ccgucaccau cgaccgcguc auguccuacc ucaacgccuc cuga 594

<210> 39

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt2

<400> 39

augugccacc agcagcucgu caucuccugg uucucccucg ucuuccucgc cuccccccuc

gucgccaucu gggagcucaa gaaggacguc uacgucgucg agcucgacug guaccccgac 120

gcccccggcg agauggucgu ccucaccugu gacacccccg aggaggacgg caucaccugg 180

acccucgacc aguccuccga gguccucggc uccggcaaga cccucaccau ccaggucaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgagguccu cucccacucc 300

cuccuccucc uccacaagaa ggaggacggc aucuggucca ccgacauccu caaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgcuuc 420

accuguuggu ggcucaccac caucuccacc gaccucaccu ucuccgucaa guccucccgc 480

ggcuccuccg acccccaggg cgucaccugu ggcgccgcca cccucuccgc cgagcgcguc 540

cgcggcgaca acaaggagua cgaguacucc gucgagugcc aggaggacuc cgccugcccc 600

gccgccgagg agucccuccc caucgagguc auggucgacg ccguccacaa gcucaaguac 660

gagaacuaca ccuccuccuu cuucauccgc gacaucauca agcccgaccc ccccaagaac 720

cuccagcuca agcccccucaa gaacucccgc caggucgagg ucuccuggga guaccccgac 780

accuggucca ccccccacuc cuacuucucc cucaccuucu gcguccaggu cggggcaag 840

uccaagcgcg agaagaagga ccgcgucuuc accgacaaga ccuccgccac cgucaucugc 900

cgcaagaacg ccuccaucuc cguccgcgcc caggaccgcu acuacuccuc cuccuggucc 960

gagugggccu ccguccccug cuccuga 987

<210> 40

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt2

<400> 40

augugccacc agcagcucgu caucuccugg uucucccucg ucuuccucgc cuccccccuc

gucgccaucu gggagcucaa gaaggacguc uacgucgucg agcucgacug guaccccgac 120

gcccccggcg agauggucgu ccucaccugu gacacccccg aggaggacgg caucaccugg 180

acccucgacc aguccuccga gguccucggc uccggcaaga cccucaccau ccaggucaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgagguccu cucccacucc 300

cuccuccucc uccacaagaa ggaggacggc aucuggucca ccgacauccu caaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgcuuc 420

accuguuggu ggcucaccac caucuccacc gaccucaccu ucuccgucaa guccucccgc 480

ggcuccuccg acccccaggg cgucaccugu ggcgccgcca cccucuccgc cgagcgcguc 540

cgcggcgaca acaaggagua cgaguacucc gucgagugcc aggaggacuc cgccugcccc 600

gccgccgagg agucccuccc caucgagguc auggucgacg ccguccacaa gcucaaguac 660

gagaacuaca ccuccuccuu cuucauccgc gacaucauca agcccgaccc ccccaagaac 720

cuccagcuca agccccucaa gaacucccgc caggucgagg ucuccuggga guaccccgac 780

accuggucca ccccccacuc cuacuucucc cucaccuucu gcguccaggu cggggcaag 840

uccaagcgcg agaagaagga ccgcgucuuc accgacaaga ccuccgccac cgucaucugc 900

cgcaagaacg ccuccaucuc cguccgcgcc caggaccgcu acuacuccuc cuccuggucc 960

gagugggccu ccguccccug cucc 984

<210> 41

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt2

<400> 41

aucgggagc ucaagaagga cgucuacguc gucgagcucg acugguaccc cgacgccccc 60

ggcgagaugg ucguccucac cugugacacc cccgaggagg acggcaucac cuggacccuc 120

gaccaguccu ccgagguccu cggcuccggc aagacccuca ccauccaggu caaggaguuc 180

ggcgacgccg gccaguacac cugucacaag ggcggcgagg uccucuccca cucccuccuc 240

cuccuccaca agaaggagga cggcaucugg uccaccgaca uccucaagga ccagaaggag 300

cccaagaaca agaccuuccu ccgcugcgag gccaagaacu acuccggccg cuucaccugu 360

ugguggcuca ccaccaucuc caccgaccuc accuucuccg ucaaguccuc ccgcggcucc 420

uccgaccccc agggcgucac cuguggcgcc gccacccucu ccgccgagcg cguccgcggc 480

gacaacaagg aguacgagua cuccgucgag ugccaggagg acuccgccug ccccgccgcc 540

gaggaguccc uccccaucga ggucaugguc gacgccgucc acaagcucaa guacgagaac 600

uacaccuccu ccuucuucau ccgcgacauc aucaagcccg acccccccaa gaaccuccag 660

cucaagcccc ucaagaacuc ccgccagguc gaggucuccu gggaguaccc cgacaccugg 720

uccacccccc acuccuacuu cucccucacc uucugcgucc agguccaggg caaguccaag 780

840

aacgccucca ucuccguccg cgcccaggac cgcuacuacu ccuccuccug guccgagugg 900

gccuccgucc ccugcuccug a 921

<210> 42

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt2

<400> 42

ggcuccaccu ccggcuccgg caagcccggc uccggcgagg gcuccaccaa gggc 54

<210> 43

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt2

<400> 43

augugccacc agcagcucgu caucuccugg uucucccucg ucuuccucgc cuccccccuc

gucgccaucu gggagcucaa gaaggacguc uacgucgucg agcucgacug guaccccgac 120

gcccccggcg agauggucgu ccucaccugu gacacccccg aggaggacgg caucaccugg 180

acccucgacc aguccuccga gguccucggc uccggcaaga cccucaccau ccaggucaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgagguccu cucccacucc 300

cuccuccucc uccacaagaa ggaggacggc aucuggucca ccgacauccu caaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgcuuc 420

accuguuggu ggcucaccac caucuccacc gaccucaccu ucuccgucaa guccucccgc 480

ggcuccuccg acccccaggg cgucaccugu ggcgccgcca cccucuccgc cgagcgcguc 540

cgcggcgaca acaaggagua cgaguacucc gucgagugcc aggaggacuc cgccugcccc 600

gccgccgagg agucccuccc caucgagguc auggucgacg ccguccacaa gcucaaguac 660

gagaacuaca ccuccuccuu cuucauccgc gacaucauca agcccgaccc ccccaagaac 720

cuccagcuca agcccccucaa gaacucccgc caggucgagg ucuccuggga guaccccgac 780

accuggucca ccccccacuc cuacuucucc cucaccuucu gcguccaggu cggggcaag 840

uccaagcgcg agaagaagga ccgcgucuuc accgacaaga ccuccgccac cgucaucugc 900

cgcaagaacg ccuccaucuc cguccgcgcc caggaccgcu acuacuccuc cuccuggucc 960

gagugggccu ccguccccug cuccggcucc accuccggcu ccggcaagcc cggcuccggc 1020

gagggcucca ccaagggccg caaccucccc gucgccaccc ccgaccccgg cauguucccc 1080

ugccuccacc acucccagaa ccuccuccgc gccgucucca acaugcucca gaaggcccgc 1140

cagacccucg aguucuaccc cugcaccucc gaggagaucg accacgagga caucaccaag 1200

gacaagaccu ccaccgucga ggccugccuc ccccucgagc ucaccaagaa cgaguccugc 1260

cucaacuccc gcgagaccuc cuucaucacc aacggcuccu gccucgccuc ccgcaagacc 1320

uccuucauga uggccucug ccucuccucc aucuacgagg accucaagau guaccagguc 1380

1440

cagaacaugc ucgccgucau cgacgagcuc augcaggccc ucaacuucaa cuccgagacc 1500

gucccccaga aguccucccu cgaggagccc gacuucuaca agaccaagau caagcucugc 1560

1620

aacgccuccu ga 1632

<210> 44

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt2

<400> 44

augaucgaga ccuacacca gaccuccccc cgcuccgccg ccaccggccu ccccaucucc 60

augaagaucu ucauguaccu ccucaccguc uuccucauca cccagaugau cggcuccgcc 120

cucuucgccg ucuaccucca ccgccgccuc gacaagaucg aggacgagcg caaccuccac 180

gaggacuucg ucuucaugaa gaccauccag cgcugcaaca ccggcgagcg cucccucucc 240

cuccucaacu gcgaggagau caagucccag uucgagggcu ucgucaagga caucaugcuc 300

aacaaggagg agaccaagaa ggagaacucc uucgagaugc agaagggcga ccagaacccc 360

cagaucgccg cccacgucau cuccgaggcc uccuccaaga ccaccuccgu ccuccagugg 420

gccgagaagg gcuacuacac cauguccaac aaccucguca cccucgagaa cggcaagcag 480

cucaccguca agcgccaggg ccucuacuac aucuacgcc aggucaccuu cugcuccaac 540

cgcgaggccu ccucccaggc ccccuucauc gccucccucu gccucaaguc ccccggccgc 600

uucgagcgca uccuccuccg cgccgccaac acccacuccu ccgccaagcc cugcggccag 660

caguccaucc accucggcgg cgucuucgag cuccagcccg gcgccuccgu cuucgucaac 720

gucaccgacc ccucccaggu cucccacggc accggcuuca ccuccuucgg ccuccucaag 780

cucuga 786

<210> 45

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt3

<400> 45

augcagaucc cccaagcccc uuggccagug gucugggcug uucugcagcu cggcuggaga 60

ccgggguggu uccuugacag ccccgauagg ccuuggaacc cacccaccuu uuccccugca 120

cuguuggugg uaacagaggg agacaaugcc acuuucacgu gcucuuuuuc aaacaccagu 180

gagagcuucg uguuaaauug guaccggaug uccccaucua accagacaga uaagcuggcg 240

gcuuuucccg aagaccgcuc gcagccuggu caagauuguc gauuccgugu cacucagcua 300

ccaaauggca gagacuuuca caugucagug guuagggccc ggcgcaacga uagcgggacc 360

uaucucugcg gagcaauuag ucuggccccg aaagcucaga uaaaggaauc ccuuagagca 420

gagcugaggg ugacagaacg gcgcgccgag guccccaccg cucauccuuc uccaagcccc 480

cgaccugccg gccaguucca aacuuuggug guagguguug ucgggggacu ccugggcucc 540

cuggugcucu uagugugggu gcuggcgguc aucuguucaa gagcagccag gggcacaauu 600

ggggcucggc guaccggaca gccacuuaaa gaggacccca gugccguucc gguguuuagc 660

guagauuacg gugaauugga cuuccagugg cgcgagaaga cgccugaacc cccagugccu 720

ugcguccccg agcagacuga guaugcaacc aucguguuuc caucuggcau ggggacaucc 780

ucacccgcua gaaggggaag cgccgauggc ccucggagug cgcaaccacu gcgaccggaa 840

gacggucacu guucuuggcc ccuauga 867

<210> 46

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt3

<400> 46

augcagaucc cccaagcccc uuggccagug gucugggcug uucugcagcu cggcuggaga 60

ccgggguggu uccuugacag ccccgauagg ccuuggaacc cacccaccuu uuccccugca 120

cuguuggugg uaacagaggg agacaaugcc acuuucacgu gcucuuuuuc aaacaccagu 180

gagagcuucg uguuaaauug guaccggaug uccccaucua accagacaga uaagcuggcg 240

gcuuuucccg aagaccgcuc gcagccuggu caagauuguc gauuccgugu cacucagcua 300

ccaaauggca gagacuuuca caugucagug guuagggccc ggcgcaacga uagcgggacc 360

uaucucugcg gagcaauuag ucuggccccg aaagcucaga uaaaggaauc ccuuagagca 420

gagcugaggg ugacagaacg gcgcgccuga 450

<210> 47

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt3

<400> 47

augugccccg ccagaagccu gcuccuugug gcuacccugg ucuuguuaga ccaccugucc 60

cuagcaagga accucccugu ugccacacca gauccgggca uguuccccug ucugcaucac 120

ucucagaauc uucugcgggc ggugucaaac auguugcaaa aggcucgcca gacucucgag 180

uuuuacccuu gcacgaguga agagaucgac caugaagaua uuaccaaaga caagacaagc 240

acuguagagg ccugucugcc acuggaacuc accaaaaaug aguccugcuu aaacucucga 300

gagacaucgu ucauaaccaa ugggucaugu cuggcaagcc guaagacaag uuuuaugaug 360

gcccuuugcu uguccucuau cuaugaagau cugaaaaugu accaggugga guucaagacu 420

augaacgcua agcuacucau ggaccccaaa agacagauuu uucuggauca aaauaugcuu 480

gcagucaucg acgaacugau gcaggccuug aacuucaaua gcgagaccgu gccucagaag 540

uccucacucg aggaaccaga uuuuuauaaa acgaagauua aacuguguau cuuacugcac 600

gcuuucagga uacgggccgu uacuaucgac cgcgugauga guuaccucaa cgcgagcuga 660

<210> 48

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt3

<400> 48

augugccccg ccagaagccu gcuccuugug gcuacccugg ucuuguuaga ccaccugucc 60

cuagcaagga accucccugu ugccacacca gauccgggca uguuccccug ucugcaucac 120

ucucagaauc uucugcgggc ggugucaaac auguugcaaa aggcucgcca gacucucgag 180

uuuuacccuu gcacgaguga agagaucgac caugaagaua uuaccaaaga caagacaagc 240

acuguagagg ccugucugcc acuggaacuc accaaaaaug aguccugcuu aaacucucga 300

gagacaucgu ucauaaccaa ugggucaugu cuggcaagcc guaagacaag uuuuaugaug 360

gcccuuugcu uguccucuau cuaugaagau cugaaaaugu accaggugga guucaagacu 420

augaacgcua agcuacucau ggaccccaaa agacagauuu uucuggauca aaauaugcuu 480

gcagucaucg acgaacugau gcaggccuug aacuucaaua gcgagaccgu gccucagaag 540

uccucacucg aggaaccaga uuuuuauaaa acgaagauua aacuguguau cuuacugcac 600

gcuuucagga uacgggccgu uacuaucgac cgcgugauga guuaccucaa cgcgagc 657

<210> 49

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt3

<400> 49

aggaaccucc cuguugccac accagauccg ggcauguucc ccugucugca ucacucucag 60

aaucuucugc gggcgguguc aaacauguug caaaaggcuc gccagacucu cgaguuuuac 120

ccuugcacga gugaagagau cgaccaugaa gauauuacca aagacaagac aagcacugua 180

gaggccuguc ugccacugga acucaccaaa aaugaguccu gcuuaaacuc ucgagagaca 240

ucguucauaa ccaauggguc augucuggca agccguaaga caaguuuuau gauggcccuu 300

ugcuuguccu cuaucuauga agaucugaaa auguaccagg uggaguucaa gacuaugaac 360

gcuaagcuac ucauggaccc caaaagacag auuuuucugg aucaaaauau gcuugcaguc 420

aucgacgaac ugaugcaggc cuugaacuuc aauagcgaga ccgugccuca gaaguccuca 480

cucgaggaac cagauuuuua uaaaacgaag auuaaacugu guaucuuacu gcacgcuuuc 540

aggauacggg ccguuacuau cgaccgcgug augaguuacc ucaacgcgag cuga 594

<210> 50

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt3

<400> 50

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuugc cucuccccug 60

guugcuauuu gggaguugaa gaaagacgug uacguagugg aauuagauug guauccugac 120

gcaccaggcg agauggucgu gcugaccugu gauacaccgg aagaggacgg gauaacuugg 180

acgcuagauc agucaaguga aguucucgga agcgguaaga cccugacaau ccaggugaaa 240

gaguucggcg acgccggggca guacacuugc cauaagggag gcgagguccu uucccacucu 300

cuguugcucc ugcauaaaaa ggaagauggu auuuggucga ccgacauccu gaaggaucaa 360

aaagagccca agaacaaaac auuucucaga ugugaagcga agaauuauuc agggagguuu 420

accugcuggu gguuaacuac aauuagcacc gaccugacgu ucagugugaa auccucucgg 480

ggaagcuccg auccucaggg cguaacuugu ggcgcugcca cccuuucagc agagcgcguu 540

cgaggggaca acaaggagua cgaauauagu guggagugcc aggaagauag cgccugucca 600

gcugcagagg aaucuuugcc caucgagguc augguggacg ccgugcacaa gcugaaauac 660

gagaauuaua cauccucauu cuuuauacgu gacaucauua agccugaucc acccaaaaac 720

cuacagcuca agccucugaa aaauagcaga caagucgaag uuaguuggga guacccagac 780

acuuggucua ccccgcauuc cuacuucagc cuuacauuuu gcgugcaggu acagggaaag 840

ucgaaaaggg aaaagaagga ucggguguuc accgacaaaa cgucugcuac ugucaucugu 900

960

gagugggcaa gcguucccug cucauga 987

<210> 51

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt3

<400> 51

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuugc cucuccccug 60

guugcuauuu gggaguugaa gaaagacgug uacguagugg aauuagauug guauccugac 120

gcaccaggcg agauggucgu gcugaccugu gauacaccgg aagaggacgg gauaacuugg 180

acgcuagauc agucaaguga aguucucgga agcgguaaga cccugacaau ccaggugaaa 240

gaguucggcg acgccggggca guacacuugc cauaagggag gcgagguccu uucccacucu 300

cuguugcucc ugcauaaaaa ggaagauggu auuuggucga ccgacauccu gaaggaucaa 360

aaagagccca agaacaaaac auuucucaga ugugaagcga agaauuauuc agggagguuu 420

accugcuggu gguuaacuac aauuagcacc gaccugacgu ucagugugaa auccucucgg 480

ggaagcuccg auccucaggg cguaacuugu ggcgcugcca cccuuucagc agagcgcguu 540

cgaggggaca acaaggagua cgaauauagu guggagugcc aggaagauag cgccugucca 600

gcugcagagg aaucuuugcc caucgagguc augguggacg ccgugcacaa gcugaaauac 660

gagaauuaua cauccucauu cuuuauacgu gacaucauua agccugaucc acccaaaaac 720

cuacagcuca agccucugaa aaauagcaga caagucgaag uuaguuggga guacccagac 780

acuuggucua ccccgcauuc cuacuucagc cuuacauuuu gcgugcaggu acagggaaag 840

ucgaaaaggg aaaagaagga ucggguguuc accgacaaaa cgucugcuac ugucaucugu 900

960

gagugggcaa gcguucccug cuca 984

<210> 52

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt3

<400> 52

auuugggagu ugaagaaaga cguguacgua guggaauuag auugguaucc ugacgcacca 60

ggcgagaugg ucgugcugac cugugauaca ccggaagagg acgggauaac uuggacgcua 120

gaucagucaa gugaaguucu cggaagcggu aagacccuga caauccaggu gaaagaguuc 180

ggcgacgccg ggcaguacac uugccauaag ggaggcgagg uccuuuccca cucucuguug 240

cuccugcaua aaaaggaaga ugguauuugg ucgaccgaca uccugaagga ucaaaaagag 300

cccaagaaca aaacauuucu cagaugugaa gcgaagaauu auucagggag guuuaccugc 360

uggugguuaa cuacaauuag caccgaccug acguucagug ugaaauccuc ucggggaagc 420

uccgauccuc agggcguaac uuguggcgcu gccacccuuu cagcagagcg cguucgaggg 480

gacaacaagg aguacgaaua uaguguggag ugccaggaag auagcgccug uccagcugca 540

gaggaaucuu ugcccaucga ggucauggug gacgccgugc acaagcugaa auacgagaau 600

uauacauccu cauucuuuau acgugacauc auuaagccug auccacccaa aaaccuacag 660

cucaagccuc ugaaaaauag cagacaaguc gaaguuaguu gggaguaccc agacacuugg 720

ucuaccccgc auuccuacuu cagccuuaca uuuugcgugc agguaacaggg aaagucgaaa 780

agggaaaaga aggaucgggu guucaccgac aaaacgucug cuacugucau cugucgcaag 840

aacgccucca uuucagugag agcgcaggau agguauuaca guagcuccug gucugagugg 900

gcaagcguuc ccugcucaug a 921

<210> 53

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt3

<400> 53

ggcagcaccu ccgggucugg aaagcccggu ucaggcgagg ggaguacaaa agga 54

<210> 54

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt3

<400> 54

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuugc cucuccccug 60

guugcuauuu gggaguugaa gaaagacgug uacguagugg aauuagauug guauccugac 120

gcaccaggcg agauggucgu gcugaccugu gauacaccgg aagaggacgg gauaacuugg 180

acgcuagauc agucaaguga aguucucgga agcgguaaga cccugacaau ccaggugaaa 240

gaguucggcg acgccggggca guacacuugc cauaagggag gcgagguccu uucccacucu 300

cuguugcucc ugcauaaaaa ggaagauggu auuuggucga ccgacauccu gaaggaucaa 360

aaagagccca agaacaaaac auuucucaga ugugaagcga agaauuauuc agggagguuu 420

accugcuggu gguuaacuac aauuagcacc gaccugacgu ucagugugaa auccucucgg 480

ggaagcuccg auccucaggg cguaacuugu ggcgcugcca cccuuucagc agagcgcguu 540

cgaggggaca acaaggagua cgaauauagu guggagugcc aggaagauag cgccugucca 600

gcugcagagg aaucuuugcc caucgagguc augguggacg ccgugcacaa gcugaaauac 660

gagaauuaua cauccucauu cuuuauacgu gacaucauua agccugaucc acccaaaaac 720

cuacagcuca agccucugaa aaauagcaga caagucgaag uuaguuggga guacccagac 780

acuuggucua ccccgcauuc cuacuucagc cuuacauuuu gcgugcaggu acagggaaag 840

ucgaaaaggg aaaagaagga ucggguguuc accgacaaaa cgucugcuac ugucaucugu 900

960

gagugggcaa gcguucccug cucaggcagc accuccgggu cuggaaagcc cgguucaggc 1020

1080

ugucugcauc acucucagaa ucuucugcgg gcggugucaa acauguugca aaaggcucgc 1140

cagacucucg aguuuuaccc uugcacgagu gaagagaucg accaugaaga uauuaccaaa 1200

gacaagacaa gcacuguaga ggccugucug ccacuggaac ucaccaaaaa ugaguccugc 1260

uuaaacucuc gagagacauc guucauaacc aaugggucau gucuggcaag ccguaagaca 1320

aguuuuauga uggcccuuug cuuguccucu aucuaugaag aucugaaaau guaccaggug 1380

gaguucaaga cuaugaacgc uaagcuacuc auggaccca aaagacagau uuuucuggau 1440

caaaauauugc uugcagucau cgacgaacug augcaggccu ugaacuucaa uagcgagacc 1500

gugccucaga aguccucacu cgaggaacca gauuuuuaua aaacgaagau uaaacugugu 1560

1620 aucuuacugc acgcuuucag gauacgggcc guuacuaucg

aacgcgagcu ga 1632

<210> 55

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt3

<400> 55

augaucgaga ccuacacacca gacaagcccc agauccgccg cuacuggccu gccuauuucu 60

augaagauau ucauguaucu ccuuacggug uuucugauca cccaaaugau ugggucagca 120

uuguucgccg ucuacuuaca caggcggcug gacaaaaucg aagaugagcg caaucuacau 180

gaagacuuug uuuucaugaa gacaauucag cgaugcaaca cuggagagcg uagucucagc 240

cugcuuaauu gugaagagau caaaucccag uuugaggguu ucgugaagga uauaaugcug 300

aacaaagaag agaccaagaa ggaaaauucu uuugagaugc agaaaggcga ccaaaaccca 360

cagaucgcgg cucacguaau uucggaggcc ucaagcaaga caaccagugu guugcagugg 420

gcagaaaaag gguauuacac uauguccaau aaccucguca cacuggagaa uggaaagcag 480

cugaccguga aaagacaagg ccucuauuac aucuaugccc agguuacguu cugcucuaac 540

agggaagcua gcucccaggc accguuuauu gccucauuau gucugaagag ucccggucgg 600

uucgagcgca uccuuuugag agcugccaau acucauagcu cugcgaagcc uugcgggcag 660

caauccauac accugggagg cguguuugaa cuacagccag gcgcaucagu cuucgugaac 720

guaaccgauc ccagccaggu uagucauggg acaggauuua cuucuuucgg ucuccugaaa 780

cuuuga 786

<210> 56

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt3v

<400> 56

augcagaucc cucaggcucc uuggccuguu gugugggcug uucugcaacu uggauggcgg 60

ccuggcuggu uccuggacuc uccugacaga ccuggaauc cuccaacauu cagccccgcu 120

cugcuggugg uuaccgaggg cgauaaugcc accuucaccu guagcuucag caacaccagc 180

gagagcuucg ugcugaacug guacagaaug agccccagca accagaccga caagcuggcc 240

gccuuuccug aggauagauc ucagcccggc caggacugcc gguucagagu uacacagcug 300

360

uaucugugcg gcgccauuuc ucuggccccu aaggcucaga ucaaagagag ccugagagcc 420

gagcugagag ugacagaaag acgggccgaa gugcccacag cucacccuuc accuucucca 480

agaccugccg gccaguucca gacacugguc gugggaguug uuggcggacu gcugggaucu 540

cuggugcugc uuguuugggu gcucgccgug aucuguagca gagccgccag aggaacaauc 600

ggcgccagaa ggacaggcca gccucugaaa gaggaucccu cugcuguccc cguguucagc 660

guggacuaug gcgagcugga uuuccagugg cgggaaaaga cacccgagcc uccagugccu 720

ugugugccug agcagacaga guacgccacc aucguguucc cuagcggcau gggcacaucu 780

agcccugcca gaagaggauc ugccgacgga ccuagaucug cccagccucu cagaccugag 840

gauggccacu guagcuggcc ucuguaa 867

<210> 57

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt3v

<400> 57

augcagaucc cucaggcucc uuggccuguu gugugggcug uucugcaacu uggauggcgg 60

ccuggcuggu uccuggacuc uccugacaga ccuggaauc cuccaacauu cagccccgcu 120

cugcuggugg uuaccgaggg cgauaaugcc accuucaccu guagcuucag caacaccagc 180

gagagcuucg ugcugaacug guacagaaug agccccagca accagaccga caagcuggcc 240

gccuuuccug aggauagauc ucagcccggc caggacugcc gguucagagu uacacagcug 300

360

uaucugugcg gcgccauuuc ucuggccccu aaggcucaga ucaaagagag ccugagagcc 420

gagcugagag ugacagaaag acgggccuga 450

<210> 58

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt3v

<400> 58

60

cuggccagaa accugccagu ggccacgccu gauccuggca uguuuccuug ucugcaccac 120

agccagaacc ugcugagagc cguguccaac augcugcaga aggccagaca gacccucgag 180

uucuaccccu gcaccagcga ggaaaucgac cacgaggaca ucaccaagga caagaccagc 240

accguggaag ccugccugcc ucuggaacug acccaagaacg agagcugccu gaacagccgg 300

gaaaccagcu ucaucaccaa cggcucuugc cuggccucca gaaagaccuc cuucaugaug 360

gcccugugcc ugagcagcau cuacgaggac cugaagaugu accaggucga guucaagacc 420

augaacgcca agcugcugau ggaccccaag cggcagaucu uccuggacca gaauaugcug 480

gccgugaucg acgagcugau gcaggcccug aacuucaaca gcgagacagu gccccagaag 540

uccagccugg aagaacccga cuucuacaag accaagauca agcugugcau ccugcugcac 600

gccuuccgga ucagagccgu gaccaucgac agagugauga gcuaccugaa cgccuccuga 660

<210> 59

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt3v

<400> 59

60

cuggccagaa accugccagu ggccacgccu gauccuggca uguuuccuug ucugcaccac 120

agccagaacc ugcugagagc cguguccaac augcugcaga aggccagaca gacccucgag 180

uucuaccccu gcaccagcga ggaaaucgac cacgaggaca ucaccaagga caagaccagc 240

accguggaag ccugccugcc ucuggaacug acccaagaacg agagcugccu gaacagccgg 300

gaaaccagcu ucaucaccaa cggcucuugc cuggccucca gaaagaccuc cuucaugaug 360

gcccugugcc ugagcagcau cuacgaggac cugaagaugu accaggucga guucaagacc 420

augaacgcca agcugcugau ggaccccaag cggcagaucu uccuggacca gaauaugcug 480

gccgugaucg acgagcugau gcaggcccug aacuucaaca gcgagacagu gccccagaag 540

uccagccugg aagaacccga cuucuacaag accaagauca agcugugcau ccugcugcac 600

gccuuccgga ucagagccgu gaccaucgac agagugauga gcuaccugaa cgccucc 657

<210> 60

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt3v

<400> 60

agaaaccugc caguggccac gccugauccu ggcauguuuc cuugucugca ccacagccag 60

aaccugcuga gagccguguc caacaugcug cagaaggcca gacagacccu cgaguucuac 120

cccugcacca gcgaggaaau cgaccacgag gacaucacca aggacaagac cagcaccgug 180

gaagccugcc ugccucugga acugaccaag aacgagagcu gccugaacag ccgggaaacc 240

agcuucauca ccaacggcuc uugccuggcc uccagaaaga ccuccuucau gauggcccug 300

ugccuagca gcaucuacga ggaccugaag auguaccagg ucgaguucaa gaccaugaac 360

gccaagcugc ugauggaccc caagcggcag aucuuccugg accagaauau gcuggccgug 420

aucgacgagc ugaugcaggc ccugaacuuc aacagcgaga cagugcccca gaaguccagc 480

cuggaagaac ccgacuucua caagaccaag aucaagcugu gcauccugcu gcacgccuuc 540

cggaucagag ccgugaccau cgacagagug augagcuacc ugaacgccuc cuga 594

<210> 61

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt3v

<400> 61

augugucacc agcagcuggu caucagcugg uucagccugg uguuccuggc cucuccug

guggccaucu gggagcugaa gaaagacgug uacguggugg aacuggacug guaucccgau 120

gcuccuggcg agaugguggu gcugaccugc gauaccccug aagaggacgg caucaccugg 180

acacuggauc agucuagcga ggugcucggc agcggcaaga cccugaccau ccaagugaaa 240

gaguuuggcg acgccggcca guacaccugu cacaaaggcg gagaagugcu gagccacagc 300

cugcugcugc uccacaagaa agaggauggc auuuggagca ccgacauccu gaaggaccag 360

aaagagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggccgguuc 420

acauguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa guccagcaga 480

ggcagcagug auccucaggg cguuacaugu ggcgccgcua cacugucugc cgaaagagug 540

cggggcgaca acaaagaaua cgaguacagc guggaaugcc aagaggacag cgccugucca 600

gccgccgaag agucucugcc uaucgaagug agguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccuccagcuu uuucauccgg gacaucauca agcccgaucc uccaaagaac 720

cugcagcuga agccucugaa gaacagcaga cagguggaag uguccuggga guaccccgac 780

accuggucua caccccacag cuacuucagc cugaccuuuu gcgugcaagu gcagggcaag 840

uccaagcgcg agaaaaagga ccggguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgucagagcc caggaccggu acuacagcag cucuuggagc 960

gaaugggcca gcgugccaug uagcuaa 987

<210> 62

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt3v

<400> 62

augugucacc agcagcuggu caucagcugg uucagccugg uguuccuggc cucuccug

guggccaucu gggagcugaa gaaagacgug uacguggugg aacuggacug guaucccgau 120

gcuccuggcg agaugguggu gcugaccugc gauaccccug aagaggacgg caucaccugg 180

acacuggauc agucuagcga ggugcucggc agcggcaaga cccugaccau ccaagugaaa 240

gaguuuggcg acgccggcca guacaccugu cacaaaggcg gagaagugcu gagccacagc 300

cugcugcugc uccacaagaa agaggauggc auuuggagca ccgacauccu gaaggaccag 360

aaagagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggccgguuc 420

acauguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa guccagcaga 480

ggcagcagug auccucaggg cguuacaugu ggcgccgcua cacugucugc cgaaagagug 540

cggggcgaca acaaagaaua cgaguacagc guggaaugcc aagaggacag cgccugucca 600

gccgccgaag agucucugcc uaucgaagug agguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccuccagcuu uuucauccgg gacaucauca agcccgaucc uccaaagaac 720

cugcagcuga agccucugaa gaacagcaga cagguggaag uguccuggga guaccccgac 780

accuggucua caccccacag cuacuucagc cugaccuuuu gcgugcaagu gcagggcaag 840

uccaagcgcg agaaaaagga ccggguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgucagagcc caggaccggu acuacagcag cucuuggagc 960

gaaugggcca gcgugccaug uagc 984

<210> 63

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt3v

<400> 63

aucgggagc ugaagaaaga cguguacgug guggaacugg acugguaucc cgaugcuccu 60

ggcgagaugg uggugcugac cugcgauacc ccugaagagg acggcaucac cuggacacug 120

gaucagucua gcgaggugcu cggcagcggc aagacccuga ccauccaagu gaaagaguuu 180

ggcgacgccg gccaguacac cugucacaaa ggcggagaag ugcugagcca cagccugcug 240

cugcuccaca agaaagagga uggcauuugg agcaccgaca uccugaagga ccagaaagag 300

cccaagaaca agaccuuccu gagaugcgag gccaagaacu acagcggccg guucacaugu 360

ugguggcuga ccaccaucag caccgaccug accuucagcg ugaaguccag cagaggcagc 420

agugauccuc agggcguuac auguggcgcc gcuacacugu cugccgaaag agugcggggc 480

gacaacaaag aauacgagua cagcguggaa ugccaagagg acagcgccug uccagccgcc 540

gaagagucuc ugccuaucga agugauggug gacgccgugc acaagcugaa guacgagaac 600

uacaccucca gcuuuuucau ccgggacauc aucaagcccg auccuccaaa gaaccugcag 660

cugaagccuc ugaagaacag cagacaggug gaaguguccu gggaguaccc cgacaccugg 720

ucuacacccc acagcuacuu cagccugacc uuuugcgugc aagucaggg caaguccaag 780

840

aacgccagca ucagcgucag agcccaggac cgguacuaca gcagcucuug gagcgaaugg 900

gccagcgugc cauguagcua a 921

<210> 64

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt3v

<400> 64

ggcucuacau cuggcucugg caaaccugga ucuggcgagg gcucuacaaa gggc 54

<210> 65

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt3v

<400> 65

augugucacc agcagcuggu caucagcugg uucagccugg uguuccuggc cucuccug

guggccaucu gggagcugaa gaaagacgug uacguggugg aacuggacug guaucccgau 120

gcuccuggcg agaugguggu gcugaccugc gauaccccug aagaggacgg caucaccugg 180

acacuggauc agucuagcga ggugcucggc agcggcaaga cccugaccau ccaagugaaa 240

gaguuuggcg acgccggcca guacaccugu cacaaaggcg gagaagugcu gagccacagc 300

cugcugcugc uccacaagaa agaggauggc auuuggagca ccgacauccu gaaggaccag 360

aaagagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggccgguuc 420

acauguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa guccagcaga 480

ggcagcagug auccucaggg cguuacaugu ggcgccgcua cacugucugc cgaaagagug 540

cggggcgaca acaaagaaua cgaguacagc guggaaugcc aagaggacag cgccugucca 600

gccgccgaag agucucugcc uaucgaagug agguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccuccagcuu uuucauccgg gacaucauca agcccgaucc uccaaagaac 720

cugcagcuga agccucugaa gaacagcaga cagguggaag uguccuggga guaccccgac 780

accuggucua caccccacag cuacuucagc cugaccuuuu gcgugcaagu gcagggcaag 840

uccaagcgcg agaaaaagga ccggguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgucagagcc caggaccggu acuacagcag cucuuggagc 960

gaaugggcca gcgugccaug uagcggcucu acaucuggcu cuggcaaacc uggaucuggc 1020

gagggcucua caaagggcag aaaccugcca guggccacgc cugauccugg cauguuuccu 1080

ugucugcacc acagccagaa ccugcugaga gccgugucca acaugcugca gaaggccaga 1140

cagacccucg aguucuaccc cugcaccagc gaggaaaucg accacgagga caucaccaag 1200

gacaagacca gcaccgugga agccugccug ccucuggaac ugaccaagaa cgagagcugc 1260

cugaacagcc gggaaaccag cuucaucacc aacggcucuu gccuggccuc cagaaagacc 1320

uccuucauga uggccugug ccuagcagc aucuacgagg accugaagau guaccagguc 1380

gaguucaaga ccaugaacgc caagcugcug auggaccca agcggcagau cuuccuggac 1440

1500

gugccccaga aguccagccu ggaagaaccc gacuucuaca agaccaagau caagcugugc 1560

aucugcugc acgccuuccg gaucagagcc gugaccaucg acagagugau gagcuaccug 1620

aacgccuccu ga 1632

<210> 66

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt3v

<400> 66

augaucgaga cauacaacca gacaagcccc agaagcgccg ccacaggacu gccuaucagc 60

augaagaucu uuauguaccu gcugaccgug uuccugauca cccagaugau cggcagcgcc 120

cuguuugccg uguaccugca cagacggcug gacaagaucg aggacgagag aaaccugcac 180

gaggacuucg uguucaugaa gaccauccag cggugcaaca ccggcgagag aagucugagc 240

cugcugaacu gcgaggaaau caagagccag uucgagggcu ucgugaagga caucaugcug 300

aacaaagagg aaacgaagaa agaaaacucc uucgagaugc agaagggcga ccagaauccu 360

cagaucgccg cucacgugau cagcgaggcc agcagcaaga caacaagcgu gcugcagugg 420

gccgagaagg gcuacuacac caugagcaac aaccugguca cccuggaaaa cggcaagcag 480

cugacaguga agcggcaggg ccuguacuac aucuacgccc aagugaccuu cugcagcaac 540

agagaggcca gcucucaggc cccuuuuauc gccagccugu gccugaaguc cccuggcaga 600

660

cagucuauuc accucggcgg aguguuugag cugcagccug gcgcaagcgu guucgugaau 720

gugacagacc cuagccaggu gucccacggc accggcuuua caucuuucgg acugcugaag 780

cuguga 786

<210> 67

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt4

<400> 67

augcagaucc cccaggcccc cuggcccgug gugugggccg ugcugcagcu gggcuggaga 60

cccggcuggu uccuggacag ccccgacaga ccuggaacc cccccaccuu cagccccgcc 120

cugcuggugg ugaccgaggg cgacaacgcc accuucaccu guagcuucag caacaccagc 180

gagagcuucg ugcugaacug guacagaaug agccccagca accagaccga caagcuggcc 240

gccuuccccg aggacagaag ccagcccggc caggacugca gauucagagu gacccagcug 300

360

uaccugucg gcgccaucag ccuggccccc aaggcccaga ucaaggagag ccugagagcc 420

gagcugagag ugaccgagag aagggccgag gugcccaccg cccaccccag ccccagcccc 480

agacccgccg gccaguucca gacccuggug gugggcgugg ugggcggccu gcugggcagc 540

cuggugcugc uggugugggu gcuggccgug aucugcagca gagccgccag aggcaccauc 600

ggcgccagaa gaaccggcca gccccugaag gaggacccca gcgccgugcc cguguucagc 660

guggacuacg gcgagcugga cuuccagugg agagagaaga cccccgagcc ccccgugccc 720

ugcgugcccg agcagaccga guacgccacc aucguguucc ccagcggcau gggcaccagc 780

agccccgcca gaagaggcag cgccgacggc cccagaagcg cccagccccu gagacccgag 840

gacggccacu gcagcuggcc ccuguga 867

<210> 68

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt4

<400> 68

augcagaucc cccaggcccc cuggcccgug gugugggccg ugcugcagcu gggcuggaga 60

cccggcuggu uccuggacag ccccgacaga ccuggaacc cccccaccuu cagccccgcc 120

cugcuggugg ugaccgaggg cgacaacgcc accuucaccu guagcuucag caacaccagc 180

gagagcuucg ugcugaacug guacagaaug agccccagca accagaccga caagcuggcc 240

gccuuccccg aggacagaag ccagcccggc caggacugca gauucagagu gacccagcug 300

360

uaccugucg gcgccaucag ccuggccccc aaggcccaga ucaaggagag ccugagagcc 420

gagcugagag ugaccgagag aagggccuga 450

<210> 69

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt4

<400> 69

augugccccg ccagaagccu gcugcuggug gccacccugg ugcugcugga ccaccugagc 60

cuggccagaa accugcccgu ggccaccccc gaccccggca uguuccccug ccugcaccac 120

agccagaacc ugcugagagc cgugagcaac augcugcaga aggccagaca gacccuggag 180

uucuaccccu gcaccagcga ggagaucgac cacgaggaca ucaccaagga caagaccagc 240

accguggagg ccugccugcc ccuggagcug accaagaacg agagcugccu gaacagcaga 300

gagaccagcu ucaucaccaa cggcagcugc cuggccagca gaaagaccag cuucaugaug 360

gcccugugcc ugagcagcau cuacgaggac cugaagaugu accaggugga guucaagacc 420

augaacgcca agcugcugau ggaccccaag agacagaucu uccuggacca gaacaugcug 480

gccgugaucg acgagcugau gcaggcccug aacuucaaca gcgagaccgu gccccagaag 540

aguagccugg aggagccga cuucuacaag accaagauca

gccuucagaa ucagagccgu gaccaucgac agagugauga gcuaccugaa cgccagcuga 660

<210> 70

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt4

<400> 70

augugccccg ccagaagccu gcugcuggug gccacccugg ugcugcugga ccaccugagc 60

cuggccagaa accugcccgu ggccaccccc gaccccggca uguuccccug ccugcaccac 120

agccagaacc ugcugagagc cgugagcaac augcugcaga aggccagaca gacccuggag 180

uucuaccccu gcaccagcga ggagaucgac cacgaggaca ucaccaagga caagaccagc 240

accguggagg ccugccugcc ccuggagcug accaagaacg agagcugccu gaacagcaga 300

gagaccagcu ucaucaccaa cggcagcugc cuggccagca gaaagaccag cuucaugaug 360

gcccugugcc ugagcagcau cuacgaggac cugaagaugu accaggugga guucaagacc 420

augaacgcca agcugcugau ggaccccaag agacagaucu uccuggacca gaacaugcug 480

gccgugaucg acgagcugau gcaggcccug aacuucaaca gcgagaccgu gccccagaag 540

aguagccugg aggagccga cuucuacaag accaagauca

gccuucagaa ucagagccgu gaccaucgac agagugauga gcuaccugaa cgccagc 657

<210> 71

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt4

<400> 71

agaaaccugc ccguggccac ccccgacccc ggcauguucc ccugccugca ccacagccag 60

aaccugcuga gagccgugag caacaugcug cagaaggcca gacagacccu ggaguucuac 120

cccugcacca gcgaggagau cgaccacgag gacaucacca aggacaagac cagcaccgug 180

gaggccugcc ugcccugga gcugaccaag aacgagagcu gccugaacag cagagagacc 240

agcuucauca ccaacggcag cugccuggcc agcagaaaga ccagcuucau gauggcccug 300

ugccuagca gcaucuacga ggaccugaag auguaccagg uggaguucaa gaccaugaac 360

gccaagcugc ugauggaccc caagagacag aucuuccugg accagaacau gcuggccgug 420

aucgacgagc ugaugcaggc ccugaacuuc aacagcgaga ccgugcccca gaagaguagc 480

cuggaggagc ccgacuucua caagaccaag aucaagcugu gcauccugcu gcacgccuuc 540

agaaucagag ccgugaccau cgacagagug augagcuacc ugaacgccag cuga 594

<210> 72

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt4

<400> 72

augugccacc agcagcuggu gaucagcugg uucagccugg uguuccuggc cagcccccug 60

guggccaucu gggagcugaa gaaggacgug uacguggugg agcuggacug guaccccgac 120

gcccccggcg agaugguggu gcugaccugc gacacccccg aggaggacgg caucaccugg 180

acccuggacc agagcagcga ggugcugggc agcggcaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgaggugcu gagccacagc 300

cugcugcugc ugcacaagaa ggaggacggc aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggcagauuc 420

accuguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa gaguagcaga 480

ggcagcagcg acccccaggg cgugaccugc ggcgccgcca cccugagcgc cgagagagug 540

agaggcgaca acaaggagua cgaguacagc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agagccugcc caucgaggug augguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucaucaga gacaucauca agcccgaccc ccccaagaac 720

cugcagcuga agccccugaa gaacagcaga caggugggagg ugagcuggga guaccccgac 780

accuggagca ccccccacag cuacuucagc cugaccuucu gcgugcaggu ucagggcaag 840

agcaagagag agaagaagga cagaguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgugagagcc caggacagau acuacagcag cagcuggagc 960

gagugggcca gcgugccug cagcuga 987

<210> 73

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt4

<400> 73

augugccacc agcagcuggu gaucagcugg uucagccugg uguuccuggc cagcccccug 60

guggccaucu gggagcugaa gaaggacgug uacguggugg agcuggacug guaccccgac 120

gcccccggcg agaugguggu gcugaccugc gacacccccg aggaggacgg caucaccugg 180

acccuggacc agagcagcga ggugcugggc agcggcaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgaggugcu gagccacagc 300

cugcugcugc ugcacaagaa ggaggacggc aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggcagauuc 420

accuguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa gaguagcaga 480

ggcagcagcg acccccaggg cgugaccugc ggcgccgcca cccugagcgc cgagagagug 540

agaggcgaca acaaggagua cgaguacagc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agagccugcc caucgaggug augguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucaucaga gacaucauca agcccgaccc ccccaagaac 720

cugcagcuga agccccugaa gaacagcaga caggugggagg ugagcuggga guaccccgac 780

accuggagca ccccccacag cuacuucagc cugaccuucu gcgugcaggu ucagggcaag 840

agcaagagag agaagaagga cagaguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgugagagcc caggacagau acuacagcag cagcuggagc 960

gagugggcca gcgugccug cagc 984

<210> 74

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt4

<400> 74

aucgggagc ugaagaagga cguguacgug guggagcugg acugguaccc cgacgccccc 60

ggcgagaugg uggugcugac cugcgacacc cccgaggagg acggcaucac cuggacccug 120

gaccagagca gcgaggugcu gggcagcggc aagacccuga ccauccaggu gaaggaguuc 180

ggcgacgccg gccaguacac cugucacaag ggcggcgagg ugcugagcca cagccugcug 240

cugcugcaca agaaggagga cggcaucugg agcaccgaca uccugaagga ccagaaggag 300

cccaagaaca agaccuuccu gagaugcgag gccaagaacu acagcggcag auucaccugu 360

ugguggcuga ccaccaucag caccgaccug accuucagcg ugaagaguag cagaggcagc 420

agcgaccccc agggcgugac cugcggcgcc gccacccuga gcgccgagag agugagaggc 480

acagcgccug ccccgccgcc 540

gaggagagcc ugcccaucga ggugauggug gacgccgugc acaagcugaa guacgagaac 600

uacaccagca gcuucuucau cagagacauc aucaagcccg acccccccaa gaaccugcag 660

cugaagcccc ugaagaacag cagacaggug gaggugagcu gggaguaccc cgacaccugg 720

agcacccccc acagcuacuu cagccugacc uucugcgugc agguucaggg caagagcaag 780

aggagaaga aggacagagu guucaccgac aagaccagcg ccaccgugau cugcagaaag 840

aacgccagca ucagcgugag agcccaggac agauaacuaca gcagcagcug gagcgagugg 900

gccagcgugc ccugcagcug a 921

<210> 75

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt4

<400> 75

ggcagcacca gcggcagcgg caagcccggc agcggcgagg gcagcaccaa gggc 54

<210> 76

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt4

<400> 76

augugccacc agcagcuggu gaucagcugg uucagccugg uguuccuggc cagcccccug 60

guggccaucu gggagcugaa gaaggacgug uacguggugg agcuggacug guaccccgac 120

gcccccggcg agaugguggu gcugaccugc gacacccccg aggaggacgg caucaccugg 180

acccuggacc agagcagcga ggugcugggc agcggcaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgaggugcu gagccacagc 300

cugcugcugc ugcacaagaa ggaggacggc aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggcagauuc 420

accuguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa gaguagcaga 480

ggcagcagcg acccccaggg cgugaccugc ggcgccgcca cccugagcgc cgagagagug 540

agaggcgaca acaaggagua cgaguacagc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agagccugcc caucgaggug augguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucaucaga gacaucauca agcccgaccc ccccaagaac 720

cugcagcuga agccccugaa gaacagcaga caggugggagg ugagcuggga guaccccgac 780

accuggagca ccccccacag cuacuucagc cugaccuucu gcgugcaggu ucagggcaag 840

agcaagagag agaagaagga cagaguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgugagagcc caggacagau acuacagcag cagcuggagc 960

gagugggcca gcgugccug cagcggcagc accagcggca gcggcaagcc cggcagcggc 1020

gagggcagca ccaagggcag aaaccugccc guggccaccc ccgaccccgg cauguucccc 1080

ugccugcacc acagccagaa ccugcugaga gccgugagca acaugcugca gaaggccaga 1140

cagacccugg aguucuaccc cugcaccagc gaggagaucg accacgagga caucaccaag 1200

gacaagacca gcaccgugga ggccugccug ccccuggagc ugaccaagaa cgagagcugc 1260

cugaacagca gagagaccag cuucaucacc aacggcagcu gccuggccag cagaaagacc 1320

1380

1440

cagaacaugc uggccgugau cgacgagcug augcaggccc ugaacuucaa cagcgagacc 1500

gugccccaga agaguagccu ggaggagccc gacuucuaca agaccaagau caagcugugc 1560

aucugcugc acgccuucag aaucagagcc gugaccaucg acagagugau gagcuaccug 1620

aacgccagcu ga 1632

<210> 77

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt4

<400> 77

augaucgaga ccuacacca gaccagcccc agaagcgccg ccaccggccu gcccaucagc 60

augaagaucu ucauguaccu gcugaccgug uuccugauca cccagaugau cggcagcgcc 120

cuguucgccg uguaccugca cagaagacug gacaagaucg aggacgagag aaaccugcac 180

gaggacuucg uguucaugaa gaccauccag agaugcaaca ccggcgagag aagccugagc 240

cugcugaacu gcgaggagau caaggccag uucgagggcu ucgugaagga caucaugcug 300

aacaaggagg agaccaagaa ggagaacagc uucgagaugc agaagggcga ccagaacccc 360

cagaucgccg cccacgugau cagcgaggcc agcagcaaga ccaccagcgu gcugcagugg 420

gccgagaagg gcuacuacac caugagcaac aaccugguga cccuggagaa cggcaagcag 480

cugaccguga aggacaggg ccuguacuac aucuacgccc aggugaccuu cugcagcaac 540

agagaggcca gcagccaggc ccccuucauc gccagccugu gccugaagag ucccggcaga 600

uucgagagaa uccugcugag agccgccaac acccacagca gcgccaagcc cugcggccag 660

cagagcaucc accugggcgg cguguucgag cugcagcccg gcgccagcgu guucgugaac 720

780

cuguga 786

<210> 78

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt5

<400> 78

augcagaucc cccaagcccc uuggccggug gucugggcug uucugcagcu cggcuggaga 60

cccggguggu uccggacag cccugaucgg ccgggaacc cucccaccuu uuccccugcc 120

cuucuggugg ugacagaggg agacaaugcg acguuuaccu gcucuuucag caacacaucc 180

gaaucuuucg uccucaauug guaccgcaug agcccgucca accagaccga uaagcuggcu 240

gccuuucccg aggacagauc ucagccuggc caagauuguc gguuccgcgu gacacagcuu 300

cccaauggga gagacuuuca caugagcguu gugcgggccc gcagaaacga uuccggaacc 360

uaucugugcg gcgcuauuag ccucgccccu aaagcucaga ucaaggaauc ucugcgggcc 420

gagcugcgcg ucacagaaag acgggcggag gugcccaccg cccauccguc cccuagcccc 480

cgcccugcug ggcaguucca aacgcucguu gugggagucg ugggcggccu gcuugggucu 540

cuggugcucc uggucugggu ucuugccgug auuuguucca gagcugcccg gggaaccauc 600

ggcgcgcgca gaacagggca gccccugaaa gaggacccca gcgccgugcc ugucuuuucu 660

guggauuacg gagaacucga cuuccagugg cggggagaaga ccccgggaacc cccuguuccc 720

ugcgugccug agcagacaga guaugcuacc auugucuuuc ccuccggcau ggggacgagc 780

uccccggcca gacgcggauc ugcugauggc ccucggagcg cccaaccccu gagaccugaa 840

gacggccacu guuccuggcc ccuguga 867

<210> 79

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt5

<400> 79

augcagaucc cccaagcccc uuggccggug gucugggcug uucugcagcu cggcuggaga 60

cccggguggu uccggacag cccugaucgg ccgggaacc cucccaccuu uuccccugcc 120

cuucuggugg ugacagaggg agacaaugcg acguuuaccu gcucuuucag caacacaucc 180

gaaucuuucg uccucaauug guaccgcaug agcccgucca accagaccga uaagcuggcu 240

gccuuucccg aggacagauc ucagccuggc caagauuguc gguuccgcgu gacacagcuu 300

360

uaucugugcg gcgcuauuag ccucgccccu aaagcucaga ucaaggaauc ucugcgggcc 420

gagcugcgcg ucacagaaag acgggcguga 450

<210> 80

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt5

<400> 80

augugccccg ccagaagccu gcuccuggug gcuacccuug uccugcucga ccaccugucc 60

cuugccggga accugccugu ugcgacaccg gaucccggca uguucccuug ucuccaucac 120

ucucagaauc ugcugcgcgc ugugagcaac augcuccaaa aggccagaca gacgcuggag 180

uuuuaccccu gcaccuccga agagaucgac caugaagaua uuacaaaaga caagaccucu 240

acaguggagg ccugucuucc ucuggaacuc accaaaaaug agagcugccu gaacucccgg 300

gagacaucuu ucaucaccaa ugggagcugu cuugcuuccc gcaagacgag cuuuaugaug 360

gcccugugcc ucucuuccau uuaugaagau cugaaaaugu accaggucga guucaagacc 420

augaacgcua agcugcucau ggaccccaaa agacagaucu uucuggauca aaauauugcuu 480

gccgugauug acgaacugau gcaggcgcuc aacuucaaua gcgagacagu uccucagaag 540

ucuucccugg aggaaccgga uuuuuauaaa accaagauca aacuuuguau ccugcuccac 600

gccuuccgga uucgcgcugu gacaaucgac agagucauga gcuaccugaa cgccucuuga 660

<210> 81

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt5

<400> 81

augugccccg ccagaagccu gcuccuggug gcuacccuug uccugcucga ccaccugucc 60

cuugccggga accugccugu ugcgacaccg gaucccggca uguucccuug ucuccaucac 120

ucucagaauc ugcugcgcgc ugugagcaac augcuccaaa aggccagaca gacgcuggag 180

uuuuaccccu gcaccuccga agagaucgac caugaagaua uuacaaaaga caagaccucu 240

acaguggagg ccugucuucc ucuggaacuc accaaaaaug agagcugccu gaacucccgg 300

gagacaucuu ucaucaccaa ugggagcugu cuugcuuccc gcaagacgag cuuuaugaug 360

gcccugugcc ucucuuccau uuaugaagau cugaaaaugu accaggucga guucaagacc 420

augaacgcua agcugcucau ggaccccaaa agacagaucu uucuggauca aaauauugcuu 480

gccgugauug acgaacugau gcaggcgcuc aacuucaaua gcgagacagu uccucagaag 540

ucuucccugg aggaaccgga uuuuuauaaa accaagauca aacuuuguau ccugcuccac 600

gccuuccgga uucgcgcugu gacaaucgac agagucauga gcuaccugaa cgccucu 657

<210> 82

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt5

<400> 82

60

120

cccugcaccu ccgaagagau cgaccaugaa gauauuacaa aagacaagac cucuacagug 180

gaggccuguc uuccucugga acucaccaaa augagagcu gccugaacuc ccgggagaca 240

ucuuucauca ccaaugggag cugucuugcu ucccgcaaga cgagcuuuau gauggcccug 300

ugccucucuu ccauuuauga agaucugaaa auguaccagg ucgaguucaa gaccaugaac 360

gcuaagcugc ucauggaccc caaaagacag aucuuucugg aucaaaauau gcuugccgug 420

auugacgaac ugaugcaggc gcucaacuuc aauagcgaga caguuccuca gaagucuucc 480

cuggaggaac cggauuuuua uaaaaccaag aucaaacuuu guauccugcu ccacgccuuc 540

cggauucgcg cugugacaau cgacagaguc augagcuacc ugaacgccuc uuga 594

<210> 83

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt5

<400> 83

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cucuccccuu 60

guugcuauuu gggagcugaa gaaagacgug uacguggucg aacucgauug guauccugac 120

gccccgggcg agaugguggu ucugaccugu gauacacccg aagaggacgg gaucacgugg 180

acccuugauc agagcuccga agugcuggga ucuggcaaga cacucaccau ucaggucaaa 240

gaguucgggg acgcgggaca guacacaugc cauaagggcg gggaggugcu gagccacucc 300

360

aaagagccua agaacaaaac auuucucaga ugugaagcua agaauuauag cggccgguuuu 420

accugcuggu ggcugacgac caucuccaca gaccuuaccu ucagcguuaa aucuucccgc 480

ggcagcucug auccccagggggugacaugu ggagccgcca cccuguccgc ugagagaguc 540

cggggcgaca acaaggagua cgaauauagc guggagugcc aggaagauuc ugccuguccu 600

gcugccgagg aaucccuccc caucgaggug auggucgacg cgguucacaa gcugaaauac 660

gagaauuaua cgagcuccuu cuuuauucgc gacaucauua agccugaucc gcccaaaaac 720

cugcagcuca agccucugaa aaauucuaga caaguggaag ugagcuggga guaccccgac 780

acauggucca ccccucauag cuacuucucu cuuacauuuu gcguccaggu gcaggggaag 840

uccaaacggg aaaagaagga ucgcguuuuc accgacaaaa ccagcgccac agugaucugu 900

agaaagaacg cuucuauuag cguccgggcc caggaucgcu auuacuccuc uagcuggucc 960

gagugggcua gcgugcccug cucuuga 987

<210> 84

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt5

<400> 84

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cucuccccuu 60

guugcuauuu gggagcugaa gaaagacgug uacguggucg aacucgauug guauccugac 120

gccccgggcg agaugguggu ucugaccugu gauacacccg aagaggacgg gaucacgugg 180

acccuugauc agagcuccga agugcuggga ucuggcaaga cacucaccau ucaggucaaa 240

gaguucgggg acgcgggaca guacacaugc cauaagggcg gggaggugcu gagccacucc 300

360

aaagagccua agaacaaaac auuucucaga ugugaagcua agaauuauag cggccgguuuu 420

accugcuggu ggcugacgac caucuccaca gaccuuaccu ucagcguuaa aucuucccgc 480

ggcagcucug auccccagggggugacaugu ggagccgcca cccuguccgc ugagagaguc 540

cggggcgaca acaaggagua cgaauauagc guggagugcc aggaagauuc ugccuguccu 600

gcugccgagg aaucccuccc caucgaggug auggucgacg cgguucacaa gcugaaauac 660

gagaauuaua cgagcuccuu cuuuauucgc gacaucauua agccugaucc gcccaaaaac 720

cugcagcuca agccucugaa aaauucuaga caaguggaag ugagcuggga guaccccgac 780

acauggucca ccccucauag cuacuucucu cuuacauuuu gcguccaggu gcaggggaag 840

uccaaacggg aaaagaagga ucgcguuuuc accgacaaaa ccagcgccac agugaucugu 900

agaaagaacg cuucuauuag cguccgggcc caggaucgcu auuacuccuc uagcuggucc 960

gagugggcua gcgugcccug cucu 984

<210> 85

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt5

<400> 85

auuugggagc ugaagaaaga cguguacgug gucgaacucg auugguaucc ugacgccccg 60

ggcgagaugg ugguucugac cugugauaca cccgaagagg acgggaucac guggacccuu 120

gaucaagcu ccgaagugcu gggaucuggc aagacacuca ccauucaggu caaagaguuc 180

ggggacgcgg gacaguacac augccauaag ggcgggggagg ugcugagcca cucccugcuc 240

cugcuucaua aaaaggaaga uggaaucugg ucuaccgaca uucugaagga ucaaaaagag 300

ccuaagaaca aaacauuucu cagaugugaa gcuaagaauu auagcggccg guuuaccugc 360

ugguggcuga cgaccaucuc cacagaccuu accuucagcg uuaaaucuuc ccgcggcagc 420

ucugaucccc aggggugac auguggagcc gccacccugu ccgcugagag aguccggggc 480

gacaacaagg aguacgaaua uagcguggag ugccaggaag auucugccug uccugcugcc 540

gaggaauccc uccccaucga ggugaugguc gacgcgguuc acaagcugaa auacgagaau 600

uauacgagcu ccuucuuuau ucgcgacauc auuaagccug auccgcccaa aaaccugcag 660

cucaagccuc ugaaaaauuc uagacaagug gaagugagcu gggaguaccc cgacacaugg 720

uccaccccuc auagcuacuu cucucuuaca uuuugcgucc aggugcaggg gaaguccaaa 780

840

aacgcuucua uuagcguccg ggcccaggau cgcuauuacu ccucuagcug guccgagugg 900

gcuagcgugc ccugcucuug a 921

<210> 86

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt5

<400> 86

ggcagcaccu ccgggucugg aaagcccggc agcggggagg gauccacaaa aggc 54

<210> 87

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt5

<400> 87

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cucuccccuu 60

guugcuauuu gggagcugaa gaaagacgug uacguggucg aacucgauug guauccugac 120

gccccgggcg agaugguggu ucugaccugu gauacacccg aagaggacgg gaucacgugg 180

acccuugauc agagcuccga agugcuggga ucuggcaaga cacucaccau ucaggucaaa 240

gaguucgggg acgcgggaca guacacaugc cauaagggcg gggaggugcu gagccacucc 300

360

aaagagccua agaacaaaac auuucucaga ugugaagcua agaauuauag cggccgguuuu 420

accugcuggu ggcugacgac caucuccaca gaccuuaccu ucagcguuaa aucuucccgc 480

ggcagcucug auccccagggggugacaugu ggagccgcca cccuguccgc ugagagaguc 540

cggggcgaca acaaggagua cgaauauagc guggagugcc aggaagauuc ugccuguccu 600

gcugccgagg aaucccuccc caucgaggug auggucgacg cgguucacaa gcugaaauac 660

gagaauuaua cgagcuccuu cuuuauucgc gacaucauua agccugaucc gcccaaaaac 720

cugcagcuca agccucugaa aaauucuaga caaguggaag ugagcuggga guaccccgac 780

acauggucca ccccucauag cuacuucucu cuuacauuuu gcguccaggu gcaggggaag 840

uccaaacggg aaaagaagga ucgcguuuuc accgacaaaa ccagcgccac agugaucugu 900

agaaagaacg cuucuauuag cguccgggcc caggaucgcu auuacuccuc uagcuggucc 960

gagugggcua gcgugccug cucuggcagc accuccgggu cuggaaagcc cggcagcggg 1020

gagggaucca caaaaggccg gaaccugccu guugcgacac cggaucccgg cauguucccu 1080

ugucuccauc acucucagaa ucugcugcgc gcugugagca acaugcucca aaaggccaga 1140

cagacgcugg aguuuuaccc cugcaccucc gaagagaucg accaugaaga uauuacaaaa 1200

1260

cugaacuccc gggagacauc uuucaucacc aaugggagcu gucuugcuuc ccgcaagacg 1320

agcuuuauga uggccugug ccucucuucc auuuaugaag aucugaaaau guaccagguc 1380

gaguucaaga ccaugaacgc uaagcugcuc auggaccca aaagacagau cuuucuggau 1440

1500

guuccucaga agucuucccu ggaggaaccg gauuuuuaua aaaccaagau caaacuuugu 1560

auccugcucc acgccuuccg gauucgcgcu gugacaaucg acagagucau gagcuaccug 1620

aacgccucuu ga 1632

<210> 88

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt5

<400> 88

augaucgaga ccuacacacca gacaagcccc agauccgccg cuacggggccu gccuauuucu 60

augaagaucu ucauguaucu ccugaccgug uuucuuauua cacaaaugau cgggagcgcc 120

cuguucgcgg ucuaccucca ccggcgccug gacaaaauug aagaugagag aaaucuucau 180

gaagacuuug uuuucaugaa gaccauccag cggugcaaca caggagagcg cucccugucu 240

cuccugaauu gugaagagau caaaagccag uuugagggcu ucgugaagga uauuaugcug 300

aacaaagaag agaccaagaa ggaaaauucc uuugagaugc agaaagggga ccaaaacccg 360

cagaucgcug cccacgugau uucugaggcc agcuccaaga caaccagcgu ccuccagugg 420

gcugaaaaag gauauuacac gauguucuaau aaccugguga cccuugagaa uggcaagcag 480

cugacaguua aaagacaagg gcucuauuac aucuaugccc aggugaccuu cugcuccaac 540

cgggaagcua gcucucaggc ccccuuuauu gcgucccugu gucuuaagag cccuggacgc 600

uucgagagaa uccugcuccg ggccgcuaau acacauucuu ccgccaagcc cugcggccag 660

caaagcauuc accugggcgg ggucuuugaa cugcagccug gagcuuccgu guucguuaac 720

gugaccgauc ccucucaggu cagccauggc acgggguuua cauccuucgg acuccugaaa 780

cuuuga 786

<210> 89

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt6

<400> 89

augcaaauac cacaagcacc auggccagua guaugggcug uacuacaauu agguuggcga 60

ccaggauggu uuuuagacuc accagaucgu ccauggaacc caccaacauu uucaccagca 120

uuauuaguag uaacagaagg agauaaugca accuuuacau guucauucag uaacacauca 180

240

gcauuuccag aagauagauc acaaccagga caagauugca gauuuagagu aacacaauua 300

ccuaauggac gagacuuuca uaugucagua guaagagcuc gacguaacga uucaggaaca 360

uacuuaugug gagcaauuuc auuagcacca aaagcacaaa uaaaagaauc uuuaagagca 420

gaauuaagag uaacagaaag acgcgcagaa guaccaacag cacauccaag cccuucacca 480

cgaccugcag gacaauuuca aacauuagua gucggaguag uaggaggauu auuagguuca 540

cugguauuau uaguaugggu auuagcagua auaugcucca gagcagcaag aggaacaaua 600

ggagcaagaa gaacaggaca accauuaaaa gaagacccau cugcaguacc aguauuuuca 660

guugacuaug gagaacuaga uuuccaaugg agggaaaaaa caccagaacc uccaguucca 720

uguguaccag aacaaacaga auaugcaaca auuguauuuc ccucaggaau gggaacaucu 780

aguccagcaa gaagaggauc agcugaugga ccaagaucag cacaaccauu aagaccagaa 840

gauggacauu guucauggcc auuauaa 867

<210> 90

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt6

<400> 90

augcaaauac cacaagcacc auggccagua guaugggcug uacuacaauu agguuggcga 60

ccaggauggu uuuuagacuc accagaucgu ccauggaacc caccaacauu uucaccagca 120

uuauuaguag uaacagaagg agauaaugca accuuuacau guucauucag uaacacauca 180

240

gcauuuccag aagauagauc acaaccagga caagauugca gauuuagagu aacacaauua 300

ccuaauggac gagacuuuca uaugucagua guaagagcuc gacguaacga uucaggaaca 360

uacuuaugug gagcaauuuc auuagcacca aaagcacaaa uaaaagaauc uuuaagagca 420

gaauuaagag uaacagaaag acgcgcauaa 450

<210> 91

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt6

<400> 91

augugcccag caagaucacu acuacuggua gcaacacugg uacuacuaga ccaccuauca 60

cucgccagaa accucccagu agccacacca gacccaggaa uguuccccug ccuccaccau 120

ucccaaaacc uacuaagagc aguaucaaac augcuacaaa aagcaagaca aacacuagag 180

uucuauccau gcacaucaga agaaauagac cacgaagaca uaacaaaaga caaaacauca 240

accguagaag caugccuccc acucgaacuc acaaaaaacg aaucaugccu aaacucaaga 300

360

420

augaacgcaa aauuacuaau ggacccaaaa agacaaauau uccuagacca aaacaugcua 480

gcaguaauag acgaacuaau gcaagcacua aacuucaacu cagaaaccgu accccaaaaa 540

ucaucucuag aagaaccaga cuucuacaaa acaaaaauaa aacuaugcau acuacuacac 600

gccuucagaa cgccucauaa cgccucauaa 660

<210> 92

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt6

<400> 92

augugcccag caagaucacu acuacuggua gcaacacugg uacuacuaga ccaccuauca 60

cucgccagaa accucccagu agccacacca gacccaggaa uguuccccug ccuccaccau 120

ucccaaaacc uacuaagagc aguaucaaac augcuacaaa aagcaagaca aacacuagag 180

uucuauccau gcacaucaga agaaauagac cacgaagaca uaacaaaaga caaaacauca 240

accguagaag caugccuccc acucgaacuc acaaaaaacg aaucaugccu aaacucaaga 300

360

420

augaacgcaa aauuacuaau ggacccaaaa agacaaauau uccuagacca aaacaugcua 480

gcaguaauag acgaacuaau gcaagcacua aacuucaacu cagaaaccgu accccaaaaa 540

ucaucucuag aagaaccaga cuucuacaaa acaaaaauaa aacuaugcau acuacuacac 600

gccuucagaa cgccuca 657

<210> 93

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt6

<400> 93

agaaaccucc caguagccac accagaccca ggaauguucc ccugccucca ccauucccaa 60

120

ccaugcacau cagaagaaau agaccacgaa gacauaacaa aagacaaaac aucaaccgua 180

gaagcaugcc ucccacucga acucacaaaa aacgaaucau gccuaaacuc aagagaaaca 240

ucauucauaa caaacggcuc augcuuagcc ucaagaaaaa caucauucau gauggcacua 300

ugccucucau ccauauauga agacuuaaaa auguaccaag uagaauuuaa aaccaugaac 360

gcaaaauuac uaauggaccc aaaaagacaa auauuccuag accaaaacau gcuagcagua 420

auagacgaac uaaugcaagc acuaaacuuc aacucagaaa ccguacccca aaaaucaucu 480

cuagaagaac cagacuucua caaaacaaaa auaaaacuau gcauacuacu acacgccuuc 540

agaauaagag ccgucacaau agacagaguc augucauacc uaaacgccuc auaa 594

<210> 94

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt6

<400> 94

augugccacc aacaacuggu aauaucaugg uucucacugg uauucuuggc aucaccccua 60

guagcaauau gggaacuaaa aaaagacgua uacguaguag aacuagacug guacccagac 120

gcaccaggag aaaugguagu auuaacaugc gacacaccag aagaagaugg aauaacuugg 180

acauuagacc aaucaaguga aguauuagga ucaggcaaaa cacuaacuau acaaguaaaa 240

gaauuuggag acgcaggaca auacacgugc cacaaaggag gcgaaguccu aucacauuca 300

cuacuauuau uacacaaaaa agaagacgga aucuggagca cagacauauu aaaagaccaa 360

aaagaaccaa aaaacaaaac auuucuaaga ugcgaagcua aaaacuauuc aggaagauuc 420

acaugcuggu ggcuaacaac caucaguacc gacuuaacau ucucaguaaa aucaucaaga 480

ggaucaucag acccacaagg aguaacaugu ggagcagcaa cacuaagcgc agaaagagua 540

cgaggagaca acaaagaaua cgaauauuca guagaauguc aagaagacuc agcaugcccu 600

gcagcagaag aaucauuacc aauagaagua auggucgacg cuguacacaa acuaaaauau 660

gaaaauuaca caagcaguuu cuucauaaga gacauaauaa aacccgaccc accaaaaaac 720

cuacaacuaa aaccauuaaa aaauucaaga caaguagaag uaucauggga auacccagau 780

acauggagca caccacacag uuacuucuca uuaacauucu gcguacaagu acaaggaaaa 840

aguaaaagag aaaaaaaaga cagaguauuc acagauaaga cuucagcaac aguaauauugc 900

agaaaaaacg caagcauaag cguacgagca caagacagau auuacucaag cucaugguca 960

gaaugggcau caguaccaug uucauaa 987

<210> 95

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt6

<400> 95

augugccacc aacaacuggu aauaucaugg uucucacugg uauucuuggc aucaccccua 60

guagcaauau gggaacuaaa aaaagacgua uacguaguag aacuagacug guacccagac 120

gcaccaggag aaaugguagu auuaacaugc gacacaccag aagaagaugg aauaacuugg 180

acauuagacc aaucaaguga aguauuagga ucaggcaaaa cacuaacuau acaaguaaaa 240

gaauuuggag acgcaggaca auacacgugc cacaaaggag gcgaaguccu aucacauuca 300

cuacuauuau uacacaaaaa agaagacgga aucuggagca cagacauauu aaaagaccaa 360

aaagaaccaa aaaacaaaac auuucuaaga ugcgaagcua aaaacuauuc aggaagauuc 420

acaugcuggu ggcuaacaac caucaguacc gacuuaacau ucucaguaaa aucaucaaga 480

ggaucaucag acccacaagg aguaacaugu ggagcagcaa cacuaagcgc agaaagagua 540

cgaggagaca acaaagaaua cgaauauuca guagaauguc aagaagacuc agcaugcccu 600

gcagcagaag aaucauuacc aauagaagua auggucgacg cuguacacaa acuaaaauau 660

gaaaauuaca caagcaguuu cuucauaaga gacauaauaa aacccgaccc accaaaaaac 720

cuacaacuaa aaccauuaaa aaauucaaga caaguagaag uaucauggga auacccagau 780

acauggagca caccacacag uuacuucuca uuaacauucu gcguacaagu acaaggaaaa 840

aguaaaagag aaaaaaaaga cagaguauuc acagauaaga cuucagcaac aguaauauugc 900

agaaaaaacg caagcauaag cguacgagca caagacagau auuacucaag cucaugguca 960

gaaugggcau caguaccaug uuca 984

<210> 96

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt6

<400> 96

auaugggaac uaaaaaaaga cguauacgua guagaacuag acugguaccc agacgcacca 60

ggagaaaugg uaguauuaac augcgacaca ccagaagaag auggaauaac uuggacauua 120

gaccaaucaa gugaaguauu aggaucaggc aaaacacuaa cuauacaagu aaaagaauuu 180

ggagacgcag gacaauacac gugccacaaa ggaggcgaag uccuaucaca uucacuaacua 240

300

ccaaaaaaca aaacauuucu aagaugcgaa gcuaaaaacu auucaggaag auucacaugc 360

ugguggcuaa caaccaucag uaccgacuua acauucucag uaaaaucauc aagaggauca 420

ucagacccac aaggaguaac auguggagca gcaacacuaa gcgcagaaag aguacgagga 480

gacaacaaag aauacgaaua uucaguagaa ugucaagaag acucagcaug cccugcagca 540

gaagaaucau uaccaauaga aguaaugguc gacgcuguac acaaacuaaa auaugaaaau 600

uacacaagca guuucuucau aagagacaua auaaaacccg acccaccaaa aaaccuacaa 660

cuaaaaccau uaaaaaauuc aagacaagua gaaguaucau gggaauaccc agauacaugg 720

agcacaccac acaguuacuu cucauuaaca uucugcguac aaguacaagg aaaaaguaaa 780

agagaaaaaa aagacagagu auucacagau aagacuucag caacaguaau augcagaaaa 840

aacgcaagca uaagcguacg agcacaagac agauauuacu caagcucaug gucagaaugg 900

gcaucaguac cauguucaua a 921

<210> 97

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt6

<400> 97

ggaaguacaa guggaagugg aaaaccagga aguggagaag gaaguacaaa agga 54

<210> 98

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt6

<400> 98

augugccacc aacaacuggu aauaucaugg uucucacugg uauucuuggc aucaccccua 60

guagcaauau gggaacuaaa aaaagacgua uacguaguag aacuagacug guacccagac 120

gcaccaggag aaaugguagu auuaacaugc gacacaccag aagaagaugg aauaacuugg 180

acauuagacc aaucaaguga aguauuagga ucaggcaaaa cacuaacuau acaaguaaaa 240

gaauuuggag acgcaggaca auacacgugc cacaaaggag gcgaaguccu aucacauuca 300

cuacuauuau uacacaaaaa agaagacgga aucuggagca cagacauauu aaaagaccaa 360

aaagaaccaa aaaacaaaac auuucuaaga ugcgaagcua aaaacuauuc aggaagauuc 420

acaugcuggu ggcuaacaac caucaguacc gacuuaacau ucucaguaaa aucaucaaga 480

ggaucaucag acccacaagg aguaacaugu ggagcagcaa cacuaagcgc agaaagagua 540

cgaggagaca acaaagaaua cgaauauuca guagaauguc aagaagacuc agcaugcccu 600

gcagcagaag aaucauuacc aauagaagua auggucgacg cuguacacaa acuaaaauau 660

gaaaauuaca caagcaguuu cuucauaaga gacauaauaa aacccgaccc accaaaaaac 720

cuacaacuaa aaccauuaaa aaauucaaga caaguagaag uaucauggga auacccagau 780

acauggagca caccacacag uuacuucuca uuaacauucu gcguacaagu acaaggaaaa 840

aguaaaagag aaaaaaaaga cagaguauuc acagauaaga cuucagcaac aguaauauugc 900

agaaaaaacg caagcauaag cguacgagca caagacagau auuacucaag cucaugguca 960

gaaugggcau caguaccaug uucaggaagu acaaguggaa guggaaaacc aggaagugga 1020

gaaggaagua caaaaggaag aaaccuccca guagccacac cagacccagg aauguucccc 1080

ugccuccacc auucccaaaa ccuacuaaga gcaguaucaa acaugcuaca aaaagcaaga 1140

1200

gacaaaacau caaccguaga agcaugccuc ccacucgaac ucacaaaaaa cgaaucaugc 1260

1320

ucauucauga uggcacuaug ccucucaucc auauaugaag acuuaaaaau guaccaagua 1380

1440

caaaacaugc uagcaguaau agacgaacua augcaagcac uaaacuucaa cucagaaacc 1500

guaccccaaa aaucaucucu agaagaacca gacuucuaca aaacaaaaau aaaacuaugc 1560

1620 auacuacuac acgccuucag aauaagagcc gucacaauag

aacgccucau aa 1632

<210> 99

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt6

<400> 99

augauagaaa cauauaauca aacaagccca agaucagcag caacaggacu accaauauca 60

augaaaauau ucauguaccu acucacaguc uuccuaauaa cacaaaugau aggaucugcc 120

cuauuugcag uauaccuaca cagaagacua gauaaaauag aagacgaaag aaaccuacau 180

gaagacuucg uauucaugaa aacaauacaa agaugcaaca ccggagaaag aucccuauca 240

cuacuaaacu gcgaagaaau aaaaucacaa uucgaaggau ucguaaaaga cauaaugcua 300

aacaaagaag aaaaaaaaa agaaaacucu uucgaaaugc aaaaaggaga ccaaaaccca 360

caaauagcug cacacgucau aucagaagca ucaucaaaaa caacaucagu acuucaaugg 420

480

cuaacaguaa aaagacaagg acuauacuau auauacgcac aaguaacauu cugcucaaac 540

agagaagcau caucacaagc accauucauc gcaucacuau gccuaaaauc cccaggaaga 600

uucgaacgaa uccuacuaag agcagcaaac acacacucau cagcaaaacc augcggccaa 660

caaucaauac accuaggagg aguauucgaa cuacaaccag gagcaucagu auucguaaac 720

guaacagacc ccucacaagu aagccggc acaggauuca caucauuugg acuauuaaaa 780

uuauaa 786

<210> 100

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt7

<400> 100

augcagaucc cccaagcccc auggccggug gucugggcag ugcugcagcu cggcuggagg 60

cccggguggu uccggacag cccagaucgg ccuggaacc cacccaccuu uuccccagcc 120

uugcugguag ugacugggg ugacaaugcg accuucacgu gcaguuuuag caacacuucc 180

gaaaguuucg uccucaauug guaccgcaug agcccgucca accagaccga uaagcuggcc 240

gcauuucccg aggacaggag ccagccaggc caagauuguc gguuccgcgu gacccaguug 300

360

uaucugugcg gugcaauuag ccucgcccca aaagcgcaga ucaaggaauc ccugcgggcc 420

gagcugcgcg ugaccgaaag gcgggcagag guaccacgg cccauccgag ccccagucca 480

cgccccgccg ggcaguucca aacucucgug gucggcgugg ugggcggggcu guuggguucc 540

cugguccucc uggugugggu acuggcagug auuuguagca gggccgcgcg gggcaccauc 600

ggggcccgca ggacuggcca gccauugaaa gaggaccccu ccgcaguccc aguguuuagu 660

guggauuacg gugaacucga cuuccagugg cggggagaaga cccgggaacc cccagucccc 720

ugcgugccag agcagaccga guaugccacg auuguauuuc ccagcgggau gggcacuucc 780

agcccggcac gcaggggcag ugccgauggg cccacgguccg cccaaccccu gaggcccgaa 840

gacggucacu guagcuggcc acuguga 867

<210> 101

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt7

<400> 101

augcagaucc cccaagcccc auggccggug gucugggcag ugcugcagcu cggcuggagg 60

cccggguggu uccggacag cccagaucgg ccuggaacc cacccaccuu uuccccagcc 120

uugcugguag ugacugggg ugacaaugcg accuucacgu gcaguuuuag caacacuucc 180

gaaaguuucg uccucaauug guaccgcaug agcccgucca accagaccga uaagcuggcc 240

gcauuucccg aggacaggag ccagccaggc caagauuguc gguuccgcgu gacccaguug 300

360

uaucugugcg gugcaauuag ccucgcccca aaagcgcaga ucaaggaauc ccugcgggcc 420

gagcugcgcg ugaccgaaag gcgggcauga 450

<210> 102

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt7

<400> 102

augugccccg ccaggagccu gcuccuggug gcaaccuugg uccugcucga ccaccugucc 60

uuggccggga accugccagu ggcgacuccg gaucccggca uguucccaug ucuccaucac 120

agucagaauc ugcugcgcgc cguaagcaac augcuccaaa aggcaaggca gacccuggag 180

uuuuaccccu gcacguccga agagaucgac caugaagaua uuacuaaaga caagaccagu 240

accguggagg ccuguuugcc acuggaacuc acuaaaaaug agagcugccu gaacucccgg 300

gagaccagcu ucaucacgaa uggguccugu cuggcaaguc gcaagacuag cuuuaugaug 360

gccuugugcc ucuccagcau uuaugaagau cugaaaaugu accaggucga guucaagacc 420

augaacgcga agcugcucau ggaccccaaa aggcagaucu uucuggauca aaauauguug 480

gccgugauug acgaacugau gcaggcacuc aacuucaaua gugagacugu gccacagaag 540

uccagccugg aggaaccggga uuuuuauaaa accaagauca aacuguguau cuugcuccac 600

gccuuccgaa cgcaaguuga 660

<210> 103

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt7

<400> 103

augugccccg ccaggagccu gcuccuggug gcaaccuugg uccugcucga ccaccugucc 60

uuggccggga accugccagu ggcgacuccg gaucccggca uguucccaug ucuccaucac 120

agucagaauc ugcugcgcgc cguaagcaac augcuccaaa aggcaaggca gacccuggag 180

uuuuaccccu gcacguccga agagaucgac caugaagaua uuacuaaaga caagaccagu 240

accguggagg ccuguuugcc acuggaacuc acuaaaaaug agagcugccu gaacucccgg 300

gagaccagcu ucaucacgaa uggguccugu cuggcaaguc gcaagacuag cuuuaugaug 360

gccuugugcc ucuccagcau uuaugaagau cugaaaaugu accaggucga guucaagacc 420

augaacgcga agcugcucau ggaccccaaa aggcagaucu uucuggauca aaauauguug 480

gccgugauug acgaacugau gcaggcacuc aacuucaaua gugagacugu gccacagaag 540

uccagccugg aggaaccggga uuuuuauaaa accaagauca aacuguguau cuugcuccac 600

657

<210> 104

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt7

<400> 104

cggaaccugc caguggcgac uccggauccc ggcauguucc caugucucca ucacagucag 60

aaucugcugc gcgccguaag caacaugcuc caaaaggcaa ggcagacccu ggaguuuuac 120

cccugcacgu ccgaagagau cgaccaugaa gauauuacua aagacaagac caguaccgug 180

gaggccuguu ugccacugga acucacuaaa aaugagagcu gccugaacuc ccggggagacc 240

agcuucauca cgaauggguc cugucuggca agucgcaaga cuagcuuuau gauggccuug 300

ugccucucca gcauuuauga agaucugaaa auguaccagg ucgaguucaa gaccaugaac 360

gcgaagcugc ucauggaccc caaaaggcag aucuuucugg aucaaaauau guuggccgug 420

auugacgaac ugaugcaggc acucaacuuc aauagugaga cugugccaca gaaguccagc 480

cuggaggaac cggauuuuua uaaaaccaag aucaaacugu guaucuugcu ccacgccuuc 540

cggauucgcg ccgucaccau cgacagggug auguccuacc ugaacgcaag uuga 594

<210> 105

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt7

<400> 105

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cagucccuug 60

guggcaauuu gggagcugaa gaaagacgua uacguggucg aacucgauug guauccagac 120

gccccgggcg agaugguggu gcugaccugu gauacucccg aagaggacgg gaucaccugg 180

acguuggauc agagcuccga aguccugggu aguggcaaga cucucaccau ucaggugaaa 240

gaguucgggg acgcggggcca guauaccugc cauaagggug gggagguacu gagccacucc 300

cugcuccugu ugcauaaaaa ggaagauggc aucuggagca cugacauucu gaaggaucaa 360

aaagagccaa agaacaaaac cuuucucagg ugugaagcca agaauuacuc cggccgguuc 420

acgugcuggu ggcugacuac caucaguacu gaccugaccu uuagcgugaa auccagccgc 480

gggaguuccg auccccaggg ugucaccugu ggcgcagcca cguugagcgc agagaggggug 540

cgcggggaca acaaggagua cgaauauucc guggagugcc aggaagauag ugccugucca 600

gcggccgagg aaagccuccc caucgagguc augguggacg caguacacaa acugaaguac 660

gagaauuaua cuuccagcuu cuuuauucgg gacaucauua agccagaucc gcccaaaaac 720

cugcagcuca agccacugaa aaauaguagg caaguggaag ucuccuggga guaccccgac 780

accuggagca cuccacauag uuacuucucc uugaccuuuu gcguccaggu gcagggcaag 840

agcaaacggg aaaagaagga ucgcguguuc accgacaaaa cuagcgccac ggugaucugu 900

aggaagaacg ccuccauuag uguacgggca caggaucgcu auuacagcuc cagcuggagu 960

gagugggccu cggugccug cagcuga 987

<210> 106

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt7

<400> 106

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cagucccuug 60

guggcaauuu gggagcugaa gaaagacgua uacguggucg aacucgauug guauccagac 120

gccccgggcg agaugguggu gcugaccugu gauacucccg aagaggacgg gaucaccugg 180

acguuggauc agagcuccga aguccugggu aguggcaaga cucucaccau ucaggugaaa 240

gaguucgggg acgcggggcca guauaccugc cauaagggug gggagguacu gagccacucc 300

cugcuccugu ugcauaaaaa ggaagauggc aucuggagca cugacauucu gaaggaucaa 360

aaagagccaa agaacaaaac cuuucucagg ugugaagcca agaauuacuc cggccgguuc 420

acgugcuggu ggcugacuac caucaguacu gaccugaccu uuagcgugaa auccagccgc 480

gggaguuccg auccccaggg ugucaccugu ggcgcagcca cguugagcgc agagaggggug 540

cgcggggaca acaaggagua cgaauauucc guggagugcc aggaagauag ugccugucca 600

gcggccgagg aaagccuccc caucgagguc augguggacg caguacacaa acugaaguac 660

gagaauuaua cuuccagcuu cuuuauucgg gacaucauua agccagaucc gcccaaaaac 720

cugcagcuca agccacugaa aaauaguagg caaguggaag ucuccuggga guaccccgac 780

accuggagca cuccacauag uuacuucucc uugaccuuuu gcguccaggu gcagggcaag 840

agcaaacggg aaaagaagga ucgcguguuc accgacaaaa cuagcgccac ggugaucugu 900

aggaagaacg ccuccauuag uguacgggca caggaucgcu auuacagcuc cagcuggagu 960

gagugggccu cggugccug cagc 984

<210> 107

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt7

<400> 107

auuugggagc ugaagaaaga cguauacgug gucgaacucg auugguaucc agacgccccg 60

ggcgagaugg uggugcugac cugugauacu cccgaagagg acgggaucac cuggacguug 120

gaucagagcu ccgaaguccu ggguaguggc aagacucuca ccauucaggu gaaagaguuc 180

ggggacgcgg gccaguauac cugccauaag ggugggggagg uacugagcca cucccugcuc 240

cuguugcaua aaaaggaaga uggcaucugg agcacugaca uucugaagga ucaaaaagag 300

ccaaagaaca aaaccuuucu caggugugaa gccaagaauu acuccggccg guucacgugc 360

ugguggcuga cuaccaucag uacugaccug accuuuagcg ugaaauccag ccgcgggagu 420

uccgaucccc agggugucac cuguggcgca gccacguuga gcgcagagag ggugcgcggg 480

gacaacaagg aguacgaaua uuccguggag ugccaggaag auagugccug uccagcggcc 540

gaggaaagcc uccccaucga ggucauggug gacgcaguac acaaacugaa guacgagaau 600

uauacuucca gcuucuuuau ucgggacauc auuaagccag auccgcccaa aaaccugcag 660

cucaagccac ugaaaaauag uaggcaagug gaagucuccu gggaguaccc cgacaccugg 720

agcacuccac auaguuacuu cuccuugacc uuuugcgucc agggcaggg caagagcaaa 780

840 cgggaaaaga aggaucgcgu guucaccgac

aacgccucca uuaguguacg ggcacaggau cgcuauuaca gcuccagcug gagugagugg 900

gccuccgugc ccuccagcug a 921

<210> 108

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt7

<400> 108

ggcagcaccu ccgggagugg uaagcccggc agcggggagg gcuccacuaa aggu 54

<210> 109

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt7

<400> 109

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cagucccuug 60

guggcaauuu gggagcugaa gaaagacgua uacguggucg aacucgauug guauccagac 120

gccccgggcg agaugguggu gcugaccugu gauacucccg aagaggacgg gaucaccugg 180

acguuggauc agagcuccga aguccugggu aguggcaaga cucucaccau ucaggugaaa 240

gaguucgggg acgcggggcca guauaccugc cauaagggug gggagguacu gagccacucc 300

cugcuccugu ugcauaaaaa ggaagauggc aucuggagca cugacauucu gaaggaucaa 360

aaagagccaa agaacaaaac cuuucucagg ugugaagcca agaauuacuc cggccgguuc 420

acgugcuggu ggcugacuac caucaguacu gaccugaccu uuagcgugaa auccagccgc 480

gggaguuccg auccccaggg ugucaccugu ggcgcagcca cguugagcgc agagaggggug 540

cgcggggaca acaaggagua cgaauauucc guggagugcc aggaagauag ugccugucca 600

gcggccgagg aaagccuccc caucgagguc augguggacg caguacacaa acugaaguac 660

gagaauuaua cuuccagcuu cuuuauucgg gacaucauua agccagaucc gcccaaaaac 720

cugcagcuca agccacugaa aaauaguagg caaguggaag ucuccuggga guaccccgac 780

accuggagca cuccacauag uuacuucucc uugaccuuuu gcguccaggu gcagggcaag 840

agcaaacggg aaaagaagga ucgcguguuc accgacaaaa cuagcgccac ggugaucugu 900

aggaagaacg ccuccauuag uguacgggca caggaucgcu auuacagcuc cagcuggagu 960

gagugggccu cggugccug cagcggcagc accuccggga gugguaagcc cggcagcggg 1020

gagggcucca cuaaaggucg gaaccugcca guggcgacuc cggaucccgg cauguuccca 1080

ugucuccauc acagucagaa ucugcugcgc gccguaagca acaugcucca aaaggcaagg 1140

cagacccugg aguuuuaccc cugcacgucc gaagagaucg accaugaaga uauuuacuaaa 1200

gacaagacca guaccgugga ggccuguuug ccacuggaac ucacuaaaaa ugagagcugc 1260

cugaacuccc gggagaccag cuucaucacg aauggguccu gucuggcaag ucgcaagacu 1320

agcuuuauga uggccuugug ccucuccagc auuuaugaag aucugaaaau guaccagguc 1380

gaguucaaga ccaugaacgc gaagcugcuc auggaccca aaaggcagau cuuucuggau 1440

1500

gugccacaga aguccagccu ggaggaaccg gauuuuuaua aaaccaagau caaacugugu 1560

1620 gauucgcgcc gucaccaucg acagggugau guccuaccug

aacgcaaguu ga 1632

<210> 110

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt7

<400> 110

augaucgaga ccuacacca gacuagcccc agguccgccg caaccggccu gccaauuagu 60

augaagaucu ucauguaucu ccugacggug uuuuugauua cucaaaugau cgggagcgcc 120

cuguucgcgg ucuaccucca ccggcgccug gacaaaauug aagaugagag gaauuugcau 180

gaagacuuug uguucaugaa gaccauccag cggugcaaca ccggugagcg cucccugagu 240

cuccugaauu gugaagagau caaaagccag uuugagggcu ucguaaagga uauuaugcug 300

360

cagaucgccg cacacgugau uagcgaggcc uccaguaaga ccacgagcgu ccuccagugg 420

gcagaaaaag gcuauuacac uauguccaau aaccugguga ccuuggagaa ugguaagcag 480

cugacuguga aaaggcaagg gcucuauuac aucuaugccc aggucaccuu cugcagcaac 540

cgggaagcga guucccaggc ccccuuuauu gcaagccugu gucugaaguc cccaggccgc 600

uucgagagga ucuugcuccg ggccgccaau acccauagua gcgcaaaacc cugcggccag 660

caauccauuc accucgggg uguguuugaa cugcagccag gcgccagcgu auucgugaac 720

gucacggauc ccagucaggu gucccauggg acuggcuuca ccagcuuugg ucugcugaag 780

uuguga 786

<210> 111

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt8

<400> 111

augcaaaucc cacaagcccc cuggcccgua gucugggccg uacuacaacu aggcuggaga 60

cccggcuggu uucucgacag ccccgaccga ccuggaacc cccccaccuu cucacccgcc 120

cuccucgucg ucaccgaagg cgacaacgcc acauucacau gcuccuucuc caacaccucu 180

gaaucauucg uccuaaacug guaccgaaug ucacccucca accaaacuga caaacucgcc 240

gccuuucccg aagaccgcuc ccaacccggc caagacugcc gauuccgagu cacacaacuu 300

ccuaacggca gagacuucca cauguccgua guccgagccc gccgaaacga cucgggaacc 360

uaccucugcg gagccaucuc ccucgccccc aaagcccaaa ucaaagaauc ccuccgagca 420

gaacccgcg ucaccgaacg ccgcgccgaa guccccaccg cacacccauc acccuccccc 480

cgccccgccg gccaauucca aacacuugua guaggcgucg ucggcggccu ccuuggauca 540

cucguccuac uuguaugggu ccuagccguc aucugcucuc gcgccgcacg cggcaccauc 600

ggcgcacgac gaaccggcca accucuaaaa gaagaccccu ccgcaguccc cgucuucucc 660

gucgacuacg gcgaacucga cuuccaaugg cgcgaaaaaa cccccgaacc cccagucccc 720

ugcguaaccg aacaaaccga auacgcaaca aucguauucc ccugggaau gggcaccuca 780

840

gacggccacu gcucauggcc ccuuuaa 867

<210> 112

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt8

<400> 112

augcaaaucc cacaagcccc cuggcccgua gucugggccg uacuacaacu aggcuggaga 60

cccggcuggu uucucgacag ccccgaccga ccuggaacc cccccaccuu cucacccgcc 120

cuccucgucg ucaccgaagg cgacaacgcc acauucacau gcuccuucuc caacaccucu 180

gaaucauucg uccuaaacug guaccgaaug ucacccucca accaaacuga caaacucgcc 240

gccuuucccg aagaccgcuc ccaacccggc caagacugcc gauuccgagu cacacaacuu 300

ccuaacggca gagacuucca cauguccgua guccgagccc gccgaaacga cucgggaacc 360

uaccucugcg gagccaucuc ccucgccccc aaagcccaaa ucaaagaauc ccuccgagca 420

gaacccgcg ucaccgaacg ccgcgccuaa 450

<210> 113

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt8

<400> 113

augugccccg ccagaucccu ccuacucguc gcaacacuug uccuccucga ccaccucucc 60

cucgcccgca aucuccccgu cgccaccccc gaccccggaa uguuucccug ccuccaccac 120

uccaaaaacc uccuacgcgc cgucucaaac augcuucaaa aagcccgaca aacccucgaa 180

uuuuaccccu gcaccuccga agaaaucgac cacgaagaca uaaccaaaga caaaaccucc 240

accgucgaag ccugccuacc auuagaacua acccaaaaacg aauccugccu caacucacgc 300

gaaaccuccu ucaucacaaa cggcucaugc cucgccucac gcaaaaccuc cuucaugaug 360

gcccucugcc uaucaucaau cuaugaagac cucaaaaugu accaaguaga auuuaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gcagucaucg acgaacucau gcaagcccuc aacuucaacu cagaaacagu cccacaaaaa 540

uccuccucg aagaacccga cuucuauaaa accaaaauca aacucugcau ccuccuccac 600

gccuuccgca uacgcgccgu aaccaucgac cgcguaaugu cauaccuaaa ugccucuuaa 660

<210> 114

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt8

<400> 114

augugccccg ccagaucccu ccuacucguc gcaacacuug uccuccucga ccaccucucc 60

cucgcccgca aucuccccgu cgccaccccc gaccccggaa uguuucccug ccuccaccac 120

uccaaaaacc uccuacgcgc cgucucaaac augcuucaaa aagcccgaca aacccucgaa 180

uuuuaccccu gcaccuccga agaaaucgac cacgaagaca uaaccaaaga caaaaccucc 240

accgucgaag ccugccuacc auuagaacua acccaaaaacg aauccugccu caacucacgc 300

gaaaccuccu ucaucacaaa cggcucaugc cucgccucac gcaaaaccuc cuucaugaug 360

gcccucugcc uaucaucaau cuaugaagac cucaaaaugu accaaguaga auuuaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gcagucaucg acgaacucau gcaagcccuc aacuucaacu cagaaacagu cccacaaaaa 540

uccuccucg aagaacccga cuucuauaaa accaaaauca aacucugcau ccuccuccac 600

gccuuccgca uacgcgccgu aaccaucgac cgcguaaugu cauaccuaaa ugccucu 657

<210> 115

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt8

<400> 115

cgcaaucucc ccgucgccac ccccgacccc ggaauguuuc ccugccucca ccacucacaa 60

aaccuccuac gcgccgucuc aaacaugcuu caaaaagccc gacaaacccu cgaauuuuac 120

cccugcaccu ccgaagaaau cgaccacgaa gacauaacca aagacaaaac cuccaccguc 180

gaagccugcc uaccauuaga acuaaccaaa aacgaauccu gccucaacuc acgcgaaacc 240

uccuucauca caaacggcuc augccucgcc ucacgcaaaa ccuccuucau gauggcccuc 300

ugccuaucau caaucuauga agaccucaaa auguaccaag uagaauuuaa aaccaugaac 360

gccaaacucc ucauggaccc caaacgccaa aucuuccucg accaaaacau gcucgcaguc 420

aucgacgaac ucaugcaagc ccucaacuuc aacucagaaa cagucccaca aaaauccucc 480

cucgaagaac ccgacuucua uaaaaccaaa aucaaacucu gcauccuccu ccacgccuuc 540

cgcauacgcg ccguaaccau cgaccgcgua augucauacc uaaaugccuc uuaa 594

<210> 116

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt8

<400> 116

augugccacc aacaacucgu cauaagcugg uucagccuag uauuccucgc cucaccccuc 60

gucgccaucu gggaacucaa gaaagacgua uacgucgucg aacuagacug guaccccgac 120

gcacccggag aaaugguagu acucacaugc gacacccccg aagaagacgg caucacaugg 180

accuuagacc aaucaucaga aguccucgga uccggaaaaa cccucacaau ccaagucaaa 240

gaguucggcg acgccggcca auacacaugc cacaaaggcg gagaaguccu cucacacuca 300

cuccuucuac uacacaagaa agaagacggc aucuggucca ccgacauacu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

acaugcuggu ggcucaccac caucuccacc gaccugaccu ucuccgucaa auccagcagg 480

ggcuccucag acccacaagg cguaaccugc ggcgcagcca cccuaucggc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacagc gucgaaugcc aagaagacuc agcaugccca 600

gcagccgaag acuaaaauac 660

gaaaacuaca caagcucauu cuucauccgc gacauaauca aacccgaccc accgaaaaac 720

cuccaacuca aaccccuuaa aaacagccgc caagucgaag ucuccuggga auaccccgac 780

accuggucca caccccacuc cuacuucuca cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaagaaaga ccgcguauuc accgacaaaa ccuccgccac agucaucugc 900

cgcaaaaacg ccucaaucuc cguccgcgcc caagaccgau acuacagcuc cuccugguca 960

gaaugggccu ccgucccaug cuccuaa 987

<210> 117

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt8

<400> 117

augugccacc aacaacucgu cauaagcugg uucagccuag uauuccucgc cucaccccuc 60

gucgccaucu gggaacucaa gaaagacgua uacgucgucg aacuagacug guaccccgac 120

gcacccggag aaaugguagu acucacaugc gacacccccg aagaagacgg caucacaugg 180

accuuagacc aaucaucaga aguccucgga uccggaaaaa cccucacaau ccaagucaaa 240

gaguucggcg acgccggcca auacacaugc cacaaaggcg gagaaguccu cucacacuca 300

cuccuucuac uacacaagaa agaagacggc aucuggucca ccgacauacu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

acaugcuggu ggcucaccac caucuccacc gaccugaccu ucuccgucaa auccagcagg 480

ggcuccucag acccacaagg cguaaccugc ggcgcagcca cccuaucggc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacagc gucgaaugcc aagaagacuc agcaugccca 600

gcagccgaag acuaaaauac 660

gaaaacuaca caagcucauu cuucauccgc gacauaauca aacccgaccc accgaaaaac 720

cuccaacuca aaccccuuaa aaacagccgc caagucgaag ucuccuggga auaccccgac 780

accuggucca caccccacuc cuacuucuca cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaagaaaga ccgcguauuc accgacaaaa ccuccgccac agucaucugc 900

cgcaaaaacg ccucaaucuc cguccgcgcc caagaccgau acuacagcuc cuccugguca 960

gaaugggccu ccgucccaug cucc 984

<210> 118

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt8

<400> 118

aucgggaac ucaagaaaga cguauacguc gucgaacuag acugguaccc cgacgcaccc 60

ggagaaaugg uaguacucac augcgacacc cccgaagaag acggcaucac auggaccuua 120

gaccaaucaau cagaaguccu cggauccggga aaaacccuca caauccaagu caaagaguuc 180

ggcgacgccg gccaauacac augccacaaa ggcggagaag uccucucaca cucacuccuu 240

cuacuacaca agaaagaaga cggcaucugg uccaccgaca uacucaaaga ccaaaaagaa 300

cccaaaaaca aaaccuuccu ccgcugcgaa gccaaaaacu acuccggccg auucacaugc 360

ugguggcuca ccaccaucuc caccgaccug accuucuccg ucaaauccag caggggcucc 420

ucagacccac aaggcguaac cugcggcgca gccacccuau cggccgaacg aguccgcgga 480

gacaacaaag aauacgaaua cagcgucgaa ugccaagaag acucagcaug cccagcagcc 540

gaagaaucac uccccaucga agucaugguc gacgccgucc acaaacuaaa auacgaaaac 600

uacacaagcu cauucuucau ccgcgacaua aucaaacccg acccaccgaa aaaccuccaa 660

cucaaacccc uuaaaaacag ccgccaaguc gaagucuccu gggaauaccc cgacaccugg 720

uccacacccc acuccuacuu cucacucacc uucugcgucc aaguccaagg caaauccaaa 780

cgcgaaaaga aagaccgcgu auucaccgac aaaaccuccg ccacagucau cugccgcaaa 840

aacgccucaa ucuccguccg cgcccaagac cgauacuaca gcuccuccug gucagaaugg 900

gccuccgucc caugcuccua a 921

<210> 119

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt8

<400> 119

gggagcacga gcgggagcgg gaagccggga aguggagagg gaaguacaaa ggga 54

<210> 120

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt8

<400> 120

augugccacc aacaacucgu cauaagcugg uucagccuag uauuccucgc cucaccccuc 60

gucgccaucu gggaacucaa gaaagacgua uacgucgucg aacuagacug guaccccgac 120

gcacccggag aaaugguagu acucacaugc gacacccccg aagaagacgg caucacaugg 180

accuuagacc aaucaucaga aguccucgga uccggaaaaa cccucacaau ccaagucaaa 240

gaguucggcg acgccggcca auacacaugc cacaaaggcg gagaaguccu cucacacuca 300

cuccuucuac uacacaagaa agaagacggc aucuggucca ccgacauacu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

acaugcuggu ggcucaccac caucuccacc gaccugaccu ucuccgucaa auccagcagg 480

ggcuccucag acccacaagg cguaaccugc ggcgcagcca cccuaucggc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacagc gucgaaugcc aagaagacuc agcaugccca 600

gcagccgaag acuaaaauac 660

gaaaacuaca caagcucauu cuucauccgc gacauaauca aacccgaccc accgaaaaac 720

cuccaacuca aaccccuuaa aaacagccgc caagucgaag ucuccuggga auaccccgac 780

accuggucca caccccacuc cuacuucuca cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaagaaaga ccgcguauuc accgacaaaa ccuccgccac agucaucugc 900

cgcaaaaacg ccucaaucuc cguccgcgcc caagaccgau acuacagcuc cuccugguca 960

1020

gagggaagua caaagggacg caaucucccc gucgccaccc ccgaccccgg aauguuuccc 1080

ugccuccacc acucacaaaa ccuccuacgc gccgucucaa acaugcuuca aaaagcccga 1140

caaacccucg aauuuuuaccc cugcaccucc gaagaaaucg accacgaaga cauaaccaaa 1200

gacaaaaccu ccaccgucga agccugccua ccauuagaac uaaccaaaaa cgaauccugc 1260

cucaacucac gcgaaaccuc cuucaucaca aacggcucau gccucgccuc acgcaaaacc 1320

uccuucauga uggccucug ccuaucauca aucuaugaag accucaaaau guaccaagua 1380

1440

caaaacaugc ucgcagucau cgacgaacuc augcaagccc ucaacuucaa cucagaaaca 1500

gucccacaaa aauccucccu cgaagaaccc gacuucuaua aaaccaaaau caaacucugc 1560

1620

aaugccucuu aa 1632

<210> 121

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt8

<400> 121

augauagaaa ccuacaacca aaccucuccc cgauccgcag ccaccggccu ccccaucucc 60

augaaaaucu ucauguaccu ccuaaccguc uuccuaauca cucaaaugau cggcuccgcu 120

cucuucgcag ucuaccucca ccgccgccua gacaaaaucg aagacgaacg caaccuacac 180

gaagacuucg ucuucaugaa aaccauucaa cgcugcaaca caggcgaacg aucccuaucc 240

cuacucaacu gcgaagaaau caaaucccaa uucgaaggcu uuguaaaaga caucaugcuc 300

aacaaagaag aaaccaaaaa agaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaauagccg cccaugucau aucagaagcc uccuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac cauguccaac aaccuaguaa cccuugaaaa cggcaaacaa 480

cucaccguaa aacgccaagg ccucuacuac aucuacgccc aagucaccuu cugcuccaac 540

agagaagcau ccucccaagc acccuucauc gccucccuau gccucaaauc ccccggccgc 600

uucgaacgaa uccuccuccg cgccgccaac acucacuccu cagccaaacc cugcggccaa 660

caaaguauac accuuggcgg agucuucgaa cuccaacccg gcgccuccgu cuucguaaac 720

gucaccgacc ccucacaagu cuccccgga accggauuca ccuccuucgg ccuacuaaaa 780

cuauag 786

<210> 122

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt9

<400> 122

augcaaaucc cccaagcccc auggcccguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccuagacuc uccagaccgc ccuggaauc cacccaccuu cucccccgcc 120

cuccuagucg ucaccgaagg cgacaacgcc accuucaccu guucauucuc caacaccuca 180

gaauccuucg uacucaacug guaccgcaug uccccaagca accaaacaga caaacucgcc 240

gccuucccg aagaccgcuc ccaacccggu caagacugcc gauuccgcgu cacccaacuc 300

cccaacggac gcgacuucca cauguccguc guucgagcac gacgcaacga cucaggcaca 360

uaccuaugcg gagccaucuc ccuagccccc aaagcccaaa ucaaagaauc acuacgcgcc 420

gaacccgcg ucaccgaacg ccgcgccgaa guacccacag cccacccauc cccaucacca 480

cgccagcag gucaauucca aaccuuaguc gucggagucg ucggcggccu ccuaggcuca 540

cucgccucc uaugucgggu ccucgccguc auaugcagcc gcgccgcacg cggcaccauc 600

ggcgccagac gcaccggaca accccucaaa gaagaccccu cagccguccc cgucuuuucc 660

gucgacuacg gcgaacuaga cuuccaaugg cgcgaaaaaa cccccgaacc ccccguccca 720

ugcguacccg aacaaaccga auacgccaca auagucuucc cauccggcau gggaaccuca 780

ucacccgcca gacgaggcuc agcagauggc ccccgcuccg cacaaccacu ccgaccagaa 840

gacggccacu gcagcuggcc ccuguaa 867

<210> 123

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt9

<400> 123

augcaaaucc cccaagcccc auggcccguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccuagacuc uccagaccgc ccuggaauc cacccaccuu cucccccgcc 120

cuccuagucg ucaccgaagg cgacaacgcc accuucaccu guucauucuc caacaccuca 180

gaauccuucg uacucaacug guaccgcaug uccccaagca accaaacaga caaacucgcc 240

gccuucccg aagaccgcuc ccaacccggu caagacugcc gauuccgcgu cacccaacuc 300

cccaacggac gcgacuucca cauguccguc guucgagcac gacgcaacga cucaggcaca 360

uaccuaugcg gagccaucuc ccuagccccc aaagcccaaa ucaaagaauc acuacgcgcc 420

gaacccgcg ucaccgaacg ccgcgccuaa 450

<210> 124

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt9

<400> 124

60

cuagcacgua accucccagu cgccacccca gaccccggaa uguuccccug ccuccaucac 120

ucccaaaauc uccuccgugc cgucuccaac augcuccaaa aagcccgcca aacccucgaa 180

uuuuauccau gcaccuccga agaaauagac caugaagaca ucaccaaaga caaaacaucc 240

accgucgaag ccugccuccc ccucgaacuc acaaaaaacg aaucaugccu caacucccgc 300

gaaaccuccu ucauaaccaa cggcucaugc cucgccucuc gcaaaaccuc auucaugaug 360

gcccucugcc uauccucuau cuacgaagac cucaaaaugu accaagucga auuuaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gcagucaucg acgaacucau gcaagcacuc aacuucaacu cagaaaccgu cccccaaaaa 540

uccuccucg aagaacccga cuucuacaaa acaaaaauaa aacucugcau ccuccuccac 600

660

<210> 125

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt9

<400> 125

60

cuagcacgua accucccagu cgccacccca gaccccggaa uguuccccug ccuccaucac 120

ucccaaaauc uccuccgugc cgucuccaac augcuccaaa aagcccgcca aacccucgaa 180

uuuuauccau gcaccuccga agaaauagac caugaagaca ucaccaaaga caaaacaucc 240

accgucgaag ccugccuccc ccucgaacuc acaaaaaacg aaucaugccu caacucccgc 300

gaaaccuccu ucauaaccaa cggcucaugc cucgccucuc gcaaaaccuc auucaugaug 360

gcccucugcc uauccucuau cuacgaagac cucaaaaugu accaagucga auuuaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gcagucaucg acgaacucau gcaagcacuc aacuucaacu cagaaaccgu cccccaaaaa 540

uccuccucg aagaacccga cuucuacaaa acaaaaauaa aacucugcau ccuccuccac 600

gccuuccgca uccgagcagu caccaucgau cgcgucaugu ccuaccuaaa cgccucc 657

<210> 126

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt9

<400> 126

cguaaccucc cagucgccac cccagacccc ggaauguucc ccugccucca ucacucccaa 60

aaucuccucc gugccgucuc caacaugcuc caaaaagccc gccaaacccu cgaauuuuau 120

ccaugcaccu ccgaagaaau agaccaugaa gacaucacca aagacaaaac auccaccguc 180

gaagccugcc ucccccucga acucacaaaa aacgaaucau gccucaacuc ccgcgaaacc 240

uccuucauaa ccaacggcuc augccucgcc ucucgcaaaa ccucauucau gauggcccuc 300

ugccuauccu cuaucuacga agaccucaaa auguaccaag ucgaauuuaa aaccaugaac 360

gccaaacucc ucauggaccc caaacgccaa aucuuccucg accaaaacau gcucgcaguc 420

aucgacgaac ucaugcaagc acucaacuuc aacucagaaa cggucccca aaaauccucc 480

cucgaagaac ccgacuucua caaaacaaaa auaaaacucu gcauccuccu ccacgccuuc 540

cgcauccgag cagucaccau cgaucgcguc auguccuacc uaaacgccuc cuaa 594

<210> 127

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt9

<400> 127

augugucacc aacaacuugu aaucagcugg uucucccucg ucuuccucgc cucaccccuc 60

gucgccaucu gggaacucaa aaaagacguc uacguagucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu acucaccugu gacacccccg aagaagacgg caucaccugg 180

acccucgacc aauccuccga aguccucggu ucaggaaaaa cccucaccau ccaaguaaaa 240

gaauuuggcg acgccggggca auauaccugc cacaaaggcg gcgagguccu aucccacuca 300

cuccuccucc uccacaagaa agaagacgga aucuggucca ccgacauccu uaaagaccaa 360

aaagaaccaa aaaacaaaac auuccuccgc ugcgaagcca aaaacuacag cggccgcuuc 420

accuguuggu ggcuaaccac aauaucaacc gacuuaaccu ucagcgucaa auccuccaga 480

ggauccagcg acccacaagg aguuaccugc ggagccgcaa cacucagcgc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacucc gucgaaugcc aagaagacuc agcaugcccc 600

gccgcagaag aaucccuacc caucgaagua augguagacg ccguccacaa acucaaauac 660

gaaaacuaca ccagcuccuu cuucauccga gacaucauca aacccgaccc cccaaaaaac 720

cuccaacuaa aaccccucaa aaacagccgc caaguagaag uauccuggga auaccccgac 780

840

uccaaacgag aaaaaaaaga ccgcgucuuc accgacaaaa cuuccgccac cgucaucugc 900

cgcaaaaacg ccagcaucag cguccgcgca caagaccgcu acuacucaag cuccuggucc 960

gaaugggccu ccgucccaug cucauaa 987

<210> 128

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt9

<400> 128

augugucacc aacaacuugu aaucagcugg uucucccucg ucuuccucgc cucaccccuc 60

gucgccaucu gggaacucaa aaaagacguc uacguagucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu acucaccugu gacacccccg aagaagacgg caucaccugg 180

acccucgacc aauccuccga aguccucggu ucaggaaaaa cccucaccau ccaaguaaaa 240

gaauuuggcg acgccggggca auauaccugc cacaaaggcg gcgagguccu aucccacuca 300

cuccuccucc uccacaagaa agaagacgga aucuggucca ccgacauccu uaaagaccaa 360

aaagaaccaa aaaacaaaac auuccuccgc ugcgaagcca aaaacuacag cggccgcuuc 420

accuguuggu ggcuaaccac aauaucaacc gacuuaaccu ucagcgucaa auccuccaga 480

ggauccagcg acccacaagg aguuaccugc ggagccgcaa cacucagcgc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacucc gucgaaugcc aagaagacuc agcaugcccc 600

gccgcagaag aaucccuacc caucgaagua augguagacg ccguccacaa acucaaauac 660

gaaaacuaca ccagcuccuu cuucauccga gacaucauca aacccgaccc cccaaaaaac 720

cuccaacuaa aaccccucaa aaacagccgc caaguagaag uauccuggga auaccccgac 780

840

uccaaacgag aaaaaaaaga ccgcgucuuc accgacaaaa cuuccgccac cgucaucugc 900

cgcaaaaacg ccagcaucag cguccgcgca caagaccgcu acuacucaag cuccuggucc 960

gaaugggccu ccgucccaug cuca 984

<210> 129

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt9

<400> 129

aucugggaac ucaaaaaaga cgucuacgua gucgaacucg acugguaccc cgacgcccca 60

ggagaaaugg ucguacucac cugugacacc cccgaagaag acggcaucac cuggacccuc 120

gaccaauccu ccgaaguccu cgguucagga aaaacccuca ccauccaagu aaaagaauuuu 180

ggcgacgccg ggcaauauac cugccacaaa ggcggcgagg uccuauccca cucacuccuc 240

cuccuccaca agaaagaaga cggaaucugg uccaccgaca uccuuaaaga ccaaaaagaa 300

ccaaaaaaca aaacauuccu ccgcugcgaa gccaaaaacu acagcggccg cuucaccugu 360

ugguggcuaa ccacaauauuc aaccgacuua accuucagcg ucaaauccuc cagaggaucc 420

agcgacccac aaggaguuac cugcggagcc gcaacacuca gcgccgaacg aguccgcgga 480

gacaacaaag aauacgaaua cuccgucgaa ugccaagaag acucagcaug ccccgccgca 540

gaagaauccc uacccaucga aguaauggua gacgccgucc acaaacucaa auacgaaaac 600

uacaccagcu ccuucuucau ccgagacauc aucaaacccg accccccaaa aaaccuccaa 660

cuaaaacccc ucaaaaacag ccgccaagua gaaguauccu gggaauaccc cgacaccugg 720

uccaccccacuccuacuu cucgcucacg uucugcgucc aaguccaagg caaauccaaa 780

cgagaaaaaa aagaccgcgu cuucaccgac aaaacuuccg ccaccgucau cugccgcaaa 840

aacgccagca ucagcguccg cgcacaagac cgcuacuacu caagcuccug guccgaaugg 900

gccuccgucc caugcucaua a 921

<210> 130

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt9

<400> 130

gggaguacga gugggagugg gaagccgggg agugggggagg ggaguacgaa gggg 54

<210> 131

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt9

<400> 131

augugucacc aacaacuugu aaucagcugg uucucccucg ucuuccucgc cucaccccuc 60

gucgccaucu gggaacucaa aaaagacguc uacguagucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu acucaccugu gacacccccg aagaagacgg caucaccugg 180

acccucgacc aauccuccga aguccucggu ucaggaaaaa cccucaccau ccaaguaaaa 240

gaauuuggcg acgccggggca auauaccugc cacaaaggcg gcgagguccu aucccacuca 300

cuccuccucc uccacaagaa agaagacgga aucuggucca ccgacauccu uaaagaccaa 360

aaagaaccaa aaaacaaaac auuccuccgc ugcgaagcca aaaacuacag cggccgcuuc 420

accuguuggu ggcuaaccac aauaucaacc gacuuaaccu ucagcgucaa auccuccaga 480

ggauccagcg acccacaagg aguuaccugc ggagccgcaa cacucagcgc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacucc gucgaaugcc aagaagacuc agcaugcccc 600

gccgcagaag aaucccuacc caucgaagua augguagacg ccguccacaa acucaaauac 660

gaaaacuaca ccagcuccuu cuucauccga gacaucauca aacccgaccc cccaaaaaac 720

cuccaacuaa aaccccucaa aaacagccgc caaguagaag uauccuggga auaccccgac 780

840

uccaaacgag aaaaaaaaga ccgcgucuuc accgacaaaa cuuccgccac cgucaucugc 900

cgcaaaaacg ccagcaucag cguccgcgca caagaccgcu acuacucaag cuccuggucc 960

gaaugggccu ccgucccaug cucagggagu acgaguggga gugggaagcc ggggaguggg 1020

gaggggagua cgaaggggcg uaaccuccca gucgccaccc cagaccccgg aauguucccc 1080

ugccuccauc acucccaaaa ucuccuccgu gccgucucca acaugcucca aaaagcccgc 1140

caaacccucg aauuuuaucc augcaccucc gaagaaauag accaugaaga caucaccaaa 1200

gacaaaacau ccaccgucga agccugccuc ccccucgaac ucacaaaaaa cgaaucaugc 1260

cucaacuccc gcgaaaccuc cuucauaacc aacggcucau gccucgccuc ucgcaaaacc 1320

ucauucauga uggccucug ccuauccucu aucuacgaag accucaaaau guaccaaguc 1380

1440

caaaacaugc ucgcagucau cgacgaacuc augcaagcac ucaacuucaa cucagaaacc 1500

gucccccaaa aauccucccu cgaagaaccc gacuucuaca aaacaaaaau aaaacucugc 1560

1620

aacgccuccu aa 1632

<210> 132

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt9

<400> 132

augaucgaaa cauacaacca aacauccccc cgcuccgccg ccacaggccu ccccaucucc 60

augaaaaucu ucauguaccu ccucacagua uuccucauca cccaaaugau cggcuccgca 120

cucuuugcag ucuaucucca ccgucgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuucg ucuucaugaa aaccauacaa cgcugcaaca ccggcgaacg cucacucucc 240

cuacuaaacu gcgaagaaau caaaucccaa uucgaaggcu ucgucaaaga caucaugcua 300

aacaaagaag aaaaaaaaaaaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaauagccg cccacgucau cuccgaagcc uccuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac aauguccaac aaccucguca cccucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg ccucuacuac aucuacgccc aaguaaccuu cugcuccaac 540

cgcgaagccu caucucaagc ucccuucauc gccucacucu gccucaaauc acccggccgc 600

uucgaaagaa uccuccuccg cgccgcaaac acccacucau ccgccaaacc cugcggccaa 660

caauccauac accucggcgg cguuuucgag cuccaaccug gcgccuccgu cuucguaaac 720

gucaccgacc ccucacaagu cucccacggu accggcuuca ccuccuucgg acuccuaaaa 780

cucuaa 786

<210> 133

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA opt10

<400> 133

augcaaaucc cccaagcccc cuggccgguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccucgacuc ccccgaccgc ccguggaacc cccccaccuu cucccccgcc 120

cuccuagucg ucaccgaagg cgacaacgcc accuucaccu guuccuucuc caacaccuca 180

gaauccuucg uccucaacug guaccgcaug uccccccucca accaaaccga caaacucgcc 240

gccuuccccg aagaccgauc ccaacccggc caagacugcc gcuuccgcgu cacacaacuu 300

cccaacggac gcgacuuuca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc ccucgccccc aaagcccaaa ucaaagaauc ccucagagcc 420

gaacccgcg ucaccgaacg gcgcgccgaa guccccug cccaccccuc ccccuccccc 480

cgccccgccg gccaauucca aacccucguc gucggcguug ucggcggccu ccucggcuca 540

cucguccucc ucgucugggu acucgccguc aucugcuccc gcgccgcgcg cggcaccauc 600

ggcgcgcgcc gcaccggaca accccuaaaa gaagaccccu ccgccguccc cgucuucucc 660

gucgacuacg gcgaacucga cuuccaaugg cgcgaaaaaa cccgggaacc ccccgucccg 720

ugcguccccg aacaaacaga auacgcgacc aucgucuucc cguccggcau gggcacaucc 780

ucacccgccc gccgaggcuc cgccgacggc ccccgauccg cccaaccccu acgccccgaa 840

gacggccacu gcuccuggcc ccuuaa 867

<210> 134

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA opt10

<400> 134

augcaaaucc cccaagcccc cuggccgguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccucgacuc ccccgaccgc ccguggaacc cccccaccuu cucccccgcc 120

cuccuagucg ucaccgaagg cgacaacgcc accuucaccu guuccuucuc caacaccuca 180

gaauccuucg uccucaacug guaccgcaug uccccccucca accaaaccga caaacucgcc 240

gccuuccccg aagaccgauc ccaacccggc caagacugcc gcuuccgcgu cacacaacuu 300

cccaacggac gcgacuuuca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc ccucgccccc aaagcccaaa ucaaagaauc ccucagagcc 420

gaacccgcg ucaccgaacg gcgcgccuaa 450

<210> 135

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA opt10

<400> 135

60

cuggcccgca accucccagu cgccaccccc gaccccggca uguuccccug ccuccaccac 120

ucccaaaacc uccuccgcgc cgucuccaac augcuccaaa aagcccgcca aacccucgaa 180

uuuuaccccu gcaccuccga agagaucgac cacgaagaca ucaccaaaga caaaaccucc 240

acagucgaag ccugccuccc ccucgaacuc accaaaaacg aauccugccu uaacucccgc 300

gaaaccuccu ucaucaccaa cggcuccugc cucgccuccc gcaaaaccuc cuucaugaug 360

gcccucugcc ucuccuccau cuacgaagac cucaaaaugu accaagucga auuuaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gccgucaucg acgaacucau gcaagcccuc aacuucaacu ccgaaaccgu cccccaaaaa 540

uccuccucg aagaacccga cuucuacaaa accaaaauca aacuuugcau ccuccuccac 600

gcauuccgca uccgcgccgu caccaucgac cgugucauga gcuaccuaaa cgccuccuga 660

<210> 136

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA opt10

<400> 136

60

cuggcccgca accucccagu cgccaccccc gaccccggca uguuccccug ccuccaccac 120

ucccaaaacc uccuccgcgc cgucuccaac augcuccaaa aagcccgcca aacccucgaa 180

uuuuaccccu gcaccuccga agagaucgac cacgaagaca ucaccaaaga caaaaccucc 240

acagucgaag ccugccuccc ccucgaacuc accaaaaacg aauccugccu uaacucccgc 300

gaaaccuccu ucaucaccaa cggcuccugc cucgccuccc gcaaaaccuc cuucaugaug 360

gcccucugcc ucuccuccau cuacgaagac cucaaaaugu accaagucga auuuaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gccgucaucg acgaacucau gcaagcccuc aacuucaacu ccgaaaccgu cccccaaaaa 540

uccuccucg aagaacccga cuucuacaaa accaaaauca aacuuugcau ccuccuccac 600

gcauuccgca uccgcgccgu caccaucgac cgugucauga gcuaccuaaa cgccucc 657

<210> 137

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA opt10

<400> 137

cgcaaccucc cagucgccac ccccgacccc ggcauguucc ccugccucca ccacucccaa 60

aaccuccucc gcgccgucuc caacaugcuc caaaaagccc gccaaacccu cgaauuuuac 120

cccugcaccu ccgaagagau cgaccacgaa gacaucacca aagacaaaac cuccacaguc 180

gaagccugcc ucccccucga acucaccaaa aacgaauccu gccuuaacuc ccgcgaaacc 240

uccuucauca ccaacggcuc cugccucgcc ucccgcaaaa ccuccuucau gauggcccuc 300

ugccucuccu ccaucuacga agaccucaaa auguaccaag ucgaauuuaa aaccaugaac 360

gccaaacucc ucauggaccc caaacgccaa aucuuccucg accaaaacau gcucgccguc 420

aucgacgaac ucaugcaagc ccucaacuuc aacuccgaaa cgguccccca aaaauccucc 480

cucgaagaac ccgacuucua caaaaccaaa aucaaacuuu gcauccuccu ccacgcauuc 540

cgcauccgcg ccgucaccau cgaccguguc augagcuacc uaaacgccuc cuga 594

<210> 138

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA opt10

<400> 138

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagggggccu caguccccug cagcuaa 987

<210> 139

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA opt10

<400> 139

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagc 984

<210> 140

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA opt10

<400> 140

aucugggaac ucaaaaaaga cguauacguc gucgaacucg acugguaccc cgacgcccca 60

ggagaaaugg ucguccuaac cugcgacaca cccgaagaag acgguaucac cuggacccuc 120

gaccaauccu ccgaaguccu aggcuccggc aagacccuca ccauccaagu caaagaauuu 180

ggcgacgcag gacaauacac cugucacaaa ggcggcgaag uccucagcca cagccuucuc 240

cuacuccaua aaaaagaaga cggcaucugg uccacugaca uccucaaaga ccaaaaagaa 300

cccaaaaaua aaaccuuccu ccgcugcgaa gccaaaaacu acuccggccg auucaccugu 360

ugguggcuaa ccacaaucag caccgaccuc accuucucag ucaaauccuc ccgcggcuca 420

ucugaccccc aaggcgucac augcggcgcc gccacccucu ccgccgaacg cguccgcggc 480

gacaacaaag aauacgaaua cuccgucgaa ugucaagaag acuccgccug ccccgccgcc 540

gaagaaucac uccccaucga agucaugguc gacgcagucc acaaacucaa auacgaaaac 600

uaacccuccu ccuucuucau ccgcgacaua auaaaacccg acccacccaa aaaccuccaa 660

cucaagccac ucaaaaacuc ccgacaaguc gaagucuccu gggaguaccc cgacaccugg 720

uccaccaccac acuccuacuu cucccucacc uucugcgucc aaguccaagg caaauccaaa 780

cgcgaaaaaa aagaccgcgu uuucacagac aaaaccuccg ccacaguaau augccgcaaa 840

aacgccucca ucuccguccg ggcccaagac cgcuacuacu ccuccuccug guccgagugg 900

gccucagucc ccucagcua a 921

<210> 141

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA opt10

<400> 141

gggaguacga gugggagugg gaagccgggg agugggggagg ggaguacgaa gggg 54

<210> 142

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA opt10

<400> 142

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccuggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagcgggagu acgaguggga gugggaagcc ggggaguggg 1020

gaggggagua cgaaggggcg caaccuccca gucgccaccc ccgaccccgg cauguucccc 1080

ugccuccacc acucccaaaa ccuccuccgc gccgucucca acaugcucca aaaagcccgc 1140

caaacccucg aauuuuaccc cugcaccucc gaagagaucg accacgaaga caucaccaaa 1200

gacaaaaccu ccacagucga agccugccuc ccccucgaac ucaccaaaaa cgaauccugc 1260

cuuaacuccc gcgaaaccuc cuucaucacc aacggcuccu gccucgccuc ccgcaaaacc 1320

uccuucauga uggccucug ccucuccucc aucuacgaag accucaaaau guaccaaguc 1380

1440

caaaacaugc ucgccgucau cgacgaacuc augcaagccc ucaacuucaa cuccgaaacc 1500

gucccccaaa aauccucccu cgaagaaccc gacuucuaca aaaccaaaau caaacuuugc 1560

auccuccucc acgcauuccg cauccgcgcc gucaccaucg accgugucau gagcuaccua 1620

aacgccuccu ga 1632

<210> 143

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA opt10

<400> 143

augaucgaaa ccuacaauca aaccuccccc cgcagcgccg caacaggccu ccccaucucc 60

augaaaaucu ucauguaccu ccucaccguc uuccuaauca cccaaaugau cggcuccgcc 120

cuauucgccg ucuaccucca ccgccgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuuug ucuucaugaa aacuauccaa cgaugcaaca ccggcgaacg aucccuaucc 240

cuccucaacu gcgaagaaau aaaaucccaa uucgaaggau ucgucaaaga caucaugcua 300

aacaaagaag aaaccaaaaa agaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaaucgcag cccacgucau cucagaagca ucuuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac caugucaaac aaccucguca cccucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg ccucuacuac aucuacgcac aagucaccuu cugcuccaac 540

cgcgaagcau ccucccaagc ccccuucauc gccucccucu gccucaaauc ccccggccgc 600

uucgaacgca uccuccuccg cgccgcaaau acccacuccu ccgccaaacc augcggccaa 660

caauccaucc accucggcgg cgucuucgaa cuccaacccg gcgccuccgu cuucgucaac 720

gucaccgacc ccucccaagu aucccaugga accggcuuca ccuccuucgg ccuccucaaa 780

cucuag 786

<210> 144

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product wild type

<400> 144

gggagaaagc uuaccaugca gaucccacag gcgcccuggc cagucgucug ggcggugcua 60

caacugggcu ggcggccagg augguucuua gacuccccag acaggcccug gaaccccccc 120

accuucuccc cagccugcu cguggugacc gaaggggaca acgccaccuu caccugcagc 180

uucuccaaca caucggagag cuucgugcua aacugguacc gcaugagccc cagcaaccag 240

acggacaagc uggccgcuuu ccccgaggac cgcagccagc ccggccagga cugccgcuuc 300

cgugucacac aacugcccaa cgggcgugac uuccacauga gcguggucag ggcccggcgc 360

augacagcg gcaccuaccu cuguggggcc aucucccugg cccccaaggc gcagaucaaa 420

gagagccugc gggcagagcu cagggugaca gagagaaggg cagaagugcc cacagcccac 480

cccagccccu cacccaggcc agccggccag uuccaaaccc uggugguugg ugucgugggc 540

ggccugcugg gcagccuggu gcugcuaguc uggguccugg ccgucaucug cucccggggcc 600

gcacgaggga caauaggagc caggcgcacc ggccagcccc ugaaggagga ccccucagcc 660

gugccugugu ucucugugga cuauggggag cuggauuucc aguggcgaga gaagaccccg 720

gagccccccg ugcccugugu cccuagcag acggaguaug ccaccauugu cuuuccuagc 780

ggaaugggca ccucaucccc cgcccgcagg ggcucagccg acggcccucg gagugcccag 840

ccacugaggc cugaggaugg acacugcucu uggccccucu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 145

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product wild type

<400> 145

gggagaaagc uuaccaugca gaucccacag gcgcccuggc cagucgucug ggcggugcua 60

caacugggcu ggcggccagg augguucuua gacuccccag acaggcccug gaaccccccc 120

accuucuccc cagccugcu cguggugacc gaaggggaca acgccaccuu caccugcagc 180

uucuccaaca caucggagag cuucgugcua aacugguacc gcaugagccc cagcaaccag 240

acggacaagc uggccgcuuu ccccgaggac cgcagccagc ccggccagga cugccgcuuc 300

cgugucacac aacugcccaa cgggcgugac uuccacauga gcguggucag ggcccggcgc 360

augacagcg gcaccuaccu cuguggggcc aucucccugg cccccaaggc gcagaucaaa 420

gagagccugc gggcagagcu cagggugaca gagagaaggg cauggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 146

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product wild type

<400> 146

gggagaaagc uuaccaugug uccagcgcgc agccuccucc uuguggcuac ccugguccuc 60

cuggaccacc ucaguuuggc cagaaaccuc cccguggcca cuccagaccc aggaauguuc 120

ccaugccuuc accacuccca aaaccugcug agggccguca gcaacaugcu ccagaaggcc 180

agacaaacuc uagaauuuua cccuugcacu ucugaagaga uugaucauga agauaucaca 240

aaagauaaaa ccagcacagu ggaggccugu uuaccauugg aauuaaccaa gaaugagagu 300

360

accucuuuua ugaggcccu gugccuuagu aguauuuaug aagacuugaa gauguaccag 420

guggaguuca agaccaugaa ugcaaagcuu cugauggauc cuaagaggca gaucuuucua 480

gaucaaaaca ugcuggcagu uauugaugag cugaugcagg cccugaauuu caacagugag 540

acugugccac aaaaauccuc ccuugaagaa ccggauuuuu auaaaacuaa aaucaagcuc 600

ugcauacuuc uucaugcuuu cagaauucgg gcagugacua uugauagagu gaugagcuau 660

cugaaugcuu ccuaaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 147

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product wild type

<400> 147

gggagaaagc uuaccaugug uccagcgcgc agccuccucc uuguggcuac ccugguccuc 60

cuggaccacc ucaguuuggc cagaaaccuc cccguggcca cuccagaccc aggaauguuc 120

ccaugccuuc accacuccca aaaccugcug agggccguca gcaacaugcu ccagaaggcc 180

agacaaacuc uagaauuuua cccuugcacu ucugaagaga uugaucauga agauaucaca 240

aaagauaaaa ccagcacagu ggaggccugu uuaccauugg aauuaaccaa gaaugagagu 300

360

accucuuuua ugaggcccu gugccuuagu aguauuuaug aagacuugaa gauguaccag 420

guggaguuca agaccaugaa ugcaaagcuu cugauggauc cuaagaggca gaucuuucua 480

gaucaaaaca ugcuggcagu uauugaugag cugaugcagg cccugaauuu caacagugag 540

acugugccac aaaaauccuc ccuugaagaa ccggauuuuu auaaaacuaa aaucaagcuc 600

ugcauacuuc uucaugcuuu cagaauucgg gcagugacua uugauagagu gaugagcuau 660

cugaaugcuu ccggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 148

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product wild type

<400> 148

gggagaaagc uuaccagaaa ccuccccgg gccacuccag acccaggaau guucccaugc 60

cuucaccacu cccaaaaccu gcugaggggcc gucagcaaca ugcuccagaa ggccagacaa 120

acucuagaau uuuacccuug cacuucugaa gagauugauc augaagauau cacaaaagau 180

aaaaccagca caguggaggc cuguuuacca uuggaauuaa ccaagaauga gaguugccua 240

aauuccagag agaccucuuu cauaacuaau gggaguugcc uggccuccag aaagaccucu 300

uuuaugaugg cccugugccu uaguaguauu uaugaagacu ugaagaugua ccagguggag 360

uucaagacca ugaaugcaaa gcuucugaug gauccuaaga ggcagaucuu ucuagaucaa 420

aacaugcugg caguuauuga ugagcugaug caggcccuga

ccacaaaaau ccucccuuga agaaccggau uuuuauaaaa cuaaaaucaa gcucugcaua 540

cuucuucaug cuuucagaau ucgggcagug acuauugaua gagugaugag cuaucugaau 600

gcuuccuaag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 149

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product wild type

<400> 149

60 gggagaaagc uuaccaugug ucaccagcag uuggucaucu cuugguuuuc

cuggcaucuc cccucguggc cauaugggaa cugaagaaag auguuuaugu cguagaauug 120

gauugguauc cggaugcccc uggagaaaug gugguccuca ccugugacac cccugaagaa 180

gaugguauca ccuggaccuu ggaccagagc agugaggucu uaggcucugg caaaacccug 240

accauccaag ucaaagaguu uggagaugcu ggccaguaca ccugucacaa aggaggcgag 300

guucuaagcc auucgcuccu gcugcuucac aaaaaggaag auggaauuug guccacugau 360

auuuuaaagg accagaaaga acccaaaaau aagaccuuuc uaagaugcga ggccaagaau 420

uauucuggac guuucaccug cugguggcug acgacaauca guacugauuu gacauucagu 480

gucaaaagca gcagaggcuc uucugacccc caagggguga cgugcggagc ugcuacacuc 540

ucugcagaga gagucagagg ggacaacaag gaguaugagu acucagugga gugccaggag 600

gacagugccu gcccagcugc ugaggagagu cugcccauug aggucauggu ggaugccguu 660

cacaagcuca aguaugaaaa cuacaccagc agcuucuuca ucagggacau caucaaaccu 720

gacccaccca agaacuugca gcugaagcca uuaaagaauu cucggcaggu ggaggucagc 780

ugggaguacc cugacaccug gaguacucca cauuccuacu ucucccugac auucugcguu 840

cagguccagg gcaagagcaa gagagaaaag aaagauagag ucuucacgga caagaccuca 900

gccacgguca ucugccgcaa aaugccagc auuagcgugc gggccgga ccgcuacuau 960

1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 150

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product wild type

<400> 150

60 gggagaaagc uuaccaugug ucaccagcag uuggucaucu cuugguuuuc

cuggcaucuc cccucguggc cauaugggaa cugaagaaag auguuuaugu cguagaauug 120

gauugguauc cggaugcccc uggagaaaug gugguccuca ccugugacac cccugaagaa 180

gaugguauca ccuggaccuu ggaccagagc agugaggucu uaggcucugg caaaacccug 240

accauccaag ucaaagaguu uggagaugcu ggccaguaca ccugucacaa aggaggcgag 300

guucuaagcc auucgcuccu gcugcuucac aaaaaggaag auggaauuug guccacugau 360

auuuuaaagg accagaaaga acccaaaaau aagaccuuuc uaagaugcga ggccaagaau 420

uauucuggac guuucaccug cugguggcug acgacaauca guacugauuu gacauucagu 480

gucaaaagca gcagaggcuc uucugacccc caagggguga cgugcggagc ugcuacacuc 540

ucugcagaga gagucagagg ggacaacaag gaguaugagu acucagugga gugccaggag 600

gacagugccu gcccagcugc ugaggagagu cugcccauug aggucauggu ggaugccguu 660

cacaagcuca aguaugaaaa cuacaccagc agcuucuuca ucagggacau caucaaaccu 720

gacccaccca agaacuugca gcugaagcca uuaaagaauu cucggcaggu ggaggucagc 780

ugggaguacc cugacaccug gaguacucca cauuccuacu ucucccugac auucugcguu 840

cagguccagg gcaagagcaa gagagaaaag aaagauagag ucuucacgga caagaccuca 900

gccacgguca ucugccgcaa aaugccagc auuagcgugc gggccgga ccgcuacuau 960

agcucaucuu ggagcgaaug ggcaucugug cccugcagug gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 151

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product wild type

<400> 151

gggagaaagc uuaccauaug ggaacugaag aaagauguuu augucguaga auuggauugg 60

uauccggaug ccccggaga aaugggguc cucaccugug acaccccuga agaagauggu 120

aucaccugga ccuuggacca gagcagugag gucuuaggcu cuggcaaaac ccugaccauc 180

caagucaaag aguuuggaga ugcuggccag uacaccuguc acaaaggagg cgagguucua 240

agccauucgc uccugcugcu ucacaaaaag gaagauggaa uuugguccac ugauauuuua 300

aaggaccaga aagaacccaa aaauaagacc uuucuaagau gcgaggccaa gaauuauucu 360

ggacguuuca ccugcuggug gcugacgaca aucaguacug auuugacauu cagugucaaa 420

agcagcagag gcucuucuga cccccaaggg gugacgugcg gagcugcuac acucucugca 480

gagagaguca gaggggacaa caaggaguau gaguacucag uggagugcca ggaggacagu 540

gccugcccag cugcugagga gagucugccc auugagguca ugguggaugc cguucacaag 600

cucaaguaug aaaacuacac cagcagcuuc uucaucaggg acaucaucaa accugaccca 660

cccaagaacu ugcagcugaa gccauuaaag aauucucggc agguggaggu cagcugggag 720

uacccugaca ccuggaguac uccacauucc uacuucuccc ugacauucug cguucagguc 780

cagggcaaga gcaagagaga aaagaaagau agagucuuca cggacaagac cucagccg 840

gucaucugcc gcaaaaaugc cagcauuagc gugcgggccc aggaccgcua cuauagcuca 900

ucuuggagcg aaugggcauc ugugcccugc aguuagggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 152

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product wild type

<400> 152

gggagaaagc uuaccggcag uacuucggggc agugguaagc cugguagugg ugaggguagu 60

acuaagggug gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 153

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product wild type

<400> 153

60 gggagaaagc uuaccaugug ucaccagcag uuggucaucu cuugguuuuc

cuggcaucuc cccucguggc cauaugggaa cugaagaaag auguuuaugu cguagaauug 120

gauugguauc cggaugcccc uggagaaaug gugguccuca ccugugacac cccugaagaa 180

gaugguauca ccuggaccuu ggaccagagc agugaggucu uaggcucugg caaaacccug 240

accauccaag ucaaagaguu uggagaugcu ggccaguaca ccugucacaa aggaggcgag 300

guucuaagcc auucgcuccu gcugcuucac aaaaaggaag auggaauuug guccacugau 360

auuuuaaagg accagaaaga acccaaaaau aagaccuuuc uaagaugcga ggccaagaau 420

uauucuggac guuucaccug cugguggcug acgacaauca guacugauuu gacauucagu 480

gucaaaagca gcagaggcuc uucugacccc caagggguga cgugcggagc ugcuacacuc 540

ucugcagaga gagucagagg ggacaacaag gaguaugagu acucagugga gugccaggag 600

gacagugccu gcccagcugc ugaggagagu cugcccauug aggucauggu ggaugccguu 660

cacaagcuca aguaugaaaa cuacaccagc agcuucuuca ucagggacau caucaaaccu 720

gacccaccca agaacuugca gcugaagcca uuaaagaauu cucggcaggu ggaggucagc 780

ugggaguacc cugacaccug gaguacucca cauuccuacu ucucccugac auucugcguu 840

cagguccagg gcaagagcaa gagagaaaag aaagauagag ucuucacgga caagaccuca 900

gccacgguca ucugccgcaa aaugccagc auuagcgugc gggccgga ccgcuacuau 960

agcucaucuu ggagcgaaug ggcaucugug cccugcagug gcaguacuuc gggcaguggu 1020

aagccuggua guggugaggg uaguacuaag gguagaaacc uccccguggc cacuccagac 1080

ccaggaaugu ucccaugccu ucaccacucc caaaaccugc ugaggggccgu cagcaacaug 1140

cuccagaagg ccagacaaac ucuagaauuu uacccuugca cuucugaaga gauugaucau 1200

gaagauauca caaaagauaa aaccagcaca guggaggccu guuuaccauu ggaauuaacc 1260

1320

gccucgaa agaccucuuu uaugauggcc cugugccuua guaguauuua ugaagacuug 1380

aagauguacc agguggaguu caagaccaug aaugcaaagc uucugaugga uccuaagagg 1440

cagaucuuuc uagaucaaaa caugcuggca guuauugaug agcugaugca ggcccugaau 1500

1560

1620

gugaugagcu aucugaaugc uuccuaagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 154

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product wild type

<400> 154

gggagaaagc uuaccaugau cgaaacauac aaccaaacuu cuccccgauc ugcggccacu 60

ggacugccca ucagcaugaa aauuuuuaug uauuuacuua cuguuuuucu uaucacccag 120

augauugggu cagcacuuuu ugcuguguau cuucauagaa gguuggacaa gauagaagau 180

gaaaggaauc uucaugaaga uuuuguauuc augaaaacga

gaaagauccu uauccuuacu gaacugugag gagauuaaaa gccaguuuga aggcuuugug 300

360

ggugaucaga auccucaaau ugcggcacau gucauaagug aggccagcag uaaaacaaca 420

ucuguguuac agugggcuga aaaaggauac uacaccauga gcaacaacuu gguaacccug 480

gaaaauggga aacagcugac cguuaaaaga caaggacucu auuauaucua ugcccaaguc 540

accuucuguu ccaaucggga agcuucgagu caagcuccau uuauagccag ccucugccua 600

aagucccccg guagauucga gagaaucuua cucagagcug caaauaccca caguuccgcc 660

aaaccuugcg ggcaacaauc cauucacuug ggaggaguau uugaauugca accaggugcu 720

ucgguguuug ucaugugac ugauccaagc caagugagcc auggcacugg cuucacgucc 780

uuuggcuuac ucaaacucug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 155

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt1

<400> 155

gggagaaagc uuaccaugca gaucccccag gccccguggc ccguggucug ggccgugcug 60

cagcucggcu ggcgccccgg gugguuccug gacagccccg accggccgug gaacccgccc 120

accuucuccc ccgcgcugcu cguggucacc gagggcgaca acgccacguu cacgugcagc 180

uucuccaaca ccagcgaguc cuucgugcug aacugguacc gcaugagccc cuccaaccag 240

accgacaagc uggccgccuu ccccgaggac cggagccagc ccgggcagga cugccgcuuc 300

360 cgggugaccc agcuccccaa cggccgcgac

aacgacagcg ggaccuaccu gugcggcgcg aucucccugg ccccgaaggc ccagaucaag 420

gagagccucc gcgccgagcu gcgggugacc gagcgccggg cggagguccc caccgcccac 480

cccuccccca gcccgcgccc cgccggccag uuccagacgc uggugguggg ggucgugggc 540

gggcuccugg gcucccuggu gcuccugguc ugggugcugg ccgugaucug cagccggggcc 600

660 gcgcgcggga ccaucggcgc ccggcgcacc

gucccggugu ucagcgugga cuacggggag cuggacuucc aguggcggga gaagaccccc 720

gagccgcccg uccccugcgu gcccgagcag acggaguacg ccaccaucgu guuccccucc 780

ggcaugggga ccagcagccc cgcccgccgg ggcuccgcgg acggcccgcg cagcgcccag 840

ccccugcgcc ccgaggacgg gcacugcucc uggccgcucu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 156

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt1

<400> 156

gggagaaagc uuaccaugca gaucccccag gccccguggc ccguggucug ggccgugcug 60

cagcucggcu ggcgccccgg gugguuccug gacagccccg accggccgug gaacccgccc 120

accuucuccc ccgcgcugcu cguggucacc gagggcgaca acgccacguu cacgugcagc 180

uucuccaaca ccagcgaguc cuucgugcug aacugguacc gcaugagccc cuccaaccag 240

accgacaagc uggccgccuu ccccgaggac cggagccagc ccgggcagga cugccgcuuc 300

360 cgggugaccc agcuccccaa cggccgcgac

aacgacagcg ggaccuaccu gugcggcgcg aucucccugg ccccgaaggc ccagaucaag 420

gagagccucc gcgccgagcu gcgggugacc gagcgccggg cgugaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 157

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt1

<400> 157

gggagaaagc uuaccaugug ccccgcccgc agccugcucc ugguggccac ccugguccuc 60

cuggaccacc ugucccucgc gcggaaccug ccgguggcca cccccgaccc cggcauguuc 120

cccugccugc accacagcca gaaccuccug cgcgccgugu ccaacaugcu gcagaaggcc 180

cggcagacgc ucgaguucua cccgugcacc agcgaggaga ucgaccacga ggacaucacc 240

aaggacaaga ccuccacggu cgaggccugc cugccccugg agcucaccaa gaacgagagc 300

ugccugaacu ccgcgagac cagcuucauc accaacgggu ccugccuggc gagccggaag 360

acguccuuca ugaggcccu cugccuagc uccaucuacg aggaccugaa gauguaccag 420

guggaguuca agaccaugaa cgccaagcuc cugauggacc ccaagcgcca gaucuuccug 480

gaccagaaca ugcucgccgu gaucgacgag cugaugcagg cgcugaacuu caacagcgag 540

accguccccc agaaguccag ccucgaggag ccggacuucu acaagaccaa gaucaagcug 600

ugcauccugc uccacgccuu ccggauccgc gccgugacga ucgaccgggu gauguccuac 660

cugaacgcca gcugaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 158

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt1

<400> 158

gggagaaagc uuaccaugug ccccgcccgc agccugcucc ugguggccac ccugguccuc 60

cuggaccacc ugucccucgc gcggaaccug ccgguggcca cccccgaccc cggcauguuc 120

cccugccugc accacagcca gaaccuccug cgcgccgugu ccaacaugcu gcagaaggcc 180

cggcagacgc ucgaguucua cccgugcacc agcgaggaga ucgaccacga ggacaucacc 240

aaggacaaga ccuccacggu cgaggccugc cugccccugg agcucaccaa gaacgagagc 300

ugccugaacu ccgcgagac cagcuucauc accaacgggu ccugccuggc gagccggaag 360

acguccuuca ugaggcccu cugccuagc uccaucuacg aggaccugaa gauguaccag 420

guggaguuca agaccaugaa cgccaagcuc cugauggacc ccaagcgcca gaucuuccug 480

gaccagaaca ugcucgccgu gaucgacgag cugaugcagg cgcugaacuu caacagcgag 540

accguccccc agaaguccag ccucgaggag ccggacuucu acaagaccaa gaucaagcug 600

ugcauccugc uccacgccuu ccggauccgc gccgugacga ucgaccgggu gauguccuac 660

cugaacgcca gcggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 159

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt1

<400> 159

gggagaaagc uuacccggaa ccugccggug gccacccccg accccggcau guuccccugc 60

cugcaccaca gccagaaccu ccugcgcgcc guguccaaca ugcugcagaa ggcccggcag 120

acgcucgagu ucuacccgug caccagcgag gagaucgacc acgaggacau caccaaggac 180

aagaccucca cggucgaggc cugccugccc cuggagcuca ccaagaacga gagcugccug 240

aacuccgcg agaccagcuu caucaccaac ggguccugcc uggcgagccg gaagacgucc 300

uucaugaugg cccucugccu gagcuccauc uacgaggacc ugaagaugua ccagguggag 360

uucaagacca ugaacgccaa gcuccugaug gaccccaagc gccagaucuu ccuggaccag 420

aacaugcucg ccgugaucga cgagcugaug caggcgcuga acuucaacag cgagaccguc 480

ccccagaagu ccagccucga ggagccggac uucuacaaga ccaagaucaa gcugugcauc 540

cugcuccacg ccuuccggau ccgcgccgug acgaucgacc gggugauguc cuaccugaac 600

gccagcugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 160

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt1

<400> 160

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucuc ccucgucuuc 60

cuggccagcc cccugguggc caucugggag cucaagaagg acguguacgu cguggagcug 120

gacugguacc cggacgcgcc cggcgagaug gugguccuga ccugcgacac ccccgaggag 180

gacgggauca cguggacccu cgaccagucc agcgaggugc ugggcuccgg gaagacccug 240

accauccagg ugaaggaguu cggcgacgcc gggcaguaca cgugccacaa gggcggcgag 300

guccucagcc acucccugcu gcuccugcac aagaaggagg acgggaucug gagcaccgac 360

auccuagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gguucacgug cugguggcug accaccauca gcaccgaccu gaccuucucc 480

gucaagagcu cccgcgggag cuccgacccg cagggcguga cgugcggggc cgccacccuc 540

agcgcggagc gggugcgcgg cgacaacaag gaguacgagu acuccgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagucc cugcccaucg aggugauggu cgacgcggug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca uccgggacau caucaagccc 720

gacccgccca agaaccucca gcugaagccc cugaagaacu cccgccaggu ggaggucagc 780

ugggaguacc ccgacaccug guccacgccg cacagcuacu ucucccucac cuucugcguc 840

caggugcagg gcaagagcaa gcgggagaag aaggaccgcg uguucaccga caagaccucc 900

gccacgguga ucugccggaa gaacgccagc aucuccgugc gcgccggaga ccgguacuac 960

agcuccagcu gguccgagug ggccagcguc cccugcuccu gaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 161

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt1

<400> 161

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucuc ccucgucuuc 60

cuggccagcc cccugguggc caucugggag cucaagaagg acguguacgu cguggagcug 120

gacugguacc cggacgcgcc cggcgagaug gugguccuga ccugcgacac ccccgaggag 180

gacgggauca cguggacccu cgaccagucc agcgaggugc ugggcuccgg gaagacccug 240

accauccagg ugaaggaguu cggcgacgcc gggcaguaca cgugccacaa gggcggcgag 300

guccucagcc acucccugcu gcuccugcac aagaaggagg acgggaucug gagcaccgac 360

auccuagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gguucacgug cugguggcug accaccauca gcaccgaccu gaccuucucc 480

gucaagagcu cccgcgggag cuccgacccg cagggcguga cgugcggggc cgccacccuc 540

agcgcggagc gggugcgcgg cgacaacaag gaguacgagu acuccgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagucc cugcccaucg aggugauggu cgacgcggug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca uccgggacau caucaagccc 720

gacccgccca agaaccucca gcugaagccc cugaagaacu cccgccaggu ggaggucagc 780

ugggaguacc ccgacaccug guccacgccg cacagcuacu ucucccucac cuucugcguc 840

caggugcagg gcaagagcaa gcgggagaag aaggaccgcg uguucaccga caagaccucc 900

gccacgguga ucugccggaa gaacgccagc aucuccgugc gcgccggaga ccgguacuac 960

agcuccagcu gguccgagug ggccagcguc cccugcuccg gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 162

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt1

<400> 162

gggagaaagc uuaccaucug ggagcucaag aaggacgugu acgucgugga gcuggacugg 60

uacccggacg cgcccggcga gauggugguc cugaccugcg acacccccga ggaggacggg 120

aucacgugga cccucgacca guccagcgag gugcugggcu ccgggaagac ccugaccauc 180

caggugaagg aguucggcga cgccgggcag uacacgugcc acaagggcgg cgagguccuc 240

agccacuccc ugcugcuccu gcacaagaag gaggacggga ucuggagcac cgacauccug 300

aaggaccaga aggagcccaa gaacaagacc uuccuccgcu gcgaggccaa gaacuacucc 360

ggccgguuca cgugcuggug gcugaccacc aucagcaccg accugaccuu cuccgucaag 420

agcucccgcg ggagcuccga cccgcagggc gugacgugcg gggccgccac ccucagcgcg 480

gagcgggugc gcggcgacaa caaggaguac gaguacuccg uggagugcca ggaggacagc 540

gccugccccg ccgccgagga gucccugccc aucgagguga uggucgacgc ggugcacaag 600

cugaaguacg agaacuacac cagcagcuuc uucauccggg acaucaucaa gcccgacccg 660

cccaagaacc uccagcugaa gccccugaag aacucccgcc agguggaggu cagcugggag 720

uaccccgaca ccugguccac gccgcacagc uacuucuccc ucaccuucug cguccaggug 780

cagggcaaga gcaagcggga gaagaaggac cgcguguuca ccgacaagac cuccgccacg 840

gugaucugcc ggaagaacgc cagcaucucc gugcgcgccc aggaccggua cuacagcucc 900

agcugguccg agugggccag cguccccugc uccugaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 163

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt1

<400> 163

gggagaaagc uuaccggcag caccuccggg agcggcaagc ccggguccgg cgaggggagc 60

accaagggcg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 164

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt1

<400> 164

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucuc ccucgucuuc 60

cuggccagcc cccugguggc caucugggag cucaagaagg acguguacgu cguggagcug 120

gacugguacc cggacgcgcc cggcgagaug gugguccuga ccugcgacac ccccgaggag 180

gacgggauca cguggacccu cgaccagucc agcgaggugc ugggcuccgg gaagacccug 240

accauccagg ugaaggaguu cggcgacgcc gggcaguaca cgugccacaa gggcggcgag 300

guccucagcc acucccugcu gcuccugcac aagaaggagg acgggaucug gagcaccgac 360

auccuagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gguucacgug cugguggcug accaccauca gcaccgaccu gaccuucucc 480

gucaagagcu cccgcgggag cuccgacccg cagggcguga cgugcggggc cgccacccuc 540

agcgcggagc gggugcgcgg cgacaacaag gaguacgagu acuccgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagucc cugcccaucg aggugauggu cgacgcggug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca uccgggacau caucaagccc 720

gacccgccca agaaccucca gcugaagccc cugaagaacu cccgccaggu ggaggucagc 780

ugggaguacc ccgacaccug guccacgccg cacagcuacu ucucccucac cuucugcguc 840

caggugcagg gcaagagcaa gcgggagaag aaggaccgcg uguucaccga caagaccucc 900

gccacgguga ucugccggaa gaacgccagc aucuccgugc gcgccggaga ccgguacuac 960

agcuccagcu gguccgagug ggccagcguc cccugcuccg gcagcaccuc cgggagcggc 1020

aagcccgggu ccggcgaggg gagcaccaag ggccggaacc ugccgguggc cacccccgac 1080

cccggcaugu uccccugccu gcaccacagc cagaaccucc ugcgcgccgu guccaacaug 1140

cugcagaagg cccggcagac gcucgaguuc uacccgugca ccagcgagga gaucgaccac 1200

gaggacauca ccaaggacaa gaccuccacg gucgaggccu gccugccccu ggagcucacc 1260

aagaacgaga gcugccugaa cucccgcgag accagcuuca ucaccaacgg guccugccug 1320

gcgagccgga agacguccuu caugauggcc cucugccuga gcuccaucua cgaggaccug 1380

aagauguacc agguggaguu caagaccaug aacgccaagc uccugaugga ccccaagcgc 1440

cagaucuucc uggaccagaa caugcucgcc gugaucgacg agcugaugca ggcgcugaac 1500

1560

aagaucaagc ugugcauccu gcuccacgcc uuccggaucc gcgccgugac gaucgaccgg 1620

gugauguccu accugaacgc cagcugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 165

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt1

<400> 165

gggagaaagc uuaccaugau cgagaccuac aaccagacca gcccccgcuc cgccgccacg 60

ggccugccga ucagcaugaa gaucuucaug uaccuccuga ccguguuccu gaucacccag 120

augaucgggu ccgcgcuguu cgccgucuac cugcaccggc gccuggacaa gaucgaggac 180

gagcggaacc uccacgagga cuucguguuc augaagacca uccagcgcug caacacgggc 240

gagcggagcc ugucccugcu caacugcgag gagaucaaga gccaguucga gggguucgug 300

aaggacauca ugcugaacaa ggaggagacc aagaaggaga acuccuucga gaugcagaag 360

ggcgaccaga acccccagau cgccgcccac gucaucagcg aggccuccag caagaccacc 420

uccgugcugc agugggcgga gaagggguac uacacgauga gcaacaaccu cgugacccug 480

gagaacggca agcagcugac cgucaagcgc cagggccucu acuacaucua cgcccaggug 540

accuucugcu ccaaccggga ggccagcucc caggcccccu ucaucgcgag ccugugccug 600

aagucccccg ggcgcuucga gcggauccuc cugcgcgccg ccaacacgca cagcuccgcc 660

aagccgugcg gccagcagag cauccaccuc gggggcgugu ucgagcucca gcccggggcc 720

agcgucuucg ugaacgugac cgaccccucc caggucagcc acggcaccgg cuucaccucc 780

uucgggcugc ugaagcucug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 166

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt2

<400> 166

gggagaaagc uuaccaugca gaucccccag gccccccuggc ccgucgucug ggccguccuc 60

cagcucggcu ggcgccccgg cugguuccuc gacucccccg accgccccug gaaccccccc 120

accuucuccc cgcccuccu cgucgucacc gagggcgaca acgccaccuu caccuguucc 180

uucuccaaca ccuccgaguc cuucguccuc aacugguacc gcaugucccc cuccaaccag 240

accgacaagc ucgccgccuu ccccgaggac cgcucccagc ccggccagga cugccgcuuc 300

cgcgucaccc agcuccccaa cggccgcgac uuccacaugu ccgucguccg cgcccgccgc 360

aacgacuccg gcaccuaccu cugcggcgcc aucucccucg cccccaaggc cggaucaag 420

gagucccucc gcgccgagcu ccgcgucacc gagcgccgcg ccgagguccc caccgcccac 480

cccucccccu ccccccgccc cgccggccag uuccagaccc ucgucgucgg cgucgucggc 540

ggcccuccg gcucccucgu ccuccucguc uggguccucg ccgucaucug cucccgcgcc 600

gcccgcggca ccaucggcgc ccgccgcacc ggccagcccc ucaagggagga ccccuccgcc 660

guccccgucu ucuccgucga cuacggcgag cucgacuucc aguggcgcga gaagaccccc 720

gagccccccg uccccugcgu ccccgagcag accgaguacg ccaccaucgu cuuccccucc 780

ggcaugggca ccuccucccc cgcccgccgc ggcuccgccg acggcccccg cuccgcccag 840

ccccuccgcc ccgaggacgg ccacugcucc uggccccucu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 167

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223>PDCD1(1-149) mRNA product opt2

<400> 167

gggagaaagc uuaccaugca gaucccccag gccccccuggc ccgucgucug ggccguccuc 60

cagcucggcu ggcgccccgg cugguuccuc gacucccccg accgccccug gaaccccccc 120

accuucuccc cgcccuccu cgucgucacc gagggcgaca acgccaccuu caccuguucc 180

uucuccaaca ccuccgaguc cuucguccuc aacugguacc gcaugucccc cuccaaccag 240

accgacaagc ucgccgccuu ccccgaggac cgcucccagc ccggccagga cugccgcuuc 300

cgcgucaccc agcuccccaa cggccgcgac uuccacaugu ccgucguccg cgcccgccgc 360

aacgacuccg gcaccuaccu cugcggcgcc aucucccucg cccccaaggc cggaucaag 420

gagucccucc gcgccgagcu ccgcgucacc gagcgccgcg ccuggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 168

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt2

<400> 168

gggagaaagc uuaccaugug ccccgcccgc ucccuccucc ucgucgccac ccucguccuc 60

cucgaccacc ucucccucgc ccgcaaccuc cccgucgcca cccccgaccc cggcauguuc 120

cccugccucc accacuccca gaaccuccuc cgcgccgucu ccaacaugcu ccagaaggcc 180

cgccagaccc ucgaguucua ccccugcacc uccgaggaga ucgaccacga ggacaucacc 240

aaggacaaga ccuccaccgu cgaggccugc cucccccucg agcucaccaa gaacgagucc 300

ugccucaacu cccgcgagac cuccuucauc accaacggcu ccugccucgc cucccgcaag 360

accuccuuca ugaggcccu cugccucucc uccaucuacg aggaccucaa gauguaccag 420

gucgaguuca agaccaugaa cgccaagcuc cucauggacc ccaagcgcca gaucuuccuc 480

gaccagaaca ugcucgccgu caucgacgag cucaugcagg cccucaacuu caacuccgag 540

accguccccc agaaguccuc ccucgaggag cccgacuucu acaagaccaa gaucaagcuc 600

ugcauccucc uccacgccuu ccgcauccgc gccgucacca ucgaccgcgu cauguccuac 660

cucaacgccu ccuggaccu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 169

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt2

<400> 169

gggagaaagc uuaccaugug ccccgcccgc ucccuccucc ucgucgccac ccucguccuc 60

cucgaccacc ucucccucgc ccgcaaccuc cccgucgcca cccccgaccc cggcauguuc 120

cccugccucc accacuccca gaaccuccuc cgcgccgucu ccaacaugcu ccagaaggcc 180

cgccagaccc ucgaguucua ccccugcacc uccgaggaga ucgaccacga ggacaucacc 240

aaggacaaga ccuccaccgu cgaggccugc cucccccucg agcucaccaa gaacgagucc 300

ugccucaacu cccgcgagac cuccuucauc accaacggcu ccugccucgc cucccgcaag 360

accuccuuca ugaggcccu cugccucucc uccaucuacg aggaccucaa gauguaccag 420

gucgaguuca agaccaugaa cgccaagcuc cucauggacc ccaagcgcca gaucuuccuc 480

gaccagaaca ugcucgccgu caucgacgag cucaugcagg cccucaacuu caacuccgag 540

accguccccc agaaguccuc ccucgaggag cccgacuucu acaagaccaa gaucaagcuc 600

ugcauccucc uccacgccuu ccgcauccgc gccgucacca ucgaccgcgu cauguccuac 660

cucaacgccu ccggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 170

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt2

<400> 170

gggagaaagc uuacccgcaa ccuccccguc gccacccccg accccggcau guuccccugc 60

cuccaccacu cccagaaccu ccuccgcgcc gucuccaaca ugcuccagaa ggcccgccag 120

acccucgagu ucuaccccug caccuccgag gagaucgacc acgaggacau caccaaggac 180

240

aacucccgcg agaccuccuu caucaccaac ggcuccugcc ucgccucccg caagaccucc 300

uucaugaugg cccucugccu cuccuccauc uacgaggacc ucaagaugua ccaggucgag 360

uucaagacca ugaacgccaa gcuccucaug gaccccaagc gccagaucuu ccucgaccag 420

aacaugcucg ccgucaucga cgagcucaug caggcccuca acuucaacuc cgagaccguc 480

ccccagaagu ccucccucga ggagcccgac uucuacaaga ccaagaucaa gcucugcauc 540

cuccuccacg ccuuccgcau ccgcgccguc accaucgacc gcgucauguc cuaccucaac 600

gccuccugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 171

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt2

<400> 171

gggagaaagc uuaccaugug ccaccagcag cucgucaucu ccugguucuc ccucgucuuc 60

cucgccuccc cccucgucgc caucugggag cucaagaagg acgucuacgu cgucgagcuc 120

gacugguacc ccgacgcccc cggcgagaug gucguccuca ccugugacac ccccgaggag 180

gacggcauca ccuggacccu cgaccagucc uccgaggucc ucggcuccgg caagacccuc 240

accauccagg ucaaggaguu cggcgacgcc ggccaguaca ccugucacaa gggcggcgag 300

guccucuccc acucccuccu ccuccuccac aagaaggagg acggcaucug guccaccgac 360

auccucaagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gcuucaccug uugguggcuc accaccaucu ccaccgaccu caccuucucc 480

gucaaguccu cccgcggcuc cuccgacccc cagggcguca ccuguggcgc cgccacccuc 540

uccgccgagc gcguccgcgg cgacaacaag gaguacgagu acuccgucga gugccaggag 600

gacuccgccu gccccgccgc cgaggagucc cuccccaucg aggucauggu cgacgccguc 660

cacaagcuca aguacgagaa cuacaccucc uccuucuuca uccgcgacau caucaagccc 720

gaccccccca agaaccucca gcucaagccc cucaagaacu cccgccaggu cgaggucucc 780

ugggaguacc ccgacaccug guccaccccc cacuccuacu ucucccucac cuucugcguc 840

cagguccagg gcaaguccaa gcgcgagaag aaggaccgcg ucuucaccga caagaccucc 900

gccaccguca ucugccgcaa gaacgccucc aucuccgucc gcgccgga ccgcuacuac 960

uccuccuccu gguccgagug ggccuccguc cccugcuccu gaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 172

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt2

<400> 172

gggagaaagc uuaccaugug ccaccagcag cucgucaucu ccugguucuc ccucgucuuc 60

cucgccuccc cccucgucgc caucugggag cucaagaagg acgucuacgu cgucgagcuc 120

gacugguacc ccgacgcccc cggcgagaug gucguccuca ccugugacac ccccgaggag 180

gacggcauca ccuggacccu cgaccagucc uccgaggucc ucggcuccgg caagacccuc 240

accauccagg ucaaggaguu cggcgacgcc ggccaguaca ccugucacaa gggcggcgag 300

guccucuccc acucccuccu ccuccuccac aagaaggagg acggcaucug guccaccgac 360

auccucaagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gcuucaccug uugguggcuc accaccaucu ccaccgaccu caccuucucc 480

gucaaguccu cccgcggcuc cuccgacccc cagggcguca ccuguggcgc cgccacccuc 540

uccgccgagc gcguccgcgg cgacaacaag gaguacgagu acuccgucga gugccaggag 600

gacuccgccu gccccgccgc cgaggagucc cuccccaucg aggucauggu cgacgccguc 660

cacaagcuca aguacgagaa cuacaccucc uccuucuuca uccgcgacau caucaagccc 720

gaccccccca agaaccucca gcucaagccc cucaagaacu cccgccaggu cgaggucucc 780

ugggaguacc ccgacaccug guccaccccc cacuccuacu ucucccucac cuucugcguc 840

cagguccagg gcaaguccaa gcgcgagaag aaggaccgcg ucuucaccga caagaccucc 900

gccaccguca ucugccgcaa gaacgccucc aucuccgucc gcgccgga ccgcuacuac 960

uccuccuccu gguccgagug ggccuccguc cccugcuccg gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 173

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt2

<400> 173

gggagaaagc uuaccaucug ggagcucaag aaggacgucu acgucgucga gcucgacugg 60

uaccccgacg cccccggcga gauggucguc cucaccugug acacccccga ggaggacggc 120

aucaccugga cccucgacca guccuccgag guccucggcu ccggcaagac ccucaccauc 180

caggucaagg aguucggcga cgccggccag uacaccuguc acaagggcgg cgagguccuc 240

ucccacuccc uccuccuccu ccacaagaag gaggacggca ucgguccac cgacauccuc 300

aaggaccaga aggagcccaa gaacaagacc uuccuccgcu gcgaggccaa gaacuacucc 360

ggccgcuuca ccuguuggug gcucaccacc aucuccaccg accucaccuu cuccgucaag 420

uccucccgcg gcuccuccga cccccagggc gucaccugug gcgccgccac ccucuccgcc 480

gagcgcgucc gcggcgacaa caaggaguac gaguacuccg ucgagugcca ggaggacucc 540

gccugccccg ccgccgagga gucccucccc aucgagguca uggucgacgc cguccacaag 600

cucaaguacg agaacuacac cuccuccuuc uucauccgcg acaucaucaa gcccgacccc 660

cccaagaacc uccagcucaa gccccucaag aacucccgcc aggucgaggu cuccugggag 720

uaccccgaca ccugguccac cccccacucc uacuucuccc ucaccuucug cguccagguc 780

cagggcaagu ccaagcgcga gaagaaggac cgcgucuuca ccgacaagac cuccgccacc 840

gucaucugcc gcaagaacgc cuccaucucc guccgcgccc aggaccgcua cuacuccucc 900

uccgguccg agugggccuc cguccccugc uccugaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 174

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt2

<400> 174

gggagaaagc uuaccggcuc caccuccggc uccggcaagc ccggcuccgg cgagggcucc 60

accaagggcg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 175

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt2

<400> 175

gggagaaagc uuaccaugug ccaccagcag cucgucaucu ccugguucuc ccucgucuuc 60

cucgccuccc cccucgucgc caucugggag cucaagaagg acgucuacgu cgucgagcuc 120

gacugguacc ccgacgcccc cggcgagaug gucguccuca ccugugacac ccccgaggag 180

gacggcauca ccuggacccu cgaccagucc uccgaggucc ucggcuccgg caagacccuc 240

accauccagg ucaaggaguu cggcgacgcc ggccaguaca ccugucacaa gggcggcgag 300

guccucuccc acucccuccu ccuccuccac aagaaggagg acggcaucug guccaccgac 360

auccucaagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gcuucaccug uugguggcuc accaccaucu ccaccgaccu caccuucucc 480

gucaaguccu cccgcggcuc cuccgacccc cagggcguca ccuguggcgc cgccacccuc 540

uccgccgagc gcguccgcgg cgacaacaag gaguacgagu acuccgucga gugccaggag 600

gacuccgccu gccccgccgc cgaggagucc cuccccaucg aggucauggu cgacgccguc 660

cacaagcuca aguacgagaa cuacaccucc uccuucuuca uccgcgacau caucaagccc 720

gaccccccca agaaccucca gcucaagccc cucaagaacu cccgccaggu cgaggucucc 780

ugggaguacc ccgacaccug guccaccccc cacuccuacu ucucccucac cuucugcguc 840

cagguccagg gcaaguccaa gcgcgagaag aaggaccgcg ucuucaccga caagaccucc 900

gccaccguca ucugccgcaa gaacgccucc aucuccgucc gcgccgga ccgcuacuac 960

uccuccuccu gguccgagug ggccuccguc cccugcuccg gcuccaccuc cggcuccggc 1020

aagcccggcu ccggcgagg cuccaccaag ggccgcaacc uccccgucgc cacccccgac 1080

cccggcaugu uccccugccu ccaccacucc cagaaccucc uccgcgccgu cuccaacaug 1140

cuccagaagg cccgccagac ccucgaguuc uaccccugca ccuccgagga gaucgaccac 1200

gaggacauca ccaaggacaa gaccuccacc gucgaggccu gccucccccu cgagcucacc 1260

aagaacgagu ccugccucaa cucccgcgag accuccuuca ucaccaacgg cuccugccuc 1320

gccucccgca agaccuccuu caugauggcc cucugccucu ccuccaucua cgaggaccuc 1380

aagauguacc aggucgaguu caagaccaug aacgccaagc uccucaugga ccccaagcgc 1440

cagaucuucc ucgaccagaa caugcucgcc gucaucgacg agcucaugca ggcccucaac 1500

uucaacuccg agaccguccc ccagaagucc ucccucgagg agcccgacuu cuacaagacc 1560

aagaucaagc ucugcauccu ccuccacgcc uuccgcaucc gcgccgucac caucgaccgc 1620

gucauguccu accucaacgc cuccuggga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 176

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt2

<400> 176

gggagaaagc uuaccaugau cgagaccuac aaccagaccu ccccccgcuc cgccgccacc 60

ggccucccca ucuccaugaa gaucuucaug uaccuccuca ccgucuuccu caucacccag 120

augaucggcu ccgcccucuu cgccgucuac cuccaccgcc gccucgacaa gaucgaggac 180

gagcgcaacc uccacgagga cuucgucuuc augaagacca uccagcgcug caacaccggc 240

gagcgcuccc ucucccuccu caacugcgag gagaucaagu cccaguucga gggcuucguc 300

aaggacauca ugcucaacaa ggaggagacc aagaaggaga acuccuucga gaugcagaag 360

ggcgaccaga accccagau cgccgcccac gucaucuccg aggccuccuc caagaccacc 420

uccguccucc agugggccga gaagggcuac uacaccaugu ccaacaaccu cgucacccuc 480

gagaacggca agcagcucac cgucaagcgc cagggccucu acuacaucua cgcccagguc 540

accuucugcu ccaaccgcga ggccuccucc caggcccccu ucaucgccuc ccucugccuc 600

aagucccccg gccgcuucga gcgcauccuc cuccgcgccg ccaacaccca cuccuccgcc 660

aagcccugcg gccagcaguc cauccaccuc ggcggcgucu ucgagcucca gcccggcgcc 720

uccgucuucg ucaacgucac cgaccccucc caggucuccc acggcaccgg cuucaccucc 780

uucggccucc ucaagcucug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 177

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt3

<400> 177

gggagaaagc uuaccaugca gaucccccaa gccccuuggc caguggucug ggcuguucug 60

cagcucggcu ggagaccggg gugguuccuu gacagccccg auaggccuug gaacccaccc 120

accuuuuccc cugcacuguu ggugguaaca gagggagaca augccacuuu cacgugcucu 180

uuuucaaaca ccagugagag cuucguguua aauugguacc ggaugucccc aucuaaccag 240

acagauaagc uggcggcuuu ucccgaagac cgcucgcagc cuggucaaga uugucgauuc 300

360

aacgauagcg ggaccuaucu cugcggagca auuagucugg ccccgaaagc ucagauaaag 420

gaaucccuua gagcagagcu gaggugaca gaacggcgcg ccgagguccc caccgcucau 480

ccuucuccaa gcccccgacc ugccggccag uuccaaacuu uggugguagg uguugucggg 540

ggacuccugg gcucccuggu gcucuuagug ugggugcugg cggucaucug uucaagagca 600

gccaggggca caauuggggc ucggcguacc ggacagccac uuaaagagga ccccagugcc 660

guuccggugu uuagcguaga uuacggugaa uuggacuucc aguggcgcga gaagacgccu 720

gaacccccag ugccuugcgu ccccgagcag acugaguaug caaccaucgu guuuccaucu 780

ggcaugggga cauccucacc cgcuagaagg ggaagcgccg auggcccucg gagugcgcaa 840

ccacugcgac cggaagacgg ucacuguucu uggccccuau gagacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 178

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt3

<400> 178

gggagaaagc uuaccaugca gaucccccaa gccccuuggc caguggucug ggcuguucug 60

cagcucggcu ggagaccggg gugguuccuu gacagccccg auaggccuug gaacccaccc 120

accuuuuccc cugcacuguu ggugguaaca gagggagaca augccacuuu cacgugcucu 180

uuuucaaaca ccagugagag cuucguguua aauugguacc ggaugucccc aucuaaccag 240

acagauaagc uggcggcuuu ucccgaagac cgcucgcagc cuggucaaga uugucgauuc 300

360

aacgauagcg ggaccuaucu cugcggagca auuagucugg ccccgaaagc ucagauaaag 420

gaaucccuua gagcagagcu gagggugaca gaacggcgcg ccuggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 179

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt3

<400> 179

gggagaaagc uuaccaugug ccccgccaga agccugcucc uuguggcuac ccggucuug 60

uuagaccacc ugucccuagc aaggaaccuc ccuguugcca caccagaucc gggcauguuc 120

cccugucugc aucacucuca gaaucuucug cgggcggugu caaacauguu gcaaaaggcu 180

cgccagacuc ucgaguuuua cccuugcacg agugaagaga ucgaccauga agauauuacc 240

aaagacaaga caagcacugu agaggccugu cugccacugg aacucaccaa aaaugagucc 300

ugcuuaaacu cucgagagac aucguucaua accaaugggu caugucuggc aagccguaag 360

acaaguuuua ugauggcccu uugcuugucc ucuaucuaug aagaucugaa aauguaccag 420

guggaguuca agacuaugaa cgcuaagcua cucauggacc ccaaaagaca gauuuuucug 480

gaucaaaaua ugcuugcagu caucgacgaa cugaugcagg ccuugaacuu caauagcgag 540

accgugccuc agaaguccuc acucgaggaa cggauuuuu auaaaacgaa gauuaaacug 600

uguaucuuac ugcacgcuuu caggauacgg gccguuuacua ucgaccgcgu gaugaguuac 660

cucaacgcga gcugaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 180

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt3

<400> 180

gggagaaagc uuaccaugug ccccgccaga agccugcucc uuguggcuac ccggucuug 60

uuagaccacc ugucccuagc aaggaaccuc ccuguugcca caccagaucc gggcauguuc 120

cccugucugc aucacucuca gaaucuucug cgggcggugu caaacauguu gcaaaaggcu 180

cgccagacuc ucgaguuuua cccuugcacg agugaagaga ucgaccauga agauauuacc 240

aaagacaaga caagcacugu agaggccugu cugccacugg aacucaccaa aaaugagucc 300

ugcuuaaacu cucgagagac aucguucaua accaaugggu caugucuggc aagccguaag 360

acaaguuuua ugauggcccu uugcuugucc ucuaucuaug aagaucugaa aauguaccag 420

guggaguuca agacuaugaa cgcuaagcua cucauggacc ccaaaagaca gauuuuucug 480

gaucaaaaua ugcuugcagu caucgacgaa cugaugcagg ccuugaacuu caauagcgag 540

accgugccuc agaaguccuc acucgaggaa cggauuuuu auaaaacgaa gauuaaacug 600

uguaucuuac ugcacgcuuu caggauacgg gccguuuacua ucgaccgcgu gaugaguuac 660

cucaacgcga gcggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 181

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt3

<400> 181

gggagaaagc uuacggaa ccucccuguu gccacaccag auccgggcau guuccccugu 60

cugcaucacu cucagaaucu ucugcgggcg gugucaaaca uguugcaaaa ggcucgccag 120

acucucgagu uuuacccuug cacgagugaa gagaucgacc augaagauau uaccaaagac 180

aagacaagca cuguagaggc cugucugcca cuggaacuca ccaaaaauga guccugcuua 240

aacucucgag agacaucguu cauaaccaau gggucauguc uggcaagccg uaagacaagu 300

uuuaugaugg cccuuugcuu guccucuauc uaugaagauc ugaaaaugua ccagguggag 360

uucaagacua ugaacgcuaa gcuacucaug gaccccaaaa gacagauuuu ucuggaucaa 420

480

ccucagaagu ccucacucga ggaaccagau uuuuuaaaa cgaagauuaa acuguguauc 540

600

gcgagcugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 182

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt3

<400> 182

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuugccucuc cccugguugc uauuugggag uugaagaaag acguguacgu aguggaauua 120

gauugguauc cugacgcacc aggcgagaug gucgugcuga ccugugauac accggaagag 180

gacgggauaa cuuggacgcu agaucaguca agugaaguuc ucggaagcgg uaagacccug 240

acaauccagg ugaaagaguu cggcgacgcc gggcaguaca cuugccauaa gggaggcgag 300

guccuuuccc acucucuguu gcuccugcau aaaaaggaag augguauuug gucgaccgac 360

auccugaagg aucaaaaaga gcccaagaac aaaacauuuc ucagauguga agcgaagaau 420

uauucaggga gguuuaccug cuggugguua acuacaauua gcaccgaccu gacguucagu 480

gugaaauccu cucggggaag cuccgauccu cagggcguaa cuuguggcgc ugccacccuu 540

ucagcagagc gcguucgagg ggacaacaag gaguacgaau auagugugga gugccaggaa 600

660

cacaagcuga aauacgagaa uuauacaucc ucauucuuua uacgugacau cauuaagccu 720

gauccaccca aaaaccuaca gcucaagccu cugaaaaaua gcagacaagu cgaaguuagu 780

ugggaguacc cagacacuug gucuacccg cauuccuacu ucagccuuac auuuugcgug 840

cagguacagg gaaagucgaa aagggaaaag aaggaucggg uguucaccga caaaacgucu 900

gcuacuguca ucugucgcaa gaacgccucc auuucaguga gagcgcagga uagguauuac 960

aguagcuccu ggucugagug ggcaagcguu cccugcucau gaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 183

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt3

<400> 183

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuugccucuc cccugguugc uauuugggag uugaagaaag acguguacgu aguggaauua 120

gauugguauc cugacgcacc aggcgagaug gucgugcuga ccugugauac accggaagag 180

gacgggauaa cuuggacgcu agaucaguca agugaaguuc ucggaagcgg uaagacccug 240

acaauccagg ugaaagaguu cggcgacgcc gggcaguaca cuugccauaa gggaggcgag 300

guccuuuccc acucucuguu gcuccugcau aaaaaggaag augguauuug gucgaccgac 360

auccugaagg aucaaaaaga gcccaagaac aaaacauuuc ucagauguga agcgaagaau 420

uauucaggga gguuuaccug cuggugguua acuacaauua gcaccgaccu gacguucagu 480

gugaaauccu cucggggaag cuccgauccu cagggcguaa cuuguggcgc ugccacccuu 540

ucagcagagc gcguucgagg ggacaacaag gaguacgaau auagugugga gugccaggaa 600

660

cacaagcuga aauacgagaa uuauacaucc ucauucuuua uacgugacau cauuaagccu 720

gauccaccca aaaaccuaca gcucaagccu cugaaaaaua gcagacaagu cgaaguuagu 780

ugggaguacc cagacacuug gucuacccg cauuccuacu ucagccuuac auuuugcgug 840

cagguacagg gaaagucgaa aagggaaaag aaggaucggg uguucaccga caaaacgucu 900

gcuacuguca ucugucgcaa gaacgccucc auuucaguga gagcgcagga uagguauuac 960

aguagcuccu ggucugagug ggcaagcguu cccugcucag gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 184

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt3

<400> 184

gggagaaagc uuaccauuug ggaguugaag aaagacgugu acguagugga auuagauugg 60

uauccuacg caccaggcga gauggucgug cugaccugug auacaccggga agaggacggg 120

auaacuugga cgcuagauca gucaagugaa guucucggaa gcgguaagac ccugacaauc 180

caggugaaag aguucggcga cgccgggcag uacacuugcc auaagggagg cgagguccuu 240

ucccacucuc uguugcuccu gcauaaaaag gaagauggua uuuggucgac cgacauccug 300

360

gggagguuua ccugcuggug guuaacuaca auuagcaccg accugacguu cagugugaaa 420

uccuccggg gaagcuccga uccucagggc guaacuugug gcgcugccac ccuuucagca 480

gagcgcguuc gaggggacaa caaggaguac gaauauagug uggagugcca ggaagauagc 540

gccuguccag cugcagagga aucuuugccc aucgagguca ugguggacgc cgugcacaag 600

cugaaauacg agaauuauac auccucauuc uuuauacgug acaucauuaa gccugaucca 660

cccaaaaacc uacagcucaa gccucugaaa aauagcagac aagucgaagu uaguugggag 720

uacccagaca cuuggucuac ccgcauucc uacuucagcc uuacauuuug cgugcaggua 780

cagggaaagu cgaaaaggga aaagaaggau cggguguuca ccgacaaaac gucugcuacu 840

gucaucuguc gcaagaacgc cuccauuuca gugagagcgc aggauaggua uuacaguagc 900

uccggucug agugggcaag cguucccugc ucaugaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 185

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt3

<400> 185

60

acaaaaggag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 186

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt3

<400> 186

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuugccucuc cccugguugc uauuugggag uugaagaaag acguguacgu aguggaauua 120

gauugguauc cugacgcacc aggcgagaug gucgugcuga ccugugauac accggaagag 180

gacgggauaa cuuggacgcu agaucaguca agugaaguuc ucggaagcgg uaagacccug 240

acaauccagg ugaaagaguu cggcgacgcc gggcaguaca cuugccauaa gggaggcgag 300

guccuuuccc acucucuguu gcuccugcau aaaaaggaag augguauuug gucgaccgac 360

auccugaagg aucaaaaaga gcccaagaac aaaacauuuc ucagauguga agcgaagaau 420

uauucaggga gguuuaccug cuggugguua acuacaauua gcaccgaccu gacguucagu 480

gugaaauccu cucggggaag cuccgauccu cagggcguaa cuuguggcgc ugccacccuu 540

ucagcagagc gcguucgagg ggacaacaag gaguacgaau auagugugga gugccaggaa 600

660

cacaagcuga aauacgagaa uuauacaucc ucauucuuua uacgugacau cauuaagccu 720

gauccaccca aaaaccuaca gcucaagccu cugaaaaaua gcagacaagu cgaaguuagu 780

ugggaguacc cagacacuug gucuacccg cauuccuacu ucagccuuac auuuugcgug 840

cagguacagg gaaagucgaa aagggaaaag aaggaucggg uguucaccga caaaacgucu 900

gcuacuguca ucugucgcaa gaacgccucc auuucaguga gagcgcagga uagguauuac 960

aguagcuccu ggucugagug ggcaagcguu cccugcucag gcagcaccuc cgggucugga 1020

1080

ccgggcaugu uccccugucu gcaucacucu cagaaucuuc ugcgggcggu gucaaacaug 1140

uugcaaaagg cucgccagac ucucgaguuu uacccuugca cgagugaaga gaucgaccau 1200

gaagauauua ccaaagacaa gacaagcacu guagaggccu gucugccacu ggaacucacc 1260

1320

gcaagccgua agacaaguuu uaugauggcc cuuugcuugu ccucuaucua ugaagaucug 1380

1440

cagauuuuuc uggaucaaaa uaugcuugca gucaucgacg aacugaugca ggccuugaac 1500

1560

1620

gugaugaguu accucaacgc gagcugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 187

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt3

<400> 187

gggagaaagc uuaccaugau cgagaccuac aaccagacaa gccccagauc cgccgcuacu 60

ggccugccua uuucuaugaa gauauucaug uaucuccuua cgguguuucu gaucacccaa 120

augauugggu cagcauuguu cgccgucuac uuacacaggc ggcuggaca aaucgaagau 180

gagcgcaauc uacaugaaga cuuuguuuuc augaagacaa uucagcgaug caacacugga 240

gagcguaguc ucagccugcu uaauugugaa gagaucaaau cccaguuuga ggguuucgug 300

360

ggcgaccaaa acccacagau cgcggcucac guaauuucgg aggccucaag caagacaacc 420

aguguguugc agugggcaga aaaaggguau uacacuaugu ccaauaaccu cgucacacug 480

gagaauggaa agcagcugac cgugaaaaga caaggccucu auuacaucua ugcccagguu 540

acguucugcu cuaacaggga agcuagcucc caggcaccgu uuauugccuc auuaugucug 600

aagagucccg gucgguucga gcgcauccuu uugagagcug ccaauacuca uagcucugcg 660

aagccuugcg ggcagcaauc cauacaccug ggaggcgugu uugaacuaca gccaggcgca 720

ucagucuucg ugaacguaac cgaucccagc cagguuaguc augggacagg auuuacuucu 780

uucggucucc ugaaacuuug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 188

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt3v

<400> 188

gggagaaagc uuaccaugca gaucccucag gcuccuuggc cuguugugug ggcuguucug 60

caacuuggau ggcggccugg cugguuccug gacucuccug acagacccug gaauccucca 120

acauucagcc ccgcucugcu ggugguuacc gagggcgaua augccaccuu caccuguagc 180

uucagcaaca ccagcgagag cuucgugcug aacugguaca gaaugagccc cagcaaccag 240

accgacaagc uggccgccuu uccugaggau agaucucagc ccggccagga cugccgguuc 300

agaguuacac agcugcccaa cggccgggac uuccacaugu cugucguccg ggccagaaga 360

aacgacagcg gcacaauaucu gugcggcgcc auuucucugg ccccuaaggc ucagaucaaa 420

gagagccuga gagccgagcu gagagugaca gaaagacggg ccgaagugcc cacagcucac 480

ccuucaccuu cuccaagacc ugccggccag uuccagacac uggucguggg aguuguuggc 540

ggacugcugg gaucucuggu gcugcuuguu ugggugcucg ccgugaucug uagcagagcc 600

gccagaggaa caaucggcgc cagaaggaca ggccagccuc ugaaagagga ucccucugcu 660

guccccgugu ucagcgugga cuauggcgag cuggauuucc aguggcggga aaagacaccc 720

gagccuccag ugccuugugu gccugagcag acagaguacg ccaccaucgu guucccuagc 780

ggcaugggca caucuagccc ugccagaaga ggaucugccg acggaccuag aucugcccag 840

900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 189

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223>PDCD1(1-149) mRNA product opt3v

<400> 189

gggagaaagc uuaccaugca gaucccucag gcuccuuggc cuguugugug ggcuguucug 60

caacuuggau ggcggccugg cugguuccug gacucuccug acagacccug gaauccucca 120

acauucagcc ccgcucugcu ggugguuacc gagggcgaua augccaccuu caccuguagc 180

uucagcaaca ccagcgagag cuucgugcug aacugguaca gaaugagccc cagcaaccag 240

accgacaagc uggccgccuu uccugaggau agaucucagc ccggccagga cugccgguuc 300

agaguuacac agcugcccaa cggccgggac uuccacaugu cugucguccg ggccagaaga 360

aacgacagcg gcacaauaucu gugcggcgcc auuucucugg ccccuaaggc ucagaucaaa 420

gagagccuga gagccgagcu gagagugaca gaaagacggg ccuggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 190

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt3v

<400> 190

gggagaaagc uuaccaugug cccugccaga ucucugcugc ugguggcuac acuggugcug 60

cuggaucauc ugagccuggc cagaaaccug ccaguggcca cgccugaucc uggcauguuu 120

ccuugucugc accacagcca gaaccugcug agagccgugu ccaacaugcu gcagaaggcc 180

agacagaccc ucgaguucua ccccugcacc agcgaggaaa ucgaccacga ggacaucacc 240

aaggacaaga ccagcaccgu ggaagccugc cugccucugg aacugaccaa gaacgagagc 300

ugccugaaca gccgggaaac cagcuucauc accaacggcu cuugccuggc cuccagaaag 360

accuccuuca ugaggcccu gugccuagc agcaucuacg aggaccugaa gauguaccag 420

gucgaguuca agaccaugaa cgccaagcug cugauggacc ccaagcggca gaucuuccug 480

gaccagaaua ugcuggccgu gaucgacgag cugaugcagg cccugaacuu caacagcgag 540

acagugcccc agaaguccag ccuggaagaa cccgacuucu acaagaccaa gaucaagcug 600

ugcauccugc ugcacgccuu ccggaucaga gccgugacca ucgacagagu gaugagcuac 660

cugaacgccu ccuaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 191

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt3v

<400> 191

gggagaaagc uuaccaugug cccugccaga ucucugcugc ugguggcuac acuggugcug 60

cuggaucauc ugagccuggc cagaaaccug ccaguggcca cgccugaucc uggcauguuu 120

ccuugucugc accacagcca gaaccugcug agagccgugu ccaacaugcu gcagaaggcc 180

agacagaccc ucgaguucua ccccugcacc agcgaggaaa ucgaccacga ggacaucacc 240

aaggacaaga ccagcaccgu ggaagccugc cugccucugg aacugaccaa gaacgagagc 300

ugccugaaca gccgggaaac cagcuucauc accaacggcu cuugccuggc cuccagaaag 360

accuccuuca ugaggcccu gugccuagc agcaucuacg aggaccugaa gauguaccag 420

gucgaguuca agaccaugaa cgccaagcug cugauggacc ccaagcggca gaucuuccug 480

gaccagaaua ugcuggccgu gaucgacgag cugaugcagg cccugaacuu caacagcgag 540

acagugcccc agaaguccag ccuggaagaa cccgacuucu acaagaccaa gaucaagcug 600

ugcauccugc ugcacgccuu ccggaucaga gccgugacca ucgacagagu gaugagcuac 660

cugaacgccu ccggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 192

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt3v

<400> 192

gggagaaagc uuaccagaaa ccugccagug gccacgccug auccuggcau guuuccuugu 60

cugcaccaca gccagaaccu gcugagagcc guguccaaca ugcugcagaa ggccagacag 120

acccucgagu ucuaccccug caccagcgag gaaaucgacc acgaggacau caccaaggac 180

aagaccagca ccguggaagc cugccugccu cuggaacuga ccaagaacga gagcugccug 240

aacagccggg aaaccagcuu caucaccaac ggcucuugcc uggccuccag aaagaccucc 300

uucaugaugg cccugugccu gagcagcauc uacgaggacc ugaagaugua ccaggucgag 360

uucaagacca ugaacgccaa gcugcugaug gaccccaagc ggcagaucuu ccuggaccag 420

aauauugcugg ccgugaucga cgagcugaug caggcccuga acuucaacag cgagacagug 480

ccccagaagu ccagcugga agaacccgac uucuacaaga ccaagaucaa gcugugcauc 540

cugcugcacg ccuuccggau cagagccgug accaucgaca gagugaugag cuaccugaac 600

gccuccugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 193

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt3v

<400> 193

gggagaaagc uuaccaugug ucaccagcag cuggucauca gcugguucag ccugguguuc 60

cuggccucuc cucugguggc caucugggag cugaagaaag acguguacgu gguggaacug 120

gacugguauc ccgaugcucc uggcgagaug guggugcuga ccugcgauac cccugaagag 180

gacggcauca ccuggacacu ggaucagucu agcgaggugc ucggcagcgg caagacccug 240

accauccaag ugaaagaguu uggcgacgcc ggccaguaca ccugucacaa aggcggagaa 300

gugcugagcc acagccugcu gcugcuccac aagaaagagg auggcauuug gagcaccgac 360

auccugaagg accagaaaga gcccaagaac aagaccuucc ugagaugcga ggccaagaac 420

uacagcggcc gguucacaug uugguggcug accaccauca gcaccgaccu gaccuucagc 480

gugaagucca gcagaggcag cagugauccu cagggcguua cauguggcgc cgcuacacug 540

ucugccgaaa gagugcgggg cgacaacaaa gaauacgagu acagcgugga augccaagag 600

gacagcgccu guccagccgc cgaagagucu cugccuaucg aagugauggu ggacgccgug 660

cacaagcuga aguacgagaa cuacaccucc agcuuuuuca uccgggacau caucaagccc 720

gauccuccaa agaaccugca gcugaagccu cugaagaaca gcagacaggu ggaagugucc 780

ugggaguacc ccgacaccug gucuacaccc cacagcuacu ucagccugac cuuuugcgug 840

caagugcagg gcaaguccaa gcgcgagaaa aaggaccggg uguucaccga caagaccagc 900

gccaccguga ucugcagaaa gaacgccagc aucagcguca gagccggga ccgguacuac 960

1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 194

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt3v

<400> 194

gggagaaagc uuaccaugug ucaccagcag cuggucauca gcugguucag ccugguguuc 60

cuggccucuc cucugguggc caucugggag cugaagaaag acguguacgu gguggaacug 120

gacugguauc ccgaugcucc uggcgagaug guggugcuga ccugcgauac cccugaagag 180

gacggcauca ccuggacacu ggaucagucu agcgaggugc ucggcagcgg caagacccug 240

accauccaag ugaaagaguu uggcgacgcc ggccaguaca ccugucacaa aggcggagaa 300

gugcugagcc acagccugcu gcugcuccac aagaaagagg auggcauuug gagcaccgac 360

auccugaagg accagaaaga gcccaagaac aagaccuucc ugagaugcga ggccaagaac 420

uacagcggcc gguucacaug uugguggcug accaccauca gcaccgaccu gaccuucagc 480

gugaagucca gcagaggcag cagugauccu cagggcguua cauguggcgc cgcuacacug 540

ucugccgaaa gagugcgggg cgacaacaaa gaauacgagu acagcgugga augccaagag 600

gacagcgccu guccagccgc cgaagagucu cugccuaucg aagugauggu ggacgccgug 660

cacaagcuga aguacgagaa cuacaccucc agcuuuuuca uccgggacau caucaagccc 720

gauccuccaa agaaccugca gcugaagccu cugaagaaca gcagacaggu ggaagugucc 780

ugggaguacc ccgacaccug gucuacaccc cacagcuacu ucagccugac cuuuugcgug 840

caagugcagg gcaaguccaa gcgcgagaaa aaggaccggg uguucaccga caagaccagc 900

gccaccguga ucugcagaaa gaacgccagc aucagcguca gagccggga ccgguacuac 960

1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 195

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt3v

<400> 195

gggagaaagc uuaccaucug ggagcugaag aaagacgugu acguggugga acuggacugg 60

uaucccgaug cuccuggcga gaugguggug cugaccugcg auaccccuga agaggacggc 120

aucaccugga cacuggauca gucuagcgag gugcucggca gcggcaagac ccugaccauc 180

caagugaaag aguuuggcga cgccggccag uacaccuguc acaaaggcgg agaagugcug 240

agccacagcc ugcugcugcu ccacaagaaa gaggauggca uuuggagcac cgacauccug 300

aaggaccaga aagagcccaa gaacaagacc uuccugagau gcgaggccaa gaacuacagc 360

ggccgguuca cauguuggug gcugaccacc aucagcaccg accugaccuu cagcgugaag 420

uccagcagag gcagcaguga uccucagggc guuacaugug gcgccgcuac acugucugcc 480

gaaagagugc ggggcgacaa caaagaauac gaguacagcg uggaaugcca agaggacagc 540

gccuguccag ccgccgaaga gucucugccu aucgaaguga ugguggacgc cgugcacaag 600

cugaaguacg agaacuacac cuccagcuuu uucauccggg acaucaucaa gcccgauccu 660

ccaaagaacc ugcagcugaa gccucugaag aacagcagac agguggaagu guccugggag 720

uaccccgaca ccggucuac accccacagc uacuucagcc ugaccuuuug cgugcaagug 780

cagggcaagu ccaagcgcga gaaaaaggac cggguguuca ccgacaagac cagcgccacc 840

gugaucugca gaaagaacgc cagcaucagc gucagagccc aggaccggua cuacagcagc 900

ucuuggagcg aaugggccag cgugccaugu agcuaaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 196

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt3v

<400> 196

gggagaaagc uuaccggcuc uacaucuggc ucuggcaaac cuggaucugg cgagggcucu 60

acaaagggcg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 197

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt3v

<400> 197

gggagaaagc uuaccaugug ucaccagcag cuggucauca gcugguucag ccugguguuc 60

cuggccucuc cucugguggc caucugggag cugaagaaag acguguacgu gguggaacug 120

gacugguauc ccgaugcucc uggcgagaug guggugcuga ccugcgauac cccugaagag 180

gacggcauca ccuggacacu ggaucagucu agcgaggugc ucggcagcgg caagacccug 240

accauccaag ugaaagaguu uggcgacgcc ggccaguaca ccugucacaa aggcggagaa 300

gugcugagcc acagccugcu gcugcuccac aagaaagagg auggcauuug gagcaccgac 360

auccugaagg accagaaaga gcccaagaac aagaccuucc ugagaugcga ggccaagaac 420

uacagcggcc gguucacaug uugguggcug accaccauca gcaccgaccu gaccuucagc 480

gugaagucca gcagaggcag cagugauccu cagggcguua cauguggcgc cgcuacacug 540

ucugccgaaa gagugcgggg cgacaacaaa gaauacgagu acagcgugga augccaagag 600

gacagcgccu guccagccgc cgaagagucu cugccuaucg aagugauggu ggacgccgug 660

cacaagcuga aguacgagaa cuacaccucc agcuuuuuca uccgggacau caucaagccc 720

gauccuccaa agaaccugca gcugaagccu cugaagaaca gcagacaggu ggaagugucc 780

ugggaguacc ccgacaccug gucuacaccc cacagcuacu ucagccugac cuuuugcgug 840

caagugcagg gcaaguccaa gcgcgagaaa aaggaccggg uguucaccga caagaccagc 900

gccaccguga ucugcagaaa gaacgccagc aucagcguca gagccggga ccgguacuac 960

1020

aaaccuggau cuggcgagg cucuacaaag ggcagaaacc ugccaguggc cacgccugau 1080

ccuggcaugu uuccuugucu gcaccacagc cagaaccugc ugagagccgu guccaacaug 1140

1200

gaggacauca ccaaggacaa gaccagcacc guggaagccu gccugccucu ggaacugacc 1260

aagaacgaga gcugccugaa cagccgggaa accagcuuca ucaccaacgg cucuugccug 1320

gccuccagaa agaccuccuu caugauggcc cugugccuga gcagcaucua cgaggaccug 1380

aagauguacc aggucgaguu caagaccaug aacgccaagc ugcugaugga ccccaagcgg 1440

cagaucuucc uggaccagaa uaugcuggcc gugaucgacg agcugaugca ggcccugaac 1500

1560

aagaucaagc ugugcauccu gcugcacgcc uuccggauca gagccgugac caucgacaga 1620

gugaugagcu accugaacgc cuccuggga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 198

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt3v

<400> 198

gggagaaagc uuaccaugau cgagacauac aaccagacaa gccccagaag cgccgccaca 60

ggacugccua ucagcaugaa gaucuuuaug uaccugcuga ccguguuccu gaucacccag 120

augaucggca gcgcccuguu ugccguguac cugcacagac ggcuggacaa gaucgaggac 180

gagagaaacc ugcacgagga cuucguguuc augaagacca uccagcggug caacaccggc 240

gagagaaguc ugagccugcu gaacugcgag gaaaucaaga gccaguucga gggcuucgug 300

360

ggcgaccaga auccucagau cgccgcucac gugaucagcg aggccagcag caagacaaca 420

agcgugcugc agugggccga gaagggcuac uacaccauga gcaacaaccu ggucacccug 480

gaaaacggca agcagcugac agugaagcgg cagggccugu acuacaucua cgcccaagug 540

accuucugca gcaacagaga ggccagcucu caggccccuu uuaucgccag ccugugccug 600

aaguccccug gcagauucga gcggauucug

aaaccuugug gccagcaguc uauucaccuc ggcggagugu uugagcugca gccuggcgca 720

agcguguucg ugaaugugac agacccuagc cagguguccc acggcaccgg cuuuuacaucu 780

uucggacugc ugaagcugug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 199

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt4

<400> 199

gggagaaagc uuaccaugca gaucccccag gcccccuggc ccguggugug ggccgugcug 60

cagcugggcu ggagacccgg cugguuccug gacagccccg acagacccug gaaccccccc 120

accuucagcc ccgccugcu gguggugacc gagggcgaca acgccaccuu caccuguagc 180

uucagcaaca ccagcgagag cuucgugcug aacugguaca gaaugagccc cagcaaccag 240

accgacaagc uggccgccuu ccccgaggac agaagccagc ccggccagga cugcagauuc 300

agagugaccc agcugcccaa cggcagagac uuccacauga gcguggugag agccagaaga 360

aacgacagcg gcaccuaccu gugcggcgcc aucagccugg cccccaaggc cggaucaag 420

gagagccuga gagccgagcu gagagugacc gagagaaggg ccgaggugcc caccgcccac 480

cccagcccca gccccagacc cgccggccag uuccagaccc uggugguggg cguggugggc 540

ggccugcugg gcagccuggu gcugcuggug ugggugcugg ccgugaucug cagcagagcc 600

gccagaggca ccaucggcgc cagaagaacc ggccagcccc ugaaggagga ccccagcgcc 660

gugcccgugu ucagcgugga cuacggcgag cuggacuucc aguggagaga gaagaccccc 720

gagccccccg ugcccugcgu gcccgagcag accgaguacg ccaccaucgu guuccccagc 780

ggcaugggca ccagcagccc cgccagaaga ggcagcgccg acggccccag aagcgcccag 840

ccccugagac ccgaggacgg ccacugcagc uggccccugu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 200

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt4

<400> 200

gggagaaagc uuaccaugca gaucccccag gcccccuggc ccguggugug ggccgugcug 60

cagcugggcu ggagacccgg cugguuccug gacagccccg acagacccug gaaccccccc 120

accuucagcc ccgccugcu gguggugacc gagggcgaca acgccaccuu caccuguagc 180

uucagcaaca ccagcgagag cuucgugcug aacugguaca gaaugagccc cagcaaccag 240

accgacaagc uggccgccuu ccccgaggac agaagccagc ccggccagga cugcagauuc 300

agagugaccc agcugcccaa cggcagagac uuccacauga gcguggugag agccagaaga 360

aacgacagcg gcaccuaccu gugcggcgcc aucagccugg cccccaaggc cggaucaag 420

gagagccuga gagccgagcu gagagugacc gagagaaggg ccuggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 201

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt4

<400> 201

gggagaaagc uuaccaugug ccccgccaga agccugcugc ugguggccac ccuggugcug 60

cuggaccacc ugagccuggc cagaaaccug cccguggcca cccccgaccc cggcauguuc 120

cccugccugc accacagcca gaaccugcug agagccguga gcaacaugcu gcagaaggcc 180

agacagaccc uggaguucua ccccugcacc agcgaggaga ucgaccacga ggacaucacc 240

aaggacaaga ccagcaccgu ggaggccugc cugccccugg agcugaccaa gaacgagagc 300

ugccugaaca gcagagagac cagcuucauc accaacggca gcugccuggc cagcagaaag 360

accagcuuca ugaggcccu gugccuagc agcaucuacg aggaccugaa gauguaccag 420

guggaguuca agaccaugaa cgccaagcug cugauggacc ccaagagaca gaucuuccug 480

gaccagaaca ugcuggccgu gaucgacgag cugaugcagg cccugaacuu caacagcgag 540

accgugcccc agaagaguag ccuggaggag cccgacuucu acaagaccaa gaucaagcug 600

ugcauccugc ugcacgccuu cagaaucaga gccgugacca ucgacagagu gaugagcuac 660

cugaacgcca gcugaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 202

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt4

<400> 202

gggagaaagc uuaccaugug ccccgccaga agccugcugc ugguggccac ccuggugcug 60

cuggaccacc ugagccuggc cagaaaccug cccguggcca cccccgaccc cggcauguuc 120

cccugccugc accacagcca gaaccugcug agagccguga gcaacaugcu gcagaaggcc 180

agacagaccc uggaguucua ccccugcacc agcgaggaga ucgaccacga ggacaucacc 240

aaggacaaga ccagcaccgu ggaggccugc cugccccugg agcugaccaa gaacgagagc 300

ugccugaaca gcagagagac cagcuucauc accaacggca gcugccuggc cagcagaaag 360

accagcuuca ugaggcccu gugccuagc agcaucuacg aggaccugaa gauguaccag 420

guggaguuca agaccaugaa cgccaagcug cugauggacc ccaagagaca gaucuuccug 480

gaccagaaca ugcuggccgu gaucgacgag cugaugcagg cccugaacuu caacagcgag 540

accgugcccc agaagaguag ccuggaggag cccgacuucu acaagaccaa gaucaagcug 600

ugcauccugc ugcacgccuu cagaaucaga gccgugacca ucgacagagu gaugagcuac 660

cugaacgcca gcggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 203

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt4

<400> 203

gggagaaagc uuaccagaaa ccugcccgg gccacccccg accccggcau guuccccugc 60

cugcaccaca gccagaaccu gcugagagcc gugagcaaca ugcugcagaa ggccagacag 120

acccuggagu ucuaccccug caccagcgag gagaucgacc acgaggacau caccaaggac 180

aagaccagca ccguggaggc cugccugccc cuggagcuga ccaagaacga gagcugccug 240

aacagcagag agaccagcuu caucaccaac ggcagcugcc uggccagcag aaagaccagc 300

uucaugaugg cccugugccu gagcagcauc uacgaggacc ugaagaugua ccagguggag 360

uucaagacca ugaacgccaa gcugcugaug gaccccaaga gacagaucuu ccuggaccag 420

aacaugcugg ccgugaucga cgagcugaug caggcccuga acuucaacag cgagaccgug 480

ccccagaaga guagcugga ggagcccgac uucuacaaga ccaagaucaa gcugugcauc 540

cugcugcacg ccuucagaau cagagccgug accaucgaca gagugaugag cuaccugaac 600

gccagcugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 204

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt4

<400> 204

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucag ccugguguuc 60

cuggccagcc cccugguggc caucugggag cugaagaagg acguguacgu gguggagcug 120

gacugguacc ccgacgcccc cggcgagaug guggugcuga ccugcgacac ccccgaggag 180

gacggcauca ccuggacccu ggaccagagc agcgaggugc ugggcagcgg caagacccug 240

accauccagg ugaaggaguu cggcgacgcc ggccaguaca ccugucacaa gggcggcgag 300

gugcugagcc acagccugcu gcugcugcac aagaaggagg acggcaucug gagcaccgac 360

auccugaagg accagaagga gcccaagaac aagaccuucc ugagaugcga ggccaagaac 420

uacagcggca gauucaccug uugguggcug accaccauca gcaccgaccu gaccuucagc 480

gugaagagua gcagaggcag cagcgacccc cagggcguga ccugcggcgc cgccacccug 540

agcgccgaga gaggagagg cgacaacaag gaguacgagu acagcgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagagc cugcccaucg aggugauggu ggacgccgug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca ucagagacau caucaagccc 720

gaccccccca agaaccugca gcugaagccc cugaagaaca gcagacaggu ggaggugagc 780

ugggaguacc ccgacaccug gagcaccccc cacagcuacu ucagccugac cuucugcgug 840

cagguucagg gcaagagcaa gagagagaag aaggacagag uguucaccga caagaccagc 900

gccaccguga ucugcagaaa gaacgccagc aucagcguga gagccggga cagauacuac 960

agcagcagcu ggagcgagug ggccagcgug cccugcagcu gaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 205

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt4

<400> 205

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucag ccugguguuc 60

cuggccagcc cccugguggc caucugggag cugaagaagg acguguacgu gguggagcug 120

gacugguacc ccgacgcccc cggcgagaug guggugcuga ccugcgacac ccccgaggag 180

gacggcauca ccuggacccu ggaccagagc agcgaggugc ugggcagcgg caagacccug 240

accauccagg ugaaggaguu cggcgacgcc ggccaguaca ccugucacaa gggcggcgag 300

gugcugagcc acagccugcu gcugcugcac aagaaggagg acggcaucug gagcaccgac 360

auccugaagg accagaagga gcccaagaac aagaccuucc ugagaugcga ggccaagaac 420

uacagcggca gauucaccug uugguggcug accaccauca gcaccgaccu gaccuucagc 480

gugaagagua gcagaggcag cagcgacccc cagggcguga ccugcggcgc cgccacccug 540

agcgccgaga gaggagagg cgacaacaag gaguacgagu acagcgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagagc cugcccaucg aggugauggu ggacgccgug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca ucagagacau caucaagccc 720

gaccccccca agaaccugca gcugaagccc cugaagaaca gcagacaggu ggaggugagc 780

ugggaguacc ccgacaccug gagcaccccc cacagcuacu ucagccugac cuucugcgug 840

cagguucagg gcaagagcaa gagagagaag aaggacagag uguucaccga caagaccagc 900

gccaccguga ucugcagaaa gaacgccagc aucagcguga gagccggga cagauacuac 960

agcagcagcu ggagcgagug ggccagcgug cccugcagcg gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 206

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt4

<400> 206

gggagaaagc uuaccaucug ggagcugaag aaggacgugu acguggugga gcuggacugg 60

uaccccgacg cccccggcga gaugguggug cugaccugcg acacccccga ggaggacggc 120

aucaccugga cccuggacca gagcagcgag gugcugggca gcggcaagac ccugaccauc 180

caggugaagg aguucggcga cgccggccag uacaccuguc acaagggcgg cgaggugcug 240

agccacagcc ugcugcugcu gcacaagaag gaggacggca ucuggagcac cgacauccug 300

aaggaccaga aggagcccaa gaacaagacc uuccugagau gcgaggccaa gaacuacagc 360

ggcagauuca ccuguuggug gcugaccacc aucagcaccg accugaccuu cagcgugaag 420

aguagcagag gcagcagcga cccccagggc gugaccugcg gcgccgccac ccugagcgcc 480

gagagaguga gaggcgacaa caaggaguac gaguacagcg uggagugcca ggaggacagc 540

gccugccccg ccgccgagga gagccugccc aucgagguga ugguggacgc cgugcacaag 600

cugaaguacg agaacuacac cagcagcuuc uucaucagag acaucaucaa gcccgacccc 660

cccaagaacc ugcagcugaa gccccugaag aacagcagac agguggaggu gagcugggag 720

uaccccgaca ccuggagcac cccccacagc uacuucagcc ugaccuucug cgugcagguu 780

cagggcaaga gcaagagaga gaagaaggac agaguguuca ccgacaagac cagcgccacc 840

gugaucugca gaaagaacgc cagcaucagc gugagagccc aggacagaua cuacagcagc 900

agcuggagcg agugggccag cgugcccugc agcugaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 207

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt4

<400> 207

gggagaaagc uuaccggcag caccagcggc agcggcaagc ccggcagcgg cgagggcagc 60

accaagggcg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 208

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt4

<400> 208

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucag ccugguguuc 60

cuggccagcc cccugguggc caucugggag cugaagaagg acguguacgu gguggagcug 120

gacugguacc ccgacgcccc cggcgagaug guggugcuga ccugcgacac ccccgaggag 180

gacggcauca ccuggacccu ggaccagagc agcgaggugc ugggcagcgg caagacccug 240

accauccagg ugaaggaguu cggcgacgcc ggccaguaca ccugucacaa gggcggcgag 300

gugcugagcc acagccugcu gcugcugcac aagaaggagg acggcaucug gagcaccgac 360

auccugaagg accagaagga gcccaagaac aagaccuucc ugagaugcga ggccaagaac 420

uacagcggca gauucaccug uugguggcug accaccauca gcaccgaccu gaccuucagc 480

gugaagagua gcagaggcag cagcgacccc cagggcguga ccugcggcgc cgccacccug 540

agcgccgaga gaggagagg cgacaacaag gaguacgagu acagcgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagagc cugcccaucg aggugauggu ggacgccgug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca ucagagacau caucaagccc 720

gaccccccca agaaccugca gcugaagccc cugaagaaca gcagacaggu ggaggugagc 780

ugggaguacc ccgacaccug gagcaccccc cacagcuacu ucagccugac cuucugcgug 840

cagguucagg gcaagagcaa gagagagaag aaggacagag uguucaccga caagaccagc 900

gccaccguga ucugcagaaa gaacgccagc aucagcguga gagccggga cagauacuac 960

agcagcagcu ggagcgagug ggccagcgug cccugcagcg gcagcaccag cggcagcggc 1020

aagcccggca gcggcgaggg cagcaccaag ggcagaaacc ugcccguggc cacccccgac 1080

cccggcaugu uccccugccu gcaccacagc cagaaccugc ugagagccgu gagcaacaug 1140

1200

gaggacauca ccaaggacaa gaccagcacc guggaggccu gccugccccu ggagcugacc 1260

aagaacgaga gcugccugaa cagcagagag accagcuuca ucaccaacgg cagcugccug 1320

gccagcagaa agaccagcuu caugauggcc cugugccuga gcagcaucua cgaggaccug 1380

aagauguacc agguggaguu caagaccaug aacgccaagc ugcugaugga ccccaagaga 1440

cagaucuucc uggaccagaa caugcuggcc gugaucgacg agcugaugca ggcccugaac 1500

1560

aagaucaagc ugugcauccu gcugcacgcc uucagaauca gagccgugac caucgacaga 1620

gugaugagcu accugaacgc cagcugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 209

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt4

<400> 209

gggagaaagc uuaccaugau cgagaccuac aaccagacca gccccagaag cgccgccacc 60

ggccugccca ucagcaugaa gaucuucaug uaccugcuga ccguguuccu gaucacccag 120

augaucggca gcgcccuguu cgccguguac cugcacagaa gacuggacaa gaucgaggac 180

gagagaaacc ugcacgagga cuucguguuc augaagacca uccagagaug caacaccggc 240

gagagaagcc ugagccugcu gaacugcgag gagaucaaga gccaguucga gggcuucgug 300

aaggacauca ugcugaacaa ggaggagacc aagaaggaga acagcuucga gaugcagaag 360

ggcgaccaga accccagau cgccgcccac gugaucagcg aggccagcag caagaccacc 420

agcgugcugc agugggccga gaagggcuac uacaccauga gcaacaaccu ggugacccug 480

gagaacggca agcagcugac cgugaagaga cagggccugu acuacaucua cgcccaggug 540

accuucugca gcaacagaga ggccagcagc caggcccccu ucaucgccag ccugugccug 600

aagagucccg gcagauucga gagaauccug cugagagccg ccaacaccca cagcagcgcc 660

aagcccugcg gccagcagag cauccaccug ggcggcgugu ucgagcugca gcccggcgcc 720

agcguguucg ugaacgugac cgaccccagc caggugagcc acggcaccgg cuucaccagc 780

uucggccugc ugaagcugug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 210

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt5

<400> 210

gggagaaagc uuaccaugca gaucccccaa gccccuuggc cgguggucug ggcuguucug 60

cagcucggcu ggagacccgg gugguuccug gacagcccug aucggcccug gaacccuccc 120

accuuuuccc cugcccuucu gguggugaca gagggagaca augcgacguu uaccugcucu 180

uucagcaaca cauccgaauc uuucguccuc aauugguacc gcaugagccc guccaaccag 240

accgauaagc uggcugccuu ucccgaggac agaucucagc cuggccaaga uugucgguuc 300

360

aacgauuccg gaaccuaucu gugcggcgcu auuagccucg ccccuaagc ucagaucaag 420

gaaucucugc gggccgagcu gcgcgucaca gaaagacggg cggaggugcc caccgcccau 480

ccguccccua gcccccgccc ugcugggcag uuccaaacgc ucguuguggg agucgugggc 540

ggccugcuug ggucucuggu gcuccugguc uggguucuug ccgugauuug uuccagagcu 600

gcccggggaa ccaucggcgc gcgcagaaca gggcagcccc ugaaagagga cccagcgcc 660

gugccugucu uuucugugga uuacggagaa cucgacuucc aguggcggga gaagaccccg 720

780

ggcaugggga cgagcucccc ggccagacgc ggaucugcug auggcccucg gagcgcccaa 840

ccccugagac cugaagacgg ccacuguucc uggccccugu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 211

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223>PDCD1(1-149) mRNA product opt5

<400> 211

gggagaaagc uuaccaugca gaucccccaa gccccuuggc cgguggucug ggcuguucug 60

cagcucggcu ggagacccgg gugguuccug gacagcccug aucggcccug gaacccuccc 120

accuuuuccc cugcccuucu gguggugaca gagggagaca augcgacguu uaccugcucu 180

uucagcaaca cauccgaauc uuucguccuc aauugguacc gcaugagccc guccaaccag 240

accgauaagc uggcugccuu ucccgaggac agaucucagc cuggccaaga uugucgguuc 300

360

aacgauuccg gaaccuaucu gugcggcgcu auuagccucg ccccuaagc ucagaucaag 420

gaaucucugc gggccgagcu gcgcgucaca gaaagacggg cgugaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 212

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt5

<400> 212

gggagaaagc uuaccaugug ccccgccaga agccugcucc ugguggcuac ccuuguccug 60

cucgaccacc ugucccuugc cgggaaccug ccuguugcga caccggaucc cggcauguuc 120

180

agacagacgc uggaguuuua ccccugcacc uccgaagaga ucgaccauga agauauuaca 240

aaagacaaga ccucuacagu ggaggccugu cuuccucugg aacucaccaa aaaugagagc 300

ugccugaacu ccggggagac aucuuucauc accaauggga gcugucuugc uucccgcaag 360

acgagcuuua ugauggcccu gugccucucu uccauuuaug aagaucugaa aauguaccag 420

gucgaguuca agaccaugaa cgcuaagcug cucauggacc ccaaaagaca gaucuuucug 480

gaucaaaaua ugcuugccgu gauugacgaa cugaugcagg cgcucaacuu caauagcgag 540

acaguuccuc agaagucuuc ccuggaggaa ccggauuuuu auaaaaccaa gaucaaacuu 600

uguauccugc uccacgccuu ccggauucgc gcugugacaa ucgacagagu caugagcuac 660

cugaacgccu cuugaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 213

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt5

<400> 213

gggagaaagc uuaccaugug ccccgccaga agccugcucc ugguggcuac ccuuguccug 60

cucgaccacc ugucccuugc cgggaaccug ccuguugcga caccggaucc cggcauguuc 120

180

agacagacgc uggaguuuua ccccugcacc uccgaagaga ucgaccauga agauauuaca 240

aaagacaaga ccucuacagu ggaggccugu cuuccucugg aacucaccaa aaaugagagc 300

ugccugaacu ccggggagac aucuuucauc accaauggga gcugucuugc uucccgcaag 360

acgagcuuua ugauggcccu gugccucucu uccauuuaug aagaucugaa aauguaccag 420

gucgaguuca agaccaugaa cgcuaagcug cucauggacc ccaaaagaca gaucuuucug 480

gaucaaaaua ugcuugccgu gauugacgaa cugaugcagg cgcucaacuu caauagcgag 540

acaguuccuc agaagucuuc ccuggaggaa ccggauuuuu auaaaaccaa gaucaaacuu 600

uguauccugc uccacgccuu ccggauucgc gcugugacaa ucgacagagu caugagcuac 660

cugaacgccu cuggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 214

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt5

<400> 214

gggagaaagc uuacccggaa ccugccuguu gcgacaccgg aucccggcau guucccuugu 60

cuccaucacu cucagaaucu gcugcgcgcu gugagcaaca ugcuccaaaa ggccagacag 120

acgcuggagu uuuaccccug caccuccgaa gagaucgacc augaagauau uacaaaagac 180

aagaccucua caguggaggc cugucuuccu cuggaacuca ccaaaaauga gagcugccug 240

aacucccggg agacaucuuu caucaccaau gggagcuguc uugcuucccg caagacgagc 300

uuuaugaugg cccuugccu cucuuccauu uaugaagauc ugaaaaugua ccaggucgag 360

uucaagacca ugaacgcuaa gcugcucaug gaccccaaaa gacagaucuu ucuggaucaa 420

480

ccucagaagu cuuccugga ggaaccggau uuuuauaaaa ccaagaucaa acuuuguauc 540

cugcuccacg ccuuccggau ucgcgcugug acaaucgaca gagucaugag cuaccugaac 600

gccucuugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 215

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt5

<400> 215

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuggccucuc cccuuguugc uauuugggag cugaagaaag acguguacgu ggucgaacuc 120

gauugguauc cugacgcccc gggcgagaug gugguucuga ccugugauac acccgaagag 180

gacgggauca cguggacccu ugaucagagc uccgaagugc ugggaucugg caagacacuc 240

accauucagg ucaaagaguu cggggacgcg ggacaguaca caugccauaa gggcggggag 300

gugcugagcc acucccugcu ccugcuucau aaaaaggaag auggaaucug gucuaccgac 360

auucugaagg aucaaaaaga gccuaagaac aaaacauuuc ucagauguga agcuaagaau 420

uauagcggcc gguuuaccug cugguggcug acgaccaucu ccacagaccu uaccuucagc 480

guuaaaucuu cccgcggcag cucugauccc caggggguga cauguggagc cgccacccug 540

uccgcugaga gaguccgggg cgacaacaag gaguacgaau auagcgugga gugccaggaa 600

gauucugccu guccugcugc cgaggaaucc cuccccaucg aggugauggu cgacgcgguu 660

cacaagcuga aauacgagaa uuauacgagc uccuucuuua uucgcgacau cauuaagccu 720

gauccgccca aaaaccugca gcucaagccu cugaaaaauu cuagacaagu ggaagugagc 780

ugggaguacc ccgacacaug guccaccccu cauagcuacu ucucucuuac auuuugcguc 840

caggugcagg ggaaguccaa acgggaaaag aaggaucgcg uuuucaccga caaaaccagc 900

gccacaguga ucuguagaaa gaacgcuucu auuagcgucc gggcccagga ucgcuauuac 960

uccucuagcu gguccgagug ggcuagcgug cccugcucuu gaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 216

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt5

<400> 216

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuggccucuc cccuuguugc uauuugggag cugaagaaag acguguacgu ggucgaacuc 120

gauugguauc cugacgcccc gggcgagaug gugguucuga ccugugauac acccgaagag 180

gacgggauca cguggacccu ugaucagagc uccgaagugc ugggaucugg caagacacuc 240

accauucagg ucaaagaguu cggggacgcg ggacaguaca caugccauaa gggcggggag 300

gugcugagcc acucccugcu ccugcuucau aaaaaggaag auggaaucug gucuaccgac 360

auucugaagg aucaaaaaga gccuaagaac aaaacauuuc ucagauguga agcuaagaau 420

uauagcggcc gguuuaccug cugguggcug acgaccaucu ccacagaccu uaccuucagc 480

guuaaaucuu cccgcggcag cucugauccc caggggguga cauguggagc cgccacccug 540

uccgcugaga gaguccgggg cgacaacaag gaguacgaau auagcgugga gugccaggaa 600

gauucugccu guccugcugc cgaggaaucc cuccccaucg aggugauggu cgacgcgguu 660

cacaagcuga aauacgagaa uuauacgagc uccuucuuua uucgcgacau cauuaagccu 720

gauccgccca aaaaccugca gcucaagccu cugaaaaauu cuagacaagu ggaagugagc 780

ugggaguacc ccgacacaug guccaccccu cauagcuacu ucucucuuac auuuugcguc 840

caggugcagg ggaaguccaa acgggaaaag aaggaucgcg uuuucaccga caaaaccagc 900

gccacaguga ucuguagaaa gaacgcuucu auuagcgucc gggcccagga ucgcuauuac 960

uccucuagcu gguccgagug ggcuagcgug cccugcucug gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

auccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 217

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt5

<400> 217

gggagaaagc uuaccauuug ggagcugaag aaagacgugu acguggucga acucgauugg 60

uauccuacg ccccggggcga gauggugguu cugaccugug auacacccga agaggacggg 120

aucacgugga cccuugauca gagcuccgaa gugcugggau cuggcaagac acucaccauu 180

caggucaaag aguucgggga cgcgggcag uacacaugcc auaagggcgg ggaggugcug 240

agccacuccc ugcuccugcu ucauaaaaag gaagauggaa ucuggucuac cgacauucug 300

360

ggccgguuua ccugcuggug gcugacgacc aucuccacag accuuaccuu cagcguuaaa 420

ucuucccgcg gcagcucuga uccccagggg gugacaugug gagccgccac ccuguccgcu 480

gagagagucc ggggcgacaa caaggaguac gaauauagcg uggagugcca ggaagauucu 540

gccuguccug cugccgagga aucccucccc aucgagguga uggucgacgc gguucacaag 600

cugaaauacg agaauuauac gagcuccuuc uuuauucgcg acaucauuaa gccugauccg 660

cccaaaaacc ugcagcucaa gccucugaaa aauucuagac aaguggaagu gagcugggag 720

uaccccgaca caugguccac cccucauagc uacuucucuc uuacauuuug cguccaggug 780

caggggaagu ccaaacggga aaagaaggau cgcguuuuca ccgacaaaac cagcgccaca 840

gugaucugua gaaagaacgc uucuauuagc guccgggccc aggaucgcua uuacuccucu 900

agcugguccg agugggcuag cgugcccugc ucuugaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 218

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt5

<400> 218

gggagaaagc uuaccggcag caccuccggg ucuggaaagc ccggcagcgg ggagggaucc 60

acaaaaggcg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 219

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt5

<400> 219

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuggccucuc cccuuguugc uauuugggag cugaagaaag acguguacgu ggucgaacuc 120

gauugguauc cugacgcccc gggcgagaug gugguucuga ccugugauac acccgaagag 180

gacgggauca cguggacccu ugaucagagc uccgaagugc ugggaucugg caagacacuc 240

accauucagg ucaaagaguu cggggacgcg ggacaguaca caugccauaa gggcggggag 300

gugcugagcc acucccugcu ccugcuucau aaaaaggaag auggaaucug gucuaccgac 360

auucugaagg aucaaaaaga gccuaagaac aaaacauuuc ucagauguga agcuaagaau 420

uauagcggcc gguuuaccug cugguggcug acgaccaucu ccacagaccu uaccuucagc 480

guuaaaucuu cccgcggcag cucugauccc caggggguga cauguggagc cgccacccug 540

uccgcugaga gaguccgggg cgacaacaag gaguacgaau auagcgugga gugccaggaa 600

gauucugccu guccugcugc cgaggaaucc cuccccaucg aggugauggu cgacgcgguu 660

cacaagcuga aauacgagaa uuauacgagc uccuucuuua uucgcgacau cauuaagccu 720

gauccgccca aaaaccugca gcucaagccu cugaaaaauu cuagacaagu ggaagugagc 780

ugggaguacc ccgacacaug guccaccccu cauagcuacu ucucucuuac auuuugcguc 840

caggugcagg ggaaguccaa acgggaaaag aaggaucgcg uuuucaccga caaaaccagc 900

gccacaguga ucuguagaaa gaacgcuucu auuagcgucc gggcccagga ucgcuauuac 960

uccucuagcu gguccgagug ggcuagcgug cccugcucug gcagcaccuc cgggucugga 1020

aagcccggca gcggggaggg auccacaaaa ggccggaacc ugccuguugc gacaccggau 1080

cccggcaugu ucccuugucu ccaucacucu cagaaucugc ugcgcgcugu gagcaacaug 1140

cuccaaaagg ccagacagac gcuggaguuu uaccccugca ccuccgaaga gaucgaccau 1200

gaagauauua caaaagacaa gaccucuaca guggaggccu gucuuccucu ggaacucacc 1260

1320

gcuucccgca agacgagcuu uaugauggcc cugugccucu cuuccauuua ugaagaucug 1380

aaaauguacc aggucgaguu caagaccaug aacgcuaagc ugcucaugga ccccaaaaga 1440

cagaucuuuc uggaucaaaa uaugcuugcc gugauugacg aacugaugca ggcgcucaac 1500

1560

aagaucaaac uuuguauccu gcuccacgcc uuccggauuc gcgcugugac aaucgacaga 1620

gucaugagcu accugaacgc cucuugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 220

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt5

<400> 220

gggagaaagc uuaccaugau cgagaccuac aaccagacaa gccccagauc cgccgcuacg 60

ggccugccua uuucuaugaa gaucuucaug uaucuccuga ccguguuucu uauuacacaa 120

augaucggga gcgcccuguu cgcggucuac cuccaccggc gccuggacaa aauugaagau 180

gagagaaauc uucaugaaga cuuuguuuuc augaagacca uccagcggug caacacagga 240

gagcgcuccc ugucucuccu gaauugugaa gagaucaaaa gccaguuuga gggcuucgug 300

360

ggggaccaaa acccgcagau cgcugcccac gugauuucug aggccagcuc caagacaacc 420

agcguccucc agugggcuga aaaaggauau uacacgaugu cuaauaaccu ggugacccuu 480

gagaauggca agcagcugac aguuaaaaga caagggcucu auuacaucua ugcccaggug 540

accuucugcu ccaaccggga agcuagcucu caggcccccu uuauugcguc ccugugucuu 600

uucuuccgcc 660

aagcccugcg gccagcaaag cauucaccug ggcggggucu uugaacugca gccuggagcu 720

uccguguucg uuaacgugac cgaucccucu caggucagcc auggcacgggg guuuacaucc 780

uucggacucc ugaaacuuug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 221

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt6

<400> 221

gggagaaagc uuaccaugca aauaccacaa gcaccauggc caguaguaug ggcuguacua 60

caauuagguu ggcgaccagg augguuuuua gacucaccag aucguccaug gaacccacca 120

acauuuucac cagcauuauu aguaguaaca gaaggagaua augcaaccuu uacauguuca 180

uucaguaaca caucagaaag uuuuguacua aauugguaua gaaugucacc uucaaaucaa 240

acagauaaau uagcagcauu uccagaagau agaucacaac caggacaaga uugcagauuuu 300

agaguaacac aauuaccuaa uggacgagac uuucauaugu caguaguaag agcucgacgu 360

420

gaaucuuuaa gagcagaauu aagaguaaca gaaagacgcg cagaaguacc aacagcacau 480

ccaagcccuu caccacgacc ugcaggaca uuucaaacau uaguagucgg aguaguagga 540

ggauuauuag guucacuggu auuauuagua uggguauuag caguaauuag cucgagca 600

gcaagaggaa caauaggagc aagaagaaca ggacaaccau uaaaagaaga cccaucugca 660

guaccaguau uuucaguuga cuauggagaa cuagauuucc aauggaggga aaaaacacca 720

780

ggaaugggaa caucuagucc agcaagaaga ggaucagcug auggaccaag aucagcacaa 840

ccauuaagac cagaagaugg acauuguuca uggccauuau aaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 222

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt6

<400> 222

gggagaaagc uuaccaugca aauaccacaa gcaccauggc caguaguaug ggcuguacua 60

caauuagguu ggcgaccagg augguuuuua gacucaccag aucguccaug gaacccacca 120

acauuuucac cagcauuauu aguaguaaca gaaggagaua augcaaccuu uacauguuca 180

uucaguaaca caucagaaag uuuuguacua aauugguaua gaaugucacc uucaaaucaa 240

acagauaaau uagcagcauu uccagaagau agaucacaac caggacaaga uugcagauuuu 300

agaguaacac aauuaccuaa uggacgagac uuucauaugu caguaguaag agcucgacgu 360

420

gaaucuuuaa gagcagaauu aagaguaaca gaaagacgcg cauaaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 223

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt6

<400> 223

gggagaaagc uuaccaugug cccagcaaga ucacuacuac ugguagcaac acugguacua 60

cuagaccacc uaucacucgc cagaaaccuc ccaguagcca caccagaccc aggaauguuc 120

cccugccucc accauuccca aaaccuacua agagcaguau caaacaugcu acaaaaagca 180

agacaaacac uagaguucua uccaugcaca ucagaagaaa uagaccacga agacauaaca 240

aaagacaaaa caucaaccgu agaagcaugc cucccacucg aacucacaaa aaacgaauca 300

ugccuaaacu caagagaaac aucauucaua acaaacggcu caugcuuagc cucaagaaaa 360

acaucauuca ugauggcacu augccucuca uccauauaug aagacuuaaa aauguaccaa 420

guagaauuua aaaccaugaa cgcaaaauua cuaauggacc caaaaagaca aauauuccua 480

540

accguacccc aaaaaucauc ucuagaagaa ccagacuucu acaaaacaaa aauaaaacua 600

ugcauacuac uacacgccuu cagaauaaga gccgucacaa uagacagagu caugucauac 660

cuaaacgccu cauaaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 224

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt6

<400> 224

gggagaaagc uuaccaugug cccagcaaga ucacuacuac ugguagcaac acugguacua 60

cuagaccacc uaucacucgc cagaaaccuc ccaguagcca caccagaccc aggaauguuc 120

cccugccucc accauuccca aaaccuacua agagcaguau caaacaugcu acaaaaagca 180

agacaaacac uagaguucua uccaugcaca ucagaagaaa uagaccacga agacauaaca 240

aaagacaaaa caucaaccgu agaagcaugc cucccacucg aacucacaaa aaacgaauca 300

ugccuaaacu caagagaaac aucauucaua acaaacggcu caugcuuagc cucaagaaaa 360

acaucauuca ugauggcacu augccucuca uccauauaug aagacuuaaa aauguaccaa 420

guagaauuua aaaccaugaa cgcaaaauua cuaauggacc caaaaagaca aauauuccua 480

540

accguacccc aaaaaucauc ucuagaagaa ccagacuucu acaaaacaaa aauaaaacua 600

ugcauacuac uacacgccuu cagaauaaga gccgucacaa uagacagagu caugucauac 660

cuaaacgccu caggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 225

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt6

<400> 225

gggagaaagc uuaccagaaa ccucccagua gccacaccag acccaggaau guuccccugc 60

cuccaccauu cccaaaaccu acuaagagca guaucaaaca ugcuacaaaa agcaagacaa 120

acacuagagu ucuauccaug cacaucagaa gaaauagacc acgaagacau aacaaaagac 180

aaaacaucaa ccguagaagc augccuccca cucgaacuca caaaaaacga aucaugccua 240

aacucaagag aaacaucaauu cauaacaaac ggcucaugcu uagccucaag aaaaacauca 300

uucaugaugg cacuaugccu cucauccaua uaugaagacu

uuuaaaacca ugaacgcaaa auuacuaaug gacccaaaaa gacaaauauu ccuagaccaa 420

aacaugcuag caguaauaga cgaacuaaug caagcacuaa acuucaacuc agaaaccgua 480

ccccaaaaau caucucuaga agaaccagac uucuacaaaa caaaaauaaa acuaugcaua 540

cuacuacacg ccuucagaau aagagccguc acaauagaca gagucauguc auaccuaaac 600

gccucauaag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 226

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt6

<400> 226

gggagaaagc uuaccaugug ccaccaaca cugguaauau caugguucuc acugguauuc 60

uuggcaucac cccuaguagc aauaugggaa cuaaaaaaag acguauacgu aguagaacua 120

gacugguacc cagacgcacc aggagaaaug guaguauuaa caugcgacac accagaagaa 180

gauggaauaa cuuggacauu agaccaauca agugaaguau uaggaucagg caaaacacua 240

acuauacaag uaaaagaauu uggagacgca ggacaauaca cgugccacaa aggaggcgaa 300

guccuaucac auucacuacu auuauuacac aaaaaagaag acggaaucug gagcacagac 360

420

uauucaggaa gauucacaug cugguggcua acaaccauca guaccgacuu aacauucuca 480

guaaaaucau caagaggauc aucagaccca caaggaguaa cauguggagc agcaacacua 540

agcgcagaaa gaguacgagg agacaacaaa gaauacgaau auucaguaga augucaagaa 600

gacucagcau gcccugcagc agaagaauca uuaccaauag aaguaauggu cgacgcugua 660

720

gacccaccaa aaaaccuaca acuaaaacca uuaaaaaauu caagacaagu agaaguauca 780

ugggaauacc cagauacaug gagcacacca cacaguuacu ucucauuaac auucugcgua 840

caaguacaag gaaaaaguaa aagagaaaaa aaagacagag uauucacaga uaagacuuca 900

gcaacaguaa uaugcagaaa aaacgcaagc auaagcguac gagcacaaga cagauauuac 960

ucaagcucau ggucagaaug ggcaucagua ccauguucau aaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 227

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt6

<400> 227

gggagaaagc uuaccaugug ccaccaaca cugguaauau caugguucuc acugguauuc 60

uuggcaucac cccuaguagc aauaugggaa cuaaaaaaag acguauacgu aguagaacua 120

gacugguacc cagacgcacc aggagaaaug guaguauuaa caugcgacac accagaagaa 180

gauggaauaa cuuggacauu agaccaauca agugaaguau uaggaucagg caaaacacua 240

acuauacaag uaaaagaauu uggagacgca ggacaauaca cgugccacaa aggaggcgaa 300

guccuaucac auucacuacu auuauuacac aaaaaagaag acggaaucug gagcacagac 360

420

uauucaggaa gauucacaug cugguggcua acaaccauca guaccgacuu aacauucuca 480

guaaaaucau caagaggauc aucagaccca caaggaguaa cauguggagc agcaacacua 540

agcgcagaaa gaguacgagg agacaacaaa gaauacgaau auucaguaga augucaagaa 600

gacucagcau gcccugcagc agaagaauca uuaccaauag aaguaauggu cgacgcugua 660

720

gacccaccaa aaaaccuaca acuaaaacca uuaaaaaauu caagacaagu agaaguauca 780

ugggaauacc cagauacaug gagcacacca cacaguuacu ucucauuaac auucugcgua 840

caaguacaag gaaaaaguaa aagagaaaaa aaagacagag uauucacaga uaagacuuca 900

gcaacaguaa uaugcagaaa aaacgcaagc auaagcguac gagcacaaga cagauauuac 960

ucaagcucau ggucagaaug ggcaucagua ccauguucag gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 228

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt6

<400> 228

gggagaaagc uuaccauaug ggaacuaaaa aaagacguau acguaguaga acuagacugg 60

uacccagacg caccaggaga aaugguagua uuaacaugcg acacaccaga agaagaugga 120

auaacuugga cauuagacca aucaagugaa guauuaggau caggcaaaac acuaacuaua 180

caaguaaaag aauuuggaga cgcaggacaa uacacgugcc acaaaggagg cgaaguccua 240

ucacauucac uacuauuauu acacaaaaaa gaagacggaa ucuggagcac agacauauua 300

360

ggaagauuca caugcuggug gcuaacaacc aucaguaccg acuuaacauu cucaguaaaa 420

ucaucaagag gaucaucaga cccacaagga guaacaugug gagcagcaac acuaagcgca 480

gaaagaguac gaggagacaa caaagaauac gaauauucag uagaauguca agaagacuca 540

gcaugcccug cagcagaaga aucauuacca auagaaguaa uggucgacgc uguacacaaa 600

cuaaaauuug aaaauuacac aagcaguuuc uucauaagag acauaauaaa acccgaccca 660

ccaaaaaacc uacaacuaaa accauuaaaa aauucaagac aaguagaagu aucaugggaa 720

uacccagaua cauggagcac accacacagu uacuucucau uaacauucug cguacaagua 780

caaggaaaaa guaaaagaga aaaaaaagac agaguauuca cagauaagac uucagcaaca 840

guaauauugca gaaaaaacgc aagcauaagc guacgagcac aagacagaua uuacucaagc 900

ucauggucag aaugggcauc aguaccaugu ucauaaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 229

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt6

<400> 229

60

acaaaaggag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 230

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt6

<400> 230

gggagaaagc uuaccaugug ccaccaaca cugguaauau caugguucuc acugguauuc 60

uuggcaucac cccuaguagc aauaugggaa cuaaaaaaag acguauacgu aguagaacua 120

gacugguacc cagacgcacc aggagaaaug guaguauuaa caugcgacac accagaagaa 180

gauggaauaa cuuggacauu agaccaauca agugaaguau uaggaucagg caaaacacua 240

acuauacaag uaaaagaauu uggagacgca ggacaauaca cgugccacaa aggaggcgaa 300

guccuaucac auucacuacu auuauuacac aaaaaagaag acggaaucug gagcacagac 360

420

uauucaggaa gauucacaug cugguggcua acaaccauca guaccgacuu aacauucuca 480

guaaaaucau caagaggauc aucagaccca caaggaguaa cauguggagc agcaacacua 540

agcgcagaaa gaguacgagg agacaacaaa gaauacgaau auucaguaga augucaagaa 600

gacucagcau gcccugcagc agaagaauca uuaccaauag aaguaauggu cgacgcugua 660

720

gacccaccaa aaaaccuaca acuaaaacca uuaaaaaauu caagacaagu agaaguauca 780

ugggaauacc cagauacaug gagcacacca cacaguuacu ucucauuaac auucugcgua 840

caaguacaag gaaaaaguaa aagagaaaaa aaagacagag uauucacaga uaagacuuca 900

gcaacaguaa uaugcagaaa aaacgcaagc auaagcguac gagcacaaga cagauauuac 960

ucaagcucau ggucagaaug ggcaucagua ccauguucag gaaguacaag uggaagugga 1020

aaaccaggaa guggagaagg aaguacaaaa ggaagaaacc ucccaguagc cacaccagac 1080

1140

cuacaaaaag caagacaaac acuagaguuc uauccaugca caucagaaga aauagaccac 1200

gaagacauaa caaaagacaa aacaucaacc guagaagcau gccucccacu cgaacucaca 1260

1320

gccucaagaa aaacaucauu caugauggca cuaugccucu cauccauaua ugaagacuua 1380

aaaauguacc aaguagaauu uaaaaccaug aacgcaaaau uacuaaugga cccaaaaaga 1440

caaauauucc uagaccaaaa caugcuagca guaauagacg aacuaaugca agcacuaaac 1500

1560

aaaauaaaac uaugcauacu acuacacgcc uucagaauaa gagccgucac aauagacaga 1620

gucaugucau accuaaacgc cucauaagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 231

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt6

<400> 231

gggagaaagc uuaccaugau agaaacauau aaucaaacaa gcccaagauc agcagcaaca 60

ggacuaccaa uaucaaugaa aauauucaug uaccuacuca cagucuuccu aauaacacaa 120

augauaggau cugcccuauu ugcaguauac cuacacagaa gacuagauaa aauagaagac 180

gaaagaaacc uacaugaaga cuucguauuc augaaaacaa uacaaagaug caacaccggga 240

gaaagauccc uaucacuacu aaacugcgaa gaaauaaaau cacaauucga aggauucgua 300

360

ggagaccaaa acccacaaau agcugcacac gucauaucag aagcaucauc aaaaacaaca 420

ucaguacuuc aaugggcaga aaaaggauac uauacaaugu caaacaaucu aguaacccua 480

gaaaacggaa aacaacuaac aguaaaaaga caaggacuau acuauauaua cgcacaagua 540

acauucugcu caaacagaga agcaucauca caagcaccau ucaucgcauc acuaugccua 600

660

aaaccaugcg gccaacaauc aauacaccua ggaggaguau ucgaacuaca accaggagca 720

ucaguauucg uaaacguaac agaccccuca caaguaagcc acggcacagg auucacauca 780

uuuggacuau uaaaauuaua aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 232

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt7

<400> 232

gggagaaagc uuaccaugca gaucccccaa gccccauggc cgguggucug ggcagugcug 60

cagcucggcu ggaggcccgg gugguuccug gacagcccag aucggcccug gaacccaccc 120

accuuuuccc cagccuugcu gguagugacu gagggugaca augcgaccuu cacgugcagu 180

uuuagcaaca cuuccgaaag uuucguccuc aauugguacc gcaugagccc guccaaccag 240

accgauaagc uggccgcauu ucccgaggac aggagccagc caggccaaga uugucgguuc 300

360

aacgauagug gcacuuaucu gugcggugca auuagccucg ccccaaaagc gcagaucaag 420

gaaucccugc gggccgagcu gcgcgugacc gaaaggcggg cagagguacc cacggcccau 480

ccgagcccca guccacgccc cgccgggcag uuccaaacuc ucguggucgg cguggugggc 540

gggcuguugg guucccuggu ccuccuggug uggguacugg cagugauuug uagcagggcc 600

gcgcggggca ccaucggggc ccgcaggacu ggccagccau ugaaagagga ccccuccgca 660

gucccagugu uuagugugga uuacggugaa cucgacuucc aguggcggga gaagaccccg 720

gaacccccag uccccugcgu gccagagcag accgaguaug ccacgauugu auuucccagc 780

gggaugggca cuuccagccc ggcacgcagg ggcagugccg augggccacg guccgcccaa 840

ccccugaggc ccgaagacgg ucacuguagc uggccacugu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 233

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt7

<400> 233

gggagaaagc uuaccaugca gaucccccaa gccccauggc cgguggucug ggcagugcug 60

cagcucggcu ggaggcccgg gugguuccug gacagcccag aucggcccug gaacccaccc 120

accuuuuccc cagccuugcu gguagugacu gagggugaca augcgaccuu cacgugcagu 180

uuuagcaaca cuuccgaaag uuucguccuc aauugguacc gcaugagccc guccaaccag 240

accgauaagc uggccgcauu ucccgaggac aggagccagc caggccaaga uugucgguuc 300

360

aacgauagug gcacuuaucu gugcggugca auuagccucg ccccaaaagc gcagaucaag 420

gaaucccugc gggccgagcu gcgcgugacc gaaaggcggg caugaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 234

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt7

<400> 234

gggagaaagc uuaccaugug ccccgccagg agccugcucc ugguggcaac cuugguccug 60

cucgaccacc uguccuuggc cgggaaccug ccaguggcga cuccggaucc cggcauguuc 120

ccaugucucc aucacaguca gaaucugcug cgcgccguaa gcaacaugcu ccaaaaggca 180

aggcagaccc uggaguuuua ccccugcacg uccgaagaga ucgaccauga agauauuacu 240

aaagacaaga ccaguaccgu ggaggccugu uugccacugg aacucacuaa aaaugagagc 300

ugccugaacu ccggggagac cagcuucauc acgaaugggu ccugucuggc aagucgcaag 360

acuagcuuua ugauggccuu gugccucucc agcauuuaug aagaucugaa aauguaccag 420

gucgaguuca agaccaugaa cgcgaagcug cucauggacc ccaaaaggca gaucuuucug 480

gaucaaaaua uguuggccgu gauugacgaa cugaugcagg cacucaacuu caauagugag 540

acugugccac agaaguccag ccuggaggaa ccggauuuuu auaaaaccaa gaucaaacug 600

uguaucuugc uccacgccuu ccggauucgc gccgucacca ucgacagggu gauguccuac 660

cugaacgcaa guugaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 235

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt7

<400> 235

gggagaaagc uuaccaugug ccccgccagg agccugcucc ugguggcaac cuugguccug 60

cucgaccacc uguccuuggc cgggaaccug ccaguggcga cuccggaucc cggcauguuc 120

ccaugucucc aucacaguca gaaucugcug cgcgccguaa gcaacaugcu ccaaaaggca 180

aggcagaccc uggaguuuua ccccugcacg uccgaagaga ucgaccauga agauauuacu 240

aaagacaaga ccaguaccgu ggaggccugu uugccacugg aacucacuaa aaaugagagc 300

ugccugaacu ccggggagac cagcuucauc acgaaugggu ccugucuggc aagucgcaag 360

acuagcuuua ugauggccuu gugccucucc agcauuuaug aagaucugaa aauguaccag 420

gucgaguuca agaccaugaa cgcgaagcug cucauggacc ccaaaaggca gaucuuucug 480

gaucaaaaua uguuggccgu gauugacgaa cugaugcagg cacucaacuu caauagugag 540

acugugccac agaaguccag ccuggaggaa ccggauuuuu auaaaaccaa gaucaaacug 600

uguaucuugc uccacgccuu ccggauucgc gccgucacca ucgacagggu gauguccuac 660

cugaacgcaa guggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 236

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt7

<400> 236

gggagaaagc uuacccggaa ccugccagug gcgacuccgg aucccggcau guucccaugu 60

cuccaucaca gucagaaucu gcugcgcgcc guaagcaaca ugcuccaaaa ggcaaggcag 120

acccuggagu uuuaccccug cacguccgaa gagaucgacc augaagauau uacuaaagac 180

aagaccagua ccguggaggc cuguuugcca cuggaacuca cuaaaaauga gagcugccug 240

aacucccggg agaccagcuu caucacgaau ggguccuguc uggcaagucg caagacuagc 300

uuuaugaugg ccuugugccu cuccagcauu uaugaagauc ugaaaaugua ccaggucgag 360

uucaagacca ugaacgcgaa gcugcucaug gaccccaaaa ggcagaucuu ucuggaucaa 420

480

ccacagaagu ccagcugga ggaaccggau uuuuauaaaa ccaagaucaa acuguguauc 540

uugcuccacg ccuuccggau ucgcgccguc accaucgaca gggugauguc cuaccugaac 600

gcaaguugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 237

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt7

<400> 237

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuggccaguc ccuuggggc aauuugggag cugaagaaag acguauacgu ggucgaacuc 120

gauugguauc cagacgcccc gggcgagaug guggugcuga ccugugauac ucccgaagag 180

gacgggauca ccuggacguu ggaucagagc uccgaagucc uggguagugg caagacucuc 240

accauucagg ugaaagaguu cggggacgcg ggccaguaua ccugccauaa ggguggggag 300

guacugagcc acucccugcu ccuguugcau aaaaaggaag auggcaucug gagcacugac 360

auucugaagg aucaaaaaga gccaaagaac aaaaccuuuc ucagguguga agccaagaau 420

uacuccggcc gguucacgug cugguggcug acuaccauca guacugaccu gaccuuuagc 480

gugaaaucca gccgcgggag uuccgauccc caggguguca ccuguggcgc agccacguug 540

agcgcagaga gggugcgcgg ggacaacaag gaguacgaau auuccgugga gugccaggaa 600

660

cacaaacuga aguacgagaa uuauacuucc agcuucuuua uucgggacau cauuaagcca 720

gauccgccca aaaaccugca gcucaagcca cugaaaaaua guaggcaagu ggaagucucc 780

ugggaguacc ccgacaccug gagcacucca cauaguuacu ucuccuugac cuuuugcguc 840

caggugcagg gcaagagcaa acgggaaaag aaggaucgcg uguucaccga caaaacuagc 900

gccacgguga ucuguaggaa gaacgccucc auuaguguac gggcacagga ucgcuauuac 960

1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 238

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt7

<400> 238

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuggccaguc ccuuggggc aauuugggag cugaagaaag acguauacgu ggucgaacuc 120

gauugguauc cagacgcccc gggcgagaug guggugcuga ccugugauac ucccgaagag 180

gacgggauca ccuggacguu ggaucagagc uccgaagucc uggguagugg caagacucuc 240

accauucagg ugaaagaguu cggggacgcg ggccaguaua ccugccauaa ggguggggag 300

guacugagcc acucccugcu ccuguugcau aaaaaggaag auggcaucug gagcacugac 360

auucugaagg aucaaaaaga gccaaagaac aaaaccuuuc ucagguguga agccaagaau 420

uacuccggcc gguucacgug cugguggcug acuaccauca guacugaccu gaccuuuagc 480

gugaaaucca gccgcgggag uuccgauccc caggguguca ccuguggcgc agccacguug 540

agcgcagaga gggugcgcgg ggacaacaag gaguacgaau auuccgugga gugccaggaa 600

660

cacaaacuga aguacgagaa uuauacuucc agcuucuuua uucgggacau cauuaagcca 720

gauccgccca aaaaccugca gcucaagcca cugaaaaaua guaggcaagu ggaagucucc 780

ugggaguacc ccgacaccug gagcacucca cauaguuacu ucuccuugac cuuuugcguc 840

caggugcagg gcaagagcaa acgggaaaag aaggaucgcg uguucaccga caaaacuagc 900

gccacgguga ucuguaggaa gaacgccucc auuaguguac gggcacagga ucgcuauuac 960

1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 239

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt7

<400> 239

gggagaaagc uuaccauuug ggagcugaag aaagacguau acguggucga acucgauugg 60

uauccagacg ccccggggcga gauggggug cugaccugug auacucccga agaggacggg 120

aucaccugga cguuggauca gagcuccgaa guccugggua guggcaagac ucucaccauu 180

caggugaaag aguucgggga cgcggggccag uauaccugcc auaagggugg ggagguacug 240

agccacuccc ugcuccuguu gcauaaaaag gaagauggca ucuggagcac ugacauucug 300

aaggaucaaa aagagccaaa gaacaaaacc uuucucaggu gugaagccaa gaauuucucc 360

ggccgguuca cgugcuggug gcugacuacc aucaguacug accugaccuu uagcgugaaa 420

uccagccgcg ggaguuccga uccccagggu gucaccugug gcgcagccac guugagcgca 480

gagagggugc gcggggacaa caaggaguac gaauauuccg uggagugcca ggaagauagu 540

gccuguccag cggccgagga aagccucccc aucgagguca ugguggacgc aguacacaaa 600

cugaaguacg agaauuauac uuccagcuuc uuuauucggg acaucauuaa gccagauccg 660

cccaaaaacc ugcagcucaa gccacugaaa aauaguaggc aaguggaagu cuccugggag 720

uaccccgaca ccuggagcac uccacauagu uacuucuccu ugaccuuuug cguccaggug 780

cagggcaaga gcaaacggga aaagaaggau cgcguguuca ccgacaaaac uagcgccacg 840

gugaucugua ggaagaacgc cuccauuagu guacgggcac aggaucgcua uuacagcucc 900

agcuggagug agugggccuc cgugcccugc agcugaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 240

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt7

<400> 240

gggagaaagc uuaccggcag caccuccggg agugguaagc ccggcagcgg ggagggcucc 60

acuaaaggug gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 241

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt7

<400> 241

gggagaaagc uuaccaugug ccaccagcaa cuggugauca gcugguucuc ccucgucuuuu 60

cuggccaguc ccuuggggc aauuugggag cugaagaaag acguauacgu ggucgaacuc 120

gauugguauc cagacgcccc gggcgagaug guggugcuga ccugugauac ucccgaagag 180

gacgggauca ccuggacguu ggaucagagc uccgaagucc uggguagugg caagacucuc 240

accauucagg ugaaagaguu cggggacgcg ggccaguaua ccugccauaa ggguggggag 300

guacugagcc acucccugcu ccuguugcau aaaaaggaag auggcaucug gagcacugac 360

auucugaagg aucaaaaaga gccaaagaac aaaaccuuuc ucagguguga agccaagaau 420

uacuccggcc gguucacgug cugguggcug acuaccauca guacugaccu gaccuuuagc 480

gugaaaucca gccgcgggag uuccgauccc caggguguca ccuguggcgc agccacguug 540

agcgcagaga gggugcgcgg ggacaacaag gaguacgaau auuccgugga gugccaggaa 600

660

cacaaacuga aguacgagaa uuauacuucc agcuucuuua uucgggacau cauuaagcca 720

gauccgccca aaaaccugca gcucaagcca cugaaaaaua guaggcaagu ggaagucucc 780

ugggaguacc ccgacaccug gagcacucca cauaguuacu ucuccuugac cuuuugcguc 840

caggugcagg gcaagagcaa acgggaaaag aaggaucgcg uguucaccga caaaacuagc 900

gccacgguga ucuguaggaa gaacgccucc auuaguguac gggcacagga ucgcuauuac 960

1020

1080

cccggcaugu ucccaugucu ccaucacagu cagaaucugc ugcgcgccgu aagcaacaug 1140

cuccaaaagg caaggcagac ccuggaguuu uaccccugca cguccgaaga gaucgaccau 1200

gaagauauua cuaaagacaa gaccaguacc guggaggccu guuugccacu ggaacucacu 1260

1320

1380

aaaauguacc aggucgaguu caagaccaug aacgcgaagc ugcucaugga ccccaaaagg 1440

cagaucuuuc uggaucaaaa uauguuggcc gugauugacg aacugaugca ggcacucaac 1500

1560

1620

gugauguccu accugaacgc aaguugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 242

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt7

<400> 242

gggagaaagc uuaccaugau cgagaccuac aaccagacua gccccagguc cgccgcaacc 60

ggccugccaa uuaguaugaa gaucuucaug uaucuccuga cgguguuuuu gauuacucaa 120

augaucggga gcgcccuguu cgcggucuac cuccaccggc gccuggacaa aauugaagau 180

gagaggaauu ugcaugaaga cuuuguguuc augaagacca uccagcggug caacaccggu 240

gagcgcuccc ugagucuccu gaauugugaa gagaucaaaa gccaguuuga gggcuucgua 300

360

ggggaccaaa acccgcagau cgccgcacac gugauuagcg aggccuccag uaagccacg 420

agcguccucc agugggcaga aaaaggcuau uacacuaugu ccaauaaccu ggugaccuug 480

gagaauggua agcagcugac ugugaaaagg caagggcucu auuacaucua ugcccagguc 540

accuucugca gcaaccggga agcgaguucc caggcccccu uuauugcaag ccugugucug 600

660

aaacccugcg gccagcaauc cauucaccuc gggggugugu uugaacugca gccaggcgcc 720

agcguauucg ugaacgucac ggaucccagu cagguguccc augggacugg cuucaccagc 780

uuuggucugc ugaaguugug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 243

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt8

<400> 243

gggagaaagc uuaccaugca aaucccacaa gcccccuggc ccguagucug ggccguacua 60

caacuaggcu ggagacccgg cugguuucuc gacagccccg accgacccug gaaccccccc 120

accuucucac ccgcccuccu cgucgucacc gaaggcgaca acgccacauu cacaugcucc 180

uucuccaaca ccucugaauc auucguccua aacugguacc gaaugucacc cuccaaccaa 240

acugacaaac ucgccgccuu ucccgaagac cgcucccaac ccggccaaga cugccgauuc 300

360

aacgacuccg gaaccuaccu cugcggagcc aucucccucg cccccaaagc ccaaaucaaa 420

gaaucccucc gagcagaacu ccgcgucacc gaacgccgcg ccgaaguccc caccgcacac 480

ccaucacccu ccccccgccc cgccggccaa uuccaaacac uuguaguagg cgucgucggc 540

ggccuccuug gaucacucgu ccuacuugua uggguccuag ccgucaucug cucucgcgcc 600

gcacgcggca ccaucggcgc acgacgaacc ggccaaccuc uaaaagaaga ccccuccgca 660

guccccgucu ucuccgucga cuacggcgaa cucgacuucc aauggcgcga aaaaaccccc 720

780

ggaaugggca ccucaucccc cgccgacga ggaucagccg acggccccg auccgcccaa 840

ccccuccgac cagaagacgg ccacugcuca uggccccuuu aaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 244

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt8

<400> 244

gggagaaagc uuaccaugca aaucccacaa gcccccuggc ccguagucug ggccguacua 60

caacuaggcu ggagacccgg cugguuucuc gacagccccg accgacccug gaaccccccc 120

accuucucac ccgcccuccu cgucgucacc gaaggcgaca acgccacauu cacaugcucc 180

uucuccaaca ccucugaauc auucguccua aacugguacc gaaugucacc cuccaaccaa 240

acugacaaac ucgccgccuu ucccgaagac cgcucccaac ccggccaaga cugccgauuc 300

360

aacgacuccg gaaccuaccu cugcggagcc aucucccucg cccccaaagc ccaaaucaaa 420

gaaucccucc gagcagaacu ccgcgucacc gaacgccgcg ccuaaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 245

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt8

<400> 245

gggagaaagc uuaccaugug ccccgccaga ucccuccuac ucgucgcaac acuuguccuc 60

cucgaccacc ucucccucgc ccgcaaucuc cccgucgcca cccccgaccc cggaauguuuu 120

cccugccucc accacucaca aaaccuccua cgcgccgucu caaacaugcu ucaaaaagcc 180

cgacaaaccc ucgaauuuua ccccugcacc uccgaagaaa ucgaccacga agacauaacc 240

aaagacaaaa ccuccaccgu cgaagccugc cuaccauuag aacuaaccaa aaacgaaucc 300

ugccucaacu cacgcgaaac cuccuucauc acaaacggcu caugccucgc cucacgcaaa 360

accuccuuca ugaggcccu cugccuauca ucaaucuaug aagaccucaa aauguaccaa 420

guagaauuua aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc 480

gaccaaaaca ugcucgcagu caucgacgaa cucaugcaag cccucaacuu caacucagaa 540

acagucccac aaaaauccuc ccucgaagaa cccgacuucu auaaaaccaa aaucaaacuc 600

ugcauccucc uccacgccuu ccgcauacgc gccguaacca ucgaccgcgu aaugucauac 660

cuaaaugccu cuuaaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 246

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt8

<400> 246

gggagaaagc uuaccaugug ccccgccaga ucccuccuac ucgucgcaac acuuguccuc 60

cucgaccacc ucucccucgc ccgcaaucuc cccgucgcca cccccgaccc cggaauguuuu 120

cccugccucc accacucaca aaaccuccua cgcgccgucu caaacaugcu ucaaaaagcc 180

cgacaaaccc ucgaauuuua ccccugcacc uccgaagaaa ucgaccacga agacauaacc 240

aaagacaaaa ccuccaccgu cgaagccugc cuaccauuag aacuaaccaa aaacgaaucc 300

ugccucaacu cacgcgaaac cuccuucauc acaaacggcu caugccucgc cucacgcaaa 360

accuccuuca ugaggcccu cugccuauca ucaaucuaug aagaccucaa aauguaccaa 420

guagaauuua aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc 480

gaccaaaaca ugcucgcagu caucgacgaa cucaugcaag cccucaacuu caacucagaa 540

acagucccac aaaaauccuc ccucgaagaa cccgacuucu auaaaaccaa aaucaaacuc 600

ugcauccucc uccacgccuu ccgcauacgc gccguaacca ucgaccgcgu aaugucauac 660

cuaaaugccu cuggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 247

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt8

<400> 247

gggagaaagc uuacccgcaa ucuccccguc gccacccccg accccggaau guuucccugc 60

cuccaccacu cacaaaaccu ccuacgcgcc gucucaaaca ugcuucaaaa agcccgacaa 120

acccucgaau uuuaccccug caccuccgaa gaaaucgacc acgaagacau aaccaaagac 180

aaaaccucca ccgucgaagc cugccuacca uuagaacuaa ccaaaaacga auccugccuc 240

aacucacgcg aaaccuccuu caucacaaac ggcucaugcc ucgccucacg caaaaccucc 300

uucaugaugg cccucugccu aucaucaauc uaugaagacc ucaaaaugua ccaaguagaa 360

uuuaaaacca ugaacgccaa acuccucaug gaccccaaac gccaaaucuu ccucgaccaa 420

aacaugcucg cagucaucga cgaacucaug caagcccuca acuucaacuc agaaacaguc 480

ccacaaaaau ccucccucga agaacccgac uucuauaaaa ccaaaaucaa acucugcauc 540

cuccuccacg ccuuccgcau acgcgccgua accaucgacc gcguaauguc auaccuaaau 600

gccucuuaag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 248

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt8

<400> 248

gggagaaagc uuaccaugug ccaccaacaa cucgucauaa gcugguucag ccuaguauuc 60

cucgccucac cccucgucgc caucugggaa cucaagaaag acguauacgu cgucgaacua 120

gacugguacc ccgacgcacc cggagaaaug guaguacuca caugcgacac ccccgaagaa 180

gacggcauca cauggaccuu agaccaauca ucagaagucc ucggauccgg aaaaacccuc 240

acaauccaag ucaaagaguu cggcgacgcc ggccaauaca caugccacaa aggcggagaa 300

guccucucac acucacuccu ucuacuacac aagaaagaag acggcaucug guccaccgac 360

auacucaaag acccaaaaaga acccaaaaac aaaaccuucc uccgcugcga agccaaaaac 420

uacuccggcc gauucacaug cugguggcuc accaccaucu ccaccgaccu gaccuucucc 480

gucaaaucca gcaggggcuc cucagaccca caaggcguaa ccugcggcgc agccacccua 540

ucggccgaac gaguccgcgg agacaacaaa gaauacgaau acagcgucga augccaagaa 600

gacucagcau gccagcagc cgaagaauca cuccccaucg aagucauggu cgacgccguc 660

cacaaacuaa aauacgaaaa cuacacaagc ucauucuuca uccgcgacau aaucaaaccc 720

gacccaccga aaaaccucca acucaaaccc cuuaaaaaca gccgccaagu cgaagucucc 780

ugggaauacc ccgacaccug guccacaccc cacuccuacu ucucacucac cuucugcguc 840

caaguccaag gcaaauccaa acgcgaaaag aaagaccgcg uauucaccga caaaaccucc 900

gccacaguca ucugccgcaa aaacgccuca aucuccgucc gcgcccaaga ccgauacuac 960

1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 249

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt8

<400> 249

gggagaaagc uuaccaugug ccaccaacaa cucgucauaa gcugguucag ccuaguauuc 60

cucgccucac cccucgucgc caucugggaa cucaagaaag acguauacgu cgucgaacua 120

gacugguacc ccgacgcacc cggagaaaug guaguacuca caugcgacac ccccgaagaa 180

gacggcauca cauggaccuu agaccaauca ucagaagucc ucggauccgg aaaaacccuc 240

acaauccaag ucaaagaguu cggcgacgcc ggccaauaca caugccacaa aggcggagaa 300

guccucucac acucacuccu ucuacuacac aagaaagaag acggcaucug guccaccgac 360

auacucaaag acccaaaaaga acccaaaaac aaaaccuucc uccgcugcga agccaaaaac 420

uacuccggcc gauucacaug cugguggcuc accaccaucu ccaccgaccu gaccuucucc 480

gucaaaucca gcaggggcuc cucagaccca caaggcguaa ccugcggcgc agccacccua 540

ucggccgaac gaguccgcgg agacaacaaa gaauacgaau acagcgucga augccaagaa 600

gacucagcau gccagcagc cgaagaauca cuccccaucg aagucauggu cgacgccguc 660

cacaaacuaa aauacgaaaa cuacacaagc ucauucuuca uccgcgacau aaucaaaccc 720

gacccaccga aaaaccucca acucaaaccc cuuaaaaaca gccgccaagu cgaagucucc 780

ugggaauacc ccgacaccug guccacaccc cacuccuacu ucucacucac cuucugcguc 840

caaguccaag gcaaauccaa acgcgaaaag aaagaccgcg uauucaccga caaaaccucc 900

gccacaguca ucugccgcaa aaacgccuca aucuccgucc gcgcccaaga ccgauacuac 960

agcuccuccu ggucagaaug ggccuccguc ccaugcuccg gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 250

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt8

<400> 250

gggagaaagc uuaccaucug ggaacucaag aaagacguau acgucgucga acuagacugg 60

uaccccgacg cacccggaga aaugguagua cucacaugcg acacccccga agaagacggc 120

aucacaugga ccuuagacca aucaucagaa guccucggau ccggaaaaac ccucacaauc 180

caagucaaag aguucggcga cgccggccaa uacacaugcc acaaaggcgg agaaguccuc 240

ucacacucac uccuucuacu acacaagaaa gaagacggca ucugguccac cgacauacuc 300

aaagaccaaa aagaacccaa aaacaaaacc uuccuccgcu gcgaagccaa aaacuacucc 360

ggccgauuca caugcuggug gcucaccacc aucuccaccg accugaccuu cuccgucaaa 420

uccagcaggg gcuccucaga cccacaaggc guaaccugcg gcgcagccac ccuaucggcc 480

gaacgagucc gcggagacaa caaagaauac gaauacagcg ucgaaugcca agaagacuca 540

gcaugcccag cagccgaaga aucacucccc aucgaaguca uggucgacgc cguccacaaa 600

cuaaaauacg aaaacuacac aagcucauuc uucauccgcg acauaaucaa acccgaccca 660

ccgaaaaacc uccaacucaa accccuuaaa aacagccgcc aagucgaagu cuccugggaa 720

uaccccgaca ccugguccac accccacucc uacuucucac ucaccuucug cguccaaguc 780

caaggcaaau ccaaacgcga aaagaaagac cgcguauuca ccgacaaaac cuccgccaca 840

gucaucugcc gcaaaaacgc cucaaucucc guccgcgcc aagaccgaua cuacagcucc 900

uccggucag aaugggccuc cgucccaugc uccuaaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 251

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt8

<400> 251

gggagaaagc uuaccgggag cacgagcggg agcgggaagc cgggaagugg agagggaagu 60

acaaagggag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 252

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt8

<400> 252

gggagaaagc uuaccaugug ccaccaacaa cucgucauaa gcugguucag ccuaguauuc 60

cucgccucac cccucgucgc caucugggaa cucaagaaag acguauacgu cgucgaacua 120

gacugguacc ccgacgcacc cggagaaaug guaguacuca caugcgacac ccccgaagaa 180

gacggcauca cauggaccuu agaccaauca ucagaagucc ucggauccgg aaaaacccuc 240

acaauccaag ucaaagaguu cggcgacgcc ggccaauaca caugccacaa aggcggagaa 300

guccucucac acucacuccu ucuacuacac aagaaagaag acggcaucug guccaccgac 360

auacucaaag acccaaaaaga acccaaaaac aaaaccuucc uccgcugcga agccaaaaac 420

uacuccggcc gauucacaug cugguggcuc accaccaucu ccaccgaccu gaccuucucc 480

gucaaaucca gcaggggcuc cucagaccca caaggcguaa ccugcggcgc agccacccua 540

ucggccgaac gaguccgcgg agacaacaaa gaauacgaau acagcgucga augccaagaa 600

gacucagcau gccagcagc cgaagaauca cuccccaucg aagucauggu cgacgccguc 660

cacaaacuaa aauacgaaaa cuacacaagc ucauucuuca uccgcgacau aaucaaaccc 720

gacccaccga aaaaccucca acucaaaccc cuuaaaaaca gccgccaagu cgaagucucc 780

ugggaauacc ccgacaccug guccacaccc cacuccuacu ucucacucac cuucugcguc 840

caaguccaag gcaaauccaa acgcgaaaag aaagaccgcg uauucaccga caaaaccucc 900

gccacaguca ucugccgcaa aaacgccuca aucuccgucc gcgcccaaga ccgauacuac 960

agcuccuccu ggucagaaug ggccuccguc ccaugcuccg ggagcacgag cgggagcggg 1020

aagccgggaa guggagaggg aaguacaaag ggacgcaauc uccccgucgc cacccccgac 1080

ccgggaaugu uucccugccu ccaccacuca caaaaccucc uacgcgccgu cucaaacaug 1140

cuucaaaaag cccgacaaac ccucgaauuu uaccccugca ccuccgaaga aaucgaccac 1200

gaagacauaa ccaaagacaa aaccuccacc gucgaagccu gccuaccauu agaacuaacc 1260

1320

gccucacgca aaaccuccuu caugauggcc cucugccuau caucaaucua ugaagaccuc 1380

aaaauguacc aaguagaauu uaaaaccaug aacgccaaac uccucaugga ccccaaacgc 1440

caaaucuucc ucgaccaaaa caugcucgca gucaucgacg aacucaugca agcccucaac 1500

1560

aaaaucaaac ucugcauccu ccuccacgcc uuccgcauac gcgccguaac caucgaccgc 1620

guaaugucau accuaaaugc cucuuaagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 253

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt8

<400> 253

gggagaaagc uuaccaugau agaaaccuac aaccaaaccu cuccccgauc cgcagccacc 60

120

augaucggcu ccgcucucuu cgcagucuac cuccaccgcc gccuagacaa aaucgaagac 180

gaacgcaacc uacacgaaga cuucgucuuc augaaaacca uucaacgcug caacacaggc 240

gaacgauccc uaucccuacu caacugcgaa gaaaucaaau cccaauucga aggcuuugua 300

360

ggcgaccaaa acccccaaau agccgcccau gucauaucag aagccuccuc caaaaccacc 420

uccguccucc aaugggccga aaaaggcuac uacaccaugu ccaacaaccu aguaacccuu 480

gaaaacggca aacaacucac cguaaaacgc caaggccucu acuacaucua cgcccaaguc 540

accuucugcu ccaacagaga agcauccucc caagcacccu ucaucgccuc ccuaugccuc 600

aaaucccccg gccgcuucga acgaauccuc cuccgcgccg ccaacacuca cuccucagcc 660

aaacccugcg gccaacaaag uauacaccuu ggcggagucu ucgaacucca acccggcgcc 720

uccgucuucg uaaacgucac cgaccccuca caagucuccc acggaaccgg auucaccucc 780

uucggccuac uaaaacuaua gggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 254

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt9

<400> 254

gggagaaagc uuaccaugca aaucccccaa gccccauggc ccgucgucug ggccguccuc 60

caacucggcu ggcgccccgg augguuccua gacucuccag accgccccug gaauccaccc 120

accuucuccc cgcccuccu agucgucacc gaaggcgaca acgccaccuu caccuguuca 180

uucuccaaca ccucagaauc cuucguacuc aacugguacc gcaugucccc aagcaaccaa 240

acagacaaac ucgccgccuu ccccgaagac cgcucccaac ccggucaaga cugccgauuc 300

cgcgucaccc aacuccccaa cggacgcgac uuccacaugu ccgucguucg agcacgacgc 360

aacgacucag gcacauaccu augcggagcc aucucccuag cccccaaagc ccaaaucaaa 420

gaaucacuac gcgccgaacu ccgcgucacc gaacgccgcg ccgaaguacc cacagcccac 480

ccauccccau caccacgccc agcaggucaa uuccaaaccu uagucgucgg agucgucggc 540

ggccuccuag gcucacucgu ccuccuaguc uggguccucg ccgucauaug cagccgcgcc 600

gcacgcggca ccaucggcgc cagacgcacc ggacaacccc ucaaagaaga ccccucagcc 660

guccccgucu uuuccgucga cuacggcgaa cuagacuucc aauggcgcga aaaaaccccc 720

gaaccccccg ucccaugcgu acccgaacaa accgaauacg ccacaauagu cuucccaucc 780

ggcaugggaa ccucaucacc cgccagacga ggcucagcag auggcccccg cuccgcacaa 840

ccacuccgac cagaagacgg ccacugcagc uggccccugu aaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 255

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223>PDCD1(1-149) mRNA product opt9

<400> 255

gggagaaagc uuaccaugca aaucccccaa gccccauggc ccgucgucug ggccguccuc 60

caacucggcu ggcgccccgg augguuccua gacucuccag accgccccug gaauccaccc 120

accuucuccc cgcccuccu agucgucacc gaaggcgaca acgccaccuu caccuguuca 180

uucuccaaca ccucagaauc cuucguacuc aacugguacc gcaugucccc aagcaaccaa 240

acagacaaac ucgccgccuu ccccgaagac cgcucccaac ccggucaaga cugccgauuc 300

cgcgucaccc aacuccccaa cggacgcgac uuccacaugu ccgucguucg agcacgacgc 360

aacgacucag gcacauaccu augcggagcc aucucccuag cccccaaagc ccaaaucaaa 420

gaaucacuac gcgccgaacu ccgcgucacc gaacgccgcg ccuaaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 256

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt9

<400> 256

gggagaaagc uuaccaugug ccccgccaga ucccuccucc ucgucgcaac ccucguccuc 60

cucgaccacc ucucccuagc acguaaccuc ccagucgcca ccccagaccc cggaauguuc 120

cccugccucc aucacuccca aaaucuccuc cgugccgucu ccaacaugcu ccaaaaagcc 180

cgccaaaccc ucgaauuuua uccaugcacc uccgaagaaa uagaccauga agacaucacc 240

aaagacaaaa cauccaccgu cgaagccugc cucccccucg aacucacaaa aaacgaauca 300

ugccucaacu cccgcgaaac cuccuucaua accaacggcu caugccucgc cucucgcaaa 360

accucauuca ugaggcccu cugccuaucc ucuaucuacg aagaccucaa aauguaccaa 420

gucgaauuua aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc 480

gaccaaaaca ugcucgcagu caucgacgaa cucaugcaag cacucaacuu caacucagaa 540

accguccccc aaaaauccuc ccucgaagaa cccgacuucu acaaaacaaa aauaaaacuc 600

ugcauccucc uccacgccuu ccgcauccga gcagucacca ucgaucgcgu cauguccuac 660

cuaaacgccu ccuaaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 257

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt9

<400> 257

gggagaaagc uuaccaugug ccccgccaga ucccuccucc ucgucgcaac ccucguccuc 60

cucgaccacc ucucccuagc acguaaccuc ccagucgcca ccccagaccc cggaauguuc 120

cccugccucc aucacuccca aaaucuccuc cgugccgucu ccaacaugcu ccaaaaagcc 180

cgccaaaccc ucgaauuuua uccaugcacc uccgaagaaa uagaccauga agacaucacc 240

aaagacaaaa cauccaccgu cgaagccugc cucccccucg aacucacaaa aaacgaauca 300

ugccucaacu cccgcgaaac cuccuucaua accaacggcu caugccucgc cucucgcaaa 360

accucauuca ugaggcccu cugccuaucc ucuaucuacg aagaccucaa aauguaccaa 420

gucgaauuua aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc 480

gaccaaaaca ugcucgcagu caucgacgaa cucaugcaag cacucaacuu caacucagaa 540

accguccccc aaaaauccuc ccucgaagaa cccgacuucu acaaaacaaa aauaaaacuc 600

ugcauccucc uccacgccuu ccgcauccga gcagucacca ucgaucgcgu cauguccuac 660

cuaaacgccu ccggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 258

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt9

<400> 258

gggagaaagc uuacccguaa ccucccaguc gccaccccag accccggaau guuccccugc 60

cuccaucacu cccaaaaucu ccuccgugcc gucuccaaca ugcuccaaaa agcccgccaa 120

acccucgaau uuuauccaug caccuccgaa gaaauagacc augaagacau caccaaagac 180

240

aacucccgcg aaaccuccuu cauaaccaac ggcucaugcc ucgccucucg caaaaccuca 300

uucaugaugg cccucugccu auccucuauc uacgaagacc ucaaaaugua ccaagucgaa 360

uuuaaaacca ugaacgccaa acuccucaug gaccccaaac gccaaaucuu ccucgaccaa 420

aacaugcucg cagucaucga cgaacucaug caagcacuca acuucaacuc agaaaccguc 480

ccccaaaaau ccucccucga agaacccgac uucuacaaaa caaaaauaaa acucugcauc 540

cuccuccacg ccuuccgcau ccgagcaguc accaucgauc gcgucauguc cuaccuaaac 600

gccuccuaag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 259

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt9

<400> 259

gggagaaagc uuaccaugug ucaccaacaa cuuguaauca gcugguucuc ccucgucuuc 60

cucgccucac cccucgucgc caucugggaa cucaaaaaag acgucuacgu agucgaacuc 120

gacugguacc ccgacgcccc aggagaaaug gucguacuca ccugugacac ccccgaagaa 180

gacggcauca ccuggacccu cgaccaaucc uccgaagucc ucgguucagg aaaaacccuc 240

accauccaag uaaaagaauu uggcgacgcc gggcaauaua ccugccacaa aggcggcgag 300

guccuauccc acucacuccu ccuccuccac aagaaagaag acggaaucug guccaccgac 360

auccuuaaag accaaaaaga accaaaaaac aaaacauucc uccgcugcga agccaaaaac 420

uacagcggcc gcuucaccug uugguggcua accacaauau caaccgacuu aaccuucagc 480

gucaaauccu ccagaggauc cagcgaccca caaggaguua ccugcggagc cgcaacacuc 540

agcgccgaac gaguccgcgg agacaacaaa gaauacgaau acuccgucga augccaagaa 600

gacucagcau gccccgccgc agaagaaucc cuacccaucg aaguaauggu agacgccguc 660

cacaaacuca aauacgaaaa cuacaccagc uccuucuuca uccgagacau caucaaaccc 720

gaccccccaa aaaaccucca acuaaaaccc cucaaaaaca gccgccaagu agaaguaucc 780

ugggaauacc ccgacaccug guccacaccc cacuccuacu ucucgcucac guucugcguc 840

caaguccaag gcaaauccaa acgagaaaaa aaagaccgcg ucuucaccga caaaacuucc 900

gccaccguca ucugccgcaa aaacgccagc aucagcgucc gcgcacaaga ccgcuacuac 960

ucaagcuccu gguccgaaug ggccuccguc ccaugcucau aaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 260

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt9

<400> 260

gggagaaagc uuaccaugug ucaccaacaa cuuguaauca gcugguucuc ccucgucuuc 60

cucgccucac cccucgucgc caucugggaa cucaaaaaag acgucuacgu agucgaacuc 120

gacugguacc ccgacgcccc aggagaaaug gucguacuca ccugugacac ccccgaagaa 180

gacggcauca ccuggacccu cgaccaaucc uccgaagucc ucgguucagg aaaaacccuc 240

accauccaag uaaaagaauu uggcgacgcc gggcaauaua ccugccacaa aggcggcgag 300

guccuauccc acucacuccu ccuccuccac aagaaagaag acggaaucug guccaccgac 360

auccuuaaag accaaaaaga accaaaaaac aaaacauucc uccgcugcga agccaaaaac 420

uacagcggcc gcuucaccug uugguggcua accacaauau caaccgacuu aaccuucagc 480

gucaaauccu ccagaggauc cagcgaccca caaggaguua ccugcggagc cgcaacacuc 540

agcgccgaac gaguccgcgg agacaacaaa gaauacgaau acuccgucga augccaagaa 600

gacucagcau gccccgccgc agaagaaucc cuacccaucg aaguaauggu agacgccguc 660

cacaaacuca aauacgaaaa cuacaccagc uccuucuuca uccgagacau caucaaaccc 720

gaccccccaa aaaaccucca acuaaaaccc cucaaaaaca gccgccaagu agaaguaucc 780

ugggaauacc ccgacaccug guccacaccc cacuccuacu ucucgcucac guucugcguc 840

caaguccaag gcaaauccaa acgagaaaaa aaagaccgcg ucuucaccga caaaacuucc 900

gccaccguca ucugccgcaa aaacgccagc aucagcgucc gcgcacaaga ccgcuacuac 960

ucaagcuccu gguccgaaug ggccuccguc ccaugcucag gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 261

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt9

<400> 261

gggagaaagc uuaccaucug ggaacucaaa aaagacgucu acguagucga acucgacugg 60

uaccccgacg ccccaggaga aauggucgua cucaccugug acacccccga agaagacggc 120

aucaccugga cccucgacca auccuccgaa guccucgguu caggaaaaac ccucaccauc 180

caaguaaaag aauuuggcga cgccgggcaa uauaccugcc acaaaggcgg cgagguccua 240

ucccacucac uccuccuccu ccacaagaaa gaagacggaa ucgguccac cgacauccuu 300

aaagaccaaa aagaaccaaa aaacaaaaca uuccuccgcu gcgaagccaa aaacuacagc 360

ggccgcuuca ccuguuggug gcuaaccaca auaucaaccg acuuaaccuu cagcgucaaa 420

uccuccagag gauccagcga cccacaagga guuaccugcg gagccgcaac acucagcgcc 480

gaacgagucc gcggagacaa caaagaauac gaauacuccg ucgaaugcca agaagacuca 540

gcaugccccg cgcagaaga aucccuaccc aucgaaguaa ugguagacgc cguccacaaa 600

cucaaauacg aaaacuacac cagcuccuuc uucauccgag acaucaucaa acccgacccc 660

ccaaaaaacc uccaacuaaa accccucaaa aacagccgcc aaguagaagu auccugggaa 720

uaccccgaca ccugguccac accccacucc uacuucuccgc ucacguucug cguccaaguc 780

caaggcaaau ccaaacgaga aaaaaaagac cgcgucuuca ccgacaaaac uuccgccacc 840

gucaucugcc gcaaaaacgc cagcaucagc guccgcgcac aagaccgcua cuacucaagc 900

uccgguccg aaugggccuc cgucccaugc ucauaaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 262

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt9

<400> 262

60

acgaaggggg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 263

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt9

<400> 263

gggagaaagc uuaccaugug ucaccaacaa cuuguaauca gcugguucuc ccucgucuuc 60

cucgccucac cccucgucgc caucugggaa cucaaaaaag acgucuacgu agucgaacuc 120

gacugguacc ccgacgcccc aggagaaaug gucguacuca ccugugacac ccccgaagaa 180

gacggcauca ccuggacccu cgaccaaucc uccgaagucc ucgguucagg aaaaacccuc 240

accauccaag uaaaagaauu uggcgacgcc gggcaauaua ccugccacaa aggcggcgag 300

guccuauccc acucacuccu ccuccuccac aagaaagaag acggaaucug guccaccgac 360

auccuuaaag accaaaaaga accaaaaaac aaaacauucc uccgcugcga agccaaaaac 420

uacagcggcc gcuucaccug uugguggcua accacaauau caaccgacuu aaccuucagc 480

gucaaauccu ccagaggauc cagcgaccca caaggaguua ccugcggagc cgcaacacuc 540

agcgccgaac gaguccgcgg agacaacaaa gaauacgaau acuccgucga augccaagaa 600

gacucagcau gccccgccgc agaagaaucc cuacccaucg aaguaauggu agacgccguc 660

cacaaacuca aauacgaaaa cuacaccagc uccuucuuca uccgagacau caucaaaccc 720

gaccccccaa aaaaccucca acuaaaaccc cucaaaaaca gccgccaagu agaaguaucc 780

ugggaauacc ccgacaccug guccacaccc cacuccuacu ucucgcucac guucugcguc 840

caaguccaag gcaaauccaa acgagaaaaa aaagaccgcg ucuucaccga caaaacuucc 900

gccaccguca ucugccgcaa aaacgccagc aucagcgucc gcgcacaaga ccgcuacuac 960

ucaagcuccu gguccgaaug ggccuccguc ccaugcucag ggaguacgag ugggaguggg 1020

aagccgggga guggggaggg gaguacgaag gggcguaacc ucccagucgc caccccagac 1080

ccgggaaugu uccccugccu ccaucacucc caaaaucucc uccgugccgu cuccaacaug 1140

cuccaaaaag cccgccaaac ccucgaauuu uauccaugca ccuccgaaga aauagaccau 1200

gaagacauca ccaaagacaa aacauccacc gucgaagccu gccucccccu cgaacucaca 1260

1320

gccucucgca aaaccucauu caugauggcc cucugccuau ccucuaucua cgaagaccuc 1380

aaaauguacc aagucgaauu uaaaaccaug aacgccaaac uccucaugga ccccaaacgc 1440

caaaucuucc ucgaccaaaa caugcucgca gucaucgacg aacucaugca agcacucaac 1500

1560

aaaauaaaac ucugcauccu ccuccacgcc uuccgcaucc gagcagucac caucgaucgc 1620

gucauguccu accuaaacgc cuccuaagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 264

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt9

<400> 264

gggagaaagc uuaccaugau cgaaacauac aaccaaacau ccccccgcuc cgccgccaca 60

ggccucccca ucuccaugaa aaucuucaug uaccuccuca caguauuccu caucacccaa 120

augaucggcu ccgcacucuu ugcagucuau cuccaccguc gccucgacaa aaucgaagac 180

gaacgcaacc uccacgaaga cuucgucuuc augaaaacca uacaacgcug caacaccggc 240

gaacgcucac ucucccuacu aaacugcgaa gaaaucaaau cccaauucga aggcuucguc 300

360

ggcgaccaaa acccccaaau agccgcccac gucaucuccg aagccuccuc caaaaccacc 420

uccguccucc aaugggccga aaaaggcuac uacacaaugu ccaacaaccu cgucacccuc 480

gaaaacggca aacaacucac cgucaaacgc caaggccucu acuacaucua cgcccaagua 540

accuucugcu ccaaccgcga agccucaucu caagcucccu ucaucgccuc acucugccuc 600

660

aaacccugcg gccaacaauc cauacaccuc ggcggcguuu ucgagcucca accuggcgcc 720

uccgucuucg uaaacgucac cgaccccuca caagucuccc acgguaccgg cuucaccucc 780

uucggacucc uaaaacucua aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 265

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product opt10

<400> 265

gggagaaagc uuaccaugca aaucccccaa gcccccuggc cggucgucug ggccguccuc 60

caacucggcu ggcgccccgg augguuccuc gacucccccg accgcccgug gaaccccccc 120

accuucuccc ccgcccuccu agucgucacc gaaggcgaca acgccaccuu caccuguucc 180

uucuccaaca ccucagaauc cuucguccuc aacugguacc gcaugucccc cuccaaccaa 240

accgacaaac ucgccgccuu ccccgaagac cgaucccaac ccggccaaga cugccgcuuc 300

cgcgucacac aacuucccaa cggacgcgac uuucacaugu ccgucguccg cgcccgccgc 360

aacgacccg gcaccuaccu cugcggcgcc aucucccucg cccccaaagc ccaaaucaaa 420

gaaucccuca gagccgaacu ccgcgucacc gaacggcgcg ccgaaguccc cacugcccac 480

cccccccccu ccccccgccc cgccggccaa uuccaaaccc ucgucgucgg cguugucggc 540

ggcccuccg gcucacucgu ccuccucguc uggguacucg ccgucaucug cucccgcgcc 600

gcgcgcggca ccaucggcgc gcgccgcacc ggacaacccc uaaaagaaga ccccuccgcc 660

guccccgucu ucuccgucga cuacggcgaa cucgacuucc aauggcgcga aaaaaccccg 720

gaacccccg ucccgugcgu ccccgaacaa acagaauacg cgaccaucgu cuucccgucc 780

ggcaugggca cauccucacc cgcccgccga ggcuccgccg acggcccccg auccgcccaa 840

900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 266

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product opt10

<400> 266

gggagaaagc uuaccaugca aaucccccaa gcccccuggc cggucgucug ggccguccuc 60

caacucggcu ggcgccccgg augguuccuc gacucccccg accgcccgug gaaccccccc 120

accuucuccc ccgcccuccu agucgucacc gaaggcgaca acgccaccuu caccuguucc 180

uucuccaaca ccucagaauc cuucguccuc aacugguacc gcaugucccc cuccaaccaa 240

accgacaaac ucgccgccuu ccccgaagac cgaucccaac ccggccaaga cugccgcuuc 300

cgcgucacac aacuucccaa cggacgcgac uuucacaugu ccgucguccg cgcccgccgc 360

aacgacccg gcaccuaccu cugcggcgcc aucucccucg cccccaaagc ccaaaucaaa 420

gaaucccuca gagccgaacu ccgcgucacc gaacggcgcg ccuaaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 267

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product opt10

<400> 267

gggagaaagc uuaccaugug ccccgcccgu ucacuccucc ucgucgccac ccucguccuc 60

cuagaccacc ucucccuggc ccgcaaccuc ccagucgcca cccccgaccc cggcauguuc 120

cccugccucc accacuccca aaaccuccuc cgcgccgucu ccaacaugcu ccaaaaagcc 180

cgccaaaccc ucgaauuuua ccccugcacc uccgaagaga ucgaccacga agacaucacc 240

aaagacaaaa ccuccacagu cgaagccugc cucccccucg aacucaccaa aaacgaaucc 300

ugccuuaacu cccgcgaaac cuccuucauc accaacggcu ccugccucgc cucccgcaaa 360

accuccuuca ugaggcccu cugccucucc uccaucuacg aagaccucaa aauguaccaa 420

gucgaauuua aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc 480

gaccaaaaca ugcucgccgu caucgacgaa cucaugcaag cccucaacuu caacuccgaa 540

accguccccc aaaaauccuc ccucgaagaa cccgacuucu acaaaaccaa aaucaaacuu 600

ugcauccucc uccacgcauu ccgcauccgc gccgucacca ucgaccgugu caugagcuac 660

cuaaacgccu ccuaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 268

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product opt10

<400> 268

gggagaaagc uuaccaugug ccccgcccgu ucacuccucc ucgucgccac ccucguccuc 60

cuagaccacc ucucccuggc ccgcaaccuc ccagucgcca cccccgaccc cggcauguuc 120

cccugccucc accacuccca aaaccuccuc cgcgccgucu ccaacaugcu ccaaaaagcc 180

cgccaaaccc ucgaauuuua ccccugcacc uccgaagaga ucgaccacga agacaucacc 240

aaagacaaaa ccuccacagu cgaagccugc cucccccucg aacucaccaa aaacgaaucc 300

ugccuuaacu cccgcgaaac cuccuucauc accaacggcu ccugccucgc cucccgcaaa 360

accuccuuca ugaggcccu cugccucucc uccaucuacg aagaccucaa aauguaccaa 420

gucgaauuua aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc 480

gaccaaaaca ugcucgccgu caucgacgaa cucaugcaag cccucaacuu caacuccgaa 540

accguccccc aaaaauccuc ccucgaagaa cccgacuucu acaaaaccaa aaucaaacuu 600

ugcauccucc uccacgcauu ccgcauccgc gccgucacca ucgaccgugu caugagcuac 660

cuaaacgccu ccggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 269

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product opt10

<400> 269

gggagaaagc uuacccgcaa ccucccaguc gccacccccg accccggcau guuccccugc 60

cuccaccacu cccaaaaccu ccuccgcgcc gucuccaaca ugcuccaaaa agcccgccaa 120

acccucgaau uuuaccccug caccuccgaa gagaucgacc acgaagacau caccaaagac 180

240

aacucccgcg aaaccuccuu caucaccaac ggcuccugcc ucgccucccg caaaaccucc 300

uucaugaugg cccucugccu cuccuccauc uacgaagacc ucaaaaugua ccaagucgaa 360

uuuaaaacca ugaacgccaa acuccucaug gaccccaaac gccaaaucuu ccucgaccaa 420

aacaugcucg ccgucaucga cgaacucaug caagcccuca acuucaacuc cgaaaccguc 480

ccccaaaaau ccucccucga agaacccgac uucuacaaaa ccaaaaucaa acuuugcauc 540

cuccuccacg cauuccgcau ccgcgccguc accaucgacc gugucaugag cuaccuaaac 600

gccuccugag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 270

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product opt10

<400> 270

gggagaaagc uuaccaugug ccaccaacaa cucgucaucu ccugguucuc ccucgucuuc 60

cuagccuccc cacucgucgc caucugggaa cucaaaaaag acguauacgu cgucgaacuc 120

gacugguacc ccgacgcccc aggagaaaug gucguccuaa ccugcgacac acccgaagaa 180

gacgguauca ccuggacccu cgaccaaucc uccgaagucc uaggcuccgg caagacccuc 240

accauccaag ucaaagaauu uggcgacgca ggacaauaca ccugucacaa aggcggcgaa 300

guccucagcc acagccuucu ccuacuccau aaaaaagaag acggcaucug guccacugac 360

auccucaaag acccaaaaaga acccaaaaau aaaaccuucc uccgcugcga agccaaaaac 420

uacuccggcc gauucaccug uugguggcua accacaauca gcaccgaccu caccuucuca 480

gucaaauccu cccgcggcuc aucugacccc caaggcguca caugcggcgc cgccacccuc 540

uccgccgaac gcguccgcgg cgacaacaaa gaauacgaau acuccgucga augucaagaa 600

gacuccgccu gccccgccgc cgaagaauca cuccccaucg aagucauggu cgacgcaguc 660

cacaaacuca aauacgaaaa cuacaccucc uccuucuuca uccgcgacau aauaaaaccc 720

gacccaccca aaaaccucca acucaagcca cucaaaaacu cccgacaagu cgaagucucc 780

ugggaguacc ccgacaccug guccacacca cacuccuacu ucucccucac cuucugcguc 840

caaguccaag gcaaauccaa acgcgaaaaa aaagaccgcg uuuucacaga caaaaccucc 900

gccacaguaa uaugccgcaa aaacgccucc aucuccgucc gggcccaaga ccgcuacuac 960

uccuccuccu gguccgagug ggccucaguc cccugcagcu aaggacuagu uauaagacug 1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 271

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product opt10

<400> 271

gggagaaagc uuaccaugug ccaccaacaa cucgucaucu ccugguucuc ccucgucuuc 60

cuagccuccc cacucgucgc caucugggaa cucaaaaaag acguauacgu cgucgaacuc 120

gacugguacc ccgacgcccc aggagaaaug gucguccuaa ccugcgacac acccgaagaa 180

gacgguauca ccuggacccu cgaccaaucc uccgaagucc uaggcuccgg caagacccuc 240

accauccaag ucaaagaauu uggcgacgca ggacaauaca ccugucacaa aggcggcgaa 300

guccucagcc acagccuucu ccuacuccau aaaaaagaag acggcaucug guccacugac 360

auccucaaag acccaaaaaga acccaaaaau aaaaccuucc uccgcugcga agccaaaaac 420

uacuccggcc gauucaccug uugguggcua accacaauca gcaccgaccu caccuucuca 480

gucaaauccu cccgcggcuc aucugacccc caaggcguca caugcggcgc cgccacccuc 540

uccgccgaac gcguccgcgg cgacaacaaa gaauacgaau acuccgucga augucaagaa 600

gacuccgccu gccccgccgc cgaagaauca cuccccaucg aagucauggu cgacgcaguc 660

cacaaacuca aauacgaaaa cuacaccucc uccuucuuca uccgcgacau aauaaaaccc 720

gacccaccca aaaaccucca acucaagcca cucaaaaacu cccgacaagu cgaagucucc 780

ugggaguacc ccgacaccug guccacacca cacuccuacu ucucccucac cuucugcguc 840

caaguccaag gcaaauccaa acgcgaaaaa aaagaccgcg uuuucacaga caaaaccucc 900

gccacaguaa uaugccgcaa aaacgccucc aucuccgucc gggcccaaga ccgcuacuac 960

uccuccuccu gguccgagug ggccucaguc cccugcagcg gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 272

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product opt10

<400> 272

gggagaaagc uuaccaucug ggaacucaaa aaagacguau acgucgucga acucgacugg 60

uaccccgacg ccccaggaga aauggucguc cuaaccugcg acacacccga agaagacggu 120

aucaccugga cccucgacca auccuccgaa guccuaggcu ccggcaagac ccucaccauc 180

caagucaaag aauuuggcga cgcaggacaa uacaccuguc acaaaggcgg cgaaguccuc 240

agccacagcc uucuccuacu ccauaaaaaa gaagacggca ucugguccac ugacauccuc 300

aaagaccaaa aagaacccaa aaauaaaacc uuccuccgcu gcgaagccaa aaacuacucc 360

ggccgauuca ccuguuggug gcuaaccaca aucagcaccg accucaccuu cucagucaaa 420

uccucccgcg gcucaucuga cccccaaggc gucacaugcg gcgccgccac ccucuccgcc 480

gaacgcgucc gcggcgacaa caaagaauac gaauacuccg ucgaauguca agaagacucc 540

gccugccccg ccgccgaaga aucacucccc aucgaaguca uggucgacgc aguccacaaa 600

cucaaauacg aaaacuacac cuccuccuuc uucauccgcg acauaauaaa acccgaccca 660

cccaaaaacc uccaacucaa gccacucaaa aacucccgac aagucgaagu cuccugggag 720

uaccccgaca ccugguccac accacacucc uacuucuccc ucaccuucug cguccaaguc 780

caaggcaaau ccaaacgcga aaaaaaagac cgcguuuuca cagacaaaac cuccgccaca 840

guaauauugcc gcaaaaacgc cuccaucucc guccgggccc aagaccgcua cuacuccucc 900

uccgguccg agugggccuc aguccccugc agcuaaggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 273

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product opt10

<400> 273

60

acgaaggggg gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 274

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product opt10

<400> 274

gggagaaagc uuaccaugug ccaccaacaa cucgucaucu ccugguucuc ccucgucuuc 60

cuagccuccc cacucgucgc caucugggaa cucaaaaaag acguauacgu cgucgaacuc 120

gacugguacc ccgacgcccc aggagaaaug gucguccuaa ccugcgacac acccgaagaa 180

gacgguauca ccuggacccu cgaccaaucc uccgaagucc uaggcuccgg caagacccuc 240

accauccaag ucaaagaauu uggcgacgca ggacaauaca ccugucacaa aggcggcgaa 300

guccucagcc acagccuucu ccuacuccau aaaaaagaag acggcaucug guccacugac 360

auccucaaag acccaaaaaga acccaaaaau aaaaccuucc uccgcugcga agccaaaaac 420

uacuccggcc gauucaccug uugguggcua accacaauca gcaccgaccu caccuucuca 480

gucaaauccu cccgcggcuc aucugacccc caaggcguca caugcggcgc cgccacccuc 540

uccgccgaac gcguccgcgg cgacaacaaa gaauacgaau acuccgucga augucaagaa 600

gacuccgccu gccccgccgc cgaagaauca cuccccaucg aagucauggu cgacgcaguc 660

cacaaacuca aauacgaaaa cuacaccucc uccuucuuca uccgcgacau aauaaaaccc 720

gacccaccca aaaaccucca acucaagcca cucaaaaacu cccgacaagu cgaagucucc 780

ugggaguacc ccgacaccug guccacacca cacuccuacu ucucccucac cuucugcguc 840

caaguccaag gcaaauccaa acgcgaaaaa aaagaccgcg uuuucacaga caaaaccucc 900

gccacaguaa uaugccgcaa aaacgccucc aucuccgucc gggcccaaga ccgcuacuac 960

uccuccuccu gguccgagug ggccucaguc cccugcagcg ggaguacgag ugggaguggg 1020

aagccgggga guggggaggg gaguacgaag gggcgcaacc ucccagucgc cacccccgac 1080

cccggcaugu uccccugccu ccaccacucc caaaaccucc uccgcgccgu cuccaacaug 1140

cuccaaaaag cccgccaaac ccucgaauuu uaccccugca ccuccgaaga gaucgaccac 1200

gaagacauca ccaaagacaa aaccuccaca gucgaagccu gccucccccu cgaacucacc 1260

aaaaacgaau ccugccuuaa cucccgcgaa accuccuuca ucaccaacgg cuccugccuc 1320

gccucccgca aaaccuccuu caugauggcc cucugccucu ccuccaucua cgaagaccuc 1380

aaaauguacc aagucgaauu uaaaaccaug aacgccaaac uccucaugga ccccaaacgc 1440

caaaucuucc ucgaccaaaa caugcucgcc gucaucgacg aacucaugca agcccucaac 1500

uucaacuccg aaaccguccc ccaaaaaucc ucccucgaag aacccgacuu cuacaaaacc 1560

aaaaucaaac uuugcauccu ccuccacgca uuccgcaucc gcgccgucac caucgaccgu 1620

gucaugagcu accuaaacgc cuccuggga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 275

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product opt10

<400> 275

gggagaaagc uuaccaugau cgaaaccuac aaucaaaccu ccccccgcag cgccgcaaca 60

ggccucccca ucuccaugaa aaucuucaug uaccuccuca ccgucuuccu aaucacccaa 120

augaucggcu ccgcccuauu cgccgucuac cuccaccgcc gccucgacaa aaucgaagac 180

gaacgcaacc uccacgaaga cuuugucuuc augaaaacua uccaacgaug caacaccggc 240

gaacgauccc uaucccuccu caacugcgaa gaaauaaaau cccaauucga aggauucguc 300

360

ggcgaccaaa acccccaaau cgcagcccac gucaucucag aagcaucuuc caaaaccacc 420

uccguccucc aaugggccga aaaaggcuac uacaccaugu caaacaaccu cgucacccuc 480

gaaaacggca aacaacucac cgucaaacgc caaggccucu acuacaucua cgcacaaguc 540

accuucugcu ccaaccgcga agcauccucc caagcccccu ucaucgccuc ccucugccuc 600

660

aaaccaugcg gccaacaauc cauccaccuc ggcggcgucu ucgaacucca acccggcgcc 720

uccgucuucg ucaacgucac cgaccccucc caaguauccc auggaaccgg cuucaccucc 780

uucggccucc ucaaacucua gggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 276

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR wild type

<400> 276

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccacaggc gcccuggcca gucgucuggg cggugcuaca acugggcugg cggccaggau 120

180

uggugaccga aggggacaac gccaccuuca ccugcagcuu cuccaacaca ucggagagcu 240

ucgugcuaaa cugguaccgc augagcccca gcaaccagac ggacaagcug gccgcuuucc 300

ccgaggaccg cagccagccc ggccaggacu gccgcuuccg ugucacacaa cugcccaacg 360

ggcgugacuu ccacaugagc guggucaggg cccggcgcaa ugacagcggc accuaccucu 420

guggggccau cucccuggcc cccaaggcgc agaucaaaga gagccugcgg gcagagcuca 480

gggugacaga gagaagggca gaagugccca cagcccaccc cagccccuca cccaggccag 540

ccggccaguu ccaaacccug gugguuggug ucgugggcgg ccugcugggc agccuggugc 600

ugcuagucug gguccuggcc gucaucugcu cccgggccgc acgagggaca auaggagcca 660

ggcgcaccgg ccagccccug aaggaggacc ccucagccgu gccuguguuc ucuguggacu 720

auggggagcu ggauuuccag uggcgagaga agaccccgga gccccccgug cccugugucc 780

840

cccgcagggg cucagccgac ggcccucgga gugcccagcc acugaggccu gaggauggac 900

acugcucuug gccccucuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 277

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR wild type

<400> 277

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccacaggc gcccuggcca gucgucuggg cggugcuaca acugggcugg cggccaggau 120

180

uggugaccga aggggacaac gccaccuuca ccugcagcuu cuccaacaca ucggagagcu 240

ucgugcuaaa cugguaccgc augagcccca gcaaccagac ggacaagcug gccgcuuucc 300

ccgaggaccg cagccagccc ggccaggacu gccgcuuccg ugucacacaa cugcccaacg 360

ggcgugacuu ccacaugagc guggucaggg cccggcgcaa ugacagcggc accuaccucu 420

guggggccau cucccuggcc cccaaggcgc agaucaaaga gagccugcgg gcagagcuca 480

gggugacaga gagaagggca ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 278

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR wild type

<400> 278

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

cagcgcgcag ccuccuccuu guggcuaccc ugguccuccu ggaccaccuc aguuuggcca 120

gaaaccuccc cguggccacu ccagacccag gaauguuccc augccuucac cacucccaaa 180

accugcugag ggccgucagc aacaugcucc agaaggccag acaaacucua gaauuuuacc 240

cuugcacuuc ugaagagauu gaucaugaag auaucacaaa agauaaaacc agcacagugg 300

360

cuuucauaac uaaugggagu ugccuggccu ccagaaagac cucuuuuaug auggcccugu 420

gccuuaguag uauuuaugaa gacuugaaga uguaccaggu ggaguucaag accaugaaug 480

caaagcuucu guggauccu aagaggcaga ucuuucuaga ucaaaacaug cuggcaguua 540

uugaugagcu gaugcaggcc cugaauuuca acagugagac ugugccacaa aaauccuccc 600

uugaagaacc ggauuuuuau aaaacuaaaa

gaauucgggc agugacuauu gauagaguga ugagcuaucu gaaugcuucc uaaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 279

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR wild type

<400> 279

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

cagcgcgcag ccuccuccuu guggcuaccc ugguccuccu ggaccaccuc aguuuggcca 120

gaaaccuccc cguggccacu ccagacccag gaauguuccc augccuucac cacucccaaa 180

accugcugag ggccgucagc aacaugcucc agaaggccag acaaacucua gaauuuuacc 240

cuugcacuuc ugaagagauu gaucaugaag auaucacaaa agauaaaacc agcacagugg 300

360

cuuucauaac uaaugggagu ugccuggccu ccagaaagac cucuuuuaug auggcccugu 420

gccuuaguag uauuuaugaa gacuugaaga uguaccaggu ggaguucaag accaugaaug 480

caaagcuucu guggauccu aagaggcaga ucuuucuaga ucaaaacaug cuggcaguua 540

uugaugagcu gaugcaggcc cugaauuuca acagugagac ugugccacaa aaauccuccc 600

uugaagaacc ggauuuuuau aaaacuaaaa

gaauucgggc agugacuauu gauagaguga ugagcuaucu gaaugcuucc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 280

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR wild type

<400> 280

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accagaaacc 60

uccccguggc cacuccagac ccaggaaugu ucccaugccu ucaccacucc caaaaccugc 120

ugaggggccgu cagcaacaug cuccagaagg ccagacaaac ucuagaauuu uacccuugca 180

cuucugaaga gauugaucau gaagauauca caaaagauaa aaccagcaca guggaggccu 240

guuuaccauu ggaauuaacc aagaaugaga guugccuaaa uuccagagag accucuuuca 300

uaacuaaugg gaguugccug gccuccagaa agaccucuuu uaugauggcc cugugccuua 360

guaguauuua ugaagacuug aagauguacc agguggaguu caagaccaug aaugcaaagc 420

uucugaugga uccuaagagg cagaucuuuc uagaucaaaa caugcuggca guuauugaug 480

agcugaugca ggcccugaau uucaacagug agacugugcc acaaaaaucc ucccuugaag 540

aaccggauuu uuauaaaacu aaaaucaagc

660 gggcagugac uauugauaga gugaugagcu aucugaaugc

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 281

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR wild type

<400> 281

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcaguu ggucaucucu ugguuuuccc ugguuuuucu ggcaucuccc cucguggcca 120

uugggaacu gaagaaagau guuuaugucg uagaauugga uugguauccg gaugccccug 180

gagaaauggu gguccucacc ugugacaccc cugaagaaga ugguaucacc uggaccuugg 240

accagagcag ugaggucuua ggcucuggca aaacccugac cauccaaguc aaagaguuug 300

gagaugcugg ccaguacacc ugucacaag gaggcgaggu ucuaagccau ucgcuccugc 360

ugcuucacaa aaaggaagau ggaauuuggu ccacugauau uuuaaaggac cagaaagaac 420

ccaaaaauaa gaccuuucua agaugcgagg ccaagaauua uucuggacgu uucaccugcu 480

gguggcugac gacaaucagu acugauuuga cauucagugu caaaagcagc agaggcucuu 540

cugaccccca aggggugacg ugcggagcug cuacacucuc ugcagagaga gucagagggg 600

acaacaagga guaugaguac ucaguggagu gccaggagga cagugccugc ccagcugcug 660

aggagagucu gcccauugag gucauggugg augccguuca caagcucaag uaugaaaacu 720

acaccagcag cuucuucauc agggacauca ucaaaccuga cccacccaag aacuugcagc 780

ugaagccauu aaagaauucu cggcaggugg aggucagcug ggaguacccu gacaccugga 840

guacuccaca uuccuacuuc ucccugacau ucugcguuca gguccagggc aagagcaaga 900

gagaaaagaa agauagaguc uucacggaca agaccucagc cacggucauc ugccgcaaaa 960

augccagcau uagcgugcgg gcccaggacc gcuacuauag cucaucuugg agcgaauggg 1020

caucugugcc cugcaguuag ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 282

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR wild type

<400> 282

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcaguu ggucaucucu ugguuuuccc ugguuuuucu ggcaucuccc cucguggcca 120

uaugggaacu gaagaaagau guuuaugucg uagaauugga uugguauccg gaugccccug 180

gagaaauggu gguccucacc ugugacaccc cugaagaaga ugguaucacc uggaccuugg 240

accagagcag ugaggucuua ggcucuggca aaacccugac cauccaaguc aaagaguuug 300

gagaugcugg ccaguacacc ugucacaag gaggcgaggu ucuaagccau ucgcuccugc 360

ugcuucacaa aaaggaagau ggaauuuggu ccacugauau uuuaaaggac cagaaagaac 420

ccaaaaauaa gaccuuucua agaugcgagg ccaagaauua uucuggacgu uucaccugcu 480

gguggcugac gacaaucagu acugauuuga cauucagugu caaaagcagc agaggcucuu 540

cugaccccca aggggugacg ugcggagcug cuacacucuc ugcagagaga gucagagggg 600

acaacaagga guaugaguac ucaguggagu gccaggagga cagugccugc ccagcugcug 660

aggagagucu gcccauugag gucauggugg augccguuca caagcucaag uaugaaaacu 720

acaccagcag cuucuucauc agggacauca ucaaaccuga cccacccaag aacuugcagc 780

ugaagccauu aaagaauucu cggcaggugg aggucagcug ggaguacccu gacaccugga 840

guacuccaca uuccuacuuc ucccugacau ucugcguuca gguccagggc aagagcaaga 900

gagaaaagaa agauagaguc uucacggaca agaccucagc cacggucauc ugccgcaaaa 960

augccagcau uagcgugcgg gcccaggacc gcuacuauag cucaucuugg agcgaauggg 1020

caucugugcc cugcagugga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 283

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR wild type

<400> 283

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauauggg 60

aacugaagaa agauguuuau gucguagaau uggauuggua uccggaugcc ccuggagaaa 120

uggugguccu caccugugac accccugaag aagaugguau caccuggacc uuggaccaga 180

gcagugaggu cuuaggcucu ggcaaaaccc ugaccaucca agucaaagag uuuggagaug 240

cuggccagua caccugucac aaaggaggcg agguucuaag ccauucgcuc cugcugcuuc 300

360

auaagaccuu ucuaagaugc gaggccaaga auuauucugg acguuucacc ugcugguggc 420

ugacgacaau caguacugau uugacauuca gugucaaaag cagcagaggc ucuucugacc 480

cccaaggggu gacgugcgga gcugcuacac ucucugcaga gagagucaga ggggacaaca 540

aggaguauga guacucagug gagugccagg aggacagugc cugcccagcu gcugaggaga 600

gucugcccau ugaggucaug guggaugccg uucacaagcu caaguaugaa aacuacacca 660

gcagcuucuu caucagggac aucaucaaac cugacccacc caagaacuug cagcugaagc 720

cauuaaagaa uucucggcag guggagguca gcugggagua cccugacacc uggaguacuc 780

cacauuccua cuucucccug acauucugcg uucaggucca gggcaagagc aagagagaaa 840

agaaagauag agucuucacg gacaagaccu cagccacggu caucugccgc aaaaaugcca 900

gcauuagcgu gcgggcccag gaccgcuacu auagcucauc uuggagcgaa ugggcaucug 960

ugcccugcag uuagggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 284

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR wild type

<400> 284

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagua 60

120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 285

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR wild type

<400> 285

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcaguu ggucaucucu ugguuuuccc ugguuuuucu ggcaucuccc cucguggcca 120

uaugggaacu gaagaaagau guuuaugucg uagaauugga uugguauccg gaugccccug 180

gagaaauggu gguccucacc ugugacaccc cugaagaaga ugguaucacc uggaccuugg 240

accagagcag ugaggucuua ggcucuggca aaacccugac cauccaaguc aaagaguuug 300

gagaugcugg ccaguacacc ugucacaag gaggcgaggu ucuaagccau ucgcuccugc 360

ugcuucacaa aaaggaagau ggaauuuggu ccacugauau uuuaaaggac cagaaagaac 420

ccaaaaauaa gaccuuucua agaugcgagg ccaagaauua uucuggacgu uucaccugcu 480

gguggcugac gacaaucagu acugauuuga cauucagugu caaaagcagc agaggcucuu 540

cugaccccca aggggugacg ugcggagcug cuacacucuc ugcagagaga gucagagggg 600

acaacaagga guaugaguac ucaguggagu gccaggagga cagugccugc ccagcugcug 660

aggagagucu gcccauugag gucauggugg augccguuca caagcucaag uaugaaaacu 720

acaccagcag cuucuucauc agggacauca ucaaaccuga cccacccaag aacuugcagc 780

ugaagccauu aaagaauucu cggcaggugg aggucagcug ggaguacccu gacaccugga 840

guacuccaca uuccuacuuc ucccugacau ucugcguuca gguccagggc aagagcaaga 900

gagaaaagaa agauagaguc uucacggaca agaccucagc cacggucauc ugccgcaaaa 960

augccagcau uagcgugcgg gcccaggacc gcuacuauag cucaucuugg agcgaauggg 1020

caucugugcc cugcaguggc aguacuucgg gcagugguaa gccugguagu ggugagggua 1080

1140

accacuccca aaaccugcug agggccguca gcaacaugcu ccagaaggcc agacaaacuc 1200

uagaauuuua cccuugcacu ucugaagaga uugaucauga agauaucaca 1260

ccagcacagu ggaggccugu uuaccauugg aauuaaccaa gaaugagagu ugccuaaauu 1320

ccagagagac cucuuucaua acuaauggga guugccuggc cuccagaaag accucuuuua 1380

ugaggcccu gugccuuagu aguauuuaug aagacuugaa gauguaccag guggaguuca 1440

agaccaugaa ugcaaagcuu cugauggauc cuaagaggca gaucuuucua gaucaaaaca 1500

ugcuggcagu uauugaugag cugaugcagg cccugaauuu caacagugag acugugccac 1560

aaaaauccuc ccuugaagaa ccggauuuuu auaaaacuaa aaucaagcuc ugcauacuuc 1620

uucaugcuuu cagaauucgg gcagugacua uugauagagu gaugagcuau cugaaugcuu 1680

ccuaaggacu agugcaucac auuuaaaagc aucucagccu accaugagaa uaagagaaag 1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 286

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR wild type

<400> 286

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

120

uuuuuaugua uuuacuuacu guuuuucuua ucacccagau gauuggguca gcacuuuuug 180

cuguguaucu ucauagaagg uuggacaaga uagaagauga aaggaaucuu caugaagauu 240

uuguauucau gaaaacgaua cagagaugca acacaggaga aagauccuua uccuuacuga 300

acugugagga gauuaaaagc caguuugaag gcuuugugaa ggauauaaug uuaaacaaag 360

aggagacgaa gaaagaaaac agcuuugaaa ugcaaaaagg ugaucagaau ccucaaauug 420

cggcacaugu cauaagugag gccagcagua aaacaacauc

aaggauacua caccaugagc aacaacuugg uaaccugga aaaugggaaa cagcugaccg 540

uuaaaagaca aggacucuau uauaucuaug cccaagucac cuucuguucc aaucgggaag 600

cuucgaguca agcuccauuu auagccagcc ucugccuaaa gucccccggu agauucgaga 660

gaaucuuacu cagagcugca aauacccaca guuccgccaa accuugcggg caacaaucca 720

uucacuuggg aggaguauuu gaauugcaac caggugcuuc gguguuuguc aaugugacug 780

auccaagcca agugagccau ggcacuggcu ucacguccuu uggcuuacuc aaacucugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 287

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt1

<400> 287

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaggc cccguggccc guggucuggg ccgugcugca gcucggcugg cgccccgggu 120

gguuccugga cagccccgac cggccgugga acccgcccac cuucuccccc gcgcugcucg 180

uggucaccga gggcgacaac gccacguuca cgugcagcuu cuccaacacc agcgaguccu 240

ucgugcugaa cugguaccgc ugagccccu ccaaccagac cgacaagcug gccgccuucc 300

ccgaggaccg gagccagccc gggcaggacu gccgcuuccg ggugacccag cuccccaacg 360

gccgcgacuu ccacaugucc gucgugcggg cccgccggaa cgacagcggg accuaccugu 420

gcggcgcgau cucccuggcc ccgaaggccc agaucaagga gagccuccgc gccgagcugc 480

gggugaccga gcgccggggcg gaggucccca ccgcccaccc cucccccagc ccgcgccccg 540

ccggccaguu ccagacgcug gugguggggg ucgugggcgg gcuccugggc ucccuggugc 600

uccggucug ggugcuggcc gugaucugca gccgggccgc gcgcgggacc aucggcgccc 660

ggcgcaccgg cgccccuc aaggaggacc ccuccgccgu cccgguguguuc agcguggacu 720

acggggagcu ggacuuccag uggcgggaga agacccccga gccgcccguc cccugcgugc 780

ccgagcagac ggaguacgcc accaucgugu uccccuccgg cauggggacc agcagccccg 840

cccgccgggg cuccgcggac ggcccgcgca gcgcccagcc ccugcgcccc gaggacgggc 900

acugcuccug gccgcucuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 288

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt1

<400> 288

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaggc cccguggccc guggucuggg ccgugcugca gcucggcugg cgccccgggu 120

gguuccugga cagccccgac cggccgugga acccgcccac cuucuccccc gcgcugcucg 180

uggucaccga gggcgacaac gccacguuca cgugcagcuu cuccaacacc agcgaguccu 240

ucgugcugaa cugguaccgc ugagccccu ccaaccagac cgacaagcug gccgccuucc 300

ccgaggaccg gagccagccc gggcaggacu gccgcuuccg ggugacccag cuccccaacg 360

gccgcgacuu ccacaugucc gucgugcggg cccgccggaa cgacagcggg accuaccugu 420

gcggcgcgau cucccuggcc ccgaaggccc agaucaagga gagccuccgc gccgagcugc 480

gggugaccga gcgccgggcg ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 289

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt1

<400> 289

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgcccgcag ccugcuccug guggccaccc ugguccuccu ggaccaccug ucccucgcgc 120

ggaaccugcc gguggccacc cccgaccccg gcauguuccc cugccugcac cacagccaga 180

accuccugcg cgccgugucc aacaugcugc agaaggcccg gcagacgcuc gaguucuacc 240

cgugcaccag cgaggagauc gaccacgagg acaucaccaa ggacaagacc uccacggucg 300

aggccugccu gccccuggag cucaccaaga acgagagcug ccugaacucc cgcgagacca 360

420

gccugagcuc caucuacgag gaccugaaga uguaccaggu ggaguucaag accaugaacg 480

ccaagcuccu gauggaccc aagcgccaga ucuuccugga ccagaacaug cucgccguga 540

ucgacgagcu gaugcaggcg cugaacuuca acagcgagac cgucccccag aaguccagcc 600

ucgaggagcc ggacuucuac aagaccaaga ucaagcugug cauccugcuc cacgccuucc 660

ggauccgcgc cgugacgauc gaccggguga uguccuaccu gaacgccagc ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

1020

ucuuuucaga gccaccagaa uu 1042

<210> 290

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt1

<400> 290

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgcccgcag ccugcuccug guggccaccc ugguccuccu ggaccaccug ucccucgcgc 120

ggaaccugcc gguggccacc cccgaccccg gcauguuccc cugccugcac cacagccaga 180

accuccugcg cgccgugucc aacaugcugc agaaggcccg gcagacgcuc gaguucuacc 240

cgugcaccag cgaggagauc gaccacgagg acaucaccaa ggacaagacc uccacggucg 300

aggccugccu gccccuggag cucaccaaga acgagagcug ccugaacucc cgcgagacca 360

420

gccugagcuc caucuacgag gaccugaaga uguaccaggu ggaguucaag accaugaacg 480

ccaagcuccu gauggaccc aagcgccaga ucuuccugga ccagaacaug cucgccguga 540

ucgacgagcu gaugcaggcg cugaacuuca acagcgagac cgucccccag aaguccagcc 600

ucgaggagcc ggacuucuac aagaccaaga ucaagcugug cauccugcuc cacgccuucc 660

ggauccgcgc cgugacgauc gaccggguga uguccuaccu gaacgccagc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 291

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt1

<400> 291

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccggaacc 60

ugccgguggc cacccccgac cccggcaugu uccccugccu gcaccacagc cagaaccucc 120

ugcgcgccgu guccaacaug cugcagaagg cccggcagac gcucgaguuc uacccgugca 180

ccagcgagga gaucgaccac gaggacauca ccaaggacaa gaccuccacg gucgaggccu 240

gccugccccu ggagcucacc aagaacgaga gcugccugaa cucccgcgag accagcuuca 300

ucaccaacgg guccugccug gcgagccgga agacguccuu caugauggcc cucugccuga 360

gcuccaucua cgaggaccug aagauguacc agguggaguu caagaccaug aacgccaagc 420

uccugaugga ccccaagcgc cagaucuucc uggaccagaa caugcucgcc gugaucgacg 480

agcugaugca ggcgcugaac uucaacagcg agaccguccc ccagaagucc agccucgagg 540

agccggacuu cuacaagacc aagaucaagc ugugcauccu gcuccacgcc uuccggaucc 600

gcgccgugac gaucgaccgg gugauguccu accugaacgc cagcugagga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 292

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt1

<400> 292

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucuccc ucgucuuccu ggccagcccc cugguggcca 120

ucgggagcu caagaaggac guguacgucg uggagcugga cugguacccg gacgcgcccg 180

gcgagauggu gguccugacc ugcgacaccc ccgaggagga cgggaucacg uggacccucg 240

accaguccag cgaggugcug ggcuccggga agacccugac cauccaggug aaggaguucg 300

gcgacgccgg gcaguacacg ugccacaagg gcggcgaggu ccucagccac ucccugcugc 360

uccugcacaa gaaggaggac gggaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgg uucacgugcu 480

gguggcugac caccaucagc accgaccuga ccuucuccgu caagagcucc cgcgggagcu 540

ccgacccgca gggcgugacg ugcggggccg ccacccucag cgcggagcgg gugcgcggcg 600

acaacaagga guacgaguac uccguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagucccu gcccaucgag gugauggucg acgcggugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc cgggacauca ucaagcccga cccgcccaag aaccuccagc 780

ugaagccccu gaagaacucc cgccaggugg aggucagcug ggaguacccc gacaccuggu 840

ccacgccgca cagcuacuuc ucccucaccu ucugcgucca ggugcaggggc aagagcaagc 900

gggagaagaa ggaccgcgug uucaccgaca agaccuccgc cacggugauc ugccggaaga 960

acgccagcau cuccgugcgc gcccaggacc gguacuacag cuccagcugg uccgaguggg 1020

ccagcguccc cugcuccuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 293

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt1

<400> 293

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucuccc ucgucuuccu ggccagcccc cugguggcca 120

ucgggagcu caagaaggac guguacgucg uggagcugga cugguacccg gacgcgcccg 180

gcgagauggu gguccugacc ugcgacaccc ccgaggagga cgggaucacg uggacccucg 240

accaguccag cgaggugcug ggcuccggga agacccugac cauccaggug aaggaguucg 300

gcgacgccgg gcaguacacg ugccacaagg gcggcgaggu ccucagccac ucccugcugc 360

uccugcacaa gaaggaggac gggaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgg uucacgugcu 480

gguggcugac caccaucagc accgaccuga ccuucuccgu caagagcucc cgcgggagcu 540

ccgacccgca gggcgugacg ugcggggccg ccacccucag cgcggagcgg gugcgcggcg 600

acaacaagga guacgaguac uccguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagucccu gcccaucgag gugauggucg acgcggugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc cgggacauca ucaagcccga cccgcccaag aaccuccagc 780

ugaagccccu gaagaacucc cgccaggugg aggucagcug ggaguacccc gacaccuggu 840

ccacgccgca cagcuacuuc ucccucaccu ucugcgucca ggugcaggggc aagagcaagc 900

gggagaagaa ggaccgcgug uucaccgaca agaccuccgc cacggugauc ugccggaaga 960

acgccagcau cuccgugcgc gcccaggacc gguacuacag cuccagcugg uccgaguggg 1020

ccagcguccc cugcuccga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 294

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt1

<400> 294

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

agcucaagaa ggacguguac gucguggagc uggacuggua cccggacgcg cccggcgaga 120

uggugguccu gaccugcgac acccccgagg aggacgggau cacguggacc cucgaccagu 180

ccagcgaggu gcugggcucc gggaagaccc ugaccaucca ggugaaggag uucggcgacg 240

ccgggcagua cacgugccac aagggcggcg agguccucag ccacucccug cugcuccugc 300

acaagaagga ggacgggauc uggagcaccg acauccugaa ggaccagaag gagcccaaga 360

acaagaccuu ccuccgcugc gaggccaaga acuacuccgg ccgguucacg ugcugguggc 420

ugaccaccau cagcaccgac cugaccuucu ccgucaagag cucccgcggg agcuccgacc 480

cgcagggcgu gacgugcggg gccgccaccc ucagcgcgga gcgggugcgc ggcgacaaca 540

aggaguacga guacuccgug gagugccagg aggacagcgc cugccccgcc gccgaggagu 600

660

gcagcuucuu cauccgggac aucaucaagc cgacccgcc caagaaccuc cagcugaagc 720

cccugaagaa cucccgccag guggagguca gcugggagua ccccgacacc ugguccacgc 780

cgcacagcua cuucucccuc accuucugcg uccaggugca gggcaagagc aagcgggaga 840

agaaggaccg cguguucacc gacaagaccu ccgccacggu gaucugccgg aagaacgcca 900

gcaucuccgu gcgcgcccag gaccgguacu acagcuccag cugguccgag ugggccagcg 960

ucccugcuc cugaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 295

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt1

<400> 295

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagca 60

120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 296

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt1

<400> 296

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucuccc ucgucuuccu ggccagcccc cugguggcca 120

ucgggagcu caagaaggac guguacgucg uggagcugga cugguacccg gacgcgcccg 180

gcgagauggu gguccugacc ugcgacaccc ccgaggagga cgggaucacg uggacccucg 240

accaguccag cgaggugcug ggcuccggga agacccugac cauccaggug aaggaguucg 300

gcgacgccgg gcaguacacg ugccacaagg gcggcgaggu ccucagccac ucccugcugc 360

uccugcacaa gaaggaggac gggaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgg uucacgugcu 480

gguggcugac caccaucagc accgaccuga ccuucuccgu caagagcucc cgcgggagcu 540

ccgacccgca gggcgugacg ugcggggccg ccacccucag cgcggagcgg gugcgcggcg 600

acaacaagga guacgaguac uccguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagucccu gcccaucgag gugauggucg acgcggugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc cgggacauca ucaagcccga cccgcccaag aaccuccagc 780

ugaagccccu gaagaacucc cgccaggugg aggucagcug ggaguacccc gacaccuggu 840

ccacgccgca cagcuacuuc ucccucaccu ucugcgucca ggugcaggggc aagagcaagc 900

gggagaagaa ggaccgcgug uucaccgaca agaccuccgc cacggugauc ugccggaaga 960

acgccagcau cuccgugcgc gcccaggacc gguacuacag cuccagcugg uccgaguggg 1020

ccagcguccc cugcuccggc agcaccuccg ggagcggcaa gcccgggucc ggcgagggga 1080

1140

accacagcca gaaccuccug cgcgccgugu ccaacaugcu gcagaaggcc cggcagacgc 1200

ucgaguucua cccgugcacc agcgaggaga ucgaccacga ggacaucacc aaggacaaga 1260

ccuccacggu cgaggccugc cugccccugg agcucaccaa gaacgagagc ugccugaacu 1320

1380

ugaggcccu cugccuagc uccaucuacg aggaccugaa gauguaccag guggaguuca 1440

agaccaugaa cgccaagcuc cugauggacc ccaagcgcca gaucuuccug gaccagaaca 1500

ugcucgccgu gaucgacgag cugaugcagg cgcugaacuu caacagcgag accguccccc 1560

agaaguccag ccucgaggag ccggacuucu acaagaccaa gaucaagcug ugcauccugc 1620

uccacgccuu ccggauccgc gccgugacga ucgaccgggu gauguccuac cugaacgcca 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 297

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt1

<400> 297

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacaa ccagaccagc ccccgcuccg ccgccacggg ccugccgauc agcaugaaga 120

ucuucaugua ccuccugacc guguuccuga ucacccagau gaucgggucc gcgcuguucg 180

ccgucuaccu gcaccggcgc cuggacaaga ucgaggacga gcggaaccuc cacgaggacu 240

ucguguucau gaagaccauc cagcgcugca acacgggcga gcggagccug ucccugcuca 300

acugcgagga gaucaagagc caguucgagg gguucgugaa ggacaucaug cugaacaagg 360

aggagaccaa gaaggagaac uccuucgaga ugcagaaggg cgaccagaac ccccagaucg 420

ccgcccacgu caucagcgag gccuccagca agaccaccuc cgugcugcag ugggcggaga 480

agggguacua cacgaugagc aacaaccucg ugaccugga gaacggcaag cagcugaccg 540

ucaagcgcca gggccucuac uacaucuacg cccaggugac cuucugcucc aaccgggagg 600

ccagcuccca ggcccccuuc aucgcgagcc ugugccugaa gucccccgggg cgcuucgagc 660

ggauccuccu gcgcgccgcc aacacgcaca gcuccgccaa gccgugcggc cagcagagca 720

uccaccucgg gggcguguuc gagcuccagc ccggggccag cgucuucgug aacgugaccg 780

accccuccca ggucagccac ggcaccggcu ucaccuccuu cgggcugcug aagcucugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 298

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt2

<400> 298

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaggc ccccuggccc gucgucuggg ccguccucca gcucggcugg cgccccggcu 120

gguuccucga cucccccgac cgccccugga acccccccac cuucuccccc gcccuccucg 180

ucgucaccga gggcgacaac gccaccuuca ccuguuccuu cuccaacacc uccgaguccu 240

ucguccucaa cugguaccgc augucccccu ccaaccagac cgacaagcuc gccgccuucc 300

ccgaggaccg cucccagccc ggccaggacu gccgcuuccg cgucacccag cuccccaacg 360

gccgcgacuu ccacaugucc gucguccgcg cccgccgcaa cgacuccggc accuaccucu 420

gcggcgccau cucccucgcc cccaaggccc agaucaagga gucccuccgc gccgagcucc 480

gcgucaccga gcgccgcgcc gaggucccca ccgcccaccc cucccccucc ccccgccccg 540

ccggccaguu ccagacccuc gucgucggcg ucgucggcgg ccuccucggc ucccucgucc 600

uccucgucug gguccucgcc gucaucugcu cccgcgccgc ccgcggcacc aucggcgccc 660

gccgcaccgg cgccccuc aaggaggacc ccuccgccgu ccccgucuuc uccgucgacu 720

acggcgagcu cgacuuccag uggcgcgaga agacccccga gccccccguc cccugcgucc 780

ccgagcagac cgaguacgcc accaucgucu uccccuccgg caugggcacc uccucccccg 840

cccgccgcgg cuccgccgac ggcccccgcu ccgcccagcc ccuccgcccc gaggacggcc 900

acugcuccug gccccucuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 299

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt2

<400> 299

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaggc ccccuggccc gucgucuggg ccguccucca gcucggcugg cgccccggcu 120

gguuccucga cucccccgac cgccccugga acccccccac cuucuccccc gcccuccucg 180

ucgucaccga gggcgacaac gccaccuuca ccuguuccuu cuccaacacc uccgaguccu 240

ucguccucaa cugguaccgc augucccccu ccaaccagac cgacaagcuc gccgccuucc 300

ccgaggaccg cucccagccc ggccaggacu gccgcuuccg cgucacccag cuccccaacg 360

gccgcgacuu ccacaugucc gucguccgcg cccgccgcaa cgacuccggc accuaccucu 420

gcggcgccau cucccucgcc cccaaggccc agaucaagga gucccuccgc gccgagcucc 480

gcgucaccga gcgccgcgcc ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 300

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt2

<400> 300

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgcccgcuc ccuccuccuc gucgccaccc ucguccuccu cgaccaccuc ucccucgccc 120

gcaaccuccc cgucgccacc cccgaccccg gcauguuccc cugccuccac cacucccaga 180

accuccuccg cgccgucucc aacaugcucc agaaggcccg ccagacccuc gaguucuacc 240

ccugcaccuc cgaggagauc gaccacgagg acaucaccaa ggacaagacc uccaccgucg 300

aggccugccu cccccucgag cucaccaaga acgaguccug ccucaacucc cgcgagaccu 360

420

gccucuccuc caucuacgag gaccucaaga uguaccaggu cgaguucaag accaugaacg 480

ccaagcuccu cauggaccc aagcgccaga ucuuccucga ccagaacaug cucgccguca 540

ucgacgagcu caugcaggcc cucaacuuca acuccgagac cgucccccag aaguccuccc 600

ucgaggagcc cgacuucuac aagaccaaga ucaagcucug cauccuccuc cacgccuucc 660

gcauccgcgc cgucaccauc gaccgcguca uguccuaccu caacgccucc ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 301

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt2

<400> 301

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgcccgcuc ccuccuccuc gucgccaccc ucguccuccu cgaccaccuc ucccucgccc 120

gcaaccuccc cgucgccacc cccgaccccg gcauguuccc cugccuccac cacucccaga 180

accuccuccg cgccgucucc aacaugcucc agaaggcccg ccagacccuc gaguucuacc 240

ccugcaccuc cgaggagauc gaccacgagg acaucaccaa ggacaagacc uccaccgucg 300

aggccugccu cccccucgag cucaccaaga acgaguccug ccucaacucc cgcgagaccu 360

420

gccucuccuc caucuacgag gaccucaaga uguaccaggu cgaguucaag accaugaacg 480

ccaagcuccu cauggaccc aagcgccaga ucuuccucga ccagaacaug cucgccguca 540

ucgacgagcu caugcaggcc cucaacuuca acuccgagac cgucccccag aaguccuccc 600

ucgaggagcc cgacuucuac aagaccaaga ucaagcucug cauccuccuc cacgccuucc 660

gcauccgcgc cgucaccauc gaccgcguca uguccuaccu caacgccucc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 302

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt2

<400> 302

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccgcaacc 60

uccccgucgc cacccccgac cccggcaugu uccccugccu ccaccacucc cagaaccucc 120

uccgcgccgu cuccaacaug cuccagaagg cccgccagac ccucgaguuc uaccccugca 180

ccuccgagga gaucgaccac gaggacauca ccaaggacaa gaccuccacc gucgaggccu 240

gccuccccccu cgagcucacc aagaacgagu ccugccucaa cucccgcgag accuccuuca 300

ucaccaacgg cuccugccuc gccucccgca agaccuccuu caugauggcc cucugccucu 360

ccuccaucua cgaggaccuc aagauguacc aggucgaguu caagaccaug aacgccaagc 420

uccucaugga ccccaagcgc cagaucuucc ucgaccagaa caugcucgcc gucaucgacg 480

agcucaugca ggcccucaac uucaacuccg agaccguccc ccagaagucc ucccucgagg 540

agcccgacuu cuacaagacc aagaucaagc ucugcauccu ccuccacgcc uuccgcaucc 600

gcgccgucac caucgaccgc gucauguccu accucaacgc cuccugga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 303

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt2

<400> 303

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu cgucaucucc ugguucuccc ucgucuuccu cgccuccccc cucgucgcca 120

ucgggagcu caagaaggac gucuacgucg ucgagcucga cugguacccc gacgcccccg 180

gcgagauggu cguccucacc ugugacaccc ccgaggagga cggcaucacc uggacccucg 240

accaguccuc cgagguccuc ggcuccggca agacccucac cauccagguc aaggaguucg 300

gcgacgccgg ccaguacacc ugucacaagg gcggcgaggu ccucucccac ucccuccucc 360

uccuccacaa gaaggaggac ggcaucuggu ccaccgacau ccucaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgc uucaccuguu 480

gguggcucac caccaucucc accgaccuca ccuucuccgu caaguccucc cgcggcuccu 540

ccgaccccca gggcgucacc uguggcgccg ccacccucuc cgccgagcgc guccgcggcg 600

acaacaagga guacgaguac uccgucgagu gccaggagga cuccgccugc cccgccgccg 660

aggagucccu ccccaucgag gucauggucg acgccgucca caagcucaag uacgagaacu 720

acaccuccuc cuucuucauc cgcgacauca ucaagcccga cccccccaag aaccuccagc 780

ucaagccccu caagaacucc cgccaggucg aggucuccug ggaguacccc gacaccuggu 840

ccacccccca cuccuacuuc ucccucaccu ucugcgucca gguccagggc aaguccaagc 900

gcgagaagaa ggaccgcguc uucaccgaca agaccuccgc caccgucauc ugccgcaaga 960

acgccuccau cuccguccgc gcccaggacc gcuacuacuc cuccuccugg uccgaguggg 1020

ccuccguccc cugcuccuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 304

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt2

<400> 304

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu cgucaucucc ugguucuccc ucgucuuccu cgccuccccc cucgucgcca 120

ucgggagcu caagaaggac gucuacgucg ucgagcucga cugguacccc gacgcccccg 180

gcgagauggu cguccucacc ugugacaccc ccgaggagga cggcaucacc uggacccucg 240

accaguccuc cgagguccuc ggcuccggca agacccucac cauccagguc aaggaguucg 300

gcgacgccgg ccaguacacc ugucacaagg gcggcgaggu ccucucccac ucccuccucc 360

uccuccacaa gaaggaggac ggcaucuggu ccaccgacau ccucaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgc uucaccuguu 480

gguggcucac caccaucucc accgaccuca ccuucuccgu caaguccucc cgcggcuccu 540

ccgaccccca gggcgucacc uguggcgccg ccacccucuc cgccgagcgc guccgcggcg 600

acaacaagga guacgaguac uccgucgagu gccaggagga cuccgccugc cccgccgccg 660

aggagucccu ccccaucgag gucauggucg acgccgucca caagcucaag uacgagaacu 720

acaccuccuc cuucuucauc cgcgacauca ucaagcccga cccccccaag aaccuccagc 780

ucaagccccu caagaacucc cgccaggucg aggucuccug ggaguacccc gacaccuggu 840

ccacccccca cuccuacuuc ucccucaccu ucugcgucca gguccagggc aaguccaagc 900

gcgagaagaa ggaccgcguc uucaccgaca agaccuccgc caccgucauc ugccgcaaga 960

acgccuccau cuccguccgc gcccaggacc gcuacuacuc cuccuccugg uccgaguggg 1020

ccuccguccc cugcucggga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 305

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt2

<400> 305

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

agcucaagaa ggacgucuac gucgucgagc ucgacuggua ccccgacgcc cccggcgaga 120

uggucguccu caccugugac acccccgagg aggacggcau caccuggacc cucgaccagu 180

ccuccgaggu ccucggcucc ggcaagaccc ucaccaucca ggucaaggag uucggcgacg 240

ccggccagua caccugucac aagggcggcg agguccucuc ccacucccuc cuccuccucc 300

acaagaagga ggacggcauc ugguccaccg acauccucaa ggaccagaag gagcccaaga 360

acaagaccuu ccuccgcugc gaggccaaga acuacuccgg ccgcuucacc uguugguggc 420

ucaccaccau cuccaccgac cucaccuucu ccgucaaguc cucccgcggc uccuccgacc 480

cccagggcgu caccuguggc gccgccaccc ucuccgccga gcgcguccgc ggcgacaaca 540

aggaguacga guacuccguc gagugccagg aggacuccgc cugccccgcc gccgaggagu 600

cccuccccau cgaggucaug gucgacgccg uccacaagcu caaguacgag aacuacaccu 660

ccuccuucuu cauccgcgac aucaucaagc ccgacccccc caagaaccuc cagcucaagc 720

cccucaagaa cucccgccag gucgaggucu ccugggagua ccccgacacc ugguccaccc 780

cccacuccua cuucucccuc accuucugcg uccaggucca gggcaagucc aagcgcgaga 840

agaaggaccg cgucuucacc gacaagaccu ccgccaccgu caucugccgc aagaacgccu 900

ccaucuccgu ccgcgcccag gaccgcuacu acuccuccuc cugguccgag ugggccuccg 960

ucccugcuc cugaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 306

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt2

<400> 306

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcucca 60

ccuccggcuc cggcaagccc ggcuccggcg agggcuccac caagggcgga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 307

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt2

<400> 307

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu cgucaucucc ugguucuccc ucgucuuccu cgccuccccc cucgucgcca 120

ucgggagcu caagaaggac gucuacgucg ucgagcucga cugguacccc gacgcccccg 180

gcgagauggu cguccucacc ugugacaccc ccgaggagga cggcaucacc uggacccucg 240

accaguccuc cgagguccuc ggcuccggca agacccucac cauccagguc aaggaguucg 300

gcgacgccgg ccaguacacc ugucacaagg gcggcgaggu ccucucccac ucccuccucc 360

uccuccacaa gaaggaggac ggcaucuggu ccaccgacau ccucaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgc uucaccuguu 480

gguggcucac caccaucucc accgaccuca ccuucuccgu caaguccucc cgcggcuccu 540

ccgaccccca gggcgucacc uguggcgccg ccacccucuc cgccgagcgc guccgcggcg 600

acaacaagga guacgaguac uccgucgagu gccaggagga cuccgccugc cccgccgccg 660

aggagucccu ccccaucgag gucauggucg acgccgucca caagcucaag uacgagaacu 720

acaccuccuc cuucuucauc cgcgacauca ucaagcccga cccccccaag aaccuccagc 780

ucaagccccu caagaacucc cgccaggucg aggucuccug ggaguacccc gacaccuggu 840

ccacccccca cuccuacuuc ucccucaccu ucugcgucca gguccagggc aaguccaagc 900

gcgagaagaa ggaccgcguc uucaccgaca agaccuccgc caccgucauc ugccgcaaga 960

acgccuccau cuccguccgc gcccaggacc gcuacuacuc cuccuccugg uccgaguggg 1020

ccuccguccc cugcuccggc uccaccuccg gcuccggcaa gcccggcucc ggcgagggcu 1080

ccaccaaggg cgcaaccuc cccgucgcca cccccgaccc cggcauguuc cccugccucc 1140

accacuccca gaaccuccuc cgcgccgucu ccaacaugcu ccagaaggcc cgccagaccc 1200

ucgaguucua ccccugcacc uccgaggaga ucgaccacga ggacaucacc aaggacaaga 1260

ccuccaccgu cgaggccugc cucccccucg agcucaccaa gaacgagucc ugccucaacu 1320

1380

ugaggcccu cugccucucc uccaucuacg aggaccucaa gauguaccag gucgaguuca 1440

agaccaugaa cgccaagcuc cucauggacc ccaagcgcca gaucuuccuc gaccagaaca 1500

ugcucgccgu caucgacgag cucaugcagg cccucaacuu caacuccgag accguccccc 1560

agaaguccuc ccucgaggag cccgacuucu acaagaccaa gaucaagcuc ugcauccucc 1620

uccacgccuu ccgcauccgc gccgucacca ucgaccgcgu cauguccuac cucaacgccu 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 308

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt2

<400> 308

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacaa ccagaccucc ccccgcuccg ccgccaccgg ccuccccauc uccaugaaga 120

ucuucaugua ccuccucacc gucuuccuca ucacccagau gaucggcucc gcccucuucg 180

ccgucuaccu ccaccgccgc cucgacaaga ucgaggacga gcgcaaccuc cacgaggacu 240

ucgucuucau gaagaccauc cagcgcugca acaccggcga gcgcucccuc ucccuccuca 300

360

aggagaccaa gaaggagaac uccuucgaga ugcagaaggg cgaccagaac ccccagaucg 420

ccgcccacgu caucuccgag gccuccucca agaccaccuc cguccuccag ugggccgaga 480

agggcuacua caccaugucc aacaaccucg ucacccucga gaacggcaag cagcucaccg 540

ucaagcgcca gggccucuac uacaucuacg cccaggucac cuucugcucc aaccgcgagg 600

ccuccuccca ggcccccuuc aucgccuccc ucugccucaa gucccccggc cgcuucgagc 660

gcauccuccu ccgcgccgcc aacacccacu ccuccgccaa gcccugcggc cagcagucca 720

uccaccucgg cggcgucuuc gagcuccagc ccggcgccuc cgucuucguc aacgucaccg 780

accccuccca ggucucccac ggcaccggcu ucaccuccuu cggccuccuc aagcucugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 309

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt3

<400> 309

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaagc cccuuggcca guggucuggg cuguucugca gcucggcugg agaccggggu 120

gguuccuuga cagccccgau aggccuugga acccacccac cuuuuccccu gcacuguugg 180

ugguaacaga gggagacaau gccacuuuca cgugcucuuu uucaaacacc agugagagcu 240

ucguguuaaa uugguaccgg auguccccau cuaaccagac agauaagcug gcggcuuuuc 300

ccgaagaccg cucgcagccu ggucaagauu gucgauuccg ugucacucag cuaccaaaug 360

gcagagacuu ucacauguca gugguuaggg cccggcgcaa cgauagcggg accuaucucu 420

gcggagcaau uagucuggcc ccgaaagcuc agauaaagga aucccuuaga gcagagcuga 480

gggugacaga acggcgcgcc gaggucccca ccgcucaucc uucuccaagc ccccgaccug 540

ccggccaguu ccaaacuuug gugguaggug uugucggggg acuccugggc ucccuggugc 600

ucuuagugug ggugcuggcg gucaucuguu caagagcagc caggggcaca auuggggcuc 660

ggcguaccgg acagccacuu aaagaggacc ccagugccgu uccgguguuu agcguagauu 720

acggugaauu ggacuuccag uggcgcgaga agacgccuga acccccagug ccuugcgucc 780

840

cuagaagggg aagcgccgau ggcccucgga gugcgcaacc acugcgaccg gaagacgguc 900

acuguucuug gccccuauga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 310

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt3

<400> 310

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaagc cccuuggcca guggucuggg cuguucugca gcucggcugg agaccggggu 120

gguuccuuga cagccccgau aggccuugga acccacccac cuuuuccccu gcacuguugg 180

ugguaacaga gggagacaau gccacuuuca cgugcucuuu uucaaacacc agugagagcu 240

ucguguuaaa uugguaccgg auguccccau cuaaccagac agauaagcug gcggcuuuuc 300

ccgaagaccg cucgcagccu ggucaagauu gucgauuccg ugucacucag cuaccaaaug 360

gcagagacuu ucacauguca gugguuaggg cccggcgcaa cgauagcggg accuaucucu 420

gcggagcaau uagucuggcc ccgaaagcuc agauaaagga aucccuuaga gcagagcuga 480

gggugacaga acggcgcgcc ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 311

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt3

<400> 311

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagaag ccugcuccuu guggcuaccc uggucuuguu agaccaccug ucccuagcaa 120

ggaaccuccc uguugccaca ccagauccgg gcauguuccc cugucugcau cacucucaga 180

aucuucugcg ggcgguguca aacauguugc aaaaggcucg ccagacucuc gaguuuuacc 240

cuugcacgag ugaagauc gaccaugaag auauuaccaa agacaagaca agcacuguag 300

aggccugucu gccacuggaa cucaccaaaa augaguccug cuuaaacucu cgagagacau 360

cguucauaac caauggguca ugucuggcaa gccguaagac aaguuuuaug auggcccuuu 420

gcuuguccuc uaucuaugaa gaucugaaaa uguaccaggu ggaguucaag acuaugaacg 480

cuaagcuacu cauggacccc aaaagacaga uuuuucugga ucaaaauaug cuugcaguca 540

ucgacgaacu gaugcaggcc uugaacuuca auagcgagac cgugccucag aaguccucac 600

ucgaggaacc agauuuuuau aaaacgaaga uuaaacugug uaucuuacug cacgcuuuca 660

ggauacgggc cguuacuauc gaccgcguga ugaguuaccu caacgcgagc ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 312

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt3

<400> 312

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagaag ccugcuccuu guggcuaccc uggucuuguu agaccaccug ucccuagcaa 120

ggaaccuccc uguugccaca ccagauccgg gcauguuccc cugucugcau cacucucaga 180

aucuucugcg ggcgguguca aacauguugc aaaaggcucg ccagacucuc gaguuuuacc 240

cuugcacgag ugaagauc gaccaugaag auauuaccaa agacaagaca agcacuguag 300

aggccugucu gccacuggaa cucaccaaaa augaguccug cuuaaacucu cgagagacau 360

cguucauaac caauggguca ugucuggcaa gccguaagac aaguuuuaug auggcccuuu 420

gcuuguccuc uaucuaugaa gaucugaaaa uguaccaggu ggaguucaag acuaugaacg 480

cuaagcuacu cauggacccc aaaagacaga uuuuucugga ucaaaauaug cuugcaguca 540

ucgacgaacu gaugcaggcc uugaacuuca auagcgagac cgugccucag aaguccucac 600

ucgaggaacc agauuuuuau aaaacgaaga uuaaacugug uaucuuacug cacgcuuuca 660

ggauacgggc cguuacuauc gaccgcguga ugaguuaccu caacgcgagc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 313

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt3

<400> 313

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaggaacc 60

ucccuguugc cacaccagau ccgggcaugu uccccugucu gcaucacucu cagaaucuuc 120

ugcgggcggu gucaaacaug uugcaaaagg cucgccagac ucucgaguuu uacccuugca 180

cgagugaaga gaucgaccau gaagauauua ccaaagacaa gacaagcacu guagaggccu 240

gucugccacu ggaacucacc aaaaaugagu ccugcuuaaa cucucgagag acaucguuca 300

uaaccaaugg gucaugucug gcaagccgua agacaaguuu uaugauggcc cuuugcuugu 360

ccucuaucua ugaagaucug aaaauguacc agguggaguu caagacuaug aacgcuaagc 420

uacucaugga ccccaaaaga cagauuuuuc uggaucaaaa uaugcuugca gucaucgacg 480

aacugaugca ggccuugaac uucaauagcg agaccgugcc ucagaagucc ucacucgagg 540

600

gggccguuac uaucgaccgc gugaugaguu accucaacgc gagcugagga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 314

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt3

<400> 314

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ugccucuccc cugguugcua 120

uuugggaguu gaagaaagac guguacguag uggaauuaga uugguauccu gacgcaccag 180

gcgagauggu cgugcugacc ugugauacac cggaagagga cgggauaacu uggacgcuag 240

aucagucaag ugaaguucuc ggaagcggua agacccugac aauccaggug aaagaguucg 300

gcgacgccgg gcaguacacu ugccauaagg gaggcgaggu ccuuucccac ucucuguugc 360

uccugcauaa aaaggaagau gguauuuggu cgaccgacau ccugaaggau caaaaagagc 420

ccaagaacaa aacauuucuc agaugugaag cgaagaauua uucagggagg uuuaccugcu 480

ggugguuaac uacaauuagc accgaccuga cguucagugu gaaauccucu cggggaagcu 540

ccgauccuca gggcguaacu uguggcgcug ccacccuuuc agcagagcgc guucgagggg 600

660

aggaaucuuu gcccaucgag gucauggugg acgccgugca caagcugaaa uacgagaauu 720

auacauccuc auucuuuaua cgugacauca uuaagccuga uccacccaaa aaccuacagc 780

ucaagccucu gaaaaauagc agacaagucg aaguuaguug ggaguaccca gacacuuggu 840

cuaccccgca uuccuacuuc agccuuacau uuugcgugca gguacaggga aagucgaaaa 900

gggaaaagaa ggaucgggug uucaccgaca aaacgucugc uacugucauc ugucgcaaga 960

acgccuccau uucagugaga gcgcaggaua gguauuacag uagcuccugg ucugaguggg 1020

caagcguucc cugcucauga ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 315

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt3

<400> 315

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ugccucuccc cugguugcua 120

uuugggaguu gaagaaagac guguacguag uggaauuaga uugguauccu gacgcaccag 180

gcgagauggu cgugcugacc ugugauacac cggaagagga cgggauaacu uggacgcuag 240

aucagucaag ugaaguucuc ggaagcggua agacccugac aauccaggug aaagaguucg 300

gcgacgccgg gcaguacacu ugccauaagg gaggcgaggu ccuuucccac ucucuguugc 360

uccugcauaa aaaggaagau gguauuuggu cgaccgacau ccugaaggau caaaaagagc 420

ccaagaacaa aacauuucuc agaugugaag cgaagaauua uucagggagg uuuaccugcu 480

ggugguuaac uacaauuagc accgaccuga cguucagugu gaaauccucu cggggaagcu 540

ccgauccuca gggcguaacu uguggcgcug ccacccuuuc agcagagcgc guucgagggg 600

660

aggaaucuuu gcccaucgag gucauggugg acgccgugca caagcugaaa uacgagaauu 720

auacauccuc auucuuuaua cgugacauca uuaagccuga uccacccaaa aaccuacagc 780

ucaagccucu gaaaaauagc agacaagucg aaguuaguug ggaguaccca gacacuuggu 840

cuaccccgca uuccuacuuc agccuuacau uuugcgugca gguacaggga aagucgaaaa 900

gggaaaagaa ggaucgggug uucaccgaca aaacgucugc uacugucauc ugucgcaaga 960

acgccuccau uucagugaga gcgcaggaua gguauuacag uagcuccugg ucugaguggg 1020

caagcguucc cugcucagga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 316

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt3

<400> 316

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauuuggg 60

120

uggucgugcu gaccugugau acaccggaag aggacgggau aacuuggacg cuagaucagu 180

caagugaagu ucucggaagc gguaagaccc ugacaaucca ggugaaagag uucggcgacg 240

ccgggcagua cacuugccau aagggaggcg agguccuuuc ccacucucug uugcuccugc 300

360

acaaaacauu ucucagaugu gaagcgaaga auuauucagg gagguuuacc ugcugguggu 420

uaacuacaau uagcaccgac cugacguuca gugugaaauc cucucgggga agcuccgauc 480

cucagggcgu aacuuguggc gcugccaccc uuucagcaga gcgcguucga ggggacaaca 540

aggaguacga auauagugug gagugccagg aagauagcgc cuguccagcu gcagaggaau 600

cuuugcccau cgaggucaug guggacgccg ugcacaagcu gaaauacgag aauuauacau 660

ccucauucuu uauacgugac aucauuaagc cugauccacc caaaaaccua cagcucaagc 720

cucugaaaaa uagcagacaa gucgaaguua guugggagua cccagacacu uggucuaccc 780

cgcauuccua cuucagccuu acauuuugcg ugcagguaca gggaaagucg aaaagggaaa 840

agaaggaucg gguguucacc gacaaaacgu cugcuacugu caucugucgc aagaacgccu 900

ccauuucagu gagagcgcag gauagguauu acaguagcuc cuggucugag ugggcaagcg 960

uucccugcuc augaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 317

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt3

<400> 317

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagca 60

ccuccggguc uggaaagccc gguucaggcg agggggaguac aaaagggagga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 318

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt3

<400> 318

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ugccucuccc cugguugcua 120

uuugggaguu gaagaaagac guguacguag uggaauuaga uugguauccu gacgcaccag 180

gcgagauggu cgugcugacc ugugauacac cggaagagga cgggauaacu uggacgcuag 240

aucagucaag ugaaguucuc ggaagcggua agacccugac aauccaggug aaagaguucg 300

gcgacgccgg gcaguacacu ugccauaagg gaggcgaggu ccuuucccac ucucuguugc 360

uccugcauaa aaaggaagau gguauuuggu cgaccgacau ccugaaggau caaaaagagc 420

ccaagaacaa aacauuucuc agaugugaag cgaagaauua uucagggagg uuuaccugcu 480

ggugguuaac uacaauuagc accgaccuga cguucagugu gaaauccucu cggggaagcu 540

ccgauccuca gggcguaacu uguggcgcug ccacccuuuc agcagagcgc guucgagggg 600

660

aggaaucuuu gcccaucgag gucauggugg acgccgugca caagcugaaa uacgagaauu 720

auacauccuc auucuuuaua cgugacauca uuaagccuga uccacccaaa aaccuacagc 780

ucaagccucu gaaaaauagc agacaagucg aaguuaguug ggaguaccca gacacuuggu 840

cuaccccgca uuccuacuuc agccuuacau uuugcgugca gguacaggga aagucgaaaa 900

gggaaaagaa ggaucgggug uucaccgaca aaacgucugc uacugucauc ugucgcaaga 960

acgccuccau uucagugaga gcgcaggaua gguauuacag uagcuccugg ucugaguggg 1020

1080

guacaaaagg aaggaaccuc ccuguugcca caccagaucc gggcauguuc cccugucugc 1140

aucacucuca gaaucuucug cgggcggugu caaacauguu gcaaaaggcu cgccagacuc 1200

ucgaguuuua cccuugcacg agugaagaga ucgaccauga agauauuacc aaagacaaga 1260

caagcacugu agaggccugu cugccacugg aacucaccaa aaaugagucc ugcuuaaacu 1320

cucgagagac aucguucaua accaaugggu caugucuggc aagccguaag acaaguuuua 1380

ugaggcccu uugcuugucc ucuaucuaug aagaucugaa aauguaccag guggaguuca 1440

agacuaugaa cgcuaagcua cucauggacc ccaaaagaca gauuuuucug gaucaaaaua 1500

ugcuugcagu caucgacgaa cugaugcagg ccuugaacuu caauagcgag accgugccuc 1560

agaaguccuc acucgaggaa ccagauuuuu auaaaacgaa gauuaaacug uguaucuuac 1620

ugcacgcuuu caggauacgg gccguuacua ucgaccgcgu gaugaguuac cucaacgcga 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt3

<400> 319

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacaa ccagacaagc ccgauccg ccgcuacugg ccugccuauu ucuaugaaga 120

uauucaugua ucuccuuacg guguuucuga ucacccaaau gauuggguca gcauuguucg 180

ccgucuacuu acacaggcgg cuggacaaaa ucgaagauga gcgcaaucua caugaagacu 240

uuguuuucau gaagacaauu cagcgaugca acacuggaga gcguagucuc agccugcuua 300

auugugaaga gaucaaaucc caguuugagg guuucgugaa ggauauaaug cugaacaaag 360

aagagaccaa gaaggaaaau ucuuuugaga ugcagaaagg cgaccaaaac ccacagaucg 420

cggcucacgu aauuucggag gccucaagca agacaaccag uguguugcag ugggcagaaa 480

aaggguauua cacuaugucc aauaaccucg ucacacugga gaauggaaag cagcugaccg 540

ugaaaagaca aggccucuau uacaucuaug cccagguuac guucugcucu aacagggaag 600

cuagcuccca ggcaccguuu auugccucau uaugucugaa gagucccggu cgguucgagc 660

gcauccuuuu gagagcugcc aauacucaua gcucugcgaa gccuugcggg cagcaaucca 720

uacaccuggg aggcguguuu gaacuacagc caggcgcauc agucuucgug aacguaaccg 780

aucccagcca gguuagucau gggacaggau uuacuucuuu cggucuccug aaacuuugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 320

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt3v

<400> 320

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccucaggc uccuuggccu guuguguggg cuguucugca acuuggaugg cggccuggcu 120

180

ugguuaccga gggcgauaau gccaccuuca ccuguagcuu cagcaacacc agcgagagcu 240

ucgugcugaa cugguacaga augagcccca gcaaccagac cgacaagcug gccgccuuuc 300

cugaggauag aucucagccc ggccaggacu gccgguucag aguuacacag cugcccaacg 360

gccgggacuu ccacaugucu gucguccggg ccagaagaaa cgacagcggc acauaucugu 420

gcggcgccau uucucuggcc ccuaaggcuc agaucaaaga gagccugaga gccgagcuga 480

gagugacaga aagacgggcc gaagugccca cagcucaccc uucaccuucu ccaagaccug 540

ccggccaguu ccagacacug gucgugggag uuguuggcgg acugcuggga ucucuggugc 600

ugcuuguuug ggugcucgcc gugaucugua gcagagccgc cagaggaaca aucggcgcca 660

gaaggacagg ccagccucug aaagggauc ccucugcugu ccccguguuc agcguggacu 720

auggcgagcu ggauuuccag uggcgggaaa agacacccga gccuccagug ccuugugugc 780

cugagcagac agaguacgcc accaucgugu ucccuagcgg

ccagaagagg aucugccgac ggaccuagau cugcccagcc ucucagaccu gaggauggcc 900

acuguagcug gccucuguaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 321

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt3v

<400> 321

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccucaggc uccuuggccu guuguguggg cuguucugca acuuggaugg cggccuggcu 120

180

ugguuaccga gggcgauaau gccaccuuca ccuguagcuu cagcaacacc agcgagagcu 240

ucgugcugaa cugguacaga augagcccca gcaaccagac cgacaagcug gccgccuuuc 300

cugaggauag aucucagccc ggccaggacu gccgguucag aguuacacag cugcccaacg 360

gccgggacuu ccacaugucu gucguccggg ccagaagaaa cgacagcggc acauaucugu 420

gcggcgccau uucucuggcc ccuaaggcuc agaucaaaga gagccugaga gccgagcuga 480

gagugacaga aagacgggcc ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 322

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt3v

<400> 322

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

cugccagauc ucugcugcug guggcuacac uggugcugcu ggaucaucug agccuggcca 120

gaaaccugcc aguggccacg ccugauccug gcauguuucc uugucugcac cacagccaga 180

accugcugag agccgugucc aacaugcugc agaaggccag acagacccuc gaguucuacc 240

ccugcaccag cgaggaaauc gaccacgagg acaucaccaa ggacaagacc agcaccgugg 300

aagccugccu gccucuggaa cugaccaaga acgagagcug ccugaacagc cgggaaacca 360

gcuucaucac caacggcucu ugccuggccu ccagaaagac cuccuucaug auggcccugu 420

gccugagcag caucuacgag gaccugaaga uguaccaggu cgaguucaag accaugaacg 480

ccaagcugcu gauggacccc aagcggcaga ucuuccugga ccagaauaug cuggccguga 540

ucgacgagcu gaugcaggcc cugaacuuca acagcgagac agugccccag aaguccagcc 600

uggaagaacc cgacuucuac aagaccaaga ucaagcugug cauccugcug cacgccuucc 660

ggaucagagc cgugaccauc gacagaguga ugagcuaccu gaacgccucc ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 323

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt3v

<400> 323

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

cugccagauc ucugcugcug guggcuacac uggugcugcu ggaucaucug agccuggcca 120

gaaaccugcc aguggccacg ccugauccug gcauguuucc uugucugcac cacagccaga 180

accugcugag agccgugucc aacaugcugc agaaggccag acagacccuc gaguucuacc 240

ccugcaccag cgaggaaauc gaccacgagg acaucaccaa ggacaagacc agcaccgugg 300

aagccugccu gccucuggaa cugaccaaga acgagagcug ccugaacagc cgggaaacca 360

gcuucaucac caacggcucu ugccuggccu ccagaaagac cuccuucaug auggcccugu 420

gccugagcag caucuacgag gaccugaaga uguaccaggu cgaguucaag accaugaacg 480

ccaagcugcu gauggacccc aagcggcaga ucuuccugga ccagaauaug cuggccguga 540

ucgacgagcu gaugcaggcc cugaacuuca acagcgagac agugccccag aaguccagcc 600

uggaagaacc cgacuucuac aagaccaaga ucaagcugug cauccugcug cacgccuucc 660

ggaucagagc cgugaccauc gacagaguga ugagcuaccu gaacgccucc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 324

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt3v

<400> 324

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accagaaacc 60

ugccaguggc cacgccugau ccuggcaugu uuccuugucu gcaccacagc cagaaccugc 120

ugagagccgu guccaacaug cugcagaagg ccagacagac ccucgaguuc uaccccugca 180

ccagcgagga aaucgaccac gaggacauca ccaaggacaa gaccagcacc guggaagccu 240

gccugccucu ggaacugacc aagaacgaga gcugccugaa cagccgggaa accagcuuca 300

ucaccaacgg cucuugccug gccuccagaa agaccuccuu caugauggcc cugugccuga 360

gcagcaucua cgaggaccug aagauguacc aggucgaguu caagaccaug aacgccaagc 420

ugcugaugga ccccaagcgg cagaucuucc uggaccagaa uaugcuggcc gugaucgacg 480

agcugaugca ggcccugaac uucaacagcg agacagugcc ccagaagucc agccuggaag 540

aacccgacuu cuacaagacc aagaucaagc ugugcauccu gcugcacgcc uuccggauca 600

gagccgugac caucgacaga gugaugagcu accugaacgc cuccugga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 325

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt3v

<400> 325

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcagcu ggucaucagc ugguucagcc ugguguuccu ggccucuccu cugguggcca 120

ucgggagcu gaagaaagac guguacgugg uggaacugga cugguauccc gaugcuccug 180

gcgagauggu ggugcugacc ugcgauaccc cugaagagga cggcaucacc uggacacugg 240

aucagucuag cgaggugcuc ggcagcggca agacccugac cauccaagug aaagaguuug 300

gcgacgccgg ccaguacacc ugucacaaag gcggagaagu gcugagccac agccugcugc 360

ugcuccacaa gaaagaggau ggcauuugga gcaccgacau ccugaaggac cagaaagagc 420

ccaagaacaa gaccuuccug agaugcgagg ccaagaacua cagcggccgg uucacauguu 480

gguggcugac caccaucagc accgaccuga ccuucagcgu gaaguccagc agaggcagca 540

gugauccuca gggcguuaca uguggcgccg cuacacuguc ugccgaaaga gugcggggcg 600

acaacaaaga auacgaguac agcguggaau gccaagagga cagcgccugu ccagccgccg 660

aagagucucu gccuaucgaa gugauggugg acgccgugca caagcugaag uacgagaacu 720

acaccuccag cuuuuucauc cgggacauca ucaagcccga uccuccaaag aaccugcagc 780

ugaagccucu gaagaacagc agacaggugg aaguguccug ggaguacccc gacaccuggu 840

cuacacccca cagcuacuuc agccugaccu uuugcgugca agugcaggggc aaguccaagc 900

gcgagaaaaa ggaccgggug uucaccgaca agaccagcgc caccgugauc ugcagaaaga 960

acgccagcau cagcgucaga gcccaggacc gguacuacag cagcucuugg agcgaauggg 1020

ccagcgugcc auguagcuaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 326

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt3v

<400> 326

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcagcu ggucaucagc ugguucagcc ugguguuccu ggccucuccu cugguggcca 120

ucgggagcu gaagaaagac guguacgugg uggaacugga cugguauccc gaugcuccug 180

gcgagauggu ggugcugacc ugcgauaccc cugaagagga cggcaucacc uggacacugg 240

aucagucuag cgaggugcuc ggcagcggca agacccugac cauccaagug aaagaguuug 300

gcgacgccgg ccaguacacc ugucacaaag gcggagaagu gcugagccac agccugcugc 360

ugcuccacaa gaaagaggau ggcauuugga gcaccgacau ccugaaggac cagaaagagc 420

ccaagaacaa gaccuuccug agaugcgagg ccaagaacua cagcggccgg uucacauguu 480

gguggcugac caccaucagc accgaccuga ccuucagcgu gaaguccagc agaggcagca 540

gugauccuca gggcguuaca uguggcgccg cuacacuguc ugccgaaaga gugcggggcg 600

acaacaaaga auacgaguac agcguggaau gccaagagga cagcgccugu ccagccgccg 660

aagagucucu gccuaucgaa gugauggugg acgccgugca caagcugaag uacgagaacu 720

acaccuccag cuuuuucauc cgggacauca ucaagcccga uccuccaaag aaccugcagc 780

ugaagccucu gaagaacagc agacaggugg aaguguccug ggaguacccc gacaccuggu 840

cuacacccca cagcuacuuc agccugaccu uuugcgugca agugcaggggc aaguccaagc 900

gcgagaaaaa ggaccgggug uucaccgaca agaccagcgc caccgugauc ugcagaaaga 960

acgccagcau cagcgucaga gcccaggacc gguacuacag cagcucuugg agcgaauggg 1020

ccagcgugcc auguagcgga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 327

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt3v

<400> 327

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

agcugaagaa agacguguac gugguggaac uggacuggua ucccgaugcu ccuggcgaga 120

ugguggugcu gaccugcgau accccugaag aggacggcau caccuggaca cuggaucagu 180

cuagcgaggu gcucggcagc ggcaagaccc ugaccaucca agugaaagag uuuggcgacg 240

ccggccagua caccugucac aaaggcggag aagugcugag ccacagccug cugcugcucc 300

acaagaaaga ggauggcauu uggagcaccg acauccugaa ggaccagaaa gagcccaaga 360

acaagaccuu ccugagaugc gaggccaaga acuacagcgg ccgguucaca uguugguggc 420

ugaccaccau cagcaccgac cugaccuuca gcgugaaguc cagcagaggc agcagugauc 480

cucagggcgu uacauguggc gccgcuacac ugucugccga aagagugcgg ggcgacaaca 540

aagaauacga guacagcgug gaaugccaag aggacagcgc cuguccagcc gccgaagagu 600

cucugccuau cgaagugaug guggacgccg ugcacaagcu gaaguacgag aacuacaccu 660

ccagcuuuuu cauccgggac aucaucaagc ccgauccucc aaagaaccug cagcugaagc 720

cucugaagaa cagcagacag guggaagugu ccugggagua ccccgacacc uggucuacac 780

cccacagcua cuucagccug accuuuugcg ugcaagugca gggcaagucc aagcgcgaga 840

aaaaggaccg gguguucacc gacaagacca gcgccaccgu gaucugcaga aagaacgcca 900

gcaucagcgu cagagcccag gaccgguacu acagcagcuc uuggagcgaa ugggccagcg 960

ugccauguag cuaaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 328

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt3v

<400> 328

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcucua 60

caucuggcuc uggcaaaccu ggaucuggcg agggcucuac aaagggcggga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 329

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt3v

<400> 329

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcagcu ggucaucagc ugguucagcc ugguguuccu ggccucuccu cugguggcca 120

ucgggagcu gaagaaagac guguacgugg uggaacugga cugguauccc gaugcuccug 180

gcgagauggu ggugcugacc ugcgauaccc cugaagagga cggcaucacc uggacacugg 240

aucagucuag cgaggugcuc ggcagcggca agacccugac cauccaagug aaagaguuug 300

gcgacgccgg ccaguacacc ugucacaaag gcggagaagu gcugagccac agccugcugc 360

ugcuccacaa gaaagaggau ggcauuugga gcaccgacau ccugaaggac cagaaagagc 420

ccaagaacaa gaccuuccug agaugcgagg ccaagaacua cagcggccgg uucacauguu 480

gguggcugac caccaucagc accgaccuga ccuucagcgu gaaguccagc agaggcagca 540

gugauccuca gggcguuaca uguggcgccg cuacacuguc ugccgaaaga gugcggggcg 600

acaacaaaga auacgaguac agcguggaau gccaagagga cagcgccugu ccagccgccg 660

aagagucucu gccuaucgaa gugauggugg acgccgugca caagcugaag uacgagaacu 720

acaccuccag cuuuuucauc cgggacauca ucaagcccga uccuccaaag aaccugcagc 780

ugaagccucu gaagaacagc agacaggugg aaguguccug ggaguacccc gacaccuggu 840

cuacacccca cagcuacuuc agccugaccu uuugcgugca agugcaggggc aaguccaagc 900

gcgagaaaaa ggaccgggug uucaccgaca agaccagcgc caccgugauc ugcagaaaga 960

acgccagcau cagcgucaga gcccaggacc gguacuacag cagcucuugg agcgaauggg 1020

ccagcgugcc auguagcggc ucuacaucug gcucuggcaa accuggaucu ggcgagggcu 1080

cuacaaaggg cagaaaccug ccaguggcca cgccugaucc uggcauguuu ccuugucugc 1140

accacagcca gaaccugcug agagccgugu ccaacaugcu gcagaaggcc agacagaccc 1200

ucgaguucua ccccugcacc agcgaggaaa ucgaccacga ggacaucacc aaggacaaga 1260

ccagcaccgu ggaagccugc cugccucugg aacugaccaa gaacgagagc ugccugaaca 1320

1380

ugaggcccu gugccugagc agcaucuacg aggaccugaa gauguaccag gucgaguuca 1440

agaccaugaa cgccaagcug cugauggacc ccaagcggca gaucuuccug gaccagaaua 1500

ugcuggccgu gaucgacgag cugaugcagg cccugaacuu caacagcgag acagugcccc 1560

agaaguccag ccuggaagaa cccgacuucu acaagaccaa gaucaagcug ugcauccugc 1620

ugcacgccuu ccggaucaga gccgugacca ucgacagagu gaugagcuac cugaacgccu 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 330

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt3v

<400> 330

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agacauacaa ccagacaagc cccagaagcg ccgccacagg acugccuauc agcaugaaga 120

ucuuuaugua ccugcugacc guguuccuga ucacccagau gaucggcagc gcccuguuug 180

ccguguaccu gcacagacgg cuggacaaga ucgaggacga gagaaaccug cacgaggacu 240

ucguguucau gaagaccauc cagcggugca acaccggcga gagaagucug agccugcuga 300

acugcgagga aaucaagagc caguucgagg gcuucgugaa ggacaucaug cugaacaaag 360

aggaaacgaa gaaagaaaac uccuucgaga ugcagaaggg cgaccagaau ccucagaucg 420

ccgcucacgu gaucagcgag gccagcagca agacaacaag cgugcugcag ugggccgaga 480

agggcuacua caccaugagc aacaaccugg ucaccugga aaacggcaag cagcugacag 540

ugaagcggca gggccuguac uacaucuacg cccaagugac cuucugcagc aacagagagg 600

ccagcucuca ggccccuuuu aucgccagcc ugugccugaa guccccuggc agauucgagc 660

ggauucugcu gagagccgcc aacacacaca gcagcgccaa accuuguggc cagcagucua 720

uucaccucgg cggaguguuu gagcugcagc cuggcgcaag cguguucgug aaugugacag 780

acccuagcca ggugucccac ggcaccggcu uuacaucuuu cggacugcug aagcugugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 331

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt4

<400> 331

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaggc ccccuggccc gugguguggg ccgugcugca gcugggcugg agacccggcu 120

gguuccugga cagccccgac agacccugga acccccccac cuucagcccc gcccugcugg 180

uggugaccga gggcgacaac gccaccuuca ccuguagcuu cagcaacacc agcgagagcu 240

ucgugcugaa cugguacaga ugagcccca gcaaccagac cgacaagcug gccgccuucc 300

ccgaggacag aagccagccc ggccaggacu gcagauucag agugacccag cugcccaacg 360

gcagagacuu ccacaugagc guggugagag ccagaagaaa cgacagcggc accuaccugu 420

gcggcgccau cagccuggcc cccaaggccc agaucaagga gagccugaga gccgagcuga 480

gagugaccga gagaagggcc gaggugccca ccgcccaccc cagccccagc cccagacccg 540

ccggccaguu ccagacccug guggugggcg uggugggcgg ccugcugggc agccuggugc 600

ugcuggugug ggugcuggcc gugaucugca gcagagccgc cagaggcacc aucggcgcca 660

gaagaaccgg ccagccccug aaggaggacc ccagcgccgu gcccguguuc agcguggacu 720

acggcgagcu ggacuuccag uggagagaga agacccccga gccccccgug cccugcgugc 780

cggagcagac cgaguacgcc accaucgugu uccccagcgg caugggcacc agcagccccg 840

ccagaagagg cagcgccgac ggccccagaa gcgcccagcc ccugagaccc gaggacggcc 900

acugcagcug gccccuguga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 332

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt4

<400> 332

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaggc ccccuggccc gugguguggg ccgugcugca gcugggcugg agacccggcu 120

gguuccugga cagccccgac agacccugga acccccccac cuucagcccc gcccugcugg 180

uggugaccga gggcgacaac gccaccuuca ccuguagcuu cagcaacacc agcgagagcu 240

ucgugcugaa cugguacaga ugagcccca gcaaccagac cgacaagcug gccgccuucc 300

ccgaggacag aagccagccc ggccaggacu gcagauucag agugacccag cugcccaacg 360

gcagagacuu ccacaugagc guggugagag ccagaagaaa cgacagcggc accuaccugu 420

gcggcgccau cagccuggcc cccaaggccc agaucaagga gagccugaga gccgagcuga 480

gagugaccga gagaagggcc ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 333

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt4

<400> 333

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagaag ccugcugcug guggccaccc uggugcugcu ggaccaccug agccuggcca 120

gaaaccugcc cguggccacc cccgaccccg gcauguuccc cugccugcac cacagccaga 180

accugcugag agccgugagc aacaugcugc agaaggccag acagacccug gaguucuacc 240

ccugcaccag cgaggagauc gaccacgagg acaucaccaa ggacaagacc agcaccgugg 300

aggccugccu gccccuggag cugaccaaga acgagagcug ccugaacagc agagagacca 360

gcuucaucac caacggcagc ugccuggcca gcagaaagac cagcuucaug auggcccugu 420

gccugagcag caucuacgag gaccugaaga uguaccaggu ggaguucaag accaugaacg 480

ccaagcugcu gauggacccc aagagacaga ucuuccugga ccagaacaug cuggccguga 540

ucgacgagcu gaugcaggcc cugaacuuca acagcgagac cgugccccag aagaguagcc 600

uggaggagcc cgacuucuac aagaccaaga ucaagcugug cauccugcug cacgccuuca 660

gaaucagagc cgugaccauc gacagaguga ugagcuaccu gaacgccagc ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 334

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt4

<400> 334

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagaag ccugcugcug guggccaccc uggugcugcu ggaccaccug agccuggcca 120

gaaaccugcc cguggccacc cccgaccccg gcauguuccc cugccugcac cacagccaga 180

accugcugag agccgugagc aacaugcugc agaaggccag acagacccug gaguucuacc 240

ccugcaccag cgaggagauc gaccacgagg acaucaccaa ggacaagacc agcaccgugg 300

aggccugccu gccccuggag cugaccaaga acgagagcug ccugaacagc agagagacca 360

gcuucaucac caacggcagc ugccuggcca gcagaaagac cagcuucaug auggcccugu 420

gccugagcag caucuacgag gaccugaaga uguaccaggu ggaguucaag accaugaacg 480

ccaagcugcu gauggacccc aagagacaga ucuuccugga ccagaacaug cuggccguga 540

ucgacgagcu gaugcaggcc cugaacuuca acagcgagac cgugccccag aagaguagcc 600

uggaggagcc cgacuucuac aagaccaaga ucaagcugug cauccugcug cacgccuuca 660

gaaucagagc cgugaccauc gacagaguga ugagcuaccu gaacgccagc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 335

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt4

<400> 335

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accagaaacc 60

ugcccguggc cacccccgac cccggcaugu uccccugccu gcaccacagc cagaaccugc 120

ugagagccgu gagcaacaug cugcagaagg ccagacagac ccuggaguuc uaccccugca 180

ccagcgagga gaucgaccac gaggacauca ccaaggacaa gaccagcacc guggaggccu 240

gccugccccu ggagcugacc aagaacgaga gcugccugaa cagcagagag accagcuuca 300

ucaccaacgg cagcugccug gccagcagaa agaccagcuu caugauggcc cugugccuga 360

gcagcaucua cgaggaccug aagauguacc agguggaguu caagaccaug aacgccaagc 420

ugcugaugga ccccaagaga cagaucuucc uggaccagaa caugcuggcc gugaucgacg 480

agcugaugca ggcccugaac uucaacagcg agaccgugcc ccagaagagu agccugggagg 540

agcccgacuu cuacaagacc aagaucaagc ugugcauccu gcugcacgcc uucagaauca 600

gagccgugac caucgacaga gugaugagcu accugaacgc cagcugagga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 336

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt4

<400> 336

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucagcc ugguguuccu ggccagcccc cugguggcca 120

ucgggagcu gaagaaggac guguacgugg uggagcugga cugguacccc gacgcccccg 180

gcgagauggu ggugcugacc ugcgacaccc ccgaggagga cggcaucacc uggacccugg 240

accagagcag cgaggugcug ggcagcggca agacccugac cauccaggug aaggaguucg 300

gcgacgccgg ccaguacacc ugucacaagg gcggcgaggu gcugagccac agccugcugc 360

ugcugcacaa gaaggaggac ggcaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccug agaugcgagg ccaagaacua cagcggcaga uucaccuguu 480

gguggcugac caccaucagc accgaccuga ccuucagcgu gaagaguagc agaggcagca 540

gcgaccccca gggcgugacc ugcggcgccg ccacccugag cgccgagaga gugagaggcg 600

acaacaagga guacgaguac agcguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagagccu gcccaucgag gugauggugg acgccgugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc agagacauca ucaagcccga cccccccaag aaccugcagc 780

ugaagccccu gaagaacagc agacaggugg aggugagcug ggaguacccc gacaccugga 840

gcacccccca cagcuacuuc agccugaccu ucugcgugca gguucagggc aagagcaaga 900

gagagaagaa ggacagagug uucaccgaca agaccagcgc caccgugauc ugcagaaaga 960

1020

ccagcgugcc cugcagcuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 337

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt4

<400> 337

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucagcc ugguguuccu ggccagcccc cugguggcca 120

ucgggagcu gaagaaggac guguacgugg uggagcugga cugguacccc gacgcccccg 180

gcgagauggu ggugcugacc ugcgacaccc ccgaggagga cggcaucacc uggacccugg 240

accagagcag cgaggugcug ggcagcggca agacccugac cauccaggug aaggaguucg 300

gcgacgccgg ccaguacacc ugucacaagg gcggcgaggu gcugagccac agccugcugc 360

ugcugcacaa gaaggaggac ggcaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccug agaugcgagg ccaagaacua cagcggcaga uucaccuguu 480

gguggcugac caccaucagc accgaccuga ccuucagcgu gaagaguagc agaggcagca 540

gcgaccccca gggcgugacc ugcggcgccg ccacccugag cgccgagaga gugagaggcg 600

acaacaagga guacgaguac agcguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagagccu gcccaucgag gugauggugg acgccgugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc agagacauca ucaagcccga cccccccaag aaccugcagc 780

ugaagccccu gaagaacagc agacaggugg aggugagcug ggaguacccc gacaccugga 840

gcacccccca cagcuacuuc agccugaccu ucugcgugca gguucagggc aagagcaaga 900

gagagaagaa ggacagagug uucaccgaca agaccagcgc caccgugauc ugcagaaaga 960

1020

ccagcgugcc cugcagcgga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 338

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt4

<400> 338

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

agcugaagaa ggacguguac gugguggagc uggacuggua ccccgacgcc cccggcgaga 120

ugguggugcu gaccugcgac acccccgagg aggacggcau caccuggacc cuggaccaga 180

gcagcgaggu gcugggcagc ggcaagaccc ugaccaucca ggugaaggag uucggcgacg 240

ccggccagua caccugucac aagggcggcg aggugcugag ccacagccug cugcugcugc 300

acaagaagga ggacggcauc uggagcaccg acauccugaa ggaccagaag gagcccaaga 360

acaagaccuu ccugagaugc gaggccaaga acuacagcgg cagauucacc uguugguggc 420

ugaccaccau cagcaccgac cugaccuuca gcgugaagag uagcagaggc agcagcgacc 480

cccagggcgu gaccugcggc gccgccaccc ugagcgccga gagagugaga ggcgacaaca 540

aggaguacga guacagcgug gagugccagg aggacagcgc cugccccgcc gccgaggaga 600

gccugcccau cgaggugaug guggacgccg ugcacaagcu gaaguacgag aacuacacca 660

gcagcuucuu caucagagac aucaucaagc ccgacccccc caagaaccug cagcugaagc 720

cccugaagaa cagcagacag guggagguga gcugggagua ccccgacacc uggagcaccc 780

cccacagcua cuucagccug accuucugcg ugcagguuca gggcaagagc aagagagaga 840

agaaggacag aguguucacc gacaagacca gcgccaccgu gaucugcaga aagaacgcca 900

gcaucagcgu gagagcccag gacagauacu acagcagcag cuggagcgag ugggccagcg 960

ugcccugcag cugaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 339

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt4

<400> 339

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagca 60

ccagcggcag cggcaagccc ggcagcggcg agggcagcac caagggcgga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 340

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt4

<400> 340

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucagcc ugguguuccu ggccagcccc cugguggcca 120

ucgggagcu gaagaaggac guguacgugg uggagcugga cugguacccc gacgcccccg 180

gcgagauggu ggugcugacc ugcgacaccc ccgaggagga cggcaucacc uggacccugg 240

accagagcag cgaggugcug ggcagcggca agacccugac cauccaggug aaggaguucg 300

gcgacgccgg ccaguacacc ugucacaagg gcggcgaggu gcugagccac agccugcugc 360

ugcugcacaa gaaggaggac ggcaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccug agaugcgagg ccaagaacua cagcggcaga uucaccuguu 480

gguggcugac caccaucagc accgaccuga ccuucagcgu gaagaguagc agaggcagca 540

gcgaccccca gggcgugacc ugcggcgccg ccacccugag cgccgagaga gugagaggcg 600

acaacaagga guacgaguac agcguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagagccu gcccaucgag gugauggugg acgccgugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc agagacauca ucaagcccga cccccccaag aaccugcagc 780

ugaagccccu gaagaacagc agacaggugg aggugagcug ggaguacccc gacaccugga 840

gcacccccca cagcuacuuc agccugaccu ucugcgugca gguucagggc aagagcaaga 900

gagagaagaa ggacagagug uucaccgaca agaccagcgc caccgugauc ugcagaaaga 960

1020

ccagcgugcc cugcagcggc agcaccagcg gcagcggcaa gcccggcagc ggcgagggca 1080

gcaccaaggg cagaaaccug cccguggcca cccccgaccc cggcauguuc cccugccugc 1140

accacagcca gaaccugcug agagccguga gcaacaugcu gcagaaggcc agacagaccc 1200

uggaguucua ccccugcacc agcgaggaga ucgaccacga ggacaucacc aaggacaaga 1260

ccagcaccgu ggaggccugc cugccccugg agcugaccaa gaacgagagc ugccugaaca 1320

gcagagagac cagcuucauc accaacggca gcugccuggc cagcagaaag accagcuuca 1380

ugaggcccu gugccuagc agcaucuacg aggaccugaa gauguaccag guggaguuca 1440

agaccaugaa cgccaagcug cugauggacc ccaagagaca gaucuuccug gaccagaaca 1500

ugcuggccgu gaucgacgag cugaugcagg cccugaacuu caacagcgag accgugcccc 1560

agaagaguag ccuggaggag cccgacuucu acaagaccaa gaucaagcug ugcauccugc 1620

ugcacgccuu cagaaucaga gccgugacca ucgacagagu gaugagcuac cugaacgcca 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 341

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt4

<400> 341

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacaa ccagaccagc cccagaagcg ccgccaccgg ccugcccauc agcaugaaga 120

ucuucaugua ccugcugacc guguuccuga ucacccagau gaucggcagc gcccuguucg 180

ccguguaccu gcacagaaga cuggacaaga ucgaggacga gagaaaccug cacgaggacu 240

ucguguucau gaagaccauc cagagaugca acaccggcga gagaagccug agccugcuga 300

acugcgagga gaucaagagc caguucgagg gcuucgugaa ggacaucaug cugaacaagg 360

aggagaccaa gaaggagaac agcuucgaga ugcagaaggg cgaccagaac ccccagaucg 420

ccgcccacgu gaucagcgag gccagcagca agaccaccag cgugcugcag ugggccgaga 480

agggcuacua caccaugagc aacaaccugg ugaccugga gaacggcaag cagcugaccg 540

ugaagaca gggccuguac uacaucuacg cccaggugac cuucugcagc aacagagagg 600

ccagcagcca ggcccccuuc aucgccagcc ugugccugaa gagucccggc agauucgaga 660

gaauccugcu gagagccgcc aacacccaca gcagcgccaa gcccugcggc cagcagagca 720

uccaccuggg cggcguguuc gagcugcagc ccggcgccag cguguucgug aacgugaccg 780

accccagcca ggugagccac ggcaccggcu ucaccagcuu cggccugcug aagcugugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 342

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt5

<400> 342

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaagc cccuuggccg guggucuggg cuguucugca gcucggcugg agacccgggu 120

gguuccugga cagccugau cggcccugga acccucccac cuuuuccccu gcccuucugg 180

uggugacaga gggagacaau gcgacguuua ccugcucuuu cagcaacaca uccgaaucuu 240

ucguccucaa uugguaccgc ugagcccgu ccaaccagac cgauaagcug gcugccuuuc 300

ccgaggacag aucucagccu ggccaagauu gucgguuccg cgugacacag cuucccaaug 360

ggagagacuu ucacaugagc guugugcggg cccgcagaaa cgauuccggga accuaucugu 420

gcggcgcuau uagccucgcc ccuaaagcuc agaucaagga aucucugcgg gccgagcugc 480

gcgucacaga aagacgggcg gaggugccca ccgcccaucc guccccuagc ccccgcccug 540

cugggcaguu ccaaacgcuc guugugggag ucgugggcgg ccugcuuggg ucucuggugc 600

uccggucug gguucuugcc gugauuuguu ccagagcugc ccggggaacc aucggcgcgc 660

gcagaacagg gcagccccug aaagaggacc ccagcgccgu gccugucuuu ucuguggauu 720

acggagaacu cgacuuccag uggcgggaga agaccccgga acccccuguu cccugcgugc 780

840

ccagacgcgg aucugcugau ggcccucgga gcgcccaacc ccugagaccu gaagacggcc 900

acuguuccug gccccuguga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 343

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt5

<400> 343

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaagc cccuuggccg guggucuggg cuguucugca gcucggcugg agacccgggu 120

gguuccugga cagccugau cggcccugga acccucccac cuuuuccccu gcccuucugg 180

uggugacaga gggagacaau gcgacguuua ccugcucuuu cagcaacaca uccgaaucuu 240

ucguccucaa uugguaccgc ugagcccgu ccaaccagac cgauaagcug gcugccuuuc 300

ccgaggacag aucucagccu ggccaagauu gucgguuccg cgugacacag cuucccaaug 360

ggagagacuu ucacaugagc guugugcggg cccgcagaaa cgauuccggga accuaucugu 420

gcggcgcuau uagccucgcc ccuaaagcuc agaucaagga aucucugcgg gccgagcugc 480

gcgucacaga aagacgggcg ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 344

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt5

<400> 344

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagaag ccugcuccug guggcuaccc uuguccugcu cgaccaccug ucccuugccc 120

180 ggaaccugcc uguugcgaca ccggaucccg

240

ccugcaccuc cgaagagauc gaccaugaag auauuacaaa agacaagacc ucuacagugg 300

360

cuuucaucac caaugggagc ugucuugcuu cccgcaagac gagcuuuaug auggcccugu 420

gccucucuuc cauuuaugaa gaucugaaaa uguaccaggu cgaguucaag accaugaacg 480

cuaagcugcu cauggacccc aaaagacaga ucuuucugga ucaaaauaug cuugccguga 540

uugacgaacu gaugcaggcg cucaacuuca auagcgagac aguuccucag aagucuuccc 600

uggaggaacc ggauuuuuau aaaaccaaga ucaaacuuug uauccugcuc cacgccuucc 660

ggauucgcgc ugugacaauc gacagaguca ugagcuaccu gaacgccucu ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 345

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt5

<400> 345

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagaag ccugcuccug guggcuaccc uuguccugcu cgaccaccug ucccuugccc 120

180 ggaaccugcc uguugcgaca ccggaucccg

240

ccugcaccuc cgaagagauc gaccaugaag auauuacaaa agacaagacc ucuacagugg 300

360

cuuucaucac caaugggagc ugucuugcuu cccgcaagac gagcuuuaug auggcccugu 420

gccucucuuc cauuuaugaa gaucugaaaa uguaccaggu cgaguucaag accaugaacg 480

cuaagcugcu cauggacccc aaaagacaga ucuuucugga ucaaaauaug cuugccguga 540

uugacgaacu gaugcaggcg cucaacuuca auagcgagac aguuccucag aagucuuccc 600

uggaggaacc ggauuuuuau aaaaccaaga ucaaacuuug uauccugcuc cacgccuucc 660

ggauucgcgc ugugacaauc gacagaguca ugagcuaccu gaacgccucu ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 346

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt5

<400> 346

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccggaacc 60

ugccuguugc gacaccggau cccggcaugu ucccuugucu ccaucacucu cagaaucugc 120

ugcgcgcugu gagcaacaug cuccaaaagg ccagacagac gcuggaguuu uaccccugca 180

ccuccgaaga gaucgaccau gaagauauua caaaagacaa gaccucuaca guggaggccu 240

gucuuccucu ggaacucacc aaaaaugaga gcugccugaa cucccgggag acaucuuuca 300

ucaccaaugg gagcugucuu gcuucccgca agacgagcuu uaugauggcc cugugccucu 360

cuuccauuua ugaagaucug aaaauguacc aggucgaguu caagaccaug aacgcuaagc 420

ugcucaugga ccccaaaaga cagaucuuuc uggaucaaaa uaugcuugcc gugauugacg 480

aacugaugca ggcgcucaac uucaauagcg agacaguucc ucagaagucu ucccugggagg 540

aaccggauuu uuauaaaacc aagaucaaac uuuguauccu gcuccacgcc uuccggauuc 600

660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 347

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt5

<400> 347

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ggccucuccc cuuguugcua 120

uuugggagcu gaagaaagac guguacgugg ucgaacucga uugguauccu gacgccccgg 180

gcgagauggu gguucugacc ugugauacac ccgaagagga cgggaucacg uggacccuug 240

aucagagcuc cgaagugcug ggaucuggca agacacucac cauucagguc aaagaguucg 300

gggacgcggg acaguacaca ugccauaagg gcggggaggu gcugagccac ucccugcucc 360

ugcuucauaa aaaggaagau ggaaucuggu cuaccgacau ucugaaggau caaaaagagc 420

cuaagaacaa aacauuucuc agaugugaag cuaagaauua uagcggccgg uuuaccugcu 480

gguggcugac gaccaucucc acagaccuua ccuucagcgu uaaaucuucc cgcggcagcu 540

cugaucccca gggggugaca uguggagccg ccacccuguc cgcugagaga guccggggcg 600

660

aggaaucccu ccccaucgag gugauggucg acgcgguuca caagcugaaa uacgagaauu 720

auacgagcuc cuucuuuauu cgcgacauca uuaagccuga uccgcccaaa aaccugcagc 780

ucaagccucu gaaaaauucu agacaagugg aagugagcug ggaguacccc gacacauggu 840

uuugcgucca ggugcagggg aaguccaaac 900

gggaaaagaa ggaucgcguu uucaccgaca aaaccagcgc cacagugauc uguagaaaga 960

acgcuucuau uagcguccgg gccaggauc gcuauuuacuc cucuagcugg uccgaguggg 1020

cuagcgugcc cugcucuuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 348

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt5

<400> 348

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ggccucuccc cuuguugcua 120

uuugggagcu gaagaaagac guguacgugg ucgaacucga uugguauccu gacgccccgg 180

gcgagauggu gguucugacc ugugauacac ccgaagagga cgggaucacg uggacccuug 240

aucagagcuc cgaagugcug ggaucuggca agacacucac cauucagguc aaagaguucg 300

gggacgcggg acaguacaca ugccauaagg gcggggaggu gcugagccac ucccugcucc 360

ugcuucauaa aaaggaagau ggaaucuggu cuaccgacau ucugaaggau caaaaagagc 420

cuaagaacaa aacauuucuc agaugugaag cuaagaauua uagcggccgg uuuaccugcu 480

gguggcugac gaccaucucc acagaccuua ccuucagcgu uaaaucuucc cgcggcagcu 540

cugaucccca gggggugaca uguggagccg ccacccuguc cgcugagaga guccggggcg 600

660

aggaaucccu ccccaucgag gugauggucg acgcgguuca caagcugaaa uacgagaauu 720

auacgagcuc cuucuuuauu cgcgacauca uuaagccuga uccgcccaaa aaccugcagc 780

ucaagccucu gaaaaauucu agacaagugg aagugagcug ggaguacccc gacacauggu 840

uuugcgucca ggugcagggg aaguccaaac 900

gggaaaagaa ggaucgcguu uucaccgaca aaaccagcgc cacagugauc uguagaaaga 960

acgcuucuau uagcguccgg gccaggauc gcuauuuacuc cucuagcugg uccgaguggg 1020

cuagcgugcc cugcucugga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 349

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt5

<400> 349

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauuuggg 60

agcugaagaa agacguguac guggucgaac ucgauuggua uccugacgcc ccgggcgaga 120

uggugguucu gaccugugau acacccgaag aggacgggau cacguggacc cuugaucaga 180

gcuccgaagu gcugggaucu ggcaagacac ucaccauuca ggucaaagag uucggggacg 240

cgggacagua cacaugccau aagggcgggg aggugcugag ccacucccug cuccugcuuc 300

auaaaaagga agauggaauc uggucuaccg acauucugaa ggaucaaaaa gagccuaaga 360

acaaaacauu ucucagaugu gaagcuaaga auuauagcgg ccgguuuacc ugcugguggc 420

ugacgaccau cuccacagac cuuaccuuca gcguuaaauc uucccgcggc agcucugauc 480

cccagggggu gacaugugga gccgccaccc uguccgcuga gagaguccgg ggcgacaaca 540

aggaguacga auauagcgug gagugccagg aagauucugc cuguccugcu gccgaggaau 600

cccuccccau cgaggugaug gucgacgcgg uucacaagcu gaaauacgag aauuauacga 660

gcuccuucuu uauucgcgac aucauuaagc cugauccgcc caaaaaccug cagcucaagc 720

cucugaaaaa uucuagacaa guggaaguga gcugggagua ccccgacaca ugguccaccc 780

cucauagcua cuucucucuu acauuuugcg uccaggugca ggggaagucc aaacgggaaa 840

agaaggaucg cguuuucacc gacaaaacca gcgccacagu gaucuguaga aagaacgcuu 900

cuauuagcgu ccgggcccag gaucgcuauu acuccucuag cugguccgag ugggcuagcg 960

ugcccugcuc uugaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 350

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt5

<400> 350

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagca 60

ccuccggguc uggaaagccc ggcagcgggg agggauccac aaaaggcggga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 351

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt5

<400> 351

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ggccucuccc cuuguugcua 120

uuugggagcu gaagaaagac guguacgugg ucgaacucga uugguauccu gacgccccgg 180

gcgagauggu gguucugacc ugugauacac ccgaagagga cgggaucacg uggacccuug 240

aucagagcuc cgaagugcug ggaucuggca agacacucac cauucagguc aaagaguucg 300

gggacgcggg acaguacaca ugccauaagg gcggggaggu gcugagccac ucccugcucc 360

ugcuucauaa aaaggaagau ggaaucuggu cuaccgacau ucugaaggau caaaaagagc 420

cuaagaacaa aacauuucuc agaugugaag cuaagaauua uagcggccgg uuuaccugcu 480

gguggcugac gaccaucucc acagaccuua ccuucagcgu uaaaucuucc cgcggcagcu 540

cugaucccca gggggugaca uguggagccg ccacccuguc cgcugagaga guccggggcg 600

acaacaagga guacgaauau agcguggagu gccaggaaga uucugccugu ccugcugccg 660

aggaaucccu ccccaucgag gugauggucg acgcgguuca caagcugaaa uacgagaauu 720

auacgagcuc cuucuuuauu cgcgacauca uuaagccuga uccgcccaaa aaccugcagc 780

ucaagccucu gaaaaauucu agacaagugg aagugagcug ggaguacccc gacacauggu 840

uuugcgucca ggugcagggg aaguccaaac 900

gggaaaagaa ggaucgcguu uucaccgaca aaaccagcgc cacagugauc uguagaaaga 960

acgcuucuau uagcguccgg gccaggauc gcuauuuacuc cucuagcugg uccgaguggg 1020

1080

ccacaaaagg cgggaaccug ccuguugcga caccggaucc cggcauguuc ccuugucucc 1140

aucacucuca gaaucugcug cgcgcuguga gcaacaugcu ccaaaaggcc agacagacgc 1200

uggaguuuua ccccugcacc uccgaagaga ucgaccauga agauauuaca aaagacaaga 1260

ccucuacagu ggaggccugu cuuccucugg aacucaccaa aaaugagagc ugccugaacu 1320

1380

ugaggcccu gugccucucu uccauuuaug aagaucugaa aauguaccag gucgaguuca 1440

agaccaugaa cgcuaagcug cucauggacc ccaaaagaca gaucuuucug gaucaaaaua 1500

ugcuugccgu gauugacgaa cugaugcagg cgcucaacuu caauagcgag acaguuccuc 1560

agaagucuuc ccuggaggaa ccggauuuuu auaaaaccaa gaucaaacuu uguauccugc 1620

uccacgccuu ccggauucgc gcugugacaa ucgacagagu caugagcuac cugaacgccu 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 352

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt5

<400> 352

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacaa ccagacaagc cccagauccg ccgcuacggg ccugccuauu ucuaugaaga 120

ucuucaugua ucuccugacc guguuucuua uuacacaaau gaucgggagc gcccuguucg 180

cggucuaccu ccaccggcgc cuggacaaaa uugaagauga gagaaaucuu caugaagacu 240

uuguuuucau gaagaccauc cagcggugca acacaggaga gcgcucccug ucucuccuga 300

auugugaaga gaucaaaagc caguuugagg gcuucgugaa ggauauuaug cugaacaaag 360

aagaccaaa gaaggaaaau uccuuugaga ugcagaaagg ggaccaaaac ccgcagaucg 420

cugcccacgu gauuucugag gccagcucca agacaaccag cguccuccag ugggcugaaa 480

aaggauauua cacgaugucu aauaaccugg ugacccuuga gaauggcaag cagcugacag 540

uuaaaagaca agggcucuau uacaucuaug cccaggugac cuucugcucc aaccgggaag 600

cuagcucuca ggcccccuuu auugcguccc ugugucuuaa gagcccugga cgcuucgaga 660

gaauccugcu cggggccgcu aauacacauu cuuccgccaa gcccugcggc cagcaaagca 720

uucaccggg cggggucuuu gaacugcagc cuggagcuuc cguguucguu aacgugaccg 780

aucccucuca ggucagccau ggcacgggggu uuacauccuu cggacuccug aaacuuugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 353

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt6

<400> 353

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

uaccacaagc accauggcca guaguauggg cuguacuaca auuagguugg cgaccaggau 120

gguuuuuaga cucaccagau cguccaugga acccaccaac auuuucacca gcauuauuag 180

uaguaacaga aggagauaau gcaaccuuua cauguucauu caguaacaca ucagaaaguu 240

uuguacuaaa uugguauaga augucaccuu caaaucaaac agauaaauua gcagcauuuc 300

cagaagauag aucacaacca ggacaagauu gcagauuuag aguaacacaa uuaccuaug 360

gacgagacuu ucauauguca guaguaagag cucgacguaa cgauucagga acauacuuau 420

guggagcaau aucauuagca ccaaaagcac aaauaaaaga aucuuuaaga gcagaauuaa 480

gaguaacaga aagacgcgca gaaguaccaa cagcacaucc aagcccuuca ccacgaccug 540

caggacaauu ucaaacauua guagucggag uaguaggagg auuauuaggu ucacugguau 600

660

gaagaacagg acaaccauua aaagaagacc caucugcagu accaguauuu ucaguugacu 720

auggagaacu agauuuccaa uggagggaaa aaacaccaga accuccaguu ccauguguac 780

cagaacaaac agaauaugca acaauuguau uucccucagg aaugggaaca ucuaguccag 840

caagaagagg aucagcugau ggaccaagau cagcacaacc auuaagacca gaagauggac 900

auuguucaug gccauuauaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 354

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt6

<400> 354

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

uaccacaagc accauggcca guaguauggg cuguacuaca auuagguugg cgaccaggau 120

gguuuuuaga cucaccagau cguccaugga acccaccaac auuuucacca gcauuauuag 180

uaguaacaga aggagauaau gcaaccuuua cauguucauu caguaacaca ucagaaaguu 240

uuguacuaaa uugguauaga augucaccuu caaaucaaac agauaaauua gcagcauuuc 300

cagaagauag aucacaacca ggacaagauu gcagauuuag aguaacacaa uuaccuaug 360

gacgagacuu ucauauguca guaguaagag cucgacguaa cgauucagga acauacuuau 420

guggagcaau aucauuagca ccaaaagcac aaauaaaaga aucuuuaaga gcagaauuaa 480

gaguaacaga aagacgcgca uaaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 355

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt6

<400> 355

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

cagcaagauc acuacuacug guagcaacac ugguacuacu agaccaccua ucacucgcca 120

gaaaccuccc aguagccaca ccagacccag gaauguuccc cugccuccac cauucccaaa 180

accuacuaag agcaguauca aacaugcuac aaaaagcaag acaaacacua gaguucuauc 240

caugcacauc agaagaaaua gaccacgaag acauaacaaa agacaaaaca ucaaccguag 300

360

cauucauaac aaacggcuca ugcuuagccu caagaaaaac aucauucaug auggcacuau 420

gccucucauc cauauaugaa gacuuaaaaa uguaccaagu agaauuuaaa accaugaacg 480

caaaauuacu aauggaccca aaaagacaaa uauuccuaga ccaaaacaug cuagcaguaa 540

uagacgaacu aaugcaagca cuaaacuuca acucagaaac cguaccccaa aaaucaucuc 600

uagaagaacc agacuucuac aaaacaaaaa uaaaacuaug cauacuacua cacgccuuca 660

gaauaagagc cgucacaaua gacagaguca ugucauaccu aaacgccuca uaaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 356

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt6

<400> 356

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

cagcaagauc acuacuacug guagcaacac ugguacuacu agaccaccua ucacucgcca 120

gaaaccuccc aguagccaca ccagacccag gaauguuccc cugccuccac cauucccaaa 180

accuacuaag agcaguauca aacaugcuac aaaaagcaag acaaacacua gaguucuauc 240

caugcacauc agaagaaaua gaccacgaag acauaacaaa agacaaaaca ucaaccguag 300

360

cauucauaac aaacggcuca ugcuuagccu caagaaaaac aucauucaug auggcacuau 420

gccucucauc cauauaugaa gacuuaaaaa uguaccaagu agaauuuaaa accaugaacg 480

caaaauuacu aauggaccca aaaagacaaa uauuccuaga ccaaaacaug cuagcaguaa 540

uagacgaacu aaugcaagca cuaaacuuca acucagaaac cguaccccaa aaaucaucuc 600

uagaagaacc agacuucuac aaaacaaaaa uaaaacuaug cauacuacua cacgccuuca 660

gaauaagagc cgucacaaua gacagaguca ugucauaccu aaacgccuca ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 357

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt6

<400> 357

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accagaaacc 60

ucccaguagc cacaccagac ccaggaaugu uccccugccu ccaccauucc caaaaccuac 120

acuagaguuc uauccaugca 180

caucagaaga aauagaccac gaagacauaa caaaagacaa aacaucaacc guagaagcau 240

gccucccacu cgaacucaca aaaaacgaau caugccuaaa cucaagagaa acaucauuca 300

uaacaaacgg cucaugcuua gccucaagaa aaacaucauu caugauggca cuaugccucu 360

cauccauaua ugaagacuua aaaauguacc aaguagaauu uaaaaccaug aacgcaaaau 420

uacuaaugga cccaaaaaga caaauauucc uagaccaaaa caugcuagca guaauagacg 480

aacuaaugca agcacuaaac uucaacucag aaaccguacc ccaaaaauca ucucuagaag 540

aaccagacuu cuacaaaaca aaaauaaaac

gagccgucac aauagacaga gucaugucau accuaaacgc cucauaagga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 358

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt6

<400> 358

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu gguaauauca ugguucucac ugguauucuu ggcaucaccc cuaguagcaa 120

uaugggaacu aaaaaaagac guauacguag uagaacuaga cugguaccca gacgcaccag 180

gagaaauggu aguauuaaca ugcgacacac cagaagaaga uggaauaacu uggacauuag 240

accaaucaag ugaaguauua ggaucaggca aaacacuaac uauacaagua aaagaauuug 300

gagacgcagg acaauacacg ugccacaaag gaggcgaagu ccuaucacau ucacuacuau 360

420

caaaaaacaa aacauuucua agaugcgaag cuaaaaacua uucaggaaga uucacaugcu 480

gguggcuaac aaccaucagu accgacuuaa cauucucagu aaaaucauca agaggaucau 540

cagacccaca aggaguaaca uguggagcag caacacuaag cgcagaaaga guacgaggag 600

acaacaaaga auacgaauau ucaguagaau gucaagaaga

aagaaucauu accaauagaa guaauggucg acgcuguaca caaacuaaaa uaugaaaauu 720

acacaagcag uuucuucaua agagacauaa uaaaacccga cccaccaaaa aaccuacaac 780

uaaaaccauu aaaaaauuca agacaaguag aaguaucaug ggaauaccca gauacaugga 840

gcacaccaca caguuacuuc ucauuaacau ucugcguaca aguacaagga aaaaguaaaa 900

gagaaaaaaa agacagagua uucacagaua agacuucagc aacaguaaua ugcagaaaaa 960

acgcaagcau aagcguacga gcacaagaca gauauuacuc aagcucaugg ucagaauggg 1020

caucaguacc auguucauaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 359

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt6

<400> 359

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu gguaauauca ugguucucac ugguauucuu ggcaucaccc cuaguagcaa 120

uaugggaacu aaaaaaagac guauacguag uagaacuaga cugguaccca gacgcaccag 180

gagaaauggu aguauuaaca ugcgacacac cagaagaaga uggaauaacu uggacauuag 240

accaaucaag ugaaguauua ggaucaggca aaacacuaac uauacaagua aaagaauuug 300

gagacgcagg acaauacacg ugccacaaag gaggcgaagu ccuaucacau ucacuacuau 360

420

caaaaaacaa aacauuucua agaugcgaag cuaaaaacua uucaggaaga uucacaugcu 480

gguggcuaac aaccaucagu accgacuuaa cauucucagu aaaaucauca agaggaucau 540

cagacccaca aggaguaaca uguggagcag caacacuaag cgcagaaaga guacgaggag 600

acaacaaaga auacgaauau ucaguagaau gucaagaaga

aagaaucauu accaauagaa guaauggucg acgcuguaca caaacuaaaa uaugaaaauu 720

acacaagcag uuucuucaua agagacauaa uaaaacccga cccaccaaaa aaccuacaac 780

uaaaaccauu aaaaaauuca agacaaguag aaguaucaug ggaauaccca gauacaugga 840

gcacaccaca caguuacuuc ucauuaacau ucugcguaca aguacaagga aaaaguaaaa 900

gagaaaaaaa agacagagua uucacagaua agacuucagc aacaguaaua ugcagaaaaa 960

acgcaagcau aagcguacga gcacaagaca gauauuacuc aagcucaugg ucagaauggg 1020

caucaguacc auguucagga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 360

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt6

<400> 360

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauauggg 60

aacuaaaaaa agacguauac guaguagaac uagacuggua cccagacgca ccaggagaaa 120

ugguaguauu aacaugcgac acaccagaag aagauggaau aacuuggaca uuagaccaau 180

caagugaagu auuaggauca ggcaaaacac uaacuauaca aguaaaagaa uuuggagacg 240

caggacaaua cacgugccac aaaggaggcg aaguccuauc acauucacua cuauuuauuac 300

acauauuaaa agaccaaaaa gaaccaaaaa 360

acaaaacauu ucuaagaugc gaagcuaaaa acuauucagg aagauucaca ugcugguggc 420

uaacaaccau caguaccgac uuaacauucu caguaaaauc aucaagagga ucaucagacc 480

cacaaggagu aacaugga gcagcaacac uaagcgcaga aagaguacga ggagacaaca 540

aagaauacga auauucagua gaaugucaag aagacucagc augcccugca gcagaagaau 600

660

720

cauuaaaaaa uucaagacaa guagaaguau caugggaaua cccagauaca uggagcacac 780

cacacaguua cuucucauua acauucugcg uacaaguaca aggaaaaagu aaaagagaaa 840

900

gcauaagcgu acgagcacaa gacagauauu acucaagcuc auggucagaa ugggcaucag 960

uaccauguuc auaaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 361

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt6

<400> 361

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggaagua 60

120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 362

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt6

<400> 362

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu gguaauauca ugguucucac ugguauucuu ggcaucaccc cuaguagcaa 120

uaugggaacu aaaaaaagac guauacguag uagaacuaga cugguaccca gacgcaccag 180

gagaaauggu aguauuaaca ugcgacacac cagaagaaga uggaauaacu uggacauuag 240

accaaucaag ugaaguauua ggaucaggca aaacacuaac uauacaagua aaagaauuug 300

gagacgcagg acaauacacg ugccacaaag gaggcgaagu ccuaucacau ucacuacuau 360

420

caaaaaacaa aacauuucua agaugcgaag cuaaaaacua uucaggaaga uucacaugcu 480

gguggcuaac aaccaucagu accgacuuaa cauucucagu aaaaucauca agaggaucau 540

cagacccaca aggaguaaca uguggagcag caacacuaag cgcagaaaga guacgaggag 600

acaacaaaga auacgaauau ucaguagaau gucaagaaga

aagaaucauu accaauagaa guaauggucg acgcuguaca caaacuaaaa uaugaaaauu 720

acacaagcag uuucuucaua agagacauaa uaaaacccga cccaccaaaa aaccuacaac 780

uaaaaccauu aaaaaauuca agacaaguag aaguaucaug ggaauaccca gauacaugga 840

gcacaccaca caguuacuuc ucauuaacau ucugcguaca aguacaagga aaaaguaaaa 900

gagaaaaaaa agacagagua uucacagaua agacuucagc aacaguaaua ugcagaaaaa 960

acgcaagcau aagcguacga gcacaagaca gauauuacuc aagcucaugg ucagaauggg 1020

caucaguacc auguucagga aguacaagug gaaguggaaa accaggaagu ggagaaggaa 1080

1140

accauuccca aaaccuacua agagcaguau caaacaugcu acaaaaagca agacaaacac 1200

uagaguucua uccaugcaca ucagaagaaa uagaccacga agacauaaca aaagacaaaa 1260

1320

caagagaaac aucauucaua acaaacggcu caugcuuagc cucaagaaaa acaucauuca 1380

ugaggcacu augccucuca uccauauaug aagacuuaaa aauguaccaa guagaauuua 1440

aaaccaugaa cgcaaaauua cuaauggacc caaaaagaca aauauuccua gaccaaaaca 1500

ugcuagcagu aauagacgaa cuaaugcaag cacuaaacuu caacucagaa accguacccc 1560

1620

uacacgccuu cagaauaaga gccgucacaa uagacagagu caugucauac cuaaacgccu 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 363

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt6

<400> 363

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugauag 60

120

uauucaugua ccuacucaca gucuuccuaa uaacacaaau gauaggaucu gcccuauuug 180

caguauaccu acacagaaga cuagauaaaa uagaagacga aagaaaccua caugaagacu 240

ucguauucau gaaaacaaua caaagaugca acaccggaga aagaucccua ucacuacuaa 300

360

aagaaacaaa aaaagaaaac ucuuucgaaa ugcaaaaagg agaccaaaac ccacaaauag 420

cugcacacgu cauaucagaa gcaucaucaa aaacaacauc aguacuucaa ugggcagaaa 480

aaggauacua uacaauguca aacaaucuag uaacccuaga aaacggaaaa caacuaacag 540

uaaaaagaca aggacuauac uauauauacg cacaaguaac auucugcuca aacagagaag 600

660

gaauccuacu aagagcagca aacacacacu caucagcaaa accaugcggc caacaaucaa 720

uacaccuagg aggaguauuc gaacuacaac caggagcauc aguauucgua aacguaacag 780

accccucaca aguaagccac ggcacaggau ucacaucauu uggacuauua aaauuauaag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 364

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt7

<400> 364

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaagc cccauggccg guggucuggg cagugcugca gcucggcugg aggcccgggu 120

gguuccugga cagcccagau cggccugga acccacccac cuuuucccca gccuugcugg 180

uagugacuga gggugacaau gcgaccuuca cgugcaguuu uagcaacacu uccgaaaguu 240

ucguccucaa uugguaccgc ugagcccgu ccaaccagac cgauaagcug gccgcauuuc 300

ccgaggacag gagccagcca ggccaagauu gucgguuccg cgugacccag uugcccaaug 360

ggagggacuu ucacaugucc gugguccggg cccgcaggaa cgauaguggc acuuaucugu 420

gcggugcaau uagccucgcc ccaaaagcgc agaucaagga aucccugcgg gccgagcugc 480

gcgugaccga aaggcgggca gagguaccca cggcccaucc gagccccagu ccacgccccg 540

ccgggcaguu ccaaacucuc guggucggcg uggugggcgg gcuguugggu ucccuggucc 600

uccggugug gguacuggca gugauuugua gcagggccgc gcggggcacc aucggggccc 660

gcaggacugg ccagccauug aaagaggacc ccuccgcagu cccaguguuu aguguggauu 720

acggugaacu cgacuuccag uggcggggaga agaccccgga acccccaguc cccugcgugc 780

cagagcagac cgaguaugcc acgauuguau uucccagcgg gaugggcacu uccagcccgg 840

cacgcagggg cagugccgau gggccacggu ccgcccaacc ccugaggccc gaagacgguc 900

acuguagcug gccacuguga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 365

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt7

<400> 365

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccccaagc cccauggccg guggucuggg cagugcugca gcucggcugg aggcccgggu 120

gguuccugga cagcccagau cggccugga acccacccac cuuuucccca gccuugcugg 180

uagugacuga gggugacaau gcgaccuuca cgugcaguuu uagcaacacu uccgaaaguu 240

ucguccucaa uugguaccgc ugagcccgu ccaaccagac cgauaagcug gccgcauuuc 300

ccgaggacag gagccagcca ggccaagauu gucgguuccg cgugacccag uugcccaaug 360

ggagggacuu ucacaugucc gugguccggg cccgcaggaa cgauaguggc acuuaucugu 420

gcggugcaau uagccucgcc ccaaaagcgc agaucaagga aucccugcgg gccgagcugc 480

gcgugaccga aaggcgggca ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 366

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt7

<400> 366

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccaggag ccugcuccug guggcaaccu ugguccugcu cgaccaccug uccuuggccc 120

ggaaccugcc aguggcgacu cgggaucccg gcauguuccc augucuccau cacagucaga 180

aucugcugcg cgccguaagc aacaugcucc aaaaggcaag gcagacccug gaguuuuacc 240

ccugcacguc cgaagagauc gaccaugaag auauuacuaa agacaagacc aguaccgugg 300

aggccuguuu gccacuggaa cucacuaaaa augagagcug ccugaacucc cgggagacca 360

gcuucaucac gaaugggucc ugucuggcaa gucgcaagac uagcuuuaug auggccuugu 420

gccucuccag cauuuaugaa gaucugaaaa uguaccaggu cgaguucaag accaugaacg 480

cgaagcugcu cauggacccc aaaaggcaga ucuuucugga ucaaaauaug uuggccguga 540

uugacgaacu gaugcaggca cucaacuuca auagugagac ugugccacag aaguccagcc 600

uggaggaacc ggauuuuuau aaaaccaaga ucaaacugug uaucuugcuc cacgccuucc 660

ggauucgcgc cgucaccauc gacaggguga uguccuaccu gaacgcaagu ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 367

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt7

<400> 367

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccaggag ccugcuccug guggcaaccu ugguccugcu cgaccaccug uccuuggccc 120

ggaaccugcc aguggcgacu cgggaucccg gcauguuccc augucuccau cacagucaga 180

aucugcugcg cgccguaagc aacaugcucc aaaaggcaag gcagacccug gaguuuuacc 240

ccugcacguc cgaagagauc gaccaugaag auauuacuaa agacaagacc aguaccgugg 300

aggccuguuu gccacuggaa cucacuaaaa augagagcug ccugaacucc cgggagacca 360

gcuucaucac gaaugggucc ugucuggcaa gucgcaagac uagcuuuaug auggccuugu 420

gccucuccag cauuuaugaa gaucugaaaa uguaccaggu cgaguucaag accaugaacg 480

cgaagcugcu cauggacccc aaaaggcaga ucuuucugga ucaaaauaug uuggccguga 540

uugacgaacu gaugcaggca cucaacuuca auagugagac ugugccacag aaguccagcc 600

uggaggaacc ggauuuuuau aaaaccaaga ucaaacugug uaucuugcuc cacgccuucc 660

ggauucgcgc cgucaccauc gacaggguga uguccuaccu gaacgcaagu ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 368

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt7

<400> 368

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccggaacc 60

ugccaguggc gacuccggau cccggcaugu ucccaugucu ccaucacagu cagaaucugc 120

ugcgcgccgu aagcaacaug cuccaaaagg caaggcagac ccuggaguuu uaccccugca 180

cguccgaaga gaucgaccau gaagauauua cuaaagacaa gaccaguacc guggaggccu 240

guuugccacu ggaacucacu aaaaaugaga gcugccugaa cucccgggag accagcuuca 300

ucacgaaugg guccugucug gcaagucgca agacuagcuu uaugauggcc uugugccucu 360

ccagcauuua ugaagaucug aaaauguacc aggucgaguu caagaccaug aacgcgaagc 420

ugcucaugga ccccaaaagg cagaucuuuc uggaucaaaa uauguuggcc gugauugacg 480

aacugaugca ggcacucaac uucaauagug agacugugcc acagaagucc agccugggagg 540

aaccggauuuuuuauaaaacc aagaucaaac

gcgccgucac caucgacagg gugauguccu accugaacgc aaguugagga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 369

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt7

<400> 369

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ggccaguccc uugguggcaa 120

uuugggagcu gaagaaagac guauacgugg ucgaacucga uugguaucca gacgccccgg 180

gcgagauggu ggugcugacc ugugauacuc ccgaagagga cgggaucacc uggacguugg 240

aucagagcuc cgaaguccug gguaguggca agacucucac cauucaggug aaagaguucg 300

gggacgcggg ccaguauacc ugccauaagg guggggaggu acugagccac ucccugcucc 360

uguugcauaa aaaggaagau ggcaucugga gcacugacau ucugaaggau caaaaagagc 420

caaagaacaa aaccuuucuc aggugugaag ccaagaauua cuccggccgg uucacgugcu 480

gguggcugac uaccaucagu acugaccuga ccuuuagcgu gaaauccagc cgcgggaguu 540

ccgaucccca gggugucacc uguggcgcag ccacguugag cgcagagagg gugcgcgggg 600

acaacaagga guacgaauau uccguggagu gccaggaaga uagugccugu ccagcggccg 660

aggaaagccu ccccaucgag gucauggugg acgcaguaca caaacugaag uacgagaauu 720

auacuuccag cuucuuuauu cgggcauca uuaagccaga uccgcccaaa aaccugcagc 780

ucaagccacu gaaaaauagu aggcaagugg aagucuccug ggaguacccc gacaccugga 840

gcacuccaca uaguuacuuc uccuugaccu uuugcgucca ggugcagggc aagagcaaac 900

gggaaaagaa ggaucgcgug uucaccgaca aaacuagcgc cacggugauc uguaggaaga 960

acgccuccau uaguguacgg gcacaggauc gcuauuuacag cuccagcugg agugaguggg 1020

ccuccgugcc cugcagcuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 370

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt7

<400> 370

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ggccaguccc uugguggcaa 120

uuugggagcu gaagaaagac guauacgugg ucgaacucga uugguaucca gacgccccgg 180

gcgagauggu ggugcugacc ugugauacuc ccgaagagga cgggaucacc uggacguugg 240

aucagagcuc cgaaguccug gguaguggca agacucucac cauucaggug aaagaguucg 300

gggacgcggg ccaguauacc ugccauaagg guggggaggu acugagccac ucccugcucc 360

uguugcauaa aaaggaagau ggcaucugga gcacugacau ucugaaggau caaaaagagc 420

caaagaacaa aaccuuucuc aggugugaag ccaagaauua cuccggccgg uucacgugcu 480

gguggcugac uaccaucagu acugaccuga ccuuuagcgu gaaauccagc cgcgggaguu 540

ccgaucccca gggugucacc uguggcgcag ccacguugag cgcagagagg gugcgcgggg 600

acaacaagga guacgaauau uccguggagu gccaggaaga uagugccugu ccagcggccg 660

aggaaagccu ccccaucgag gucauggugg acgcaguaca caaacugaag uacgagaauu 720

auacuuccag cuucuuuauu cgggcauca uuaagccaga uccgcccaaa aaccugcagc 780

ucaagccacu gaaaaauagu aggcaagugg aagucuccug ggaguacccc gacaccugga 840

gcacuccaca uaguuacuuc uccuugaccu uuugcgucca ggugcagggc aagagcaaac 900

gggaaaagaa ggaucgcgug uucaccgaca aaacuagcgc cacggugauc uguaggaaga 960

acgccuccau uaguguacgg gcacaggauc gcuauuuacag cuccagcugg agugaguggg 1020

ccuccgugcc cugcagcgga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 371

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt7

<400> 371

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauuuggg 60

agcugaagaa agacguauac guggucgaac ucgauuggua uccagacgcc ccgggcgaga 120

ugguggugcu gaccugugau acucccgaag aggacgggau caccuggacg uuggaucaga 180

gcuccgaagu ccuggguagu ggcaagacuc ucaccauuca ggugaaagag uucggggacg 240

cgggccagua uaccugccau aagggugggg agguacugag ccacucccug cuccuguugc 300

auaaaaagga agauggcauc uggagcacug acauucugaa ggaucaaaaa gagccaaaga 360

acaaaaccuu ucucaggugu gaagccaaga auuacuccgg ccgguucacg ugcugguggc 420

ugacuaccau caguacuacac cugaccuuua gcgugaaauc cagccgcggg aguuccgauc 480

cccagggugu caccuguggc gcagccacgu ugagcgcaga gagggugcgc ggggacaaca 540

aggaguacga auauuccgug gagugccagg aagauagugc cuguccagcg gccgaggaaa 600

gccuccccau cgaggucaug guggacgcag uacacaaacu gaaguacgag aauuauacuu 660

ccagcuucuu uauucgggac aucauuaagc cagauccgcc caaaaaccug cagcucaagc 720

cacugaaaaa uaguaggcaa guggaagucu ccgggagua ccccgacacc uggagcacuc 780

cacauaguua cuucuccuug accuuuugcg uccaggugca gggcaagagc aaacgggaaa 840

agaaggaucg cguguucacc gacaaaacua gcgccacggu gaucuguagg aagaacgccu 900

ccauuagugu acgggcacag gaucgcuauu acagcuccag cuggagugag ugggccuccg 960

ugcccugcag cugaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 372

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt7

<400> 372

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagca 60

ccuccgggag ugguaagccc ggcagcgggg agggcuccac uaaaggugga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 373

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt7

<400> 373

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcaacu ggugaucagc ugguucuccc ucgucuuucu ggccaguccc uugguggcaa 120

uuugggagcu gaagaaagac guauacgugg ucgaacucga uugguaucca gacgccccgg 180

gcgagauggu ggugcugacc ugugauacuc ccgaagagga cgggaucacc uggacguugg 240

aucagagcuc cgaaguccug gguaguggca agacucucac cauucaggug aaagaguucg 300

gggacgcggg ccaguauacc ugccauaagg guggggaggu acugagccac ucccugcucc 360

uguugcauaa aaaggaagau ggcaucugga gcacugacau ucugaaggau caaaaagagc 420

caaagaacaa aaccuuucuc aggugugaag ccaagaauua cuccggccgg uucacgugcu 480

gguggcugac uaccaucagu acugaccuga ccuuuagcgu gaaauccagc cgcgggaguu 540

ccgaucccca gggugucacc uguggcgcag ccacguugag cgcagagagg gugcgcgggg 600

acaacaagga guacgaauau uccguggagu gccaggaaga uagugccugu ccagcggccg 660

aggaaagccu ccccaucgag gucauggugg acgcaguaca caaacugaag uacgagaauu 720

auacuuccag cuucuuuauu cgggcauca uuaagccaga uccgcccaaa aaccugcagc 780

ucaagccacu gaaaaauagu aggcaagugg aagucuccug ggaguacccc gacaccugga 840

gcacuccaca uaguuacuuc uccuugaccu uuugcgucca ggugcagggc aagagcaaac 900

gggaaaagaa ggaucgcgug uucaccgaca aaacuagcgc cacggugauc uguaggaaga 960

acgccuccau uaguguacgg gcacaggauc gcuauuuacag cuccagcugg agugaguggg 1020

ccuccgugcc cugcagcggc agcaccuccg ggagugguaa gcccggcagc ggggagggcu 1080

ccacuaaagg ucggaaccug ccaguggcga cuccggaucc cggcauguuc ccaugucucc 1140

aucacaguca gaaucugcug cgcgccguaa gcaacaugcu ccaaaaggca aggcagaccc 1200

uggaguuuua ccccugcacg uccgaagaga ucgaccauga agauauuacu aaagacaaga 1260

ccaguaccgu ggaggccugu uugccacugg aacucacuaa aaaugagagc ugccugaacu 1320

ccggggagac cagcuucauc acgaaugggu ccugucuggc aagucgcaag acuagcuuua 1380

ugaggccuu gugccucucc agcauuuaug aagaucugaa aauguaccag gucgaguuca 1440

agaccaugaa cgcgaagcug cucauggacc ccaaaaggca gaucuuucug gaucaaaaua 1500

uguuggccgu gauugacgaa cugaugcagg cacucaacuu caauagugag acugugccac 1560

agaaguccag ccuggaggaa ccggauuuuu auaaaaccaa gaucaaacug uguaucuugc 1620

uccacgccuu ccggauucgc gccgucacca ucgacagggu gauguccuac cugaacgcaa 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt7

<400> 374

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacaa ccagacuagc cccagguccg ccgcaaccgg ccugccaauu aguaugaaga 120

ucuucaugua ucuccugacg guguuuuuga uuacucaaau gaucgggagc gcccuguucg 180

cggucuaccu ccaccggcgc cuggacaaaa uugaagauga gaggaauuug caugaagacu 240

uuguguucau gaagaccauc cagcggugca acaccgguga gcgcucccug agucuccuga 300

auugugaaga gaucaaaagc caguuugagg gcuucguaaa ggauauuaug cugaacaaag 360

aagagacuaa gaaggaaaau uccuuugaga ugcagaaagg ggaccaaaac ccgcagaucg 420

ccgcacacgu gauuagcgag gccuccagua agaccacgag cguccuccag ugggcagaaa 480

aaggcuauua cacuaugucc aauaaccugg ugaccuugga gaaugguaag cagcugacug 540

ugaaaaggca agggcucuau uacaucuaug cccaggucac cuucugcagc aaccgggaag 600

cgaguuccca ggcccccuuu auugcaagcc ugugucugaa guccccaggc cgcuucgaga 660

ggaucuugcu cggggccgcc aauacccaua guagcgcaaa acccugcggc cagcaaucca 720

uucaccucgg ggguguguuu gaacugcagc caggcgccag cguauucgug aacgucacgg 780

aucccaguca ggugucccau gggacuggcu ucaccagcuu uggucugcug aaguugugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 375

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt8

<400> 375

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

ucccacaagc ccccuggccc guagucuggg ccguacuaca acuaggcugg agacccggcu 120

gguuucucga cagccccgac cgacccugga acccccccac cuucucaccc gcccuccucg 180

ucgucaccga aggcgacaac gccacauuca caugcuccuu cuccaacacc ucugaaucau 240

ucguccuaaa cugguaccga augucacccu ccaaccaaac ugacaaacuc gccgccuuuc 300

ccgaagaccg cucccaaccc ggccaagacu gccgauuccg agucacacaa cuuccuaacg 360

gcagagacuu ccacaugucc guaguccgag cccgccgaaa cgacuccggga accuaccucu 420

gcggagccau cucccucgcc cccaaagccc aaaucaaaga aucccuccga gcagaacucc 480

gcgucaccga acgccgcgcc gaagucccca ccgcacaccc aucacccucc ccccgccccg 540

ccggccaauu ccaaacacuu guaguaggcg ucgucggcgg ccuccuugga ucacucgucc 600

uacuuguaug gguccuagcc gucaucugcu cucgcgccgc acgcggcacc aucggcgcac 660

gacgaaccgg ccaaccucua aaagaagacc ccuccgcagu ccccgucuuc uccgucgacu 720

acggcgaacu cgacuuccaa uggcgcgaaa aaacccccga acccccaguc cccugcguac 780

ccgaacaaac cgaauacgca acaaucguau uccccucagg aaugggcacc ucaucccccg 840

cccgacgagg aucagccgac ggccccgau ccgcccaacc ccuccgacca gaagacggcc 900

acugcucaug gccccuuuaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 376

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt8

<400> 376

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

ucccacaagc ccccuggccc guagucuggg ccguacuaca acuaggcugg agacccggcu 120

gguuucucga cagccccgac cgacccugga acccccccac cuucucaccc gcccuccucg 180

ucgucaccga aggcgacaac gccacauuca caugcuccuu cuccaacacc ucugaaucau 240

ucguccuaaa cugguaccga augucacccu ccaaccaaac ugacaaacuc gccgccuuuc 300

ccgaagaccg cucccaaccc ggccaagacu gccgauuccg agucacacaa cuuccuaacg 360

gcagagacuu ccacaugucc guaguccgag cccgccgaaa cgacuccggga accuaccucu 420

gcggagccau cucccucgcc cccaaagccc aaaucaaaga aucccuccga gcagaacucc 480

gcgucaccga acgccgcgcc uaaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 377

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt8

<400> 377

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagauc ccuccuacuc gucgcaacac uuguccuccu cgaccaccuc ucccucgccc 120

gcaaucuccc cgucgccacc cccgaccccg gaauguuucc cugccuccac cacucacaaa 180

accuccuacg cgccgucuca aacaugcuuc aaaaagcccg acaaacccuc gaauuuuacc 240

ccugcaccuc cgaagaaauc gaccacgaag acauaaccaa agacaaaacc uccaccgucg 300

aagccugccu accauuagaa cuaaccaaaa acgaauccug ccucaacuca cgcgaaaccu 360

ccuucaucaac aaacggcuca ugccucgccu cacgcaaaac cuccuucaug auggcccucu 420

gccuaucauc aaucuaugaa gaccucaaaa uguaccaagu agaauuuaaa accaugaacg 480

ccaaacuccu cauggacccc aaacgccaaa ucuuccucga ccaaaacaug cucgcaguca 540

ucgacgaacu caugcaagcc cucaacuuca acucagaaac agucccacaa aaauccuccc 600

ucgaagaacc cgacuucuau aaaaccaaaa ucaaacucug cauccuccuc cacgccuucc 660

gcauacgcgc cguaaccauc gaccgcguaa ugucauaccu aaaugccucu uaaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 378

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt8

<400> 378

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagauc ccuccuacuc gucgcaacac uuguccuccu cgaccaccuc ucccucgccc 120

gcaaucuccc cgucgccacc cccgaccccg gaauguuucc cugccuccac cacucacaaa 180

accuccuacg cgccgucuca aacaugcuuc aaaaagcccg acaaacccuc gaauuuuacc 240

ccugcaccuc cgaagaaauc gaccacgaag acauaaccaa agacaaaacc uccaccgucg 300

aagccugccu accauuagaa cuaaccaaaa acgaauccug ccucaacuca cgcgaaaccu 360

ccuucaucaac aaacggcuca ugccucgccu cacgcaaaac cuccuucaug auggcccucu 420

gccuaucauc aaucuaugaa gaccucaaaa uguaccaagu agaauuuaaa accaugaacg 480

ccaaacuccu cauggacccc aaacgccaaa ucuuccucga ccaaaacaug cucgcaguca 540

ucgacgaacu caugcaagcc cucaacuuca acucagaaac agucccacaa aaauccuccc 600

ucgaagaacc cgacuucuau aaaaccaaaa ucaaacucug cauccuccuc cacgccuucc 660

gcauacgcgc cguaaccauc gaccgcguaa ugucauaccu aaaugccucu ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 379

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt8

<400> 379

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccgcaauc 60

uccccgucgc cacccccgac ccgggaaugu uucccugccu ccaccacuca caaaaccucc 120

uacgcgccgu cucaaacaug cuucaaaaag cccgacaaac ccucgaauuu uaccccugca 180

ccuccgaaga aaucgaccac gaagacauaa ccaaagacaa aaccuccacc gucgaagccu 240

gccuaccauu agaacuaacc aaaaacgaau ccugccucaa cucacgcgaa accuccuuca 300

ucacaaacgg cucaugccuc gccucacgca aaaccuccuu caugauggcc cucugccuau 360

caucaaucua ugaagaccuc aaaauguacc aaguagaauu uaaaaccaug aacgccaaac 420

uccucaugga ccccaaacgc caaaucuucc ucgaccaaaa caugcucgca gucaucgacg 480

aacucaugca agcccucaac uucaacucag aaacaguccc acaaaaaucc ucccucgaag 540

aacccgacuu cuauaaaacc aaaaucaaac ucugcauccu ccuccacgcc uuccgcauac 600

gcgccguaac caucgaccgc guaaugucau accuaaaugc cucuuaagga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 380

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt8

<400> 380

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu cgucauaagc ugguucagcc uaguauuccu cgccucaccc cucgucgcca 120

ucgggaacu caagaaagac guauacgucg ucgaacuaga cugguacccc gacgcacccg 180

gagaaauggu aguacucaca ugcgacaccc ccgaagaaga cggcaucaca uggaccuuag 240

accaaucauc agaaguccuc ggauccggaa aaacccucac aauccaaguc aaagaguucg 300

gcgacgccgg ccaauacaca ugccacaaag gcggagaagu ccucucacac ucacuccuuc 360

uacuacacaa gaaagaagac ggcaucuggu ccaccgacau acucaaagac caaaaagaac 420

ccaaaaaca aaccuuccuc cgcugcgaag ccaaaaacua cuccggccga uucacaugcu 480

gguggcucac caccaucucc accgaccuga ccuucuccgu caaauccagc aggggcuccu 540

cagacccaca aggcguaacc ugcggcgcag ccacccuauc ggccgaacga guccgcggag 600

acaacaaaga auacgaauac agcgucgaau gccaagaaga cucagcaugc ccagcagccg 660

aagaaucacu ccccaucgaa gucauggucg acgccgucca caaacuaaaa uacgaaaacu 720

acacaagcuc auucuucauc cgcgacauaa ucaaacccga cccaccgaaa aaccuccaac 780

ucaaaccccu uaaaaacagc cgccaagucg aagucuccug ggaauacccc gacaccuggu 840

ccacacccca cuccuacuuc ucacucaccu ucugcgucca aguccaaggc aaauccaaac 900

gcgaaaagaa agaccgcgua uucaccgaca aaaccuccgc cacagucauc ugccgcaaaa 960

acgccucaau cuccguccgc gcccaagacc gauacuacag cuccuccugg ucagaauggg 1020

ccuccguccc augcucuaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 381

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt8

<400> 381

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu cgucauaagc ugguucagcc uaguauuccu cgccucaccc cucgucgcca 120

ucgggaacu caagaaagac guauacgucg ucgaacuaga cugguacccc gacgcacccg 180

gagaaauggu aguacucaca ugcgacaccc ccgaagaaga cggcaucaca uggaccuuag 240

accaaucauc agaaguccuc ggauccggaa aaacccucac aauccaaguc aaagaguucg 300

gcgacgccgg ccaauacaca ugccacaaag gcggagaagu ccucucacac ucacuccuuc 360

uacuacacaa gaaagaagac ggcaucuggu ccaccgacau acucaaagac caaaaagaac 420

ccaaaaaca aaccuuccuc cgcugcgaag ccaaaaacua cuccggccga uucacaugcu 480

gguggcucac caccaucucc accgaccuga ccuucuccgu caaauccagc aggggcuccu 540

cagacccaca aggcguaacc ugcggcgcag ccacccuauc ggccgaacga guccgcggag 600

acaacaaaga auacgaauac agcgucgaau gccaagaaga cucagcaugc ccagcagccg 660

aagaaucacu ccccaucgaa gucauggucg acgccgucca caaacuaaaa uacgaaaacu 720

acacaagcuc auucuucauc cgcgacauaa ucaaacccga cccaccgaaa aaccuccaac 780

ucaaaccccu uaaaaacagc cgccaagucg aagucuccug ggaauacccc gacaccuggu 840

ccacacccca cuccuacuuc ucacucaccu ucugcgucca aguccaaggc aaauccaaac 900

gcgaaaagaa agaccgcgua uucaccgaca aaaccuccgc cacagucauc ugccgcaaaa 960

acgccucaau cuccguccgc gcccaagacc gauacuacag cuccuccugg ucagaauggg 1020

ccuccguccc augcucciga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 382

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt8

<400> 382

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

aacucaagaa agacguauac gucgucgaac uagacuggua ccccgacgca cccggagaaa 120

ugguaguacu cacaugcgac acccccgaag aagacggcau cacauggacc uuagaccaau 180

caucagaagu ccucggaucc ggaaaaaccc ucacaaucca agucaaagag uucggcgacg 240

ccggccaaua cacaugccac aaaggcggag aaguccucuc acacucacuc cuucuacuac 300

acaagaaaga agacggcauc ugguccaccg acauacucaa agaccaaaaa gaacccaaaa 360

acaaaaccuu ccuccgcugc gaagccaaaa acuacuccgg ccgauucaca ugcugguggc 420

ucaccaccau cuccaccgac cugaccuucu ccgucaaauc cagcaggggc uccucagacc 480

cacaaggcgu aaccugcggc gcagccaccc uaucggccga acgaguccgc ggagacaaca 540

aagaauacga auacagcguc gaaugccaag aagacucagc augcccagca gccgaagaau 600

cacuccccau cgaagucaug gucgacgccg uccacaaacu aaaauacgaa aacuacacaa 660

gcucauucuu cauccgcgac auaaucaaac ccgacccacc gaaaaaccuc caacucaaac 720

cccuuaaaaa cagccgccaa gucgaagucu ccgggaaua ccccgacacc ugguccacac 780

cccacuccua cuucucacuc accuucugcg uccaagucca aggcaaaucc aaacgcgaaa 840

agaaagaccg cguauucacc gacaaaaccu ccgccacagu caucugccgc aaaaacgccu 900

caaucuccgu ccgcgcccaa gaccgauacu acagcuccuc cuggucagaa ugggccuccg 960

ucccaugcuc cuaaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 383

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt8

<400> 383

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accgggagca 60

cgagcgggag cgggaagccg ggaaguggag agggaaguac aaagggagga cuagugcauc 120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 384

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt8

<400> 384

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu cgucauaagc ugguucagcc uaguauuccu cgccucaccc cucgucgcca 120

ucgggaacu caagaaagac guauacgucg ucgaacuaga cugguacccc gacgcacccg 180

gagaaauggu aguacucaca ugcgacaccc ccgaagaaga cggcaucaca uggaccuuag 240

accaaucauc agaaguccuc ggauccggaa aaacccucac aauccaaguc aaagaguucg 300

gcgacgccgg ccaauacaca ugccacaaag gcggagaagu ccucucacac ucacuccuuc 360

uacuacacaa gaaagaagac ggcaucuggu ccaccgacau acucaaagac caaaaagaac 420

ccaaaaaca aaccuuccuc cgcugcgaag ccaaaaacua cuccggccga uucacaugcu 480

gguggcucac caccaucucc accgaccuga ccuucuccgu caaauccagc aggggcuccu 540

cagacccaca aggcguaacc ugcggcgcag ccacccuauc ggccgaacga guccgcggag 600

acaacaaaga auacgaauac agcgucgaau gccaagaaga cucagcaugc ccagcagccg 660

aagaaucacu ccccaucgaa gucauggucg acgccgucca caaacuaaaa uacgaaaacu 720

acacaagcuc auucuucauc cgcgacauaa ucaaacccga cccaccgaaa aaccuccaac 780

ucaaaccccu uaaaaacagc cgccaagucg aagucuccug ggaauacccc gacaccuggu 840

ccacacccca cuccuacuuc ucacucaccu ucugcgucca aguccaaggc aaauccaaac 900

gcgaaaagaa agaccgcgua uucaccgaca aaaccuccgc cacagucauc ugccgcaaaa 960

acgccucaau cuccguccgc gcccaagacc gauacuacag cuccuccugg ucagaauggg 1020

ccuccguccc augcuccggg agcacgagcg ggagcgggaa gccgggaagu ggagagggaa 1080

1140

accacucaca aaaccuccua cgcgccgucu caaacaugcu ucaaaaagcc cgacaaaccc 1200

ucgaauuuua ccccugcacc uccgaagaaa ucgaccacga agacauaacc aaagacaaaa 1260

ccuccaccgu cgaagccugc cuaccauuag aacuaaccaa aaacgaaucc ugccucaacu 1320

cacgcgaaac cuccuucauc acaaacggcu caugccucgc cucacgcaaa accuccuuca 1380

ugaggcccu cugccuauca ucaaucuaug aagaccucaa aauguaccaa guagaauuua 1440

aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc gaccaaaaca 1500

ugcucgcagu caucgacgaa cucaugcaag cccucaacuu caacucagaa acagucccac 1560

aaaaauccuc ccucgaagaa cccgacuucu auaaaaccaa aaucaaacuc ugcauccucc 1620

uccacgccuu ccgcauacgc gccguaacca ucgaccgcgu aaugucauac cuaaaugccu 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 385

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt8

<400> 385

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugauag 60

aaaccuacaa ccaaaccucu ccccgauccg cagccaccgg ccuccccauc uccaugaaaa 120

ucuucaugua ccuccuuaacc gucuuccuaa ucacucaaau gaucggcucc gcucucuucg 180

cagucuaccu ccaccgccgc cuagacaaaa ucgaagacga acgcaaccua cacgaagacu 240

ucgucuucau gaaaaccauu caacgcugca acacaggcga acgaucccua ucccuacuca 300

acugcgaaga aaucaaaucc caauucgaag gcuuuguaaa agacaucaug cucaacaaag 360

aagaaaccaa aaaagaaaac uccuucgaaa ugcaaaaagg cgaccaaaac ccccaaauag 420

ccgcccaugu cauaucagaa gccuccucca aaaccaccuc cguccuccaa ugggccgaaa 480

aaggcuacua caccaugucc aacaaccuag uaacccuuga aaacggcaaa caacucaccg 540

uaaaacgcca aggccucuac uacaucuacg cccaagucac cuucugcucc aacagagaag 600

cauccuccca agcacccuuc aucgccuccc uaugccucaa aucccccggc cgcuucgaac 660

gaauccuccu ccgcgccgcc aacacucacu ccucagccaa acccugcggc caacaaagua 720

uacaccuugg cggagucuuc gaacuccaac ccggcgccuc cgucuucgua aacgucaccg 780

accccucaca agucucccac ggaaccggau ucaccuccuu cggccuacua aaacuauagg 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 386

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt9

<400> 386

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

ucccccaagc cccauggccc gucgucggg ccguccucca acucggcugg cgccccggau 120

180

ucgucaccga aggcgacaac gccaccuuca ccuguucauu cuccaacacc ucagaauccu 240

ucguacucaa cugguaccgc auguccccaa gcaaccaaac agacaaacuc gccgccuucc 300

ccgaagaccg cucccaaccc ggucaagacu gccgauuccg cgucacccaa cuccccaacg 360

gacgcgacuu ccacaugucc gucguucgag cacgacgcaa cgacucaggc acauaccuau 420

gcggagccau cucccuagcc cccaaagccc aaaucaaaga aucacuacgc gccgaacucc 480

gcgucaccga acgccgcgcc gaaguaccca cagcccaccc auccccauca ccacgcccag 540

caggucaauu ccaaaccuua gucgucggag ucgucggcgg ccuccuaggc ucacucgucc 600

uccuagucug gguccucgcc gucauaugca gccgcgccgc acgcggcacc aucggcgcca 660

gacgcaccgg acaaccccuc aaagaagacc ccucagccgu ccccgucuuu uccgucgacu 720

acggcgaacu agacuuccaa uggcgcgaaa aaacccccga accccccguc ccaugcguac 780

ccgaacaaac cgaauacgcc acaauagucu ucccauccgg caugggaacc ucauacccg 840

ccagacgagg cucagcagau ggcccccgcu ccgcacaacc acuccgacca gaagacggcc 900

acugcagcug gccccuguaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 387

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt9

<400> 387

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

ucccccaagc cccauggccc gucgucggg ccguccucca acucggcugg cgccccggau 120

180

ucgucaccga aggcgacaac gccaccuuca ccuguucauu cuccaacacc ucagaauccu 240

ucguacucaa cugguaccgc auguccccaa gcaaccaaac agacaaacuc gccgccuucc 300

ccgaagaccg cucccaaccc ggucaagacu gccgauuccg cgucacccaa cuccccaacg 360

gacgcgacuu ccacaugucc gucguucgag cacgacgcaa cgacucaggc acauaccuau 420

gcggagccau cucccuagcc cccaaagccc aaaucaaaga aucacuacgc gccgaacucc 480

gcgucaccga acgccgcgcc uaaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 388

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt9

<400> 388

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagauc ccuccuccuc gucgcaaccc ucguccuccu cgaccaccuc ucccuagcac 120

guaaccuccc agucgccacc ccagaccccg gaauguuccc cugccuccau cacucccaaa 180

aucuccuccg ugccgucucc aacaugcucc aaaaagcccg ccaaacccuc gaauuuuauc 240

caugcaccuc cgaagaaaua gaccaugaag acaucaccaa agacaaaaca uccaccgucg 300

aagccugccu cccccucgaa cucacaaaaa acgaaucaug ccucaacucc cgcgaaaccu 360

ccuucauaac caacggcuca ugccucgccu cucgcaaaac cucauucaug auggcccucu 420

gccuauccuc uaucuacgaa gaccucaaaa uguaccaagu cgaauuuaaa accaugaacg 480

ccaaacuccu cauggacccc aaacgccaaa ucuuccucga ccaaaacaug cucgcaguca 540

ucgacgaacu caugcaagca cucaacuuca acucagaaac cgucccccaa aaauccuccc 600

ucgaagaacc cgacuucuac aaaacaaaaa uaaaacucug cauccuccuc cacgccuucc 660

gcauccgagc agucaccauc gaucgcguca uguccuaccu aaacgccucc uaaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 389

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt9

<400> 389

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgccagauc ccuccuccuc gucgcaaccc ucguccuccu cgaccaccuc ucccuagcac 120

guaaccuccc agucgccacc ccagaccccg gaauguuccc cugccuccau cacucccaaa 180

aucuccuccg ugccgucucc aacaugcucc aaaaagcccg ccaaacccuc gaauuuuauc 240

caugcaccuc cgaagaaaua gaccaugaag acaucaccaa agacaaaaca uccaccgucg 300

aagccugccu cccccucgaa cucacaaaaa acgaaucaug ccucaacucc cgcgaaaccu 360

ccuucauaac caacggcuca ugccucgccu cucgcaaaac cucauucaug auggcccucu 420

gccuauccuc uaucuacgaa gaccucaaaa uguaccaagu cgaauuuaaa accaugaacg 480

ccaaacuccu cauggacccc aaacgccaaa ucuuccucga ccaaaacaug cucgcaguca 540

ucgacgaacu caugcaagca cucaacuuca acucagaaac cgucccccaa aaauccuccc 600

ucgaagaacc cgacuucuac aaaacaaaaa uaaaacucug cauccuccuc cacgccuucc 660

gcauccgagc agucaccauc gaucgcguca uguccuaccu aaacgccucc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 390

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt9

<400> 390

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccguaacc 60

ucccagucgc caccccagac ccgggaaugu uccccugccu ccaucacucc caaaaucucc 120

uccgugccgu cuccaacaug cuccaaaaag cccgccaaac ccucgaauuu uauccaugca 180

ccuccgaaga aauagaccau gaagacauca ccaaagacaa aacauccacc gucgaagccu 240

gccucccccu cgaacucaca aaaaacgaau caugccucaa cucccgcgaa accuccuuca 300

uaaccaacgg cucaugccuc gccucucgca aaaccucauu caugauggcc cucugccuau 360

ccucuaucua cgaagaccuc aaaauguacc aagucgaauu uaaaaccaug aacgccaaac 420

uccucaugga ccccaaacgc caaaucuucc ucgaccaaaa caugcucgca gucaucgacg 480

aacucaugca agcacucaac uucaacucag aaaccguccc ccaaaaaucc ucccucgaag 540

aacccgacuu cuacaaaaca aaaauaaaac ucugcauccu ccuccacgcc uuccgcaucc 600

660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 391

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt9

<400> 391

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accaacaacu uguaaucagc ugguucuccc ucgucuuccu cgccucaccc cucgucgcca 120

ucgggaacu caaaaaagac gucuacguag ucgaacucga cugguacccc gacgccccag 180

gagaaauggu cguacucacc ugugacaccc ccgaagaaga cggcaucacc uggacccucg 240

accaauccuc cgaaguccuc gguucaggaa aaacccucac cauccaagua aaagaauuug 300

gcgacgccgg gcaauauacc ugccacaaag gcggcgaggu ccuaucccac ucacuccucc 360

uccuccacaa gaaagaagac ggaaucuggu ccaccgacau ccuuaaagac caaaaagaac 420

caaaaaaca aacauuccuc cgcugcgaag ccaaaaacua cagcggccgc uucaccuguu 480

gguggcuaac cacaauauca accgacuuaa ccuucagcgu caaauccucc agaggaucca 540

gcgacccaca aggaguuacc ugcggagccg caacacucag cgccgaacga guccgcggag 600

acaacaaaga auacgaauac uccgucgaau gccaagaaga cucagcaugc cccgccgcag 660

aagaaucccu acccaucgaa guaaugguag acgccgucca caaacucaaa uacgaaaacu 720

acaccagcuc cuucuucauc cgagacauca ucaacccga ccccccaaaa aaccuccaac 780

uaaaaccccu caaaaacagc cgccaaguag aaguauccug ggaauacccc gacaccuggu 840

ccacacccca cuccuacuuc ucgcucacgu ucugcgucca aguccaaggc aaauccaaac 900

gagaaaaaaa agaccgcguc uucaccgaca aaacuuccgc caccgucauc ugccgcaaaa 960

acgccagcau cagcguccgc gcacaagacc gcuacuacuc aagcuccugg uccgaauggg 1020

ccuccguccc augcucauaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 392

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt9

<400> 392

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accaacaacu uguaaucagc ugguucuccc ucgucuuccu cgccucaccc cucgucgcca 120

ucgggaacu caaaaaagac gucuacguag ucgaacucga cugguacccc gacgccccag 180

gagaaauggu cguacucacc ugugacaccc ccgaagaaga cggcaucacc uggacccucg 240

accaauccuc cgaaguccuc gguucaggaa aaacccucac cauccaagua aaagaauuug 300

gcgacgccgg gcaauauacc ugccacaaag gcggcgaggu ccuaucccac ucacuccucc 360

uccuccacaa gaaagaagac ggaaucuggu ccaccgacau ccuuaaagac caaaaagaac 420

caaaaaaca aacauuccuc cgcugcgaag ccaaaaacua cagcggccgc uucaccuguu 480

gguggcuaac cacaauauca accgacuuaa ccuucagcgu caaauccucc agaggaucca 540

gcgacccaca aggaguuacc ugcggagccg caacacucag cgccgaacga guccgcggag 600

acaacaaaga auacgaauac uccgucgaau gccaagaaga cucagcaugc cccgccgcag 660

aagaaucccu acccaucgaa guaaugguag acgccgucca caaacucaaa uacgaaaacu 720

acaccagcuc cuucuucauc cgagacauca ucaacccga ccccccaaaa aaccuccaac 780

uaaaaccccu caaaaacagc cgccaaguag aaguauccug ggaauacccc gacaccuggu 840

ccacacccca cuccuacuuc ucgcucacgu ucugcgucca aguccaaggc aaauccaaac 900

gagaaaaaaa agaccgcguc uucaccgaca aaacuuccgc caccgucauc ugccgcaaaa 960

acgccagcau cagcguccgc gcacaagacc gcuacuacuc aagcuccugg uccgaauggg 1020

ccuccguccc augcucagga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 393

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt9

<400> 393

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

aacucaaaaa agacgucuac guagucgaac ucgacuggua ccccgacgcc ccaggagaaa 120

uggucguacu caccugugac accccgaag aagacggcau caccuggacc cucgaccaau 180

ccuccgaagu ccucgguuca ggaaaaaccc ucaccaucca aguaaaagaa uuuggcgacg 240

ccgggcaaua uaccugccac aaaggcggcg agguccuauc ccacucacuc cuccuccucc 300

360

acaaaacauu ccuccgcugc gaagccaaaa acuacagcgg ccgcuucacc uguugguggc 420

uaaccacaau aucaaccgac uuaaccuuca gcgucaaauc cuccagagga uccagcgacc 480

cacaaggagu uaccugcgga gccgcaacac ucagcgccga acgaguccgc ggagacaaca 540

aagaauacga auacuccguc gaaugccaag aagacucagc augccccgcc gcagaagaau 600

cccuacccau cgaaguaaug guagacgccg uccacaaacu caaauacgaa aacuacacca 660

gcuccuucuu cauccgagac aucaucaaac ccgacccccc aaaaaaccuc caacuaaaac 720

cccucaaaaa cagccgccaa guagaaguau ccgggaaua ccccgacacc ugguccacac 780

cccacuccua cuucucgcuc acguucugcg uccaagucca aggcaaaucc aaacgagaaa 840

aaaaagaccg cgucuucacc gacaaaacuu ccgccaccgu caucugccgc aaaaacgcca 900

gcaucagcgu ccgcgcacaa gaccgcuacu acucaagcuc cugguccgaa ugggccuccg 960

ucccaugcuc auaaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 394

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt9

<400> 394

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accgggagua 60

120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 395

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt9

<400> 395

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accaacaacu uguaaucagc ugguucuccc ucgucuuccu cgccucaccc cucgucgcca 120

ucgggaacu caaaaaagac gucuacguag ucgaacucga cugguacccc gacgccccag 180

gagaaauggu cguacucacc ugugacaccc ccgaagaaga cggcaucacc uggacccucg 240

accaauccuc cgaaguccuc gguucaggaa aaacccucac cauccaagua aaagaauuug 300

gcgacgccgg gcaauauacc ugccacaaag gcggcgaggu ccuaucccac ucacuccucc 360

uccuccacaa gaaagaagac ggaaucuggu ccaccgacau ccuuaaagac caaaaagaac 420

caaaaaaca aacauuccuc cgcugcgaag ccaaaaacua cagcggccgc uucaccuguu 480

gguggcuaac cacaauauca accgacuuaa ccuucagcgu caaauccucc agaggaucca 540

gcgacccaca aggaguuacc ugcggagccg caacacucag cgccgaacga guccgcggag 600

acaacaaaga auacgaauac uccgucgaau gccaagaaga cucagcaugc cccgccgcag 660

aagaaucccu acccaucgaa guaaugguag acgccgucca caaacucaaa uacgaaaacu 720

acaccagcuc cuucuucauc cgagacauca ucaacccga ccccccaaaa aaccuccaac 780

uaaaaccccu caaaaacagc cgccaaguag aaguauccug ggaauacccc gacaccuggu 840

ccacacccca cuccuacuuc ucgcucacgu ucugcgucca aguccaaggc aaauccaaac 900

gagaaaaaaa agaccgcguc uucaccgaca aaacuuccgc caccgucauc ugccgcaaaa 960

acgccagcau cagcguccgc gcacaagacc gcuacuacuc aagcuccugg uccgaauggg 1020

ccuccguccc augcucaggg aguacgagug ggagugggaa gccgggggagu ggggagggga 1080

1140

aucacuccca aaaucuccuc cgugccgucu ccaacaugcu ccaaaaagcc cgccaaaccc 1200

ucgaauuuua uccaugcacc uccgaagaaa uagaccauga agacaucacc aaagacaaaa 1260

cauccaccgu cgaagccugc cucccccucg aacucacaaa aaacgaauca ugccucaacu 1320

cccgcgaaac cuccuucaua accaacggcu caugccucgc cucucgcaaa accucauuca 1380

ugaggcccu cugccuaucc ucuaucuacg aagaccucaa aauguaccaa gucgaauuua 1440

aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc gaccaaaaca 1500

ugcucgcagu caucgacgaa cucaugcaag cacucaacuu caacucagaa accguccccc 1560

aaaaauccuc ccucgaagaa cccgacuucu acaaaacaaa aauaaaacuc ugcauccucc 1620

uccacgccuu ccgcauccga gcagucacca ucgaucgcgu cauguccuac cuaaacgccu 1680

ccuaaggacu agugcaucac auuuaaaagc aucucagccu accaugagaa uaagagaaag 1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 396

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt9

<400> 396

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

aaacauacaa ccaaacaucc ccccgcuccg ccgccacagg ccuccccauc uccaugaaaa 120

ucuucaugua ccuccucaca guauuccuca ucacccaaau gaucggcucc gcacucuuug 180

cagucuaucu ccaccgucgc cucgacaaaa ucgaagacga acgcaaccuc cacgaagacu 240

ucgucuucau gaaaaccaua caacgcugca acaccggcga acgcucacuc ucccuacuaa 300

360

aagaaacaaa aaaagaaaac uccuucgaaa ugcaaaaagg cgaccaaaac ccccaaauag 420

ccgcccacgu caucuccgaa gccuccucca aaaccaccuc cguccuccaa ugggccgaaa 480

aaggcuacua cacaaugucc aacaaccucg ucacccucga aaacggcaaa caacucaccg 540

ucaaacgcca aggccucuac uacaucuacg cccaaguaac cuucugcucc aaccgcgaag 600

ccucaucuca agcucccuuc aucgccucac ucugccucaa aucacccggc cgcuucgaaa 660

gaauccuccu ccgcgccgca aacacccacu cauccgccaa acccugcggc caacaaucca 720

uacaccucgg cggcguuuuc gagcuccaac cuggcgccuc cgucuucgua aacgucaccg 780

accccucaca agucucccac gguaccggcu ucaccuccuu cggacuccua aaacucuaag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 397

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR opt10

<400> 397

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

ucccccaagc ccccuggccg gucgucuggg ccguccucca acucggcugg cgccccggau 120

gguuccucga cucccccgac cgcccgugga acccccccac cuucuccccc gcccuccuag 180

ucgucaccga aggcgacaac gccaccuuca ccuguuccuu cuccaacacc ucagaauccu 240

ucguccucaa cugguaccgc augucccccu ccaaccaaac cgacaaacuc gccgccuucc 300

ccgaagaccg aucccaaccc ggccaagacu gccgcuuccg cgucacacaa cuucccaacg 360

gacgcgacuu ucacaugucc gucguccgcg cccgccgcaa cgacuccggc accuaccucu 420

gcggcgccau cucccucgcc cccaaagccc aaaucaaaga aucccucaga gccgaacucc 480

gcgucaccga acggcgcgcc gaagucccca cugcccaccc cucccccucc ccccgccccg 540

ccggccaauu ccaaacccuc gucgucggcg uugucggcgg ccuccucggc ucacucgucc 600

uccucgucug gguacucgcc gucaucugcu cccgcgccgc gcgcggcacc aucggcgcgc 660

gccgcaccgg acaaccccua aaagaagacc ccuccgccgu ccccgucuuc uccgucgacu 720

acggcgaacu cgacuuccaa uggcgcgaaa aaacccggga accccccguc ccgugcgucc 780

ccgaacaaac agaauacgcg accaucgucu ucccguccgg caugggcaca uccucacccg 840

cccgccgagg cuccgccgac ggcccccgau ccgcccaacc ccuacgcccc gaagacggcc 900

acugcuccug gccccucuaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 398

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR opt10

<400> 398

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaaa 60

ucccccaagc ccccuggccg gucgucuggg ccguccucca acucggcugg cgccccggau 120

gguuccucga cucccccgac cgcccgugga acccccccac cuucuccccc gcccuccuag 180

ucgucaccga aggcgacaac gccaccuuca ccuguuccuu cuccaacacc ucagaauccu 240

ucguccucaa cugguaccgc augucccccu ccaaccaaac cgacaaacuc gccgccuucc 300

ccgaagaccg aucccaaccc ggccaagacu gccgcuuccg cgucacacaa cuucccaacg 360

gacgcgacuu ucacaugucc gucguccgcg cccgccgcaa cgacuccggc accuaccucu 420

gcggcgccau cucccucgcc cccaaagccc aaaucaaaga aucccucaga gccgaacucc 480

gcgucaccga acggcgcgcc uaaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 399

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR opt10

<400> 399

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgcccguuc acuccuccuc gucgccaccc ucguccuccu agaccaccuc ucccuggccc 120

gcaaccuccc agucgccacc cccgaccccg gcauguuccc cugccuccac cacucccaaa 180

accuccuccg cgccgucucc aacaugcucc aaaaagcccg ccaaacccuc gaauuuuacc 240

ccugcaccuc cgaagagauc gaccacgaag acaucaccaa agacaaaacc uccacagucg 300

aagccugccu cccccucgaa cucaccaaaa acgaauccug ccuuaacucc cgcgaaaccu 360

420

gccucuccuc caucuacgaa gaccucaaaa uguaccaagu cgaauuuaaa accaugaacg 480

ccaaacuccu cauggacccc aaacgccaaa ucuuccucga ccaaaacaug cucgccguca 540

ucgacgaacu caugcaagcc cucaacuuca acuccgaaac cgucccccaa aaauccuccc 600

ucgaagaacc cgacuucuac aaaaccaaaa ucaaacuuug cauccuccuc cacgcauucc 660

gcauccgcgc cgucaccauc gaccguguca ugagcuaccu aaacgccucc ugaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 400

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR opt10

<400> 400

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

ccgcccguuc acuccuccuc gucgccaccc ucguccuccu agaccaccuc ucccuggccc 120

gcaaccuccc agucgccacc cccgaccccg gcauguuccc cugccuccac cacucccaaa 180

accuccuccg cgccgucucc aacaugcucc aaaaagcccg ccaaacccuc gaauuuuacc 240

ccugcaccuc cgaagagauc gaccacgaag acaucaccaa agacaaaacc uccacagucg 300

aagccugccu cccccucgaa cucaccaaaa acgaauccug ccuuaacucc cgcgaaaccu 360

420

gccucuccuc caucuacgaa gaccucaaaa uguaccaagu cgaauuuaaa accaugaacg 480

ccaaacuccu cauggacccc aaacgccaaa ucuuccucga ccaaaacaug cucgccguca 540

ucgacgaacu caugcaagcc cucaacuuca acuccgaaac cgucccccaa aaauccuccc 600

ucgaagaacc cgacuucuac aaaaccaaaa ucaaacuuug cauccuccuc cacgcauucc 660

gcauccgcgc cgucaccauc gaccguguca ugagcuaccu aaacgccucc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 401

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR opt10

<400> 401

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu acccgcaacc 60

ucccagucgc cacccccgac cccggcaugu uccccugccu ccaccacucc caaaaccucc 120

uccgcgccgu cuccaacaug cuccaaaaag cccgccaaac ccucgaauuu uaccccugca 180

ccuccgaaga gaucgaccac gaagacauca ccaaagacaa aaccuccaca gucgaagccu 240

gccuccccccu cgaacucacc aaaaacgaau ccugccuuaa cucccgcgaa accuccuuca 300

ucaccaacgg cuccugccuc gccucccgca aaaccuccuu caugauggcc cucugccucu 360

ccuccaucua cgaagaccuc aaaauguacc aagucgaauu uaaaaccaug aacgccaaac 420

uccucaugga ccccaaacgc caaaucuucc ucgaccaaaa caugcucgcc gucaucgacg 480

aacucaugca agcccucaac uucaacuccg aaaccguccc ccaaaaaucc ucccucgaag 540

aacccgacuu cuacaaaacc aaaaucaaac uuugcauccu ccuccacgca uuccgcaucc 600

gcgccgucac caucgaccgu gucaugagcu accuaaacgc cuccuggga cuagugcauc 660

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 402

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR opt10

<400> 402

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu cgucaucucc ugguucuccc ucgucuuccu agccucccca cucgucgcca 120

ucgggaacu caaaaaagac guauacgucg ucgaacucga cugguacccc gacgccccag 180

gagaaauggu cguccuaacc ugcgacacac ccgaagaaga cgguaucacc uggacccucg 240

accaauccuc cgaaguccua ggcuccggca agacccucac cauccaaguc aaagaauuug 300

gcgacgcagg acaauacacc ugucacaaag gcggcgaagu ccucagccac agccuucucc 360

uacuccauaa aaaagaagac ggcaucuggu ccacugacau ccucaaagac caaaaagaac 420

ccaaaaauaa aaccuuccuc cgcugcgaag ccaaaaacua cuccggccga uucaccuguu 480

gguggcuaac cacaaucagc accgaccuca ccuuucucagu caaauccucc cgcggcucau 540

cugaccccca aggcgucaca ugcggcgccg ccacccucuc cgccgaacgc guccgcggcg 600

acaacaaaga auacgaauac uccgucgaau gucaagaaga cuccgccugc cccgccgccg 660

aagaaucacu ccccaucgaa gucauggucg acgcagucca caaacucaaa uacgaaaacu 720

acaccuccuc cuucuucauc cgcgacauaa uaaaacccga cccacccaaa aaccuccaac 780

ucaagccacu caaaaacucc cgacaagucg aagucuccug ggaguacccc gacaccuggu 840

ccacaccaca cuccuacuuc ucccucaccu ucugcgucca aguccaaggc aaauccaaac 900

gcgaaaaaaa agaccgcguu uucacagaca aaaccuccgc cacaguaaua ugccgcaaaa 960

acgccuccau cuccguccgg gcccaagacc gcuacuacuc cuccuccugg uccgaguggg 1020

ccucaguccc cugcagcuaa ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 403

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR opt10

<400> 403

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu cgucaucucc ugguucuccc ucgucuuccu agccucccca cucgucgcca 120

ucgggaacu caaaaaagac guauacgucg ucgaacucga cugguacccc gacgccccag 180

gagaaauggu cguccuaacc ugcgacacac ccgaagaaga cgguaucacc uggacccucg 240

accaauccuc cgaaguccua ggcuccggca agacccucac cauccaaguc aaagaauuug 300

gcgacgcagg acaauacacc ugucacaaag gcggcgaagu ccucagccac agccuucucc 360

uacuccauaa aaaagaagac ggcaucuggu ccacugacau ccucaaagac caaaaagaac 420

ccaaaaauaa aaccuuccuc cgcugcgaag ccaaaaacua cuccggccga uucaccuguu 480

gguggcuaac cacaaucagc accgaccuca ccuuucucagu caaauccucc cgcggcucau 540

cugaccccca aggcgucaca ugcggcgccg ccacccucuc cgccgaacgc guccgcggcg 600

acaacaaaga auacgaauac uccgucgaau gucaagaaga cuccgccugc cccgccgccg 660

aagaaucacu ccccaucgaa gucauggucg acgcagucca caaacucaaa uacgaaaacu 720

acaccuccuc cuucuucauc cgcgacauaa uaaaacccga cccacccaaa aaccuccaac 780

ucaagccacu caaaaacucc cgacaagucg aagucuccug ggaguacccc gacaccuggu 840

ccacaccaca cuccuacuuc ucccucaccu ucugcgucca aguccaaggc aaauccaaac 900

gcgaaaaaaa agaccgcguu uucacagaca aaaccuccgc cacaguaaua ugccgcaaaa 960

acgccuccau cuccguccgg gcccaagacc gcuacuacuc cuccuccugg uccgaguggg 1020

ccucaguccc cugcagcgga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 404

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR opt10

<400> 404

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaucuggg 60

aacucaaaaa agacguauac gucgucgaac ucgacuggua ccccgacgcc ccaggagaaa 120

uggucguccu aaccugcgac acacccgaag aagacgguau caccuggacc cucgaccaau 180

ccuccgaagu ccuaggcucc ggcaagaccc ucaccaucca agucaaagaa uuuggcgacg 240

caggacaua caccugucac aaaggcggcg aaguccucag ccacagccuu cuccuacucc 300

auaaaaaaga agacggcauc ugguccacug acauccucaa agaccaaaaa gaacccaaaa 360

auaaaaccuu ccuccgcugc gaagccaaaa acuacuccgg cggauucacc uguugguggc 420

uaaccacaau cagcaccgac cucaccuucu cagucaaauc cucccgcggc ucaucugacc 480

cccaaggcgu cacaugcggc gccgccaccc ucuccgccga acgcguccgc ggcgacaaca 540

aagaauacga auacuccguc gaaugucaag aagacuccgc cugccccgcc gccgaagaau 600

cacuccccau cgaagucaug gucgacgcag uccacaaacu caaauacgaa aacuacaccu 660

ccuccuucuu cauccgcgac auaauaaaac ccgacccacc caaaaaccuc caacucaagc 720

cacucaaaaa cucccgacaa gucgaagucu ccugggagua ccccgacacc ugguccacac 780

cacacuccua cuucucccuc accuucugcg uccaagucca aggcaaaucc aaacgcgaaa 840

aaaaagaccg cguuuucaca gacaaaaccu ccgccacagu aauaugccgc aaaaacgccu 900

ccaucuccgu ccgggcccaa gaccgcuacu acuccuccuc cugguccgag ugggccucag 960

ucccugcag cuaaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 405

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR opt10

<400> 405

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accgggagua 60

120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 406

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR opt10

<400> 406

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accaacaacu cgucaucucc ugguucuccc ucgucuuccu agccucccca cucgucgcca 120

ucgggaacu caaaaaagac guauacgucg ucgaacucga cugguacccc gacgccccag 180

gagaaauggu cguccuaacc ugcgacacac ccgaagaaga cgguaucacc uggacccucg 240

accaauccuc cgaaguccua ggcuccggca agacccucac cauccaaguc aaagaauuug 300

gcgacgcagg acaauacacc ugucacaaag gcggcgaagu ccucagccac agccuucucc 360

uacuccauaa aaaagaagac ggcaucuggu ccacugacau ccucaaagac caaaaagaac 420

ccaaaaauaa aaccuuccuc cgcugcgaag ccaaaaacua cuccggccga uucaccuguu 480

gguggcuaac cacaaucagc accgaccuca ccuuucucagu caaauccucc cgcggcucau 540

cugaccccca aggcgucaca ugcggcgccg ccacccucuc cgccgaacgc guccgcggcg 600

acaacaaaga auacgaauac uccgucgaau gucaagaaga cuccgccugc cccgccgccg 660

aagaaucacu ccccaucgaa gucauggucg acgcagucca caaacucaaa uacgaaaacu 720

acaccuccuc cuucuucauc cgcgacauaa uaaaacccga cccacccaaa aaccuccaac 780

ucaagccacu caaaaacucc cgacaagucg aagucuccug ggaguacccc gacaccuggu 840

ccacaccaca cuccuacuuc ucccucaccu ucugcgucca aguccaaggc aaauccaaac 900

gcgaaaaaaa agaccgcguu uucacagaca aaaccuccgc cacaguaaua ugccgcaaaa 960

acgccuccau cuccguccgg gcccaagacc gcuacuacuc cuccuccugg uccgaguggg 1020

ccucaguccc cugcagcggg aguacgagug ggagugggaa gccgggggagu ggggagggga 1080

1140

accacuccca aaaccuccuc cgcgccgucu ccaacaugcu ccaaaaagcc cgccaaaccc 1200

ucgaauuuua ccccugcacc uccgaagaga ucgaccacga agacaucacc aaagacaaaa 1260

ccuccacagu cgaagccugc cucccccucg aacucaccaa aaacgaaucc ugccuuaacu 1320

cccgcgaaac cuccuucauc accaacggcu ccugccucgc cucccgcaaa accuccuuca 1380

ugaggcccu cugccucucc uccaucuacg aagaccucaa aauguaccaa gucgaauuua 1440

aaaccaugaa cgccaaacuc cucauggacc ccaaacgcca aaucuuccuc gaccaaaaca 1500

ugcucgccgu caucgacgaa cucaugcaag cccucaacuu caacuccgaa accguccccc 1560

aaaaauccuc ccucgaagaa cccgacuucu acaaaaccaa aaucaaacuu ugcauccucc 1620

uccacgcauu ccgcauccgc gccgucacca ucgaccgugu caugagcuac cuaaacgccu 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 407

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR opt10

<400> 407

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

aaaccuacaa ucaaaccucc ccccgcagcg ccgcaacagg ccuccccauc uccaugaaaa 120

ucuucaugua ccuccucacc gucuuccuaa ucacccaaau gaucggcucc gcccuauucg 180

ccgucuaccu ccaccgccgc cucgacaaaa ucgaagacga acgcaaccuc cacgaagacu 240

uugucuucau gaaaacuauc caacgaugca acaccggcga acgaucccua ucccuccuca 300

360

aagaaaccaa aaaagaaaac uccuucgaaa ugcaaaaagg cgaccaaaac ccccaaaucg 420

cagcccacgu caucucagaa gcaucuucca aaaccaccuc cguccuccaa ugggccgaaa 480

aaggcuacua caccauguca aacaaccucg ucacccucga aaacggcaaa caacucaccg 540

ucaaacgcca aggccucuac uacaucuacg cacaagucac cuucugcucc aaccgcgaag 600

cauccuccca agcccccuuc aucgccuccc ucugccucaa aucccccggc cgcuucgaac 660

gcauccuccu ccgcgccgca aauacccacu ccuccgccaa accaugcggc caacaaucca 720

uccaccucgg cggcgucuuc gaacuccaac ccggcgccuc cgucuucguc aacgucaccg 780

accccucca aguaucccau ggaaccggcu ucaccuccuu cggccuccuc aaacucuagg 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 408

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> 5-UTR of human ribosomal protein Large 32 lacking the 5 terminal

oligopyrimidine tract

<400> 408

ggcgctgcct acggaggtgg cagccatctc cttctcggca tc 42

<210> 409

<211> 42

<212>RNA

<213> Artificial Sequence

<220>

<223> 5-UTR of human ribosomal protein Large 32 lacking the 5 terminal

oligopyrimidine tract mRNA

<400> 409

ggcgcugccu acggaggugg cagccaucuc cuucucggca uc 42

<210> 410

<211> 75

<212> DNA

<213> Artificial Sequence

<220>

<223> 5-UTR of human mitochondrial ATP synthase subunit alpha lacking

the 5 terminal oligopyrimidine tract

<400> 410

gcggctcggc cattttgtcc cagtcagtcc ggaggctgcg gctgcagaag taccgcctgc 60

ggagtaactg caaag 75

<210> 411

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> 5-UTR of human mitochondrial ATP synthase subunit alpha lacking

the 5 terminal oligopyrimidine tract mRNA

<400> 411

gcggcucggc cauuuugucc cagucagucc ggaggcugcg gcugcagaag uaccgccugc 60

ggaguaacug caaag 75

<210> 412

<211> 110

<212> DNA

<213> Artificial Sequence

<220>

<223> 3-UTR of Homo sapiens hemoglobin, alpha 1 (HBA1)

<400> 412

gctggagcct cggtggccat gcttcttgcc ccttgggcct ccccccagcc cctcctcccc 60

ttcctgcacc cgtacccccg tggtctttga ataaagtctg agtgggcggc 110

<210> 413

<211> 110

<212>RNA

<213> Artificial Sequence

<220>

<223> 3-UTR of Homo sapiens hemoglobin, alpha 1 (HBA1) mRNA

<400> 413

gcuggagccu cgguggccau gcuucuugcc ccuugggccu ccccccagcc ccuccucccc 60

uuccugcacc cguacccccg uggucuuuga auaaagucug agugggcggc 110

<210> 414

<211> 108

<212> DNA

<213> Artificial Sequence

<220>

<223> 3-UTR of Homo sapiens hemoglobin, alpha 2 (HBA2)

<400> 414

gctggagcct cggtagccgt tcctcctgcc cgctgggcct cccaacggggc cctcctcccc 60

tccttgcacc ggcccttcct ggtctttgaa taaagtctga gtgggcag 108

<210> 415

<211> 108

<212>RNA

<213> Artificial Sequence

<220>

<223> 3-UTR of Homo sapiens hemoglobin, alpha 2 (HBA2) mRNA

<400> 415

gcuggagccu cgguagccgu uccuccugcc cgcugggccu cccaacgggc ccuccucccc 60

uccuugcacc gggcccuuccu ggucuuugaa uaaagucuga gugggcag 108

<210> 416

<211> 132

<212> DNA

<213> Artificial Sequence

<220>

<223> 3-UTR of Homo sapiens hemoglobin, beta (HBB)

<400> 416

gctcgctttc ttgctgtcca atttctatta aaggttcctt tgttccctaa gtccaactac 60

taaactgggg gatattatga agggccttga gcatctggat tctgcctaat aaaaaacatt 120

tattttcatt gc 132

<210> 417

<211> 132

<212>RNA

<213> Artificial Sequence

<220>

<223> 3-UTR of Homo sapiens hemoglobin, beta (HBB) mRNA

<400> 417

gcucgcuuuc uugcugucca auuucuauua aagguuccuu uguucccuaa guccaacuac 60

uaaacugggg gauauuauga agggccuuga gcaucuggau ucugccuaau aaaaaacauu 120

uauuuucauu gc 132

<210> 418

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Center, alpha-complex-binding portion of the 3UTR of an

alpha-globin gene (muag)

<400> 418

gcccgatggg cctcccaacg ggccctcctc ccctccttgc accg 44

<210> 419

<211> 44

<212>RNA

<213> Artificial Sequence

<220>

<223> Center, alpha-complex-binding portion of the 3UTR of an

alpha-globin gene (muag) mRNA

<400> 419

gcccgauggg ccucccaacg ggcccuccuc cccuccuugc accg 44

<210> 420

<211> 186

<212> DNA

<213> Artificial Sequence

<220>

<223> 3-UTR of human albumin

<400> 420

catcacattt aaaagcatct cagcctacca tgagaataag agaaagaaaa tgaagatcaa 60

aagcttattc atctgttttt ctttttcgtt ggtgtaaagc caacaccctg tctaaaaaac 120

ataaatttct ttaatcattt tgcctctttt ctctgtgctt caattaataa aaaatggaaa 180

gaatct 186

<210> 421

<211> 186

<212>RNA

<213> Artificial Sequence

<220>

<223> 3-UTR of human albumin mRNA

<400> 421

caucacauuu aaaagcaucu cagccuacca ugagaauaag agaaagaaaa ugaagaucaa

aagcuuauuc aucuguuuuu cuuuuucguu gguguaaagc caacacccug ucuaaaaaac 120

180

gaucu 186

<210> 422

<211> 186

<212> DNA

<213> Artificial Sequence

<220>

<223> 3-UTR albumin7

<400> 422

catcacattt aaaagcatct cagcctacca tgagaataag agaaagaaaa tgaagatcaa 60

tagcttattc atctcttttt ctttttcgtt ggtgtaaagc caacaccctg tctaaaaaac 120

ataaatttct ttaatcattt tgcctctttt ctctgtgctt caattaataa aaaatggaaa 180

gaacct 186

<210> 423

<211> 186

<212>RNA

<213> Artificial Sequence

<220>

<223> 3-UTR albumin7 mRNA

<400> 423

caucacauuu aaaagcaucu cagccuacca ugagaauaag agaaagaaaa ugaagaucaa 60

uagcuuauuc aucucuuuuu cuuuuucguu gguguaaagc caacacccug ucuaaaaaac 120

180

gaaccu 186

<210> 424

<211> 187

<212> DNA

<213> Artificial Sequence

<220>

<223> 3-UTR ALB7

<400> 424

gcatcacatt taaaagcatc tcagcctacc atgagaataa gagaaagaaa atgaagatca 60

atagcttatt catctctttt tctttttcgt tggtgtaaag ccaacaccct gtctaaaaaa 120

cataaatttc tttaatcatt ttgcctcttt tctctgtgct tcaattaata aaaaatggaa 180

agaacct 187

<210> 425

<211> 187

<212>RNA

<213> Artificial Sequence

<220>

<223> 3-UTR ALB7 mRNA

<400> 425

gcaucacauu uaaaagcauc ucagccuacc augagaauaa gagaaagaaa augaagauca 60

120

cauaaauuuc uuuaaucauu uugccucuuu ucucugugcu ucaauuuaaua aaaaauggaa 180

agaaccu 187

<210> 426

<211> 24

<212> DNA

<213> Artificial Sequence

<220>

<223> histone stem-loop sequence

<400> 426

caaaggctct tttcagagcc acca 24

<210> 427

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> histone stem-loop sequence mRNA

<400> 427

caaaggcucu uuucagagcc acca 24

<210> 428

<211> 13

<212> DNA

<213> Artificial Sequence

<220>

<223> Kozak

<400> 428

gccgccacca tgg 13

<210> 429

<211> 13

<212>RNA

<213> Artificial Sequence

<220>

<223> Kozak mRNA

<400> 429

gccgccacca ugg 13

<210> 430

<211> 2023

<212>RNA

<213> Artificial Sequence

<220>

<223> R2763 MmIL-12 mRNA product TOP UTR opt1

<400> 430

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

cccagaagcu gaccaucagc ugguucgcca ucgugcuccu ggucuccccg cugauggcca 120

ugugggagcu cgagaaggac guguacgugg ucgaggugga cuggaccccc gacgcgcccg 180

gcgagacggu gaaccugacc ugcgacaccc ccgaggagga cgacaucacc uggacgagcg 240

accagcggca cggggucauc ggcuccggga agacccugac caucaccgug aaggaguucc 300

ucgacgccgg ccaguaacacg ugccacaagg gcggcgagac ccugagccac ucccaccugc 360

uccugcacaa gaaggagaac gggaucugga gcaccgagau ccugaagaac uucaagaaca 420

agaccuuccu caagugcgag gccccgaacu acuccgggcg cuucacgugc agcuggcugg 480

ugcagcggaa cauggaccug aaguucaaca ucaaguccag cuccagcucc cccgacagcc 540

gcgccgucac cugcggcaug gccucccuca gcgcggagaa ggugacccug gaccagcggg 600

acuacgagaa guacuccgug agcugccagg aggacgucac cugccccacg gccgaggaga 660

cccugcccau cgagcucgcc cuggaggccc gccagcagaa caaguacgag aacuacucca 720

ccagcuucuu cauccgggac aucaucaagc cggacccccc caagaaccug cagaugaagc 780

cccucaagaa cagccaggug gagguguccu gggaguaccc ggacagcugg uccaccccgc 840

acagcuacuu cucccugaag uucuucgucc gcauccagcg gaagaaggag aagaugaagg 900

agacggagga ggggugcaac cagaagggcg cguuccuggu ggagaagacc agcaccgagg 960

ugcagugcaa gggcgggaac gucugcgugc aggccgga ccgguacuac aacuccagcu 1020

1080

agccugguag uggugagggu aguacuaagg gucgcgugau ccccgucagc ggcccggccc 1140

ggugccuguc ccagagccgc aaccugcuca agaccacggga cgacauggug aagaccgccc 1200

gggagaagcu gaagcacuac uccugcaccg ccgaggacau cgaccacgag gacaucaccc 1260

gcgaccagac gagcacccug aagaccugcc uccccugga gcugcacaag aacgaguccu 1320

1380

ccucccugau gaugacgcuc ugccugggca gcaucuacga ggaccugaag auguaccaga 1440

ccgaguucca ggcgaucaac gccgcccucc agaaccacaa ccaccagcag aucauccugg 1500

acaaggggau gcugguggcc aucgacgagc ucaugcaguc ccugaaccac aacggcgaga 1560

cccugcggca gaagccgccc gucggggagg cggaccccua ccgcgugaag augaagcucu 1620

1680

ucuccagcgc cugaggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1740

1800

1860

cuucaauuaa uaaaaaaugg aaagaaccua gaucuaaaaa aaaaaaaaaa aaaaaaaaaa 1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccccc cccccccccc 1980

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 2023

<210> 431

<211> 856

<212>RNA

<213> Artificial Sequence

<220>

<223> R3971 MmPdcd1(1-157,C83S) mRNA product TOP UTR opt1

<400> 431

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguggg 60

ugcgccaggu ccccuggagc uucaccggg ccgugcugca gcucuccugg cagagcggcu 120

ggcugcugga ggugccgaac gggcccuggc ggucccucac cuucuacccc gccuggcuga 180

cggucagcga gggcgcgaac gccaccuuca ccugcucccu gagcaacugg uccgaggacc 240

ucaugcugaa cuggaaccgc cugagccccu ccaaccagac cgagaagcag gccgccuuca 300

gcaacgggcu cucccagccg gugcaggacg cccgguucca gaucauccag cugcccaacc 360

gccacgacuu ccacaugaac auccuggaca cgcggcgcaa cgacagcggc aucuaccucu 420

gcggggcgau cucccugcac cccaaggcca agaucgagga gagccccggc gccgagcugg 480

uggucaccga gcggauccuc gagaccucca cccgcuaccc gagcugagga cuagugcauc 540

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 600

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 660

auuucuuuaa ucauuuugcc ucuuuucucu gugcuucaau uaauaaaaaa uggaaagaac 720

780

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 840

cagagccacc agaauu 856

<210> 432

<211> 1165

<212>RNA

<213> Artificial Sequence

<220>

<223> R3571 MmCd40lg mRNA product TOP UTR opt1

<400> 432

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

agaccuacag ccagcccucc ccgcggagcg uggccaccgg ccugcccgcc uccaugaaga 120

ucuucaugua ccuccuacg gucuuccuga ucacccagau gaucgggagc gugcucuucg 180

cgguguaccu gcaccgccgg cuggacaagg ucgaggagga ggugaaccuc cacgaggacu 240

ucguguucau caagaagcug aagcgcugca acaagggcga ggggucccug agccuccuga 300

acugcgagga gaugcggcgc caguucgagg accuggucaa ggacaucacc cucaacaagg 360

aggagaagaa ggagaacucc uucgagaugc agcggggcga cgaggacccc cagaucgccg 420

cccacguggu gagcgaggcc aacuccaacg ccgcgagcgu ccugcagugg gccaagaagg 480

gguacuacac caugaagucc aaccugguga ugcucgagaa cggcaagcag cugacgguga 540

agcgcgaggg ccuguacuac gucuacaccc aggugaccuu cugcagcaac cgggagcccu 600

ccagccagcg cccguucauc guggggcucu ggcugaagcc cuccagcggc uccgagcgga 660

uccugcucaa ggccgccaac acccacagcu ccagccagcu gugcgagcag cagagcgucc 720

accugggcgg cguguucgag cuccaggcgg gggccuccgu guucgucaac gugacgggagg 780

ccagccaggu gauccaccgc gucggguucu ccagcuucgg ccugcugaag cucugaggac 840

uagugcauca cauuuaaaag caucucagcc uaccaugaga auaagagaaa gaaaaugaag 900

aucaauagcu uauucaucuc uuuuucuuuu ucguuggugu aaagccaaca cccugucuaa 960

aaaacauaaaaaaaaaaaau 1020

1080

1140

ggcucuuuuc agagccacca gaauu 1165

<210> 433

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R2025/R2391

<400> 433

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacaguccu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 434

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R3630/R3631

<400> 434

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacagugcu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 435

<211> 546

<212>RNA

<213> Artificial Sequence

<220>

<223> R722

<400> 435

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacaguccu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucua 546

<210> 436

<211> 1083

<212>RNA

<213> Artificial Sequence

<220>

<223> R723

<400> 436

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacaguccu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

600

uuuuuuuuuc cucccaaca augucgauca auagcugggc uguuggagac gcgucagcaa 660

uuuuuuuuuuuuuucccggg 720

accacaaaua auauucuugc uugguugggc gcaagggccc cguaucaggu cauaaacggg 780

uacauguugc acaggcuccu uuuuuuuuuu uuuuuuuuuu uucgcugagu uauuccgguc 840

ucaaaagacg gcagacguca gucgacaaca cgucuaaag cagugcuaca aucugccgug 900

uucguguuuu uuuuuuuuuu uuuuuuguga accuacacgg cgugcacugu aguucgcaau 960

ucauagggua ccggcucaga guuaugccuu gguugaaaac ugcccagcau acuuuuuuuu 1020

uuuuuuuuuu uucauauucc caugcuaagc aagggaugcc gcgagucaug uuaagcuuga 1080

auu 1083

<210> 437

<211> 229

<212>RNA

<213> Artificial Sequence

<220>

<223> R821

<400> 437

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gcccagauc 229

<210> 438

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 CDS mRNA wild type

<400> 438

augcagaucc cacaggcgcc cuggccaguc gucugggcgg ugcuacaacu gggcuggcgg 60

cgggauggu ucuuagacuc cccagacagg ccuggaacc cccccaccuu cuccccagcc 120

cugcucgugg ugaccgaagg ggacaacgcc accuucaccu guagcuucuc caacacaucg 180

gagagcuucg ugcuaaacug guaccgcaug agccccagca accagacggga caagcuggcc 240

300

360

uaccucugug gggccaucuc ccuggccccc aaggcgcaga ucaaagagag ccugcgggca 420

gagcucaggg ugacagagag aagggcagaa gugcccacag cccaccccag ccccucaccc 480

aggccagccg gccaguucca aacccuggug guuggugucg ugggcggccu gcugggcagc 540

cuggugcugc uagucugggu ccuggccguc aucugcuccc gggccgcacg agggacaaua 600

ggagccaggc gcaccggcca gccccugaag gaggaccccu cagccgugcc uguguucucu 660

guggacuaug gggagcugga uuuccagugg cgagagaaga ccccggagcc ccccgugccc 720

ugugucccug agcagacgga guaugccacc auugucuuuc cuagcggaau gggcaccuca 780

ucccccgccc gcaggggcuc agccgacggc ccucggagug cccagccacu gaggccugag 840

gauggacacu gcucuuggcc ccucuga 867

<210> 439

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) CDS mRNA wild type

<400> 439

augcagaucc cacaggcgcc cuggccaguc gucugggcgg ugcuacaacu gggcuggcgg 60

cgggauggu ucuuagacuc cccagacagg ccuggaacc cccccaccuu cuccccagcc 120

cugcucgugg ugaccgaagg ggacaacgcc accuucaccu guagcuucuc caacacaucg 180

gagagcuucg ugcuaaacug guaccgcaug agccccagca accagacggga caagcuggcc 240

300

360

uaccucugug gggccaucuc ccuggccccc aaggcgcaga ucaaagagag ccugcgggca 420

gagcucaggg ugacagagag aagggcauga 450

<210> 440

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A CDS mRNA wild type

<400> 440

60

uuggccagaa accuccccgu ggccacucca gaccaggaa uguucccaug ccuucaccac 120

ucccaaaacc ugcugagggc cgucagcaac augcuccaga aggccagaca aacucuagaa 180

uuuuacccuu gcacuucuga agagauugau caugaagaua ucacaaaaga uaaaaccagc 240

acagugggagg ccuguuuacc auuggaauua accaagaaug agaguugccu aaauuccaga 300

gagaccucuu ucauaacuaa ugggaguugc cuggccucca gaaagaccuc uuuuaugaug 360

gcccugugcc uuaguaguau uuaugaagac uugaagaugu accaggugga guucaagacc 420

augaaugcaa aacuucugau ggaucuaag

gcaguuauug augagcugau gcaggcccug aauuucaaca gugagacugu gccacaaaaa 540

uccucccuug aagaaccgga uuuuuauaaa acuaaaauca agcuucugcau acuucuucau 600

660

<210> 441

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) CDS mRNA wild type

<400> 441

60

uuggccagaa accuccccgu ggccacucca gaccaggaa uguucccaug ccuucaccac 120

ucccaaaacc ugcugagggc cgucagcaac augcuccaga aggccagaca aacucuagaa 180

uuuuacccuu gcacuucuga agagauugau caugaagaua ucacaaaaga uaaaaccagc 240

acagugggagg ccuguuuacc auuggaauua accaagaaug agaguugccu aaauuccaga 300

gagaccucuu ucauaacuaa ugggaguugc cuggccucca gaaagaccuc uuuuaugaug 360

gcccugugcc uuaguaguau uuaugaagac uugaagaugu accaggugga guucaagacc 420

augaaugcaa aacuucugau ggaucuaag

gcaguuauug augagcugau gcaggcccug aauuucaaca gugagacugu gccacaaaaa 540

uccucccuug aagaaccgga uuuuuauaaa acuaaaauca agcuucugcau acuucuucau 600

gcuuucagaa uuagggcagu gacuauugau agagugauga gcuauucugaa ugcuucc 657

<210> 442

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) CDS mRNA wild type

<400> 442

agaaaccucc ccguggccac uccagaccca ggaauguucc caugccuuca ccacucccaa 60

aaccugcuga gggccgucag caacaugcuc cagaaggcca gacaaacucu agaauuuuac 120

ccuugcacuu cugaagagau ugaucaugaa gauaucacaa aagauaaaac cagcacagug 180

gaggccuguu uaccauugga auuaaccaag aaugagaguu gccuaaauuc cagagagacc 240

ucuuucauaa cuaaugggag uugccuggcc uccagaaaga ccucuuuuau gauggcccug 300

ugccuuagua guauuuauga agacuugaag auguaccagg uggaguucaa gaccaugaau 360

gcaaaacuuc ugauggaucc uaagaggcag aucuuucuag aucaaaacau gcuggcaguu 420

auugaugagc ugaugcaggc ccugaauuuc aacagugaga cugugccaca aaaauccucc 480

cuugaagaac cggauuuuua uaaaacuaaa aucaagcucu gcauacuucu ucaugcuuuc 540

agaauuaggg cagugacuau ugauagagug augagcuauc ugaaugcuuc cuaa 594

<210> 443

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B CDS mRNA wild type

<400> 443

augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc 60

guggccaauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau 120

gccccuggag aaauggggu ccucaccugu gacaccccug aagaagaugg uaucaccugg 180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa 240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg 300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag 360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc 420

accuguuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga 480

ggcucaucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc 540

aggggacag acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca 600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau 660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac 720

uugcagcuga agccauuaaa aaauucucgg cagguugagg ucagcuggga guacccugac 780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag 840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc 900

960

gaaugggcau cugugcccug caguuag 987

<210> 444

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) CDS mRNA wild type

<400> 444

augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc 60

guggccaauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau 120

gccccuggag aaauggggu ccucaccugu gacaccccug aagaagaugg uaucaccugg 180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa 240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg 300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag 360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc 420

accuguuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga 480

ggcucaucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc 540

aggggacag acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca 600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau 660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac 720

uugcagcuga agccauuaaa aaauucucgg cagguugagg ucagcuggga guacccugac 780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag 840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc 900

960

gaaugggcau cugugcccug cagu 984

<210> 445

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) CDS mRNA wild type

<400> 445

auaugggaac ugaagaaaga uguuuauguc guagaauugg auugguaucc ggaugccccu 60

ggagaaaugg ugguccucac cugugacacc ccugaagaag augguaucac cuggaccuug 120

gaccagagca gugaggucuu aggcucuggc aaaacccuga ccauccaagu caaagaguuu 180

ggagaugcug gccaguacac cugucacaaa ggaggcgagg uucuaagcca uucgcuccug 240

cugcuucaca aaaaggaaga uggaauuugg uccacugaua uuuuaaagga ccagaaagaa 300

360

ugguggcuga cgacaaucag uacugauuug acauucagug ucaaaagcag cagaggcuca 420

ucugaccccc aaggggugac gugcggagcu gcuacacucu cugcagagag agucagaggg 480

gacaacaagg aguaugagua cucaguggag ugccagggagg acagugccug cccagcugcu 540

gaggagaguc ugcccauuga ggucauggug gaugccguuc acaagcucaa guaugaaaac 600

uacaccagca gcuucuucau cagggacauc aucaaaccug acccacccaa gaacuugcag 660

cugaagccau uaaaaaauuc ucggcagguu gaggucagcu gggaguaccc ugacaccugg 720

aguacuccac auuccuacuu cucccugaca uucugcguuc agguccaggg caagagcaag 780

agagaaaaga aagauagagu cuucacggac aagaccucag ccacggucau cugccgcaaa 840

aaugccagca uuagcgugcg ggcccaggac cgcuacuaua gcucaucuug gagcgaaugg 900

gcaucugugc ccugcaguua g 921

<210> 446

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 CDS mRNA wild type

<400> 446

ggcaguacuu cgggcagugg uaagccuggu agggugagg guaguacuaa gggu 54

<210> 447

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 CDS mRNA wild type

<400> 447

augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc 60

guggccaauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau 120

gccccuggag aaauggggu ccucaccugu gacaccccug aagaagaugg uaucaccugg 180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa 240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg 300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag 360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc 420

accuguuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga 480

ggcucaucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc 540

aggggacag acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca 600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau 660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac 720

uugcagcuga agccauuaaa aaauucucgg cagguugagg ucagcuggga guacccugac 780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag 840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc 900

960

1020

gaggguagua cuaaggguag aaaccucccc guggccacuc cagacccagg aauguuccca 1080

ugccuucacc acucccaaaa ccugcugagg gccgucagca acaugcucca gaaggccaga 1140

1200

gauaaaacca gcacagugga ggccuguuua ccauuggaau uaaccaagaa ugagaguugc 1260

cuaaauucca gagagaccuc uuucauaacu aaugggaguu gccuggccuc cagaaagacc 1320

ucuuuuauga uggccugug ccuuaguagu auuuaugaag acuugaagau guaccaggug 1380

1440

caaaacaugc uggcaguuau ugaugagcug augcaggccc ugaauuucaa cagugagacu 1500

gugccacaaa aauccucccu ugaagaaccg gauuuuuaua aaacuaaaau caagcucugc 1560

auacuucuuc augcuuucag aauuagggca gugacuauug auagagugau gagcuaucug 1620

aaugcuuccu aa 1632

<210> 448

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG CDS mRNA wild type

<400> 448

augaucgaaa cauacaacca aacuucuccc cgaucugcgg ccacuggacu gcccaucagc 60

augaaaauuu uuauguauuu acuuacuguu uuucuuauca cccagaugau ugggucagca 120

cuuuuugcug uguaucuuca uagaagguug gacaagauag aagaugaaag gaaucuucau 180

gaagauuuug uauucauga aacgauacag agaugcaaca caggagaaag auccuuaucc 240

uuacugaacu gugaggagau uaaaagccag uuugaaggcu uugugaagga uauaauguua 300

360

caaauugcgg cacaugucau aagugaggcc agcaguaaaa caacaucugu guuacagugg 420

gcugaaaaag gauacuacac caugagcaac aacuugguaa cccuggaaaa ugggaaacag 480

cugaccguua aaagacaagg acucuauuau aucuaugccc aagucaccuu cuguuccaau 540

cgggaagcau cgagucaagc uccauuuaua gccagccucu gccuaaaguc cccgguaga 600

660

caauccauuc acuugggagg aguauuugaa uugcaaccag gugcuucggu guuugucaau 720

gugacugauc caagccaagu gagccauggc acuggcuuca cguccuuugg cuuacucaaa 780

cucuga 786

<210> 449

<211> 1084

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product wild type

<400> 449

gggagaaagc uuaccaugca gaucccacag gcgcccuggc cagucgucug ggcggugcua 60

caacugggcu ggcggccagg augguucuua gacuccccag acaggcccug gaaccccccc 120

accuucuccc cagcccugcu cguggugacc gaaggggaca acgccaccuu caccuguagc 180

uucuccaaca caucggagag cuucgugcua aacugguacc gcaugagccc cagcaaccag 240

acggacaagc uggccgcuuu ccccgaggac cgcagccagc ccggccagga cugccgcuuc 300

cgugucacac aacugcccaa cgggcgugac uuccacauga gcguggucag ggcccggcgc 360

augacagcg gcaccuaccu cuguggggcc aucucccugg cccccaaggc gcagaucaaa 420

gagagccugc gggcagagcu cagggugaca gagagaaggg cagaagugcc cacagcccac 480

cccagccccu cacccaggcc agccggccag uuccaaaccc uggugguugg ugucgugggc 540

ggccugcugg gcagccuggu gcugcuaguc uggguccugg ccgucaucug cucccggggcc 600

gcacgaggga caauaggagc caggcgcacc ggccagcccc ugaaggagga ccccucagcc 660

gugccugugu ucucugugga cuauggggag cuggauuucc aguggcgaga gaagaccccg 720

gagccccccg ugcccugugu cccuagcag acggaguaug ccaccauugu cuuuccuagc 780

ggaaugggca ccucaucccc cgcccgcagg ggcucagccg acggcccucg gagugcccag 840

ccacugaggc cugaggaugg acacugcucu uggccccucu gaggacuagu uauaagacug 900

acuagcccga ugggccuccc aacggggcccu ccuccccucc uugcaccgag auuauaaaaa 960

1020

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1080

aauu 1084

<210> 450

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product wild type

<400> 450

gggagaaagc uuaccaugca gaucccacag gcgcccuggc cagucgucug ggcggugcua 60

caacugggcu ggcggccagg augguucuua gacuccccag acaggcccug gaaccccccc 120

accuucuccc cagcccugcu cguggugacc gaaggggaca acgccaccuu caccuguagc 180

uucuccaaca caucggagag cuucgugcua aacugguacc gcaugagccc cagcaaccag 240

acggacaagc uggccgcuuu ccccgaggac cgcagccagc ccggccagga cugccgcuuc 300

cgugucacac aacugcccaa cgggcgugac uuccacauga gcguggucag ggcccggcgc 360

augacagcg gcaccuaccu cuguggggcc aucucccugg cccccaaggc gcagaucaaa 420

gagagccugc gggcagagcu cagggugaca gagagaaggg cauggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 451

<211> 877

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product wild type

<400> 451

gggagaaagc uuaccaugug uccagcgcgc agccuccucc uuguggcuac ccugguccuc 60

cuggaccacc ucaguuuggc cagaaaccuc cccguggcca cuccagaccc aggaauguuc 120

ccaugccuuc accacuccca aaaccugcug agggccguca gcaacaugcu ccagaaggcc 180

agacaaacuc uagaauuuua cccuugcacu ucugaagaga uugaucauga agauaucaca 240

aaagauaaaa ccagcacagu ggaggccugu uuaccauugg aauuaaccaa gaaugagagu 300

360

accucuuuua ugaggcccu gugccuuagu aguauuuaug aagacuugaa gauguaccag 420

guggaguuca agaccaugaa ugcaaaacuu cugauggauc cuaagaggca gaucuuucua 480

gaucaaaaca ugcuggcagu uauugaugag cugaugcagg cccugaauuu caacagugag 540

acugugccac aaaaauccuc ccuugaagaa ccggauuuuu auaaaacuaa aaucaagcuc 600

ugcauacuuc uucaugcuuu cagaauuagg gcagugacua uugauagagu gaugagcuau 660

cugaaugcuu ccuaaggacu aguuauaaga cugacuagcc cgaugggccu cccaacgggc 720

ccuccucccc uccuugcacc gagauuaaua aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaugcaucc cccccccccc cccccccccc 840

ccccccccca aaggcucuuu ucagagccac cagaauu 877

<210> 452

<211> 874

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product wild type

<400> 452

gggagaaagc uuaccaugug uccagcgcgc agccuccucc uuguggcuac ccugguccuc 60

cuggaccacc ucaguuuggc cagaaaccuc cccguggcca cuccagaccc aggaauguuc 120

ccaugccuuc accacuccca aaaccugcug agggccguca gcaacaugcu ccagaaggcc 180

agacaaacuc uagaauuuua cccuugcacu ucugaagaga uugaucauga agauaucaca 240

aaagauaaaa ccagcacagu ggaggccugu uuaccauugg aauuaaccaa gaaugagagu 300

360

accucuuuua ugaggcccu gugccuuagu aguauuuaug aagacuugaa gauguaccag 420

guggaguuca agaccaugaa ugcaaaacuu cugauggauc cuaagaggca gaucuuucua 480

gaucaaaaca ugcuggcagu uauugaugag cugaugcagg cccugaauuu caacagugag 540

acugugccac aaaaauccuc ccuugaagaa ccggauuuuu auaaaacuaa aaucaagcuc 600

ugcauacuuc uucaugcuuu cagaauuagg gcagugacua uugauagagu gaugagcuau 660

cugaaugcuu ccggacuagu uauaagacug acuagcccga ugggccuccc aacgggcccu 720

cccccccucc uugcaccgag auuaauaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 840

ccccccaaag gcucuuuuca gagccaccag aauu 874

<210> 453

<211> 811

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product wild type

<400> 453

gggagaaagc uuaccagaaa ccuccccgg gccacuccag acccaggaau guucccaugc 60

cuucaccacu cccaaaaccu gcugaggggcc gucagcaaca ugcuccagaa ggccagacaa 120

acucuagaau uuuacccuug cacuucugaa gagauugauc augaagauau cacaaaagau 180

aaaaccagca caguggaggc cuguuuacca uuggaauuaa ccaagaauga gaguugccua 240

aauuccagag agaccucuuu cauaacuaau gggaguugcc uggccuccag aaagaccucu 300

uuuaugaugg cccugugccu uaguaguauu uaugaagacu ugaagaugua ccagguggag 360

uucaagacca ugaaugcaaa acuucugaug gauccuaaga ggcagaucuu ucuagaucaa 420

aacaugcugg caguuauuga ugagcugaug caggcccuga

ccacaaaaau ccucccuuga agaaccggau uuuuauaaaa cuaaaaucaa gcucugcaua 540

cuucuucaug cuuucagaau uagggcagug acuauugaua gagugaugag cuaucugaau 600

gcuuccuaag gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 660

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 780

cccaaaggcu cuuuucagag ccaccagaau u 811

<210> 454

<211> 1204

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product wild type

<400> 454

60 gggagaaagc uuaccaugug ucaccagcag uuggucaucu cuugguuuuc

cuggcaucuc cccucguggc cauaugggaa cugaagaaag auguuuaugu cguagaauug 120

gauugguauc cggaugcccc uggagaaaug gugguccuca ccugugacac cccugaagaa 180

gaugguauca ccuggaccuu ggaccagagc agugaggucu uaggcucugg caaaacccug 240

accauccaag ucaaagaguu uggagaugcu ggccaguaca ccugucacaa aggaggcgag 300

guucuaagcc auucgcuccu gcugcuucac aaaaaggaag auggaauuug guccacugau 360

auuuuaaagg accagaaaga acccaaaaau aagaccuuuc uaagaugcga ggccaagaau 420

uauucuggac guuucaccug uugguggcug acgacaauca guacugauuu gacauucagu 480

gucaaaagca gcagaggcuc aucugacccc caagggguga cgugcggagc ugcuacacuc 540

ucugcagaga gagucagagg ggacaacaag gaguaugagu acucagugga gugccaggag 600

gacagugccu gcccagcugc ugaggagagu cugcccauug aggucauggu ggaugccguu 660

cacaagcuca aguaugaaaa cuacaccagc agcuucuuca ucagggacau caucaaaccu 720

gacccaccca agaacuugca gcugaagcca uuaaaaaauu cucggcaggu ugaggucagc 780

ugggaguacc cugacaccug gaguacucca cauuccuacu ucucccugac auucugcguu 840

cagguccagg gcaagagcaa gagagaaaag aaagauagag ucuucacgga caagaccuca 900

gccacgguca ucugccgcaa aaugccagc auuagcgugc gggccgga ccgcuacuau 960

1020

1080

1140

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1200

aauu 1204

<210> 455

<211> 1201

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product wild type

<400> 455

60 gggagaaagc uuaccaugug ucaccagcag uuggucaucu cuugguuuuc

cuggcaucuc cccucguggc cauaugggaa cugaagaaag auguuuaugu cguagaauug 120

gauugguauc cggaugcccc uggagaaaug gugguccuca ccugugacac cccugaagaa 180

gaugguauca ccuggaccuu ggaccagagc agugaggucu uaggcucugg caaaacccug 240

accauccaag ucaaagaguu uggagaugcu ggccaguaca ccugucacaa aggaggcgag 300

guucuaagcc auucgcuccu gcugcuucac aaaaaggaag auggaauuug guccacugau 360

auuuuaaagg accagaaaga acccaaaaau aagaccuuuc uaagaugcga ggccaagaau 420

uauucuggac guuucaccug uugguggcug acgacaauca guacugauuu gacauucagu 480

gucaaaagca gcagaggcuc aucugacccc caagggguga cgugcggagc ugcuacacuc 540

ucugcagaga gagucagagg ggacaacaag gaguaugagu acucagugga gugccaggag 600

gacagugccu gcccagcugc ugaggagagu cugcccauug aggucauggu ggaugccguu 660

cacaagcuca aguaugaaaa cuacaccagc agcuucuuca ucagggacau caucaaaccu 720

gacccaccca agaacuugca gcugaagcca uuaaaaaauu cucggcaggu ugaggucagc 780

ugggaguacc cugacaccug gaguacucca cauuccuacu ucucccugac auucugcguu 840

cagguccagg gcaagagcaa gagagaaaag aaagauagag ucuucacgga caagaccuca 900

gccacgguca ucugccgcaa aaugccagc auuagcgugc gggccgga ccgcuacuau 960

agcucaucuu ggagcgaaug ggcaucugug cccugcagug gacuaguuau aagacugacu 1020

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1080

1140

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1200

u 1201

<210> 456

<211> 1138

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product wild type

<400> 456

gggagaaagc uuaccauaug ggaacugaag aaagauguuu augucguaga auuggauugg 60

uauccggaug ccccggaga aaugggguc cucaccugug acaccccuga agaagauggu 120

aucaccugga ccuuggacca gagcagugag gucuuaggcu cuggcaaaac ccugaccauc 180

caagucaaag aguuuggaga ugcuggccag uacaccuguc acaaaggagg cgagguucua 240

agccauucgc uccugcugcu ucacaaaaag gaagauggaa uuugguccac ugauauuuua 300

aaggaccaga aagaacccaa aaauaagacc uuucuaagau gcgaggccaa gaauuauucu 360

ggacguuuca ccuguuggug gcugacgaca aucaguacug auuugacauu cagugucaaa 420

agcagcagag gcucaucuga cccccaaggg gugacgugcg gagcugcuac acucucugca 480

gagagaguca gaggggacaa caaggaguau gaguacucag uggagugcca ggaggacagu 540

gccugcccag cugcugagga gagucugccc auugagguca ugguggaugc cguucacaag 600

cucaaguaug aaaacuacac cagcagcuuc uucaucaggg acaucaucaa accugaccca 660

cccaagaacu ugcagcugaa gccauuaaaa aauucucggc agguugaggu cagcugggag 720

uacccugaca ccuggaguac uccacauucc uacuucuccc ugacauucug cguucagguc 780

cagggcaaga gcaagagaga aaagaaagau agagucuuca cggacaagac cucagccg 840

gucaucugcc gcaaaaaugc cagcauuagc gugcgggccc aggaccgcua cuauagcuca 900

ucuuggagcg aaugggcauc ugugcccugc aguuagggac uaguuauaag acugacuagc 960

ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau aaaaaaaaaa 1020

1080

cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca ccagaauu 1138

<210> 457

<211> 271

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product wild type

<400> 457

gggagaaagc uuaccggcag uacuucggggc agugguaagc cugguagugg ugaggguagu 60

acuaagggug gacuaguuau aagacugacu agcccgaugg gccucccaac gggcccuccu 120

ccccuccuug caccgagauu aauaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 180

aaaaaaaaaa aaaaaaaaaa aaaaaaaugc aucccccccc cccccccccc cccccccccc 240

cccaaaggcu cuuuucagag ccaccagaau u 271

<210> 458

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product wild type

<400> 458

60 gggagaaagc uuaccaugug ucaccagcag uuggucaucu cuugguuuuc

cuggcaucuc cccucguggc cauaugggaa cugaagaaag auguuuaugu cguagaauug 120

gauugguauc cggaugcccc uggagaaaug gugguccuca ccugugacac cccugaagaa 180

gaugguauca ccuggaccuu ggaccagagc agugaggucu uaggcucugg caaaacccug 240

accauccaag ucaaagaguu uggagaugcu ggccaguaca ccugucacaa aggaggcgag 300

guucuaagcc auucgcuccu gcugcuucac aaaaaggaag auggaauuug guccacugau 360

auuuuaaagg accagaaaga acccaaaaau aagaccuuuc uaagaugcga ggccaagaau 420

uauucuggac guuucaccug uugguggcug acgacaauca guacugauuu gacauucagu 480

gucaaaagca gcagaggcuc aucugacccc caagggguga cgugcggagc ugcuacacuc 540

ucugcagaga gagucagagg ggacaacaag gaguaugagu acucagugga gugccaggag 600

gacagugccu gcccagcugc ugaggagagu cugcccauug aggucauggu ggaugccguu 660

cacaagcuca aguaugaaaa cuacaccagc agcuucuuca ucagggacau caucaaaccu 720

gacccaccca agaacuugca gcugaagcca uuaaaaaauu cucggcaggu ugaggucagc 780

ugggaguacc cugacaccug gaguacucca cauuccuacu ucucccugac auucugcguu 840

cagguccagg gcaagagcaa gagagaaaag aaagauagag ucuucacgga caagaccuca 900

gccacgguca ucugccgcaa aaugccagc auuagcgugc gggccgga ccgcuacuau 960

agcucaucuu ggagcgaaug ggcaucugug cccugcagug gcaguacuuc gggcaguggu 1020

aagccuggua guggugaggg uaguacuaag gguagaaacc uccccguggc cacuccagac 1080

ccaggaaugu ucccaugccu ucaccacucc caaaaccugc ugaggggccgu cagcaacaug 1140

cuccagaagg ccagacaaac ucuagaauuu uacccuugca cuucugaaga gauugaucau 1200

gaagauauca caaaagauaa aaccagcaca guggaggccu guuuaccauu ggaauuaacc 1260

1320

gccucgaa agaccucuuu uaugauggcc cugugccuua guaguauuua ugaagacuug 1380

aagauguacc agguggaguu caagaccaug aaugcaaaac uucugaugga uccuaagagg 1440

cagaucuuuc uagaucaaaa caugcuggca guuauugaug agcugaugca ggcccugaau 1500

1560

1620

gugaugagcu aucugaaugc uuccuaagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 459

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product wild type

<400> 459

gggagaaagc uuaccaugau cgaaacauac aaccaaacuu cuccccgauc ugcggccacu 60

ggacugccca ucagcaugaa aauuuuuaug uauuuacuua cuguuuuucu uaucacccag 120

augauugggu cagcacuuuu ugcuguguau cuucauagaa gguuggacaa gauagaagau 180

gaaaggaauc uucaugaaga uuuuguauuc augaaaacga

gaaagauccu uauccuuacu gaacugugag gagauuaaaa gccaguuuga aggcuuugug 300

360

ggugaucaga auccucaaau ugcggcacau gucauaagug aggccagcag uaaaacaaca 420

ucuguguuac agugggcuga aaaaggauac uacaccauga gcaacaacuu gguaacccug 480

gaaaauggga aacagcugac cguuaaaaga caaggacucu auuauaucua ugcccaaguc 540

accuucuguu ccaaucggga agcaucgagu caagcuccau uuauagccag ccucugccua 600

aagucccccg guagauucga gagaaucuua cucagagcug caaauaccca caguuccgcc 660

aaaccuugcg ggcaacaauc cauucacuug ggaggaguau uugaauugca accaggugcu 720

ucgguguuug ucaugugac ugauccaagc caagugagcc auggcacugg cuucacgucc 780

uuuggcuuac ucaaacucug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 460

<211> 1249

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1 mRNA product TOP UTR wild type

<400> 460

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccacaggc gcccuggcca gucgucuggg cggugcuaca acugggcugg cggccaggau 120

180

uggugaccga agggacaac gccaccuuca ccuguagcuu cuccaacaca ucggagagcu 240

ucgugcuaaa cugguaccgc augagcccca gcaaccagac ggacaagcug gccgcuuucc 300

ccgaggaccg cagccagccc ggccaggacu gccgcuuccg ugucacacaa cugcccaacg 360

ggcgugacuu ccacaugagc guggucaggg cccggcgcaa ugacagcggc accuaccucu 420

guggggccau cucccuggcc cccaaggcgc agaucaaaga gagccugcgg gcagagcuca 480

gggugacaga gagaagggca gaagugccca cagcccaccc cagccccuca cccaggccag 540

ccggccaguu ccaaacccug gugguuggug ucgugggcgg ccugcugggc agccuggugc 600

ugcuagucug gguccuggcc gucaucugcu cccgggccgc acgagggaca auaggagcca 660

ggcgcaccgg ccagccccug aaggaggacc ccucagccgu gccuguguuc ucuguggacu 720

auggggagcu ggauuuccag uggcgagaga agaccccgga gccccccgug cccugugucc 780

840

cccgcagggg cucagccgac ggcccucgga gugcccagcc acugaggccu gaggauggac 900

acugcucuug gccccucuga ggacuagugc aucacauuua aaagcaucuc agccuaccau 960

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1020

gccucuuuuc 1080

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1140

1200

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1249

<210> 461

<211> 832

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149) mRNA product TOP UTR wild type

<400> 461

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugcaga 60

ucccacaggc gcccuggcca gucgucuggg cggugcuaca acugggcugg cggccaggau 120

180

uggugaccga agggacaac gccaccuuca ccuguagcuu cuccaacaca ucggagagcu 240

ucgugcuaaa cugguaccgc augagcccca gcaaccagac ggacaagcug gccgcuuucc 300

ccgaggaccg cagccagccc ggccaggacu gccgcuuccg ugucacacaa cugcccaacg 360

ggcgugacuu ccacaugagc guggucaggg cccggcgcaa ugacagcggc accuaccucu 420

guggggccau cucccuggcc cccaaggcgc agaucaaaga gagccugcgg gcagagcuca 480

gggugacaga gagaagggca ugaggacuag ugcaucacau uuaaaagcau cucagccuac 540

600

660

aaaaaaugga aagaaccuag aucuaaaaaa aaaaaaaaaa 720

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaug cauccccccc 780

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 832

<210> 462

<211> 1042

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A mRNA product TOP UTR wild type

<400> 462

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

cagcgcgcag ccuccuccuu guggcuaccc ugguccuccu ggaccaccuc aguuuggcca 120

gaaaccuccc cguggccacu ccagacccag gaauguuccc augccuucac cacucccaaa 180

accugcugag ggccgucagc aacaugcucc agaaggccag acaaacucua gaauuuuacc 240

cuugcacuuc ugaagagauu gaucaugaag auaucacaaa agauaaaacc agcacagugg 300

360

cuuucauaac uaaugggagu ugccuggccu ccagaaagac cucuuuuaug auggcccugu 420

gccuuaguag uauuuaugaa gacuugaaga uguaccaggu ggaguucaag accaugaaug 480

caaaacuucu guggauccu aagaggcaga ucuuucuaga ucaaaacaug cuggcaguua 540

uugaugagcu gaugcaggcc cugaauuuca acagugagac ugugccacaa aaauccuccc 600

uugaagaacc ggauuuuuau aaaacuaaaa

gaauuagggc agugacuauu gauagaguga ugagcuaucu gaaugcuucc uaaggacuag 720

ugcaucacau uuaaaagcau cucagccuac caugagaaua agagaaagaa aaugaagauc 780

uugguguaaa gccaacaccc ugucuaaaaa 840

acauaaauuu cuuuaaucau uuugccucuu uucucugugc uucaauuaau aaaaaaugga 900

960

aaaaaaaaaa aaaaaaaug

ucuuuucaga gccaccagaa uu 1042

<210> 463

<211> 1039

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219) mRNA product TOP UTR wild type

<400> 463

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

cagcgcgcag ccuccuccuu guggcuaccc ugguccuccu ggaccaccuc aguuuggcca 120

gaaaccuccc cguggccacu ccagacccag gaauguuccc augccuucac cacucccaaa 180

accugcugag ggccgucagc aacaugcucc agaaggccag acaaacucua gaauuuuacc 240

cuugcacuuc ugaagagauu gaucaugaag auaucacaaa agauaaaacc agcacagugg 300

360

cuuucauaac uaaugggagu ugccuggccu ccagaaagac cucuuuuaug auggcccugu 420

gccuuaguag uauuuaugaa gacuugaaga uguaccaggu ggaguucaag accaugaaug 480

caaaacuucu guggauccu aagaggcaga ucuuucuaga ucaaaacaug cuggcaguua 540

uugaugagcu gaugcaggcc cugaauuuca acagugagac ugugccacaa aaauccuccc 600

uugaagaacc ggauuuuuau aaaacuaaaa

gaauuagggc agugacuauu gauagaguga ugagcuaucu gaaugcuucc ggacuagugc 720

aucacauuua aaagcaucuc agccuaccau gagaauaaga gaaagaaaau gaagaucaau 780

840

uaaauuucuu uaaucauuuu gccucuuuuc ucugugcuuc aauuaauaaa aaauggaaag 900

960

aaaaaaaaaa aaaaaugcau cccccccccc cccccccccc cccccccccc caaaggcucu 1020

uuucagagcc accagaauu 1039

<210> 464

<211> 976

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219) mRNA product TOP UTR wild type

<400> 464

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accagaaacc 60

uccccguggc cacuccagac ccaggaaugu ucccaugccu ucaccacucc caaaaccugc 120

ugaggggccgu cagcaacaug cuccagaagg ccagacaaac ucuagaauuu uacccuugca 180

cuucugaaga gauugaucau gaagauauca caaaagauaa aaccagcaca guggaggccu 240

guuuaccauu ggaauuaacc aagaaugaga guugccuaaa uuccagagag accucuuuca 300

uaacuaaugg gaguugccug gccuccagaa agaccucuuu uaugauggcc cugugccuua 360

guaguauuua ugaagacuug aagauguacc agguggaguu caagaccaug aaugcaaaac 420

uucugaugga uccuaagagg cagaucuuuc uagaucaaaa caugcuggca guuauugaug 480

agcugaugca ggcccugaau uucaacagug agacugugcc acaaaaaucc ucccuugaag 540

600

660 gggcagugac uauugauaga gugaugagcu aucugaaugc

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 720

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 780

840

900

aaaaaaaaaa aaugcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 960

cagagccacc agaauu 976

<210> 465

<211> 1369

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B mRNA product TOP UTR wild type

<400> 465

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcaguu ggucaucucu ugguuuuccc ugguuuuucu ggcaucuccc cucguggcca 120

uaugggaacu gaagaaagau guuuaugucg uagaauugga uugguauccg gaugccccug 180

gagaaauggu gguccucacc ugugacaccc cugaagaaga ugguaucacc uggaccuugg 240

accagagcag ugaggucuua ggcucuggca aaacccugac cauccaaguc aaagaguuug 300

gagaugcugg ccaguacacc ugucacaag gaggcgaggu ucuaagccau ucgcuccugc 360

ugcuucacaa aaaggaagau ggaauuuggu ccacugauau uuuaaaggac cagaaagaac 420

ccaaaaauaa gaccuuucua agaugcgagg ccaagaauua uucuggacgu uucaccuguu 480

gguggcugac gacaaucagu acugauuuga cauucagugu caaaagcagc agaggcucau 540

cugaccccca aggggugacg ugcggagcug cuacacucuc ugcagagaga gucagagggg 600

acaacaagga guaugaguac ucaguggagu gccaggagga cagugccugc ccagcugcug 660

aggagagucu gcccauugag gucauggugg augccguuca caagcucaag uaugaaaacu 720

acaccagcag cuucuucauc agggacauca ucaaaccuga cccacccaag aacuugcagc 780

ugaagccauu aaaaaauucu cggcagguug aggucagcug ggaguacccu gacaccugga 840

guacuccaca uuccuacuuc ucccugacau ucugcguuca gguccagggc aagagcaaga 900

gagaaaagaa agauagaguc uucacggaca agaccucagc cacggucauc ugccgcaaaa 960

augccagcau uagcgugcgg gcccaggacc gcuacuauag cucaucuugg agcgaauggg 1020

caucugugcc cugcaguuag ggacuagugc aucacauuua aaagcaucuc agccuaccau 1080

gagaauaaga gaaagaaaau gaagaucaau agcuuauuca ucucuuuuuc uuuuucguug 1140

1200

ucugugcuuc aauuaauaaa aaauggaaag aaccuagauc uaaaaaaaaa aaaaaaaaaa 1260

1320

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1369

<210> 466

<211> 1366

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328) mRNA product TOP UTR wild type

<400> 466

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcaguu ggucaucucu ugguuuuccc ugguuuuucu ggcaucuccc cucguggcca 120

uaugggaacu gaagaaagau guuuaugucg uagaauugga uugguauccg gaugccccug 180

gagaaauggu gguccucacc ugugacaccc cugaagaaga ugguaucacc uggaccuugg 240

accagagcag ugaggucuua ggcucuggca aaacccugac cauccaaguc aaagaguuug 300

gagaugcugg ccaguacacc ugucacaag gaggcgaggu ucuaagccau ucgcuccugc 360

ugcuucacaa aaaggaagau ggaauuuggu ccacugauau uuuaaaggac cagaaagaac 420

ccaaaaauaa gaccuuucua agaugcgagg ccaagaauua uucuggacgu uucaccuguu 480

gguggcugac gacaaucagu acugauuuga cauucagugu caaaagcagc agaggcucau 540

cugaccccca aggggugacg ugcggagcug cuacacucuc ugcagagaga gucagagggg 600

acaacaagga guaugaguac ucaguggagu gccaggagga cagugccugc ccagcugcug 660

aggagagucu gcccauugag gucauggugg augccguuca caagcucaag uaugaaaacu 720

acaccagcag cuucuucauc agggacauca ucaaaccuga cccacccaag aacuugcagc 780

ugaagccauu aaaaaauucu cggcagguug aggucagcug ggaguacccu gacaccugga 840

guacuccaca uuccuacuuc ucccugacau ucugcguuca gguccagggc aagagcaaga 900

gagaaaagaa agauagaguc uucacggaca agaccucagc cacggucauc ugccgcaaaa 960

augccagcau uagcgugcgg gcccaggacc gcuacuauag cucaucuugg agcgaauggg 1020

caucugugcc cugcagugga cuagugcauc acauuuaaaa gcaucucagc cuaccaugag 1080

1140

uaaagccaac acccugucua aaaaacauaa auuucuuuaa ucauuuugcc ucuuuucucu 1200

1260

1320

cccccccccc ccccccccaa aggcucuuuu cagagccacc agaauu 1366

<210> 467

<211> 1303

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328) mRNA product TOP UTR wild type

<400> 467

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauauggg 60

aacugaagaa agauguuuau gucguagaau uggauuggua uccggaugcc ccuggagaaa 120

uggugguccu caccugugac accccugaag aagaugguau caccuggacc uuggaccaga 180

gcagugaggu cuuaggcucu ggcaaaaccc ugaccaucca agucaaagag uuuggagaug 240

cuggccagua caccugucac aaaggaggcg agguucuaag ccauucgcuc cugcugcuuc 300

360

auaagaccuu ucuaagaugc gaggccaaga auuauucugg acguuucacc uguugguggc 420

ugacgacaau caguacugau uugacauuca gugucaaaag cagcagaggc ucaucugacc 480

cccaaggggu gacgugcgga gcugcuacac ucucugcaga gagagucaga ggggacaaca 540

aggaguauga guacucagug gagugccagg aggacagugc cugcccagcu gcugaggaga 600

gucugcccau ugaggucaug guggaugccg uucacaagcu caaguaugaa aacuacacca 660

gcagcuucuu caucagggac aucaucaaac cugacccacc caagaacuug cagcugaagc 720

cauuaaaaaa uucucggcag guugagguca gcugggagua cccugacacc uggaguacuc 780

cacauuccua cuucucccug acauucugcg uucaggucca gggcaagagc aagagagaaa 840

agaaagauag agucuucacg gacaagaccu cagccacggu caucugccgc aaaaaugcca 900

gcauuagcgu gcgggcccag gaccgcuacu auagcucauc uuggagcgaa ugggcaucug 960

ugcccugcag uuagggacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1020

1080

1140

1200

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1303

<210> 468

<211> 436

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218 mRNA product TOP UTR wild type

<400> 468

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accggcagua 60

120

acauuuaaaa gcaucucagc cuaccaugag aauaagagaa agaaaaugaa gaucaauagc 180

uuauucaucu cuuuuucuuu uucguuggug uaaagccaac acccugucua aaaaacauaa 240

300

360

aaaaaaaaaa augcauccc cccccccccc cccccccccc ccccccccaa aggcucuuuu 420

cagagccacc agaauu 436

<210> 469

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 mRNA product TOP UTR wild type

<400> 469

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accauguguc 60

accagcaguu ggucaucucu ugguuuuccc ugguuuuucu ggcaucuccc cucguggcca 120

uaugggaacu gaagaaagau guuuaugucg uagaauugga uugguauccg gaugccccug 180

gagaaauggu gguccucacc ugugacaccc cugaagaaga ugguaucacc uggaccuugg 240

accagagcag ugaggucuua ggcucuggca aaacccugac cauccaaguc aaagaguuug 300

gagaugcugg ccaguacacc ugucacaag gaggcgaggu ucuaagccau ucgcuccugc 360

ugcuucacaa aaaggaagau ggaauuuggu ccacugauau uuuaaaggac cagaaagaac 420

ccaaaaauaa gaccuuucua agaugcgagg ccaagaauua uucuggacgu uucaccuguu 480

gguggcugac gacaaucagu acugauuuga cauucagugu caaaagcagc agaggcucau 540

cugaccccca aggggugacg ugcggagcug cuacacucuc ugcagagaga gucagagggg 600

acaacaagga guaugaguac ucaguggagu gccaggagga cagugccugc ccagcugcug 660

aggagagucu gcccauugag gucauggugg augccguuca caagcucaag uaugaaaacu 720

acaccagcag cuucuucauc agggacauca ucaaaccuga cccacccaag aacuugcagc 780

ugaagccauu aaaaaauucu cggcagguug aggucagcug ggaguacccu gacaccugga 840

guacuccaca uuccuacuuc ucccugacau ucugcguuca gguccagggc aagagcaaga 900

gagaaaagaa agauagaguc uucacggaca agaccucagc cacggucauc ugccgcaaaa 960

augccagcau uagcgugcgg gcccaggacc gcuacuauag cucaucuugg agcgaauggg 1020

caucugugcc cugcaguggc aguacuucgg gcagugguaa gccugguagu ggugagggua 1080

1140

accacuccca aaaccugcug agggccguca gcaacaugcu ccagaaggcc agacaaacuc 1200

uagaauuuua cccuugcacu ucugaagaga uugaucauga agauaucaca 1260

ccagcacagu ggaggccugu uuaccauugg aauuaaccaa gaaugagagu ugccuaaauu 1320

ccagagagac cucuuucaua acuaauggga guugccuggc cuccagaaag accucuuuua 1380

ugaggcccu gugccuuagu aguauuuaug aagacuugaa gauguaccag guggaguuca 1440

agaccaugaa ugcaaaacuu cugauggauc cuaagaggca gaucuuucua gaucaaaaca 1500

ugcuggcagu uauugaugag cugaugcagg cccugaauuu caacagugag acugugccac 1560

aaaaauccuc ccuugaagaa ccggauuuuu auaaaacuaa aaucaagcuc ugcauacuuc 1620

uucaugcuuu cagaauuagg gcagugacua uugauagagu gaugagcuau cugaaugcuu 1680

ccuaaggacu agugcaucac auuuaaaagc aucucagccu accaugagaa uaagagaaag 1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 470

<211> 1168

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG mRNA product TOP UTR wild type

<400> 470

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugaucg 60

120

uuuuuaugua uuuacuuacu guuuuucuua ucacccagau gauuggguca gcacuuuuug 180

cuguguaucu ucauagaagg uuggacaaga uagaagauga aaggaaucuu caugaagauu 240

uuguauucau gaaaacgaua cagagaugca acacaggaga aagauccuua uccuuacuga 300

acugugagga gauuaaaagc caguuugaag gcuuugugaa ggauauaaug uuaaacaaag 360

aggagacgaa gaaagaaaac agcuuugaaa ugcaaaaagg ugaucagaau ccucaaauug 420

cggcacaugu cauaagugag gccagcagua aaacaacauc

aaggauacua caccaugagc aacaacuugg uaaccugga aaaugggaaa cagcugaccg 540

uuaaaagaca aggacucuau uauaucuaug cccaagucac cuucuguucc aaucgggaag 600

caucgaguca agcuccauuu auagccagcc ucugccuaaa gucccccggu agauucgaga 660

gaaucuuacu cagagcugca aauacccaca guuccgccaa accuugcggg caacaaucca 720

uucacuuggg aggaguauuu gaauugcaac caggugcuuc gguguuuguc aaugugacug 780

auccaagcca agugagccau ggcacuggcu ucacguccuu uggcuuacuc aaacucugag 840

gacuagugca ucacauuuaa aagcaucuca gccuaccaug agaauaagag aaagaaaaug 900

aagaucaaua gcuuauucau cucuuuuucu uuuucguugg uguaaagcca acacccuguc 960

uaaaaaacau aaauuucuuu aaucauuuug ccucuuuucu cugugcuuca auuauaaaa 1020

1080

aaaaaaaaaa aaaaaaaaaa aaaaugcauc

aaaggcucuu uucagagcca ccagaauu 1168

<210> 471

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 471

gguuuuuuuuuuuuuuuggg 20

<210> 472

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 472

ggggguuuuu uuuuugggg 20

<210> 473

<211> 40

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 473

ggggguuuuu uuuuuuuuuu uuuuuuuuuu uuuuuggggg 40

<210> 474

<211> 39

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 474

gugugugugu guuuuuuuuu uuuuuuugug uguggugugu 39

<210> 475

<211> 39

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 475

gguugguugg uuuuuuuuuu uuuuuuuggu ugguugguu 39

<210> 476

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 476

gggggggggu uugggggggg 20

<210> 477

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 477

gggggggguu uugggggggg 20

<210> 478

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 478

ggggggguuu uuugggggg 20

<210> 479

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 479

ggggggguuu uuuugggggg 20

<210> 480

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 480

gggggguuuuuuuugggggg 20

<210> 481

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 481

gggggguuuu uuuuugggg 20

<210> 482

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 482

gggggguuuuuuuuuugggg 20

<210> 483

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 483

ggggguuuuuuuuuuugggg 20

<210> 484

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 484

ggggguuuuuuuuuuuuggg 20

<210> 485

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 485

gggguuuuuuuuuuuuuggg 20

<210> 486

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 486

gggguuuuuuuuuuuuuugg 20

<210> 487

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 487

gguuuuuuuuuuuuuuuugg 20

<210> 488

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 488

guuuuuuuuuuuuuuuug 20

<210> 489

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 489

gggggggggg uuugggggggg gg 22

<210> 490

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 490

gggggggggu uuugggggggg gg 22

<210> 491

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 491

gggggggguu uuuugggggg gg 22

<210> 492

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 492

gggggggguu uuuuugggggg gg 22

<210> 493

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 493

ggggggguuuuuuuugggggg gg 22

<210> 494

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 494

ggggggguuu uuuuuugggg gg 22

<210> 495

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 495

ggggggguuuuuuuuuuggg gg 22

<210> 496

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 496

gggggguuuuuuuuuuuggg gg 22

<210> 497

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 497

gggggguuuuuuuuuuuugg gg 22

<210> 498

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 498

ggggguuuuuuuuuuuuugg gg 22

<210> 499

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 499

ggggguuuuuuuuuuuuuug gg 22

<210> 500

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 500

ggguuuuuuuuuuuuuuuug gg 22

<210> 501

<211> 22

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 501

gguuuuuuuuuuuuuuuuuu gg 22

<210> 502

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 502

gggggggggg guuugggggg gggg 24

<210> 503

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 503

gggggggggg uuuugggggg gggg 24

<210> 504

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 504

gggggggggu uuuuugggggg gggg 24

<210> 505

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 505

gggggggggu uuuuuugggg gggg 24

<210> 506

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 506

gggggggguu uuuuuugggg gggg 24

<210> 507

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 507

gggggggguu uuuuuuuggg gggg 24

<210> 508

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 508

gggggggguu uuuuuuuugg gggg 24

<210> 509

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 509

ggggggguuu uuuuuuuugg gggg 24

<210> 510

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 510

ggggggguuu uuuuuuuuug gggg 24

<210> 511

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 511

gggggguuuuuuuuuuuuug gggg 24

<210> 512

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 512

gggggguuuuuuuuuuuuuu gggg 24

<210> 513

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 513

gggguuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu gggg 24

<210> 514

<211> 24

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 514

ggguuuuuuu uuuuuuuuuu ugg 24

<210> 515

<211> 32

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 515

ug 32

<210> 516

<211> 34

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 516

gguuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuugg 34

<210> 517

<211> 36

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 517

ggguuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuggg 36

<210> 518

<211> 37

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 518

gggguuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuggg 37

<210> 519

<211> 39

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 519

ggggguuuuuuuuuuuuuuuuuuuuuuuuuuuuuugggg 39

<210> 520

<211> 41

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 520

gggggguuuu uuuuuuuuuu uuuuuuuuuu uuuuuugggg g 41

<210> 521

<211> 43

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 521

ggggggguuu uuuuuuuuuu uuuuuuuuuu uuuuuuuggg ggg 43

<210> 522

<211> 45

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 522

gggggggguu uuuuuuuuuu uuuuuuuuuu uuuuuuuugg ggggg 45

<210> 523

<211> 47

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 523

gggggggggu uuuuuuuuuu uuuuuuuuuuuuuuuuuuuug ggggggg 47

<210> 524

<400> 524

000

<210> 525

<400> 525

000

<210> 526

<400> 526

000

<210> 527

<211> 10

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 527

Gguuuuuugg 10

<210> 528

<211> 11

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 528

gguuuuuug g 11

<210> 529

<211> 12

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 529

gguuuuuuuu gg 12

<210> 530

<211> 13

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 530

gguuuuuuuu ugg 13

<210> 531

<211> 14

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 531

gguuuuuuuu uugg 14

<210> 532

<211> 15

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 532

gguuuuuuuu uuugg 15

<210> 533

<211> 16

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 533

gguuuuuuuu uuuugg 16

<210> 534

<211> 17

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 534

gguuuuuuuuuuuuugg 17

<210> 535

<211> 18

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 535

gguuuuuuuuuuuuuugg 18

<210> 536

<211> 19

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 536

gguuuuuuuuuuuuuugg 19

<210> 537

<400> 537

000

<210> 538

<211> 10

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 538

Ggguuuuggg 10

<210> 539

<211> 11

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 539

ggguuuuugg g 11

<210> 540

<211> 12

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 540

ggguuuuuug gg 12

<210> 541

<211> 13

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 541

ggguuuuuuu ggg 13

<210> 542

<211> 14

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 542

ggguuuuuuu ugg 14

<210> 543

<211> 15

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 543

ggguuuuuuu uuggg 15

<210> 544

<211> 16

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 544

ggguuuuuuuuuuggg 16

<210> 545

<211> 17

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 545

ggguuuuuuuuuuuggg 17

<210> 546

<211> 18

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 546

ggguuuuuuuuuuuuggg 18

<210> 547

<211> 19

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 547

ggguuuuuuuuuuuuuggg 19

<210> 548

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 548

ggguuuuuuu uuuuuuuugg guuuuuuuuu uuuuuugggu uuuuuuuuuu uuuuggg 57

<210> 549

<211> 42

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 549

ggguuuuuuu uuuuuuuugg gggguuuuuu uuuuuuuuug gg 42

<210> 550

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 550

ggguuugggu uuggguuugg guuuggguuu ggguuugggu uuggguuugg g 51

<210> 551

<211> 20

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 551

gguuuuuuuuuuuuuuuggg 20

<210> 552

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 552

cccuuuuuuu uuuuuuuucc cuuuuuuuuu uuuuuucccu uuuuuuuuuu uuuuccc 57

<210> 553

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 553

ccccuuucccu uucccuuucc c 51

<210> 554

<211> 42

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 554

cccuuuuuuuuuuuuuuuuccccccuuuuuuuuuuuuuuuuc cc 42

<210> 555

<211> 60

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 555

uagcgaagcu cuuggaccua gguuuuuuuu uuuuuuuggg ugcguuccua gaaguacacg 60

<210> 556

<211> 120

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 556

uagcgaagcu cuuggaccua gguuuuuuuu uuuuuuuggg ugcguuccua gaaguacacg 60

aucgcuucga gaaccuggau ccaaaaaaaa aaaaaaaccc acgcaaggau cuucaugugc 120

<210> 557

<211> 229

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 557

gggagaaagc ucaagcuugg agcaaugccc gcacauugag gaaaccgagu ugcauaucuc 60

agaguauugg cccccgugua gguuauucuu gacagacagu ggagcuuauu cacucccagg 120

auccgagucg cauacuacgg uacuggugac agaccuaggu cgucaguuga ccaguccgcc 180

acuagacgug aguccgucaa agcaguuaga uguuacacuc uauuagauc 229

<210> 558

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 558

gggagaaagc ucaagcuugg agcaaugccc gcacauugag gaaaccgagu ugcauaucuc 60

agaguauugg cccccgugua gguuauucuu gacagacagu ggagcuuauu cacucccagg 120

auccgagucg cauacuacgg uacuggugac agaccuaggu cgucaguuga ccaguccgcc 180

acuagacgug aguccgucaa agcaguuaga uguuacacuc uauuagaucu cggauuacag 240

cuggaaggag caggaguagu guucuugcuc uaaguaccga gugugcccaa uacccgauca 300

gcuuauuaac gaacggcucc uccucuuaga cugcagcgua agugcggaau cuggggauca 360

aauuacugac ugccuggauu acccucggac auauaaccuu guagcacgcu guugcuguau 420

aggugaccaa cgcccacucg aguagaccag cucucuuagu ccggacaaug auaggaggcg 480

cggucaaucu acuucuggcu aguuaagaau aggcugcacc gaccucuaua aguagcgugu 540

ccucuag 547

<210> 559

<211> 1083

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 559

gggagaaagc ucaagcuugg agcaaugccc gcacauugag gaaaccgagu ugcauaucuc 60

agaguauugg cccccgugua gguuauucuu gacagacagu ggagcuuauu cacucccagg 120

auccgagucg cauacuacgg uacuggugac agaccuaggu cgucaguuga ccaguccgcc 180

acuagacgug aguccgucaa agcaguuaga uguuacacuc uauuagaucu cggauuacag 240

cuggaaggag caggaguagu guucuugcuc uaaguaccga gugugcccaa uacccgauca 300

gcuuauuaac gaacggcucc uccucuuaga cugcagcgua agugcggaau cuggggauca 360

aauuacugac ugccuggauu acccucggac auauaaccuu guagcacgcu guugcuguau 420

aggugaccaa cgcccacucg aguagaccag cucucuuagu ccggacaaug auaggaggcg 480

cggucaaucu acuucuggcu aguuaagaau aggcugcacc gaccucuaua aguagcgugu 540

ccucuagagc uacgcagguu cgcaauaaaa gcguugauua gugugcauag aacagaccuc 600

uuauucggug aaacgccaga augcuaaauu ccaauaacuc uucccaaaac gcguacggcc 660

gaagacgcgc gcuuaucuug uguacguucu cgcacaugga agaaucagcg ggcauggugg 720

uagggcaaua ggggagcugg guagcagcga aaaagggccc cugcgcacgu agcuucgcug 780

uucgucugaa acaacccggc auccguugua gcgaucccgu uaucaguguu auucuugugc 840

gcacuaagau ucauggugua gucgacaaua acagcgucuu ggcagauucu ggucacgugc 900

ccuaugcccg ggcuugugcc ucucaggugc acagcgauac uuaaagccuu caagguacuc 960

gacgugggua ccgauucgug acacuuccua agauuauucc acuguguuag ccccgcaccg 1020

ccgaccuaaa cugguccaau guauacgcau ucgcugagcg gaucgauaau aaaagcuuga 1080

auu 1083

<210> 560

<211> 229

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 560

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gcccagauc 229

<210> 561

<211> 546

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 561

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacaguccu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucua 546

<210> 562

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 562

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacaguccu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 563

<211> 1083

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 563

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacaguccu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

600

uuuuuuuuuc cucccaaca augucgauca auagcugggc uguuggagac gcgucagcaa 660

uuuuuuuuuuuuuucccggg 720

accacaaaua auauucuugc uugguugggc gcaagggccc cguaucaggu cauaaacggg 780

uacauguugc acaggcuccu uuuuuuuuuu uuuuuuuuuu uucgcugagu uauuccgguc 840

ucaaaagacg gcagacguca gucgacaaca cgucuaaag cagugcuaca aucugccgug 900

uucguguuuu uuuuuuuuuu uuuuuuguga accuacacgg cgugcacugu aguucgcaau 960

ucauagggua ccggcucaga guuaugccuu gguugaaaac ugcccagcau acuuuuuuuu 1020

uuuuuuuuuu uucauauucc caugcuaagc aagggaugcc gcgagucaug uuaagcuuga 1080

auu 1083

<210> 564

<211> 59

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 564

uagcgaagcu cuuggaccua ccuuuuuuuu uuuuuucccu gcguuccuag aaguaacacg 59

<210> 565

<211> 120

<212>RNA

<213> Artificial Sequence

<220>

<223> Immune stimulatory RNA

<400> 565

uagcgaagcu cuuggaccua ccuuuuuuuu uuuuuuuccc ugcguuccua gaaguacacg 60

aucgcuucga gaaccuggau ggaaaaaaaa aaaaaaaggg acgcaaggau cuucaugugc 120

<210> 566

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 566

Cys Arg Arg Arg Arg Arg Arg Arg Cys

fifteen

<210> 567

<211> 10

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 567

Cys Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10

<210> 568

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 568

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10

<210> 569

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 569

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10

<210> 570

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 570

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10

<210> 571

<211> 15

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 571

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10 15

<210> 572

<211> 16

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 572

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10 15

<210> 573

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 573

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Cys

<210> 574

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 574

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Cys

<210> 575

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 575

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Cys

<210> 576

<211> 20

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 576

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Arg Cys

twenty

<210> 577

<211> 21

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 577

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Arg Arg Cys

twenty

<210> 578

<211> 22

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 578

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Arg Arg Arg Cys

twenty

<210> 579

<211> 14

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 579

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10

<210> 580

<211> 13

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 580

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10

<210> 581

<211> 8

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 581

Cys Arg Arg Arg Arg Arg Arg Arg

fifteen

<210> 582

<211> 9

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 582

Cys Arg Arg Arg Arg Arg Arg Arg Arg

fifteen

<210> 583

<211> 10

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 583

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10

<210> 584

<211> 11

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 584

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10

<210> 585

<211> 12

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 585

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10

<210> 586

<211> 14

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 586

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10

<210> 587

<211> 15

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 587

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

<210> 588

<211> 16

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 588

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

<210> 589

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 589

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg

<210> 590

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 590

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg

<210> 591

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 591

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Arg

<210> 592

<211> 20

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 592

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Arg Arg

twenty

<210> 593

<211> 21

<212> PRT

<213> Artificial Sequence

<220>

<223> cationic component of the polymeric carrier

<400> 593

Cys Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg

1 5 10 15

Arg Arg Arg Arg Arg

twenty

<210> 594

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> SP_Ipilimumab-HC

<400> 594

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 595

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> SP_Ipilimumab-LC

<400> 595

gggagaaagc uuaccaugga gacccccgcc cagcugcucu uccugcugcu ccuguggcug 60

ccggacacca cgggcgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 120

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 180

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 240

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 300

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 360

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccgucgc cgcccccucc 420

guguucaucu ucccgcccag cgacgagcag cugaaguccg ggacggccag cguggucugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggugga caacgcgcug 540

caguccggca acagccagga gagcgucacc gagcaggacu ccaaggacag caccuacucc 600

cucagcucca cccugacgcu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggugaccc accagggccu cuccagcccc gucaccaagu ccuucaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 596

<211> 1003

<212>RNA

<213> Artificial Sequence

<220>

<223> Hs_CD40LG_v1(GCv3).1

<400> 596

gggagaaagc uuaccaugau cgagaccuac aaccagacca gcccccgcuc cgccgccacg 60

ggccugccga ucagcaugaa gaucuucaug uaccuccuga ccguguuccu gaucacccag 120

augaucgggu ccgcgcuguu cgccgucuac cugcaccggc gccuggacaa gaucgaggac 180

gagcggaacc uccacgagga cuucguguuc augaagacca uccagcgcug caacacgggc 240

gagcggagcc ugucccugcu caacugcgag gagaucaaga gccaguucga gggguucgug 300

aaggacauca ugcugaacaa ggaggagacc aagaaggaga acuccuucga gaugcagaag 360

ggcgaccaga acccccagau cgccgcccac gucaucagcg aggccuccag caagaccacc 420

uccgugcugc agugggcgga gaagggguac uacacgauga gcaacaaccu cgugacccug 480

gagaacggca agcagcugac cgucaagcgc cagggccucu acuacaucua cgcccaggug 540

accuucugcu ccaaccggga ggccagcucc caggcccccu ucaucgcgag ccugugccug 600

aagucccccg ggcgcuucga gcggauccuc cugcgcgccg ccaacacgca cagcuccgcc 660

aagccgugcg gccagcagag cauccaccuc gggggcgugu ucgagcucca gcccggggcc 720

agcgucuucg ugaacgugac cgaccccucc caggucagcc acggcaccgg cuucaccucc 780

uucgggcugc ugaagcucug aggacuaguu auaagacuga cuagcccgau gggccuccca 840

acgggcccuc cuccccuccu ugcaccgaga uuaauaaaaa aaaaaaaaaa aaaaaaaaaa 900

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 960

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1003

<210> 597

<211> 667

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(21-150)

<400> 597

gggagaaagc uuaccaugca gaucccccag gccccguggc ccguggucug ggccgugcug 60

cagcucggcu ggcgccccgg gugguuccug gacagccccg accggccgug gaacccgccc 120

accuucuccc ccgcgcugcu cguggucacc gagggcgaca acgccacguu cacgugcagc 180

uucuccaaca ccagcgaguc cuucgugcug aacugguacc gcaugagccc cuccaaccag 240

accgacaagc uggccgccuu ccccgaggac cggagccagc ccgggcagga cugccgcuuc 300

360 cgggugaccc agcuccccaa cggccgcgac

aacgacagcg ggaccuaccu gugcggcgcg aucucccugg ccccgaaggc ccagaucaag 420

gagagccucc gcgccgagcu gcgggugacc gagcgccggg cgugaggacu aguuauaaga 480

cugacuagcc cgaugggccu cccaacgggc ccuccucccc uccuugcacc gagauuaaua 540

600

aaaugcaucc cccccccccc cccccccccc ccccccccca aaggcucuuu ucagagccac 660

cagaauu 667

<210> 598

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328)_Linker_IL12A(23-219)

<400> 598

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucuc ccucgucuuc 60

cuggccagcc cccugguggc caucugggag cucaagaagg acguguacgu cguggagcug 120

gacugguacc cggacgcgcc cggcgagaug gugguccuga ccugcgacac ccccgaggag 180

gacgggauca cguggacccu cgaccagucc agcgaggugc ugggcuccgg gaagacccug 240

accauccagg ugaaggaguu cggcgacgcc gggcaguaca cgugccacaa gggcggcgag 300

guccucagcc acucccugcu gcuccugcac aagaaggagg acgggaucug gagcaccgac 360

auccuagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gguucacgug cugguggcug accaccauca gcaccgaccu gaccuucucc 480

gucaagagcu cccgcgggag cuccgacccg cagggcguga cgugcggggc cgccacccuc 540

agcgcggagc gggugcgcgg cgacaacaag gaguacgagu acuccgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagucc cugcccaucg aggugauggu cgacgcggug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca uccgggacau caucaagccc 720

gacccgccca agaaccucca gcugaagccc cugaagaacu cccgccaggu ggaggucagc 780

ugggaguacc ccgacaccug guccacgccg cacagcuacu ucucccucac cuucugcguc 840

caggugcagg gcaagagcaa gcgggagaag aaggaccgcg uguucaccga caagaccucc 900

gccacgguga ucugccggaa gaacgccagc aucuccgugc gcgccggaga ccgguacuac 960

agcuccagcu gguccgagug ggccagcguc cccugcuccg gcaguacuuc gggcaguggu 1020

aagccuggua guggugaggg uaguacuaag ggucggaacc ugccgguggc cacccccgac 1080

cccggcaugu uccccugccu gcaccacagc cagaaccucc ugcgcgccgu guccaacaug 1140

cugcagaagg cccggcagac gcucgaguuc uacccgugca ccagcgagga gaucgaccac 1200

gaggacauca ccaaggacaa gaccuccacg gucgaggccu gccugccccu ggagcucacc 1260

aagaacgaga gcugccugaa cucccgcgag accagcuuca ucaccaacgg guccugccug 1320

gcgagccgga agacguccuu caugauggcc cucugccuga gcuccaucua cgaggaccug 1380

aagauguacc agguggaguu caagaccaug aacgccaagc uccugaugga ccccaagcgc 1440

cagaucuucc uggaccagaa caugcucgcc gugaucgacg agcugaugca ggcgcugaac 1500

1560

aagaucaagc ugugcauccu gcuccacgcc uuccggaucc gcgccgugac gaucgaccgg 1620

gugauguccu accugaacgc cagcugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 599

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1

<400> 599

augcaaaucc cccaagcccc cuggcccgua guaugggccg uacuccagcu cggcuggcga 60

cccggcuggu uccucgacuc ccccgaccgc ccuggaacc cacccacauu cucacccgca 120

cuacucguag ucaccgaagg cgacaacgcc accuucaccu gcuccuucuc caacaccucg 180

gaauccuuug uacucaacug guaccgcaug agcccgucca accaaaccga caaacucgcc 240

gcauuccccg aagaccgcag ccaacccggga caagacugcc gauuccgcgu cacccaacua 300

ccuaacggua gagacuucca caugucaguc guccgcgccc gccgaaacga cuccgguacc 360

uaccuaugcg gagccauauc ccuugccccc aaagcacaaa ucaaagaauc ccuacgagcc 420

gaaccccgag ucaccgaacg ccgagccgaa gucccaaccg cacaccccuc ccccuccccc 480

cgaccagccg gccaauucca aacccuagua gucggcguag uaggcggccu ccuaggcuca 540

cucguacucc ucgucgggu acuagcaguc aucugcucac gagccgcccg aggcaccauc 600

ggagccgac gaaccggcca accacucaaa gaagaccccu ccgccguacc agucuucuca 660

gucgacuacg gugaacucga cuuucaaugg agagaaaaaa cccccgaacc cccagucccc 720

ugcguccccg aacaaaccga auacgccaca aucgucuucc caucaggcau gggcaccuca 780

ucccccgccc gccgaggcuc cgccgacgga ccccgcuccg cccaaccccu ccgacccgaa 840

gacggccacu gcuccuggcc ccuuaa 867

<210> 600

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149)

<400> 600

augcaaaucc cccaagcccc cuggcccguc gucugggccg uccuccaacu cggcuggcga 60

cccggcuggu uccucgacuc ccccgaccgc ccuggaacc cucccaccuu cucccccgcc 120

cuccucgucg ucaccgaagg cgacaacgcc accuucacau gcuccuucuc caacaccucc 180

gaauccuucg uccucaacug guaccgcaug uccccccucca accaaaccga caaacucgcc 240

gccuuccccg aagaccgcuc acaacccggc caagacugcc gcuuccgagu cacccaacua 300

cccaacggcc gcgacuucca cauguccguc guccgcgccc gacgcaacga cuccggcacc 360

uaccuaugcg gcgccaucuc ccucgccccc aaagcccaaa ucaaagaauc ccuccgcgcc 420

gaacuacgug ucaccgaacg ccgagccuaa 450

<210> 601

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 601

augugccccg cccgcucccu ccuccucguc gccacacucg uccuccucga ucaccucuca 60

cucgcacgaa accuaccagu cgccaccccc gaccccggca uguuccccug ccuccaccac 120

ucccaaaacc uccuccgcgc cgucuccaau augcuccaaa aagcccgcca aacccucgaa 180

uucuaccccu gcacauccga agaaaucgac cacgaagaca ucaccaaaga caaaaccucc 240

accgucgaag ccugccuccc ccuugaacuc acccaaaaacg aauccugccu aaacucacgc 300

gaaaccuccu ucaucaccaa cggaucaugc cucgccuccc gcaaaaccuc cuucaugaug 360

gcccucugcc ucuccuccau cuacgaagac cucaaaaugu accaaguaga auucaaaacc 420

augaacgcca aacuccucau ggaccccaaa cgccaaaucu uccucgacca aaacaugcuc 480

gccgucaucg acgaacucau gcaagcccuc aacuucaacu cagaaaccgu cccccaaaaa 540

ucaucccucg aagaacccga cuucuacaaa accaaaauca aacuaugcau cuuacuccac 600

660

<210> 602

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219)

<400> 602

augugccccg cccgcucucu ccuccucgua gcaacccucg uccuccucga ccaccucucc 60

cuagcccgaa accuccccgu cgccaccccc gacccaggca uguuccccug ccuccaccac 120

ucccaaaacc uccuccgagc cgucuccaac augcuccaaa aagcccgcca aacccucgaa 180

uucuaccccu gcaccuccga agaaaucgac cacgaagaca ucaccaaaga caaaaccucc 240

accgucgaag ccugccuccc ccucgaacuc acccaaaaacg aaucaugccu caacucccgc 300

gaaaccuccu ucaucaccaa cggcuccugc cuagccuccc gcaaaaccuc cuucaugaug 360

gcccucugcc ucucauccau cuacgaagac cuaaaaaugu accaagucga auucaaaacc 420

augaacgcca aacuccucau ggacccaaaa cgccaaaucu uccuagacca aaacaugcuc 480

gccgucaucg acgaacucau gcaagcccuc aacuucaacu ccgaaaccgu accccaaaaa 540

uccucacucg aagaacccga cuucuacaaa acaaaaauca aacucugcau acuccuccac 600

gccuuccgca uccgcgccgu caccaucgau cgagucaugu ccuaccucaa cgccucc 657

<210> 603

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219)

<400> 603

cgcaaccucc ccgucgccac ccccgacccc ggcauguucc ccugccucca ccacucccaa 60

aaucuccucc gcgccgucuc caacaugcuc caaaaagccc gccaaacccu cgaauucuac 120

cccugcacgu ccgaagaaau cgaccacgaa gacaucacca aagacaaaac cuccaccguc 180

gaagccugcc ucccccucga acucaccaaa aacgaauccu gccucaacuc acgcgaaacc 240

uccuucauca ccaacggcuc augccucgcc ucacgaaaaa ccuccuucau gauggcccuc 300

ugccucuccu caaucuacga agaccucaaa auguaccaag ucgaauucaa aaccaugaac 360

gccaaacucc ucauggaccc caaacgccaa aucuuccucg accaaaacau gcucgcaguc 420

aucgacgaac ucaugcaagc ccucaacuuc aacuccgaaa cgguccccca aaaaucaucc 480

cucgaagaac cagacuucua caaaaccaaa aucaaacucu gcauccuccu ccacgccuuc 540

cgcauccgcg ccguaaccau cgaccgcguc augucauacc ucaacgccuc cuaa 594

<210> 604

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 604

60

gucgccaauau gggaacucaa gaaggacguc uacguaguag aacucgacug guacccagac 120

gcccccggag aaaugguggu ccucaccugc gacacccccg aagaagacgg caucaccugg 180

acauuagacc aaucguccga aguucucggc uccggcaaaa cacucacaau ccaaguaaaa 240

gaauucggcg acgccggaca auacaccugc cacaaaggcg gagaaguacu aucccacuca 300

cuccuacucc uacacaaaaa agaagacggc auauggagca ccgacauccu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccuccga ugcgaagcca aaaacuacuc cggccgcuuc 420

accugcuggu ggcucaccac aauauccacc gaccucaccu ucuccgucaa aucaucucgc 480

ggcuccagcg acccccaagg cgucaccugc ggcgccgcca cccucucagc cgaacgcgua 540

cgcggugaca acaaagaaua cgaauacagc guagaaugcc aagaagacuc cgccuguccc 600

gccgcagaag aaucacuccc caucgaaguc augguagacg caguacacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacaucauca aacccgaccc cccaaaaaac 720

cuacacacuca aaccccuuaa aaacucccgc caagucgaag ucuccggga auacccagac 780

acauggucca ccccccacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgaguauuc accgacaaaa ccucagccac cgucaucugc 900

agaaaaaacg ccuccaucuc cguccgagcc caagaccgcu acuacuccuc cuccuggucc 960

gaaugggcau ccguccccug cucauaa 987

<210> 605

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328)

<400> 605

augugccacc aacaacucgu caucagcugg uucagccucg ucuuccucgc cuccccccua 60

guagccauau gggaacuaaa aaaagacgua uacguuguag aacuagacug guaccccgac 120

gcacccggcg aaauggucgu ccucaccugc gacacccccg aagaagaugg cauaacaugg 180

acccucgacc aauccucaga aguccucggc uccggcaaaa cccucacaau ccaagucaaa 240

gaauucggcg acgccggcca auacaccugc cacaaaggcg gcgaaguccu cucucacucu 300

cuccuccucc uccacaaaaa agaagacggc aucuggucca ccgacauacu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccugcga ugcgaagcca aaaacuacuc cggccgauuc 420

acaugcuggu ggcucaccac caucucaacc gaccucaccu ucuccgucaa auccucccgu 480

ggcagcuccg acccccaagg agucaccugc ggcgcagcca cccucuccgc cgaacgcguc 540

agaggcgaca acaaagaaua cgaauacucc gucgaaugcc aagaggacuc cgccugcccc 600

gccgccgaag acuaaaauac 660

gaaaacuaca ccucuucauu cuucauccga gacaucauca aacccgaccc ccccaaaaac 720

cuccaacuca aaccccucaa aaacucccga caagucgaag ucagcuggga auacccagac 780

accuggucca cccacacuc cuacuucuca cuaaccuucu gcguccaagu ccaaggcaaa 840

ucgaaacgcg aaaaaaaaga cagagucuuc accgacaaaa ccucagccac cgucaucugc 900

cgaaaaaacg caucaaucag cguccgcgcc caagaccgcu acuacuccuc cagcuggagc 960

gaaugggcau ccguccccug cucc 984

<210> 606

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328)

<400> 606

aucugggaac ucaaaaaaga cgucuacgua gucgaacucg acugguaccc agacgccccc 60

ggcgaaaugg ucguccucac cugcgacaca cccgaagaag acggcaucac cuggacacuc 120

gaccaauccu ccgaaguacu cggcuccggc aaaacccuca caauccaagu caaagaauuc 180

ggcgacgccg gccaauacac cugccacaaa ggcggcgaag uccucuccca cucccuccuc 240

cuacuccaca aaaaagaaga cggcaucugg uccacagaca uccucaaaga ccagaaagaa 300

cccaaaaaca agaccuuccu acgaugcgaa gccaaaaacu acagcggccg auucaccugc 360

ugguggcuca caaccaucag caccgaccua accuucuccg uaaaauccuc cagaggaucc 420

agcgaccccc aaggcgucac augcggcgcc gcaacccuau ccgcagagcg aguacgaggc 480

gacaacaaag aauacgaaua cuccguagaa ugccaagaag acuccgcaug cccugccgcc 540

gaagaaagcc uccccaucga agucaugguc gacgcagucc acaaacucaa auacgaaaac 600

uacacaagcu cuuucuucau acgcgacauc aucaaacccg accccccaaa aaaccuacaa 660

cucaaacccc uaaaaaacuc ccggcaaguc gaagucagcu gggaauaccc cgacaccugg 720

uccacccccc auuccuacuu cucccucaca uucugcguac aaguccaagg caaaaguaaa 780

cgcgagaaaa aagaccgcgu cuucaccgac aaaaccagcg caaccgucau cugccgcaaa 840

aacgccagca ucagcguacg agcccaagac cgcuacuacu caagcucaug guccgaaugg 900

gccuccgucc ccugcucaua a 921

<210> 607

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218

<400> 607

gggaguacga gugggagugg gaagccgggg agugggggagg ggaguacgaa gggg 54

<210> 608

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12

<400> 608

augugccacc aacaacucgu

guugcuauau gggaacucaa gaaagacguc uacgucgucg aacucgacug guacccggac 120

gcccccggcg aaauggucgu ccuaaccugc gauacacccg aagaagacgg caucaccugg 180

acccucgacc aguccucuga aguccuagga uccggcaaaa cccuuacaau ccaagucaaa 240

gaguucggcg acgccggcca guacacaugc cacaaaggcg gcgagguccu gagccauucc 300

uuacuccucc uacacaagaa agaagacggc aucuggucca ccgacauacu aaaagaccaa 360

aaagaaccca aaaacaaaac cuuccuacga ugcgaagcca aaaacuacuc aggccgauuc 420

accuguuggu ggcucaccac gaucagcacc gaccuaacau ucucaguaaa auccucacgc 480

ggcuccagcg acccacaagg cgucacaugc ggggccgcca cccuauccgc cgaacgaguc 540

aggggcgaca acaaagaaua cgaauacagc guagaaugcc aagaagacuc cgccugcccc 600

gcggccgaag agucccuacc cauagagguc auggucgacg ccguccacaa acucaaauac 660

gagaacuaca ccuccagcuu cuucauccgc gacauaauca aaccagaccc acccaaaaac 720

cuacacuaa aaccacucaa aaauucgcgc caggucgaag ucucuuggga auacccggac 780

840

uccaaacgcg aaaagaaaga ccgaguauuc acagacaaaa ccucagcaac gguaaucugc 900

cgcaaaaacg ccuccaucuc agucagggcc caagaccgau acuacuccuc cucauggagc 960

gagugggcau cuguaccaug cagcggggagc acauccggau cgggaaaacc cggcuccggc 1020

gaaggaagca ccaaagguag aaaccuucca guagccaccc ccgacccugg uauguuuccc 1080

ugccuccacc auagccaaaa ccuccuacga gcagucucca acaugcucca aaaagcacga 1140

caaacccuug aguucuaccc augcacaucc gaagaaauag accacgaaga caucacaaag 1200

gacaaaaccu ccacagucga agccugccuc ccacuugaac ucaccaaaaa cgaaucaugc 1260

1320

ucguucauga uggcacucug ccugucaagc aucuacgaag accucaaaau guaccaaguu 1380

gaguucaaga caaugaacgc 1440

1500

gucccccaaa aauccagccu cgaagaaccc gacuucuaca aaaccaaaau caaacuaugc 1560

auccuccucc acgccuucag aaucagggcc gugaccaucg acagagucau guccuaccuc 1620

aacgccucgu aa 1632

<210> 609

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 609

augaucgaaa cauacaacca aacauccccc cgauccgccg caacaggccu ccccaucucc 60

augaaaauau ucauguaccu ccucacagua uuccucauaa cccaaaugau cggaucagca 120

cuauucgccg ucuaccucca ccgccgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuucg ucuucaugaa aaccauccaa cgcugcaaca ccggagaacg aucccuaucc 240

cuccucaacu gcgaagagau caaaucccaa uucgaaggcu ucgucaaaga caucaugcuc 300

aacaaagaag aaaccaaaaa agaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaaucgccg cccacgucau cuccgaagcc uccuccaaaa caaccuccgu ucuccaaugg 420

gccgagaaag gcuacuacac uauguccaac aaccucguca cccucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg ccucuacuac aucuacgccc aagucacauu cugcuccaac 540

600

uucgaacgca uccuccuacg cgccgccaac acccacuccu cagccaaacc cugcggccaa 660

caauccaucc accuaggcgg cgucuucgaa cuccaacccg gugccuccgu cuuugucaac 720

guaaccgacc ccucccaagu cucccggc accggauuca cauccuucgg ccuccucaaa 780

cucuaa 786

<210> 610

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1

<400> 610

augcagauac cacaagcacc aggccagua guaugggcag uauuacaauu aggauggaga 60

120

180

gaaucuuuug uauuuuagca 240

gcauuuccag aagauagauc acaaccagga caagauugua gauuuagagu aacacaauua 300

ccuaauggua gagauuuuca uaugucagua guaaagcaa gacgaaauga uagcggaaca 360

uauuuaugug gagcaauuuc auuagcacca aaagcacaaa uaaaagaaag uuuaagagca 420

gaacuaagag uaacagaaag aagagcagaa guaccaacag cacauccauc uccaagucca 480

agaccagcag gacaauuuca aacauuagua guuggaguag uaggaggacu acuaggauca 540

uuaguauuac uaguaugggu acuagcugua auauguucaa gagcagcaag aggaacaaua 600

ggugcaagaa gaacaggaca accacuuaaa gaagacccuu cagccguacc uguauuuagu 660

guagauuaug gagaauuaga uuuccaaugg agagaaaaaa caccagaacc accuguacca 720

ugcguaccag aacaaacaga auacgcaaca auaguuuucc caucaggaau gggaacuagc 780

ucacccgcaa gaagaggauc agcagaugga ccaagaucag cacaaccacu aagacccgaa 840

gauggacauu guucauggcc auuauaa 867

<210> 611

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149)

<400> 611

augcaaauac cccaagcacc auggccagua guaugggcag uauuacaacu aggauggaga 60

ccaggauggu ucuuagacuc accagacaga ccauggaacc caccaacauu cucaccagca 120

cuauuaguag uaacagaagg agacaacgca acauucacau gcucauucuc aaacacauca 180

gaaucauucg uauuaaacug guacagaaug

gcauucccag aagacagauc acaaccagga caagacugca gauucagagu aacacaacua 300

ccaaacggaa gagacuucca caugucagua guaaagcaa gaagaaacga cucaggcacc 360

uaccuauugcg gagcaauuuc acuagcacca aaagcacaaa uaaaagaauc acuaaagca 420

gaacuaagag uaacagaaag acgagcauaa 450

<210> 612

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 612

augugcccag caagaucacu acuacuagua gcaacacuag uacuacuaga ccaccuaucc 60

cuagcacgaa accuaccagu agcaacaccu gacccaggaa uguucccaug ccuccaccac 120

ucccaaaacc uauuacgagc agucucaaac augcuacaaa aagcacgaca aacacuagaa 180

uucuacccau gcacaucaga agaaauagac cacgaagaca uaacaaaaga caaaacauca 240

acaguagaag caugccuacc acuagaacuc acaaaaaacg aaucaugccu aaacucuaga 300

360

gccuuaugcc uaucaucaau auaugaagac cuaaaaaugu accaagucga auucaaaaca 420

augaacgcaa aacuacuaau ggacccaaaa agacaaauau uccuagacca aaacaugcuc 480

gcaguaauag augaacuaau gcaagcacua aacuucaacu cagaaaccgu cccccaaaaa 540

uccucacuag aagaacccga cuucuacaaa acaaaaauaa aauuaugcau acuauuacac 600

660

<210> 613

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219)

<400> 613

augugcccag caagaucauu acuacuagua gccacacuag uccuccuaga ccaccuauca 60

cuagcaagaa accuaccagu agcaacacca gacccaggaa uguucccaug ccuacaccac 120

ucacaaaacu uacuaagagc aguaucaaac augcuacaaa aagcaagaca aacacuagaa 180

uucuacccau gcacaucaga agaaauagau caugaagaca uaacaaaaga caaaacaucc 240

acaguagaag caugccuacc acuagaacua acaaaaaacg aaucaugccu aaacucacga 300

gaaaccucau ucauaacaaa cggaucaugc cuagcauca

420

augaacgcaa aacuccucau ggacccaaaa agacaaauau uccuagacca aaacaugcua 480

540

ucaucacuag aagaaccaga cuuuuacaaa accaaaauaa aacuaugcau acuacuacac 600

gcauucagaa uaagagcagu aacaauagac agaguaaugu cuuaccuaaa cgcauca 657

<210> 614

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219)

<400> 614

agaaaccuac caguagcaac acccgaccca ggaauguucc caugccuaca ccacucacaa 60

aaccuacuac gcgcaguauc aaacauguua caaaaagcac gacaaacacu ugaauucuac 120

cccugcacau cagaagaaau agaccacgaa gacauaacaa aagacaaaac auccaccgua 180

gaagcaugcc ucccacuaga acuaacaaaa aacgaaucau gccuaaacuc aagagaaaca 240

ucauucauaa caaacggauc augccuagca ucacgaaaaa caucauucau gauggcacua 300

ugccuauccu ccauauacga agaccuaaaa auguaccaag uagaauucaa aacaugaac 360

gcaaaacuac uaauggaccc aaaaagacaa auauuccuag accaaaacau gcucgcagua 420

auagacgaac uaaugcaagc acuaaacuuu aacucagaaa caguacccca aaaaucauca 480

cuagaagaac cagacuucua caaaacaaaa auaaaauuau gcauacuccu acacgcauuc 540

agaucagag caguaacaau agaccgcgua augucauacc uaaacgcauc auaa 594

<210> 615

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 615

augugccauc aacaacuagu aaucucaugg uucagccuag uauucuuagc caguccauua 60

guagcaauau gggaauuaaa aaaagaugua uacguugugg aacuagacug guauccugac 120

gcaccaggag aaaugguugu acuaacaugu gauacacccg aagaagacgg aauaacaugg 180

acacuagacc aaucaucaga aguauuaggc ucaggaaaaa cauuaacaau acaaguaaaa 240

aucacauuca 300

360

aaagaaccua aaaacaaaac auucuuaaga ugcgaagcaa aaaacuacag uggaagauuc 420

acaugcuggu ggcugacaac aauaucaaca gaucuaacau uuucaguaaa aucaucaaga 480

ggaucaucag auccacaagg cguaacaugc ggagccgcaa cacuaagcgc agaaagaguc 540

agaggagaca acaaagaaua cgaauauuca guagaauguc aagaagauuc agcaugcccu 600

gcagcagaag aaucacuacc aauagaaguc augguagaug caguacacaa acuaaaauau 660

gaaaacuaca caucaagcuu cuuuauaaga gacauaauca aaccagaccc accaaaaaac 720

cuacaacuaa aaccauuaaa aaacucacga caaguagaag uaagcuggga auacccagac 780

acguggucga ccccacacuc auacuucagc uuaacauuuu gcguacaagu acaaggaaaa 840

ucaaaaagag aaaaaaaaga ccgaguauuu acagacaaaa caucugcaac aguaauauugc 900

cgaaaaaacg

gaaugggcaa gcguaccaug cucauaa 987

<210> 616

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328)

<400> 616

augugccauc aacaacuagu aauaucaugg uucucacuag uauucuuagc aaguccccua 60

guagcaauau gggaacuaaa aaaagacguc uacguuguag aauuagacug guacccagac 120

gcaccaggcg aaaugguagu auaacaugc gauacaccag aagaagacgg aauaacaugg 180

acacuagacc aaucaucaga aguucuagga ucaggaaaaa cauuaacaau acaaguaaaa 240

gaauucgggg acgcaggaca auauacaugc cacaaaggag gagaaguuuu aucacacuca 300

cuacuauuau uacacaaaaa agaagacgga auauggucaa cugacauacu aaaagaucaa 360

aaagaaccaa aaaacaaaac auucuuaaga ugugaagcaa aaaauuacag uggaagauuc 420

acaugcuggu ggcuaacaac aauaaguaca gaccuaacau uuucaguaaa aucaaguaga 480

ggaucaucag acccacaagg cguaacaugu ggagcagcaa cacuaucagc agaacgaguc 540

agaggagaca acaaagaaua cgaauacucc guagaaugcc aagaagacag ugcaugcccc 600

gcagccgaag acuaaaauac 660

gaaaacuaca caagcucauu cuuuauacga gauauaauaa aaccagaccc accaaaaaac 720

cuacacuaa aaccacuaaa aaacucacgc caaguagaag uauccuggga auacccagau 780

acauggucaa caccacacuc auauuucagc uuaacauucu guguacaagu acaaggaaaa 840

ucaaaaagag aaaaaaaaga uagaguauuc accgacaaga caagcgcaac aguaauuugu 900

agaaaaaacg caucaauuuc aguaaagca caagacagau acuacagcuc aagcugguca 960

gaaugggcaa guguaccaug uuca 984

<210> 617

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328)

<400> 617

auaugggaau uaaaaaaaga cguauacgua guagaacuag auugguaccc agaugcacca 60

ggagaaaugg uuguauuaac augcgacaca ccagaagaag auggaauaac auggacacua 120

gaccaaagua gugaaguacu aggaagcggc aaaacauuaa cuauacaagu aaaagaauuc 180

ggaggagaag uccuauccca caguuuauua 240

300

360

ugguggcuaa cuacaauuuc aacagaccuc acauuuucag uaaaauccag uagaggaagu 420

ucagauccac aaggaguaac auguggagca gcaacacuau cagcagaaag aguaagga 480

gacaauaaag aauauugaaua uucaguagaa ugccaagaag auagcgcuug cccagcagca 540

gaagaaagcc uuccaauaga aguaauggua gacgcaguuc acaaauuaaa auaugaaaau 600

uacaccagcu cauuucuuuau aagagacaua auaaaaccag

cuaaaaccau uaaaaaauuc aagacaagua gaaguaagcu gggaauaccc agauacaugg 720

agcaccccac acucauacuu cucauuaaca uuuuguguac aaguacaagg aaaaagcaaa 780

agagaaaaaa aagacagggu auucacagau aaaacaagcg caacaguaau auguagaaaa 840

aacgcaucaa uaagcguaag agcacaagau agauauuacu caucaucaug gucagaaugg 900

gcauccguac caugcucaua a 921

<210> 618

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218

<400> 618

ggaaguacaa guggaagugg aaaaccagga aguggagaag gaaguacaaa agga 54

<210> 619

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12

<400> 619

augugccacc aacaacuagu uauaucaugg uuuucacuag uauuucuagc cucaccacuc 60

guagccauau gggaacuaaa aaaggacgua uacguuguag aacucgacug guacccagau 120

gcaccaggcg aaaugguagu acuuacaugc gauacacccg aagaagacgg aaucacaugg 180

acauuagauc aaucaucaga aguacuagga uccggcaaaa cauuaacaau acaaguaaaa 240

gaauucggcg augccggaca auauacaugc cacaaaggag gagaaguauu aagucacuca 300

360

aaggaaccaa aaaacaaaac auuccuacga ugcgaagcaa agaauuauuc gggccgauuc 420

acaugcuggu ggcuaacaac aauuuccaca gaccuaacau ucucaguuaa guccucaaga 480

ggaaguuccg auccacaagg aguaacaugu ggcgccgcaa cauuaagcgc agaacgcgua 540

agaggagaua acaaagaaua cgaauacuca guagaaugcc aagaggacuc cgccugucca 600

gcagccgaag aaucuuuacc aauagaagua augguagaug caguacauaa acuaaaauac 660

gaaaacuaua cgucaucauu cuuuauaaga gauauaauca aaccagaccc accuaaaaau 720

cuacaacuaa aaccccuaaa aaauucacga caaguagagg uuucauggga auauccagau 780

acauggucaa caccacacag cuacuuuagu uuaacauucu guguacaagu ccagggaaaa 840

ucaaaaagag aaaaaaaaga cagaguauuu accgacaaaa cauccgcaac aguaauaugu 900

agaaaaaaug cauccauauc aguacgagca caagaccgau acuauucauc aaguugguca 960

gaaugggcau caguaccuug cucgggaagu accucaggca guggaaaacc aggaucagga 1020

gaaggaucaa ccaaaggaag aaaccuacca guagcaacac cugacccagg cauguucccu 1080

ugcuuacauc acucacaaaa ccuacuacga gcugugucaa auauguuaca aaaagcaaga 1140

caaaccuuag aauuuuaucc augcacauca gaagaaaucg accaugaaga cauaaccaaa 1200

gacaaaacaa gcacaguuga agccuguuua ccauuagaac ucacgaaaaa cgaauccugu 1260

1320

ucauucauga uggcacuaug ccuuucaucc auauacgaag accuaaaaau guaccaagua 1380

gaauucaaaa caaugaaugc 1440

1500

guaccccaaa aaucaagcuu agaagaacca gacuuuuaua aaacuaaaau aaaacuaugc 1560

auccuauuac acgcuuuuag aauaagagca guuacaauag acagagucau gagcuaucua 1620

aaugcaucau ga 1632

<210> 620

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 620

augauagaaa cauacaauca aaccucccca agauccgcag caacaggacu accaauauca 60

augaaaauau ucauguacuu acuaacagua uuccucauaa cacaaaugau aggauccgca 120

cuuuucgcag uauaccuaca cagaagauua gacaaaauag aagacgaacg aaaccuacac 180

gaagacuucg uauuuaugaa aacuauacaa cgcugcaaca caggagaaag aucucuaucu 240

cuauuaaacu gcgaagaaau caaaucacaa uuugaaggau uuguaaaaga cauaaugcua 300

aacaaagaag aaaccaaaaa agaaaacuca uucgaaaugc aaaaaggaga ccaaaaccca 360

caaauagcag cccacgucau auccgaagca agcucaaaaa caaccucagu acuacaaugg 420

gcagaaaaag gauacuacac aaugucaaac aaccuaguaa cccuagaaaa cggaaaacaa 480

cuaacaguca aaagacaagg acuauacuac auauacgcac aaguaacauu cugcucaaac 540

agagaagcau caucccaagc acccuucaua gcaucacuau gccucaaauc accaggaaga 600

660

caaucaauac accuaggagg aguauucgaa uuacaaccag gagcaucagu auucguaaau 720

guuacugacc ccucacaagu cucacacgga acaggauuca caucauucgg acuauuaaaa 780

cuauaa 786

<210> 621

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1

<400> 621

augcaaauac cacaagcacc aggccagua guaugggcag uacuacagcu agguuggaga 60

ccaggauggu uucuagauuc accagauaga ccauggaauc caccuacauu uucacccgca 120

uuauuaguag uaacugaagg agacaaugca acauuuacau gcucauuuuc aaauacaucu 180

gaaagcuuug uauuuuagca 240

gcauucccag aagauagauc acaacccgga caagauugua gauuuagagu uacacaacua 300

ccaaauggaa gagauuuuca uaugucagua guaagagcaa gaagaaauga uagcggaaca 360

uauuuaugug gagcaauaag cuuagcacca aaagcacaaa uaaaagaaag uuuaagagca 420

gaauuaagag uaacagaaag aagagcagaa guaccaaccg cacauccauc accaagucca 480

agaccagcug gucaauucca aacuuuagua guaggaguag uaggaggacu auuaggaagu 540

uuaguauuau uaguaugggu acuagcagua auauguucaa gagcagcaag aggaacaaua 600

ggugcaagaa gaacaggaca accauuaaaa gaagacccau cagcuguacc aguuuuuuca 660

guagauuaug gagaacuuga uuuucaaugg agagaaaaaa cuccugaacc accaguacca 720

uguguuccag aacaaacuga auaugcuaca auagucuucc caucaggaau gggaacaagu 780

aguccagcca gaagaggauc agcagaugga ccaagaucag cacaaccauu aagaccagaa 840

gacggacacu guagcuggcc acuauaa 867

<210> 622

<211> 450

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1(1-149)

<400> 622

augcaaauac cacaagcacc aggccagua guaugggcag uacuacaacu aggauggaga 60

ccaggauggu ucuuagacuc accagacaga ccauggaacc caccaacauu cucaccagca 120

cuacuaguag uaacagaagg agauaacgca acauucacau gcucauucag uaacacauca 180

gaaucauucg uauuaaacug guacagaaug

gcauucccag aagacagauc acaaccagga caagacugca gauucagagu aacacaauua 300

ccaaacggaa gagacuucca caugucagua guaaagcaa gaagaaauga cucaggaaca 360

uaccuauugcg gagcaauuuc acuagcacca aaagcacaaa uaaaagaauc acuaaagca 420

gaauuaagag uaacagaaag aagagcauaa 450

<210> 623

<211> 660

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 623

augugcccag cacaccuauca 60

cuagcaagaa accuaccagu agcaacacca gacccaggaa uguucccaug ccuacaccau 120

ucacaaaauu uauuaagagc aguauccaac augcuacaaa aagcaagaca aacauuagaa 180

uucuacccau gcacauccga agaaauagac cacgaagaca uaacaaaaga caaaacaucu 240

acaguagaag caugccuacc acuagaacua acaaaaaacg aaucaugccu aaacucaaga 300

360

420 gcacuaugcc uaucaucaau

augaacgcaa aacuaacuaau ggacccaaaa agacaaauau uccuagacca aaacaugcua 480

gcaguaauag augaacuaau gcaagcacua aacuucaacu cagaaacagu accccaaaaa 540

ucaucacuag aagaaccaga cuucuacaaa acaaaaauaa aacucugcau acuacuacac 600

660

<210> 624

<211> 657

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(1-219)

<400> 624

60

cuagcaagaa accuacccgu agcaacaccc gacccaggaa uguuccccug ccuacaucac 120

ucccaaaacc uacuaagagc aguaucaaac auguuacaaa aagcacgaca aacacuagaa 180

uucuaccccu gcacaucaga agaaauagac cacgaagaca uaacaaaaga caaaacauca 240

acaguagaag caugccuccc acuagaacua acaaaaaacg aaucaugccu aaacucaaga 300

360

420 gcacuaugcc uaucaucaau

augaacgcaa aacuauuaau ggacccaaaa agacaaauau uccuagacca aaacaugcuc 480

gcaguaauag acgaacuaau gcaagcacua aacuucaacu ccgaaacagu accccaaaaa 540

ucaucacucg aagaaccaga cuuuuacaaa acaaaaauaa aacuaugcau acuacuacac 600

gcauucagaa uaaagcagu aacaauagac agaguaaugu cauaccuaaa cgccuca 657

<210> 625

<211> 594

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12A(23-219)

<400> 625

agaaaccuac caguagcaac accagacccc ggaauguucc caugccucca ccacucacaa 60

aaccuacuaa gagcaguauc aaacauguua caaaaagcca gacaaacauu agaauuuuac 120

ccauguacau cagaagaaau agaccacgaa gacauaacaa aagacaaaac aucaacagua 180

240

ucauucauaa caaacggauc augccuagca ucaagaaaaa caucauucau gauggcacua 300

ugccuaucau ccauauacga agaccuaaaa auguaccaag uagaauuuaa aacaugaac 360

gcaaaacucc uaauggaccc aaaaagacaa auauuccuag accaaaauau gcucgcagua 420

auagacgaau uaaugcaagc acuaaacuuc aacucagaaa caguaccaca aaaaucaucc 480

cuagaagaac ccgacuucua caaaacaaaa auaaaacuau gcauacuacu acacgcauuc 540

agaauaagag ccguaacaau agacagagua augucauacc uaaacgcauc auaa 594

<210> 626

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 626

augugccacc aacaacuagu aaucagcugg uuuucauuag uauuucuagc aucaccacua 60

guagcaauau gggaacuaaa aaaagacgua uacguaguag aacucgacug guacccagac 120

gcaccaggag aaaugguagu acuaacaugc

acacuagauc aaucaucaga aguacuagga ucagguaaaa cacuaacaau ccaaguaaaa 240

gaauucggag acgcuggaca auacacaugu cacaaaggag gagaaguacu aagccacuca 300

cuauuauuac uacacaaaaa agaagacggc auauggucaa cagacauacu aaaagaccaa 360

420

acaugcuggu gguuaacaac aauaucaaca gaucuaacau uuucaguaaa aucaucaaga 480

ggaucaucag acccacaagg aguaacaugc ggagcagcaa cacucagcgc agaaagagua 540

agaggagaua auaaagaaua cgaauacuca guggaaugcc aagaagauag ugcaugccca 600

660

gaaaauuaca caaguucauu cuuuauaaga gacauaauaa aaccagaucc accaaaaaau 720

cuacaacuaa aaccauuaaa aaauaguaga caaguagaag uaagcuggga auauccagac 780

acauggucaa caccacacag uuauuucuca uuaacauucu guguacaagu acaaggaaaa 840

aguaaaagag aaaaaaaaga uagaguuuuc acagacaaaa cauccgcaac aguuauaugu 900

agaaaaaacg caucaauuuc aguaagagcc caagacagau acuacucauc aaguugguca 960

gaaugggcau cgguaccaug cagcuaa 987

<210> 627

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(1-328)

<400> 627

augugccacc aacaacuagu uauuuccugg uucucauuag uauuccuagc cucaccauua 60

guagcuauau gggaauuaaa aaaagaugua uacguaguag aacuagacug guacccagau 120

gcaccaggag aaaugguagu acuaccugc gacacaccag aagaagacgg aauaacaugg 180

acccuagacc aaucaucaga aguauuagga aguggaaaaa cacuaacaau acaaguaaaa 240

gaauucggag acgcaggaca auauacuugc cacaaaggag gagaaguauu aagucauuca 300

uuacuccuau uacacaaaaa agaagacgga auauggagca ccgacauacu aaaagaccaa 360

420

acaugcuggu ggcuaacaac aauaucaaca gaccuaaccu ucuccguuaa aaguucaaga 480

ggaaguucag auccacaagg aguaacaugu ggagcagcaa cacuaagcgc agaaagagua 540

agaggcgaca auaaagaaua ugaauacuca guagaaugcc aagaagauuc agcauguccc 600

gcggccgaag aaucacuacc aauagaagua augguagacg caguacacaa acucaaauau 660

gaaaacuaca caucaucauu cuuuauaaga gacauaauaa aaccagaccc accaaaaaau 720

cuacaacuaa aaccauuaaa aaacucaaga caaguugaag uaagcuggga auauccagac 780

acauggucaa caccacacuc auacuuuuca cuaacauuuu gcguacaagu acaagguaaa 840

ucaaaaagag aaaaaaaaga ucgaguauuu acagacaaaa caagugcaac agucaauaugu 900

agaaaaaacg caucaauuuc agucagagca caagacagau auuacaguag uucaugguca 960

gaaugggcaa gcguuccaug cuca 984

<210> 628

<211> 921

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B(23-328)

<400> 628

auaugggaac ucaaaaaaga uguauacgua gucgaacuag acugguaccc agacgcacca 60

ggagaaaugg uaguacuaac augugauaca ccagaagaag auggaauaac auggacacua 120

gaccaaucaau cagaaguauu aggaucagga aaaacacuaa caauacaagu aaaagaauuu 180

ggagaugcag gacaauauac augccacaaa ggaggagaag uacuaucgca cagcuuauua 240

cuacuacaca aaaaagaaga cggaauaugg agcacagaca uauuaaaaga ccaaaaagaa 300

ccaaaaaaca aaacauucuu acgaugcgaa gcaaaaaacu auucaggaag auucacaugc 360

ugguggcuaa caacaaucag cacagaccua acauuuucag uaaaaucaag cagaggauca 420

ucagauccac aaggagucac auguggagca gcaacacuuu cagccgaaag aguuagagga 480

gauaauaaag aauacgaaua cucaguagaa ugccaagaag acagcgcaug uccagcagca 540

gaagaaagcc uaccaauaga aguaauggua gacgcaguuc acaaauuaaa auacgaaaau 600

uacacaucau cauucuucau aagagacaua auaaaaccag acccaccaaa aaaccuacaa 660

uuaaaaccac uaaaaaacag cagacaagua gaaguaucau gggaauaucc agacacaugg 720

ucaacaccuc acagcuacuu uucacuaaca uucugcguac aaguacaagg aaaaucaaaa 780

agagaaaaaa aagacagagu auucacagac aaaacaagcg caacaguaau augcagaaaa 840

aacgccagca uaucaguuag agcacaagac agauauuaca gcucaagcug gucagaaugg 900

gcaucagucc ccugcucaua a 921

<210> 629

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Linker-sFvCC49-218

<400> 629

ggaaguacaa guggaagugg aaaaccagga aguggagaag gaaguacaaa agga 54

<210> 630

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12

<400> 630

augugccauc aacaacuagu aauauccugg uucuccuuag uguucuuagc aucuccacua 60

guagcaauau gggaauuaaa aaaagacgua uacguaguag aauuagacug guauccugac 120

180

acacucgacc aaucaucaga aguacuaggu ucaggaaaaa cacuaacuau ucaaguaaaa 240

gaauucggag augcaggcca auacacgugu cauaaaggag gcgaaguacu cagccauuca 300

360

aaagaaccaa aaaauaaaac auuuuugaga ugcgaagcaa aaaauuauuc aggagaauuuu 420

acauguuggu ggcuaaccac cauaucaaca gaucuaacau ucuccguaaa aucaucaaga 480

ggaucaucgg acccucaagg aguaacaugc ggagcagcaa cacuaucagc agaaagagua 540

agaggagaua auaaagaaua cgaauauuca guagaaugcc aagaggacag cgcuugcccc 600

gccgcagaag aaagcuuacc uauagaaguu augguagacg caguacauaa guuaaaauau 660

gagaauuaca caucauccuu uuucauaaga gauauuauaa aaccugaucc acccaagaac 720

cuacaauuaa aaccacuaaa aaauagucga cagguugaag uuucauggga auacccagac 780

acauggagca caccacacuc auacuucuca cuaacauucu guguacaagu acaaggaaaa 840

ucgaaacgcg aaaaaaaaga cagaguauuu acagacaaaa caagugcaac agugauaugu 900

960

1020

guggcaacac cagacccagg aauguucccc 1080

ugucuacacc acucgcaaaa ucuacuaaga gcagugucaa acaugcuaca aaaagcaaga 1140

caaacacuag aauuuuaucc auguacuuca gaagaaauag accaugaaga cauuaccaaa 1200

1260

1320

aguuucauga uggcacuaug ccucucauca auauaugaag aucuaaaaau guaucaggua 1380

1440

caaaacaugu uagcaguaau agacgaacua augcaagcac uaaacuucaa uagcgaaacc 1500

1560

1620

aaugcuucuu aa 1632

<210> 631

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 631

augauagaaa cauacaauca aacaaguccc agauccgcag caacaggucu accaauauca 60

120

cuauucgcag uauaccuaca cagaagauua gacaaaauag aagacgaaag aaaccuacac 180

240

cuacuaaacu gcgaagaaau aaaaagccaa uuugaagggu uugucaaaga cauaaugcua 300

aacaaagaag aaaccaaaaa agaaaacuca uucgaaaugc aaaaaggaga ucaaaaccca 360

caaauagcag cacacguaau aucagaagca ucaucaaaaa caacaucagu acuacaaugg 420

480

uuaacaguaa aaagacaagg acuauacuac aucuaugccc aaguaaccuu cugcuccaac 540

agagaagcau caucacaagc accauucauc gcaucacuau gccuaaaauc accaggaaga 600

660

caaucaauac accuaggagg agucuucgaa cuacaaccag gagcaucagu auucguaaac 720

guaacagauc caucacaagu aucacacgga acaggauuca caucauuugg acuacuaaaa 780

cucuaa 786

<210> 632

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 632

augugccacc agcagcuggu gaucagcugg uucucccucg ucuuccuggc cagcccccug 60

guggccaucu gggagcucaa gaaggacgug uacgucgugg agcuggacug guacccggac 120

gcgcccggcg agaugguggu ccugaccugc gacacccccg aggaggacgg gaucacgugg 180

acccucgacc aguccagcga ggugcugggc uccgggaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggggca guacacgugc cacaagggcg gcgagguccu cagccacucc 300

cugcugcucc ugcacaagaa ggaggacggg aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgguuc 420

acgugcuggu ggcugaccac caucagcacc gaccugaccu ucuccgucaa gagcucccgc 480

gggagcuccg acccgcaggg cgugacgugc ggggccgcca cccucagcgc ggagcgggug 540

cgcggcgaca acaaggagua cgaguacucc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agucccugcc caucgaggug auggucgacg cggugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucauccgg gacaucauca agcccgaccc gcccaagaac 720

cuccagcuga agccccugaa gaacucccgc cagguggagg ucagcuggga guaccccgac 780

accuggucca cgccgcacag cuacuucucc cucaccuucu gcguccaggu gcagggcaag 840

agcaagcggg agaagaagga ccgcguguuc accgacaaga ccuccgccac ggugaucugc 900

cggaagaacg cggcaucuc cgugcgcgcc caggaccggu acuacagcuc cagcuggucc 960

gagugggcca gcguccccug cuccggcagc accuccggga gcggcaagcc cggguccggc 1020

gaggggagca ccaagggccg gaaccugccg guggccaccc ccgaccccgg cauguucccc 1080

ugccugcacc acagccagaa ccuccugcgc gccgugucca acaugcugca gaaggcccgg 1140

cagacgcucg aguucuaccc gugcaccagc gaggagaucg accacgagga caucaccaag 1200

gacaagaccu ccacggucga ggccugccug ccccuggagc ucaccaagaa cgagagcugc 1260

1320

uccuucauga uggccucug ccugagcucc aucuacgagg accugaagau guaccaggug 1380

gaguucaaga ccaugaacgc caagcuccug auggaccca agcgccagau cuuccuggac 1440

1500

gucccccaga aguccagccu cgaggagccg gacuucuaca agaccaagau caagcugugc 1560

1620

aacgccagcu ga 1632

<210> 633

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 633

augugccacc agcagcucgu caucuccugg uucucccucg ucuuccucgc cuccccccuc

gucgccaucu gggagcucaa gaaggacguc uacgucgucg agcucgacug guaccccgac 120

gcccccggcg agauggucgu ccucaccugu gacacccccg aggaggacgg caucaccugg 180

acccucgacc aguccuccga gguccucggc uccggcaaga cccucaccau ccaggucaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgagguccu cucccacucc 300

cuccuccucc uccacaagaa ggaggacggc aucuggucca ccgacauccu caaggaccag 360

aaggagccca agaacaagac cuuccuccgc ugcgaggcca agaacuacuc cggccgcuuc 420

accuguuggu ggcucaccac caucuccacc gaccucaccu ucuccgucaa guccucccgc 480

ggcuccuccg acccccaggg cgucaccugu ggcgccgcca cccucuccgc cgagcgcguc 540

cgcggcgaca acaaggagua cgaguacucc gucgagugcc aggaggacuc cgccugcccc 600

gccgccgagg agucccuccc caucgagguc auggucgacg ccguccacaa gcucaaguac 660

gagaacuaca ccuccuccuu cuucauccgc gacaucauca agcccgaccc ccccaagaac 720

cuccagcuca agcccccucaa gaacucccgc caggucgagg ucuccuggga guaccccgac 780

accuggucca ccccccacuc cuacuucucc cucaccuucu gcguccaggu cggggcaag 840

uccaagcgcg agaagaagga ccgcgucuuc accgacaaga ccuccgccac cgucaucugc 900

cgcaagaacg ccuccaucuc cguccgcgcc caggaccgcu acuacuccuc cuccuggucc 960

gagugggccu ccguccccug cuccggcucc accuccggcu ccggcaagcc cggcuccggc 1020

gagggcucca ccaagggccg caaccucccc gucgccaccc ccgaccccgg cauguucccc 1080

ugccuccacc acucccagaa ccuccuccgc gccgucucca acaugcucca gaaggcccgc 1140

cagacccucg aguucuaccc cugcaccucc gaggagaucg accacgagga caucaccaag 1200

gacaagaccu ccaccgucga ggccugccuc ccccucgagc ucaccaagaa cgaguccugc 1260

cucaacuccc gcgagaccuc cuucaucacc aacggcuccu gccucgccuc ccgcaagacc 1320

uccuucauga uggccucug ccucuccucc aucuacgagg accucaagau guaccagguc 1380

1440

cagaacaugc ucgccgucau cgacgagcuc augcaggccc ucaacuucaa cuccgagacc 1500

gucccccaga aguccucccu cgaggagccc gacuucuaca agaccaagau caagcucugc 1560

1620

aacgccuccu ga 1632

<210> 634

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 634

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuugc cucuccccug 60

guugcuauuu gggaguugaa gaaagacgug uacguagugg aauuagauug guauccugac 120

gcaccaggcg agauggucgu gcugaccugu gauacaccgg aagaggacgg gauaacuugg 180

acgcuagauc agucaaguga aguucucgga agcgguaaga cccugacaau ccaggugaaa 240

gaguucggcg acgccggggca guacacuugc cauaagggag gcgagguccu uucccacucu 300

cuguugcucc ugcauaaaaa ggaagauggu auuuggucga ccgacauccu gaaggaucaa 360

aaagagccca agaacaaaac auuucucaga ugugaagcga agaauuauuc agggagguuu 420

accugcuggu gguuaacuac aauuagcacc gaccugacgu ucagugugaa auccucucgg 480

ggaagcuccg auccucaggg cguaacuugu ggcgcugcca cccuuucagc agagcgcguu 540

cgaggggaca acaaggagua cgaauauagu guggagugcc aggaagauag cgccugucca 600

gcugcagagg aaucuuugcc caucgagguc augguggacg ccgugcacaa gcugaaauac 660

gagaauuaua cauccucauu cuuuauacgu gacaucauua agccugaucc acccaaaaac 720

cuacagcuca agccucugaa aaauagcaga caagucgaag uuaguuggga guacccagac 780

acuuggucua ccccgcauuc cuacuucagc cuuacauuuu gcgugcaggu acagggaaag 840

ucgaaaaggg aaaagaagga ucggguguuc accgacaaaa cgucugcuac ugucaucugu 900

960

gagugggcaa gcguucccug cucaggcagc accuccgggu cuggaaagcc cgguucaggc 1020

1080

ugucugcauc acucucagaa ucuucugcgg gcggugucaa acauguugca aaaggcucgc 1140

cagacucucg aguuuuaccc uugcacgagu gaagagaucg accaugaaga uauuaccaaa 1200

gacaagacaa gcacuguaga ggccugucug ccacuggaac ucaccaaaaa ugaguccugc 1260

uuaaacucuc gagagacauc guucauaacc aaugggucau gucuggcaag ccguaagaca 1320

aguuuuauga uggcccuuug cuuguccucu aucuaugaag aucugaaaau guaccaggug 1380

1440

caaaauauugc uugcagucau cgacgaacug augcaggccu ugaacuucaa uagcgagacc 1500

gugccucaga aguccucacu cgaggaacca gauuuuuaua aaacgaagau uaaacugugu 1560

1620 aucuuacugc acgcuuucag gauacgggcc guuacuaucg

aacgcgagcu ga 1632

<210> 635

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 635

augugccacc agcagcuggu gaucagcugg uucagccugg uguuccuggc cagcccccug 60

guggccaucu gggagcugaa gaaggacgug uacguggugg agcuggacug guaccccgac 120

gcccccggcg agaugguggu gcugaccugc gacacccccg aggaggacgg caucaccugg 180

acccuggacc agagcagcga ggugcugggc agcggcaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggcca guacaccugu cacaagggcg gcgaggugcu gagccacagc 300

cugcugcugc ugcacaagaa ggaggacggc aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggcagauuc 420

accuguuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa gaguagcaga 480

ggcagcagcg acccccaggg cgugaccugc ggcgccgcca cccugagcgc cgagagagug 540

agaggcgaca acaaggagua cgaguacagc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agagccugcc caucgaggug augguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucaucaga gacaucauca agcccgaccc ccccaagaac 720

cugcagcuga agccccugaa gaacagcaga caggugggagg ugagcuggga guaccccgac 780

accuggagca ccccccacag cuacuucagc cugaccuucu gcgugcaggu ucagggcaag 840

agcaagagag agaagaagga cagaguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgugagagcc caggacagau acuacagcag cagcuggagc 960

gagugggcca gcgugccug cagcggcagc accagcggca gcggcaagcc cggcagcggc 1020

gagggcagca ccaagggcag aaaccugccc guggccaccc ccgaccccgg cauguucccc 1080

ugccugcacc acagccagaa ccugcugaga gccgugagca acaugcugca gaaggccaga 1140

cagacccugg aguucuaccc cugcaccagc gaggagaucg accacgagga caucaccaag 1200

gacaagacca gcaccgugga ggccugccug ccccuggagc ugaccaagaa cgagagcugc 1260

cugaacagca gagagaccag cuucaucacc aacggcagcu gccuggccag cagaaagacc 1320

1380

1440

cagaacaugc uggccgugau cgacgagcug augcaggccc ugaacuucaa cagcgagacc 1500

gugccccaga agaguagccu ggaggagccc gacuucuaca agaccaagau caagcugugc 1560

aucugcugc acgccuucag aaucagagcc gugaccaucg acagagugau gagcuaccug 1620

aacgccagcu ga 1632

<210> 636

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 636

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cucuccccuu 60

guugcuauuu gggagcugaa gaaagacgug uacguggucg aacucgauug guauccugac 120

gccccgggcg agaugguggu ucugaccugu gauacacccg aagaggacgg gaucacgugg 180

acccuugauc agagcuccga agugcuggga ucuggcaaga cacucaccau ucaggucaaa 240

gaguucgggg acgcgggaca guacacaugc cauaagggcg gggaggugcu gagccacucc 300

360

aaagagccua agaacaaaac auuucucaga ugugaagcua agaauuauag cggccgguuuu 420

accugcuggu ggcugacgac caucuccaca gaccuuaccu ucagcguuaa aucuucccgc 480

ggcagcucug auccccagggggugacaugu ggagccgcca cccuguccgc ugagagaguc 540

cggggcgaca acaaggagua cgaauauagc guggagugcc aggaagauuc ugccuguccu 600

gcugccgagg aaucccuccc caucgaggug auggucgacg cgguucacaa gcugaaauac 660

gagaauuaua cgagcuccuu cuuuauucgc gacaucauua agccugaucc gcccaaaaac 720

cugcagcuca agccucugaa aaauucuaga caaguggaag ugagcuggga guaccccgac 780

acauggucca ccccucauag cuacuucucu cuuacauuuu gcguccaggu gcaggggaag 840

uccaaacggg aaaagaagga ucgcguuuuc accgacaaaa ccagcgccac agugaucugu 900

agaaagaacg cuucuauuag cguccgggcc caggaucgcu auuacuccuc uagcuggucc 960

gagugggcua gcgugccug cucuggcagc accuccgggu cuggaaagcc cggcagcggg 1020

gagggaucca caaaaggccg gaaccugccu guugcgacac cggaucccgg cauguucccu 1080

ugucuccauc acucucagaa ucugcugcgc gcugugagca acaugcucca aaaggccaga 1140

cagacgcugg aguuuuaccc cugcaccucc gaagagaucg accaugaaga uauuacaaaa 1200

1260

cugaacuccc gggagacauc uuucaucacc aaugggagcu gucuugcuuc ccgcaagacg 1320

agcuuuauga uggccugug ccucucuucc auuuaugaag aucugaaaau guaccagguc 1380

gaguucaaga ccaugaacgc uaagcugcuc auggaccca aaagacagau cuuucuggau 1440

1500

guuccucaga agucuucccu ggaggaaccg gauuuuuaua aaaccaagau caaacuuugu 1560

auccugcucc acgccuuccg gauucgcgcu gugacaaucg acagagucau gagcuaccug 1620

aacgccucuu ga 1632

<210> 637

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 637

augugccacc aacaacuggu aauaucaugg uucucacugg uauucuuggc aucaccccua 60

guagcaauau gggaacuaaa aaaagacgua uacguaguag aacuagacug guacccagac 120

gcaccaggag aaaugguagu auuaacaugc gacacaccag aagaagaugg aauaacuugg 180

acauuagacc aaucaaguga aguauuagga ucaggcaaaa cacuaacuau acaaguaaaa 240

gaauuuggag acgcaggaca auacacgugc cacaaaggag gcgaaguccu aucacauuca 300

cuacuauuau uacacaaaaa agaagacgga aucuggagca cagacauauu aaaagaccaa 360

aaagaaccaa aaaacaaaac auuucuaaga ugcgaagcua aaaacuauuc aggaagauuc 420

acaugcuggu ggcuaacaac caucaguacc gacuuaacau ucucaguaaa aucaucaaga 480

ggaucaucag acccacaagg aguaacaugu ggagcagcaa cacuaagcgc agaaagagua 540

cgaggagaca acaaagaaua cgaauauuca guagaauguc aagaagacuc agcaugcccu 600

gcagcagaag aaucauuacc aauagaagua auggucgacg cuguacacaa acuaaaauau 660

gaaaauuaca caagcaguuu cuucauaaga gacauaauaa aacccgaccc accaaaaaac 720

cuacaacuaa aaccauuaaa aaauucaaga caaguagaag uaucauggga auacccagau 780

acauggagca caccacacag uuacuucuca uuaacauucu gcguacaagu acaaggaaaa 840

aguaaaagag aaaaaaaaga cagaguauuc acagauaaga cuucagcaac aguaauauugc 900

agaaaaaacg caagcauaag cguacgagca caagacagau auuacucaag cucaugguca 960

gaaugggcau caguaccaug uucaggaagu acaaguggaa guggaaaacc aggaagugga 1020

gaaggaagua caaaaggaag aaaccuccca guagccacac cagacccagg aauguucccc 1080

ugccuccacc auucccaaaa ccuacuaaga gcaguaucaa acaugcuaca aaaagcaaga 1140

1200

gacaaaacau caaccguaga agcaugccuc ccacucgaac ucacaaaaaa cgaaucaugc 1260

1320

ucauucauga uggcacuaug ccucucaucc auauaugaag acuuaaaaau guaccaagua 1380

1440

caaaacaugc uagcaguaau agacgaacua augcaagcac uaaacuucaa cucagaaacc 1500

guaccccaaa aaucaucucu agaagaacca gacuucuaca aaacaaaaau aaaacuaugc 1560

1620 auacuacuac acgccuucag aauaagagcc gucacaauag

aacgccucau aa 1632

<210> 638

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 638

augugccacc agcaacuggu gaucagcugg uucucccucg ucuuucuggc cagucccuug 60

guggcaauuu gggagcugaa gaaagacgua uacguggucg aacucgauug guauccagac 120

gccccgggcg agaugguggu gcugaccugu gauacucccg aagaggacgg gaucaccugg 180

acguuggauc agagcuccga aguccugggu aguggcaaga cucucaccau ucaggugaaa 240

gaguucgggg acgcggggcca guauaccugc cauaagggug gggagguacu gagccacucc 300

cugcuccugu ugcauaaaaa ggaagauggc aucuggagca cugacauucu gaaggaucaa 360

aaagagccaa agaacaaaac cuuucucagg ugugaagcca agaauuacuc cggccgguuc 420

acgugcuggu ggcugacuac caucaguacu gaccugaccu uuagcgugaa auccagccgc 480

gggaguuccg auccccaggg ugucaccugu ggcgcagcca cguugagcgc agagaggggug 540

cgcggggaca acaaggagua cgaauauucc guggagugcc aggaagauag ugccugucca 600

gcggccgagg aaagccuccc caucgagguc augguggacg caguacacaa acugaaguac 660

gagaauuaua cuuccagcuu cuuuauucgg gacaucauua agccagaucc gcccaaaaac 720

cugcagcuca agccacugaa aaauaguagg caaguggaag ucuccuggga guaccccgac 780

accuggagca cuccacauag uuacuucucc uugaccuuuu gcguccaggu gcagggcaag 840

agcaaacggg aaaagaagga ucgcguguuc accgacaaaa cuagcgccac ggugaucugu 900

aggaagaacg ccuccauuag uguacgggca caggaucgcu auuacagcuc cagcuggagu 960

gagugggccu cggugccug cagcggcagc accuccggga gugguaagcc cggcagcggg 1020

gagggcucca cuaaaggucg gaaccugcca guggcgacuc cggaucccgg cauguuccca 1080

ugucuccauc acagucagaa ucugcugcgc gccguaagca acaugcucca aaaggcaagg 1140

cagacccugg aguuuuaccc cugcacgucc gaagagaucg accaugaaga uauuuacuaaa 1200

gacaagacca guaccgugga ggccuguuug ccacuggaac ucacuaaaaa ugagagcugc 1260

cugaacuccc gggagaccag cuucaucacg aauggguccu gucuggcaag ucgcaagacu 1320

agcuuuauga uggccuugug ccucuccagc auuuaugaag aucugaaaau guaccagguc 1380

gaguucaaga ccaugaacgc gaagcugcuc auggaccca aaaggcagau cuuucuggau 1440

1500

gugccacaga aguccagccu ggaggaaccg gauuuuuaua aaaccaagau caaacugugu 1560

1620 gauucgcgcc gucaccaucg acagggugau guccuaccug

aacgcaaguu ga 1632

<210> 639

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 639

augugccacc aacaacucgu cauaagcugg uucagccuag uauuccucgc cucaccccuc 60

gucgccaucu gggaacucaa gaaagacgua uacgucgucg aacuagacug guaccccgac 120

gcacccggag aaaugguagu acucacaugc gacacccccg aagaagacgg caucacaugg 180

accuuagacc aaucaucaga aguccucgga uccggaaaaa cccucacaau ccaagucaaa 240

gaguucggcg acgccggcca auacacaugc cacaaaggcg gagaaguccu cucacacuca 300

cuccuucuac uacacaagaa agaagacggc aucuggucca ccgacauacu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

acaugcuggu ggcucaccac caucuccacc gaccugaccu ucuccgucaa auccagcagg 480

ggcuccucag acccacaagg cguaaccugc ggcgcagcca cccuaucggc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacagc gucgaaugcc aagaagacuc agcaugccca 600

gcagccgaag acuaaaauac 660

gaaaacuaca caagcucauu cuucauccgc gacauaauca aacccgaccc accgaaaaac 720

cuccaacuca aaccccuuaa aaacagccgc caagucgaag ucuccuggga auaccccgac 780

accuggucca caccccacuc cuacuucuca cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaagaaaga ccgcguauuc accgacaaaa ccuccgccac agucaucugc 900

cgcaaaaacg ccucaaucuc cguccgcgcc caagaccgau acuacagcuc cuccugguca 960

1020

gagggaagua caaagggacg caaucucccc gucgccaccc ccgaccccgg aauguuuccc 1080

ugccuccacc acucacaaaa ccuccuacgc gccgucucaa acaugcuuca aaaagcccga 1140

caaacccucg aauuuuuaccc cugcaccucc gaagaaaucg accacgaaga cauaaccaaa 1200

gacaaaaccu ccaccgucga agccugccua ccauuagaac uaaccaaaaa cgaauccugc 1260

cucaacucac gcgaaaccuc cuucaucaca aacggcucau gccucgccuc acgcaaaacc 1320

uccuucauga uggccucug ccuaucauca aucuaugaag accucaaaau guaccaagua 1380

1440

caaaacaugc ucgcagucau cgacgaacuc augcaagccc ucaacuucaa cucagaaaca 1500

gucccacaaa aauccucccu cgaagaaccc gacuucuaua aaaccaaaau caaacucugc 1560

1620

aaugccucuu aa 1632

<210> 640

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 640

augugucacc aacaacuugu aaucagcugg uucucccucg ucuuccucgc cucaccccuc 60

gucgccaucu gggaacucaa aaaagacguc uacguagucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu acucaccugu gacacccccg aagaagacgg caucaccugg 180

acccucgacc aauccuccga aguccucggu ucaggaaaaa cccucaccau ccaaguaaaa 240

gaauuuggcg acgccggggca auauaccugc cacaaaggcg gcgagguccu aucccacuca 300

cuccuccucc uccacaagaa agaagacgga aucuggucca ccgacauccu uaaagaccaa 360

aaagaaccaa aaaacaaaac auuccuccgc ugcgaagcca aaaacuacag cggccgcuuc 420

accuguuggu ggcuaaccac aauaucaacc gacuuaaccu ucagcgucaa auccuccaga 480

ggauccagcg acccacaagg aguuaccugc ggagccgcaa cacucagcgc cgaacgaguc 540

cgcggagaca acaaagaaua cgaauacucc gucgaaugcc aagaagacuc agcaugcccc 600

gccgcagaag aaucccuacc caucgaagua augguagacg ccguccacaa acucaaauac 660

gaaaacuaca ccagcuccuu cuucauccga gacaucauca aacccgaccc cccaaaaaac 720

cuccaacuaa aaccccucaa aaacagccgc caaguagaag uauccuggga auaccccgac 780

840

uccaaacgag aaaaaaaaga ccgcgucuuc accgacaaaa cuuccgccac cgucaucugc 900

cgcaaaaacg ccagcaucag cguccgcgca caagaccgcu acuacucaag cuccuggucc 960

gaaugggccu ccgucccaug cucagggagu acgaguggga gugggaagcc ggggaguggg 1020

gaggggagua cgaaggggcg uaaccuccca gucgccaccc cagaccccgg aauguucccc 1080

ugccuccauc acucccaaaa ucuccuccgu gccgucucca acaugcucca aaaagcccgc 1140

caaacccucg aauuuuaucc augcaccucc gaagaaauag accaugaaga caucaccaaa 1200

gacaaaacau ccaccgucga agccugccuc ccccucgaac ucacaaaaaa cgaaucaugc 1260

cucaacuccc gcgaaaccuc cuucauaacc aacggcucau gccucgccuc ucgcaaaacc 1320

ucauucauga uggccucug ccuauccucu aucuacgaag accucaaaau guaccaaguc 1380

1440

caaaacaugc ucgcagucau cgacgaacuc augcaagcac ucaacuucaa cucagaaacc 1500

gucccccaaa aauccucccu cgaagaaccc gacuucuaca aaacaaaaau aaaacucugc 1560

1620

aacgccuccu aa 1632

<210> 641

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 641

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagcgggagu acgaguggga gugggaagcc ggggaguggg 1020

gaggggagua cgaaggggcg caaccuccca gucgccaccc ccgaccccgg cauguucccc 1080

ugccuccacc acucccaaaa ccuccuccgc gccgucucca acaugcucca aaaagcccgc 1140

caaacccucg aauuuuaccc cugcaccucc gaagagaucg accacgaaga caucaccaaa 1200

gacaaaaccu ccacagucga agccugccuc ccccucgaac ucaccaaaaa cgaauccugc 1260

cuuaacuccc gcgaaaccuc cuucaucacc aacggcuccu gccucgccuc ccgcaaaacc 1320

uccuucauga uggccucug ccucuccucc aucuacgaag accucaaaau guaccaaguc 1380

1440

caaaacaugc ucgccgucau cgacgaacuc augcaagccc ucaacuucaa cuccgaaacc 1500

gucccccaaa aauccucccu cgaagaaccc gacuucuaca aaaccaaaau caaacuuugc 1560

auccuccucc acgcauuccg cauccgcgcc gucaccaucg accgugucau gagcuaccua 1620

aacgccuccu ga 1632

<210> 642

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 642

augugccacc aacaacucgu caucagcugg uucagccucg ucuuccucgc cuccccccua 60

guagccauau gggaacuaaa aaaagacgua uacguuguag aacuagacug guaccccgac 120

gcacccggcg aaauggucgu ccucaccugc gacacccccg aagaagaugg cauaacaugg 180

acccucgacc aauccucaga aguccucggc uccggcaaaa cccucacaau ccaagucaaa 240

gaauucggcg acgccggcca auacaccugc cacaaaggcg gcgaaguccu cucucacucu 300

cuccuccucc uccacaaaaa agaagacggc aucuggucca ccgacauacu caaagaccaa 360

aaagaaccca aaaacaaaac cuuccugcga ugcgaagcca aaaacuacuc cggccgauuc 420

acaugcuggu ggcucaccac caucucaacc gaccucaccu ucuccgucaa auccucccgu 480

ggcagcuccg acccccaagg agucaccugc ggcgcagcca cccucuccgc cgaacgcguc 540

agaggcgaca acaaagaaua cgaauacucc gucgaaugcc aagaggacuc cgccugcccc 600

gccgccgaag acuaaaauac 660

gaaaacuaca ccucuucauu cuucauccga gacaucauca aacccgaccc ccccaaaaac 720

cuccaacuca aaccccucaa aaacucccga caagucgaag ucagcuggga auacccagac 780

accuggucca cccacacuc cuacuucuca cuaaccuucu gcguccaagu ccaaggcaaa 840

ucgaaacgcg aaaaaaaaga cagagucuuc accgacaaaa ccucagccac cgucaucugc 900

cgaaaaaacg caucaaucag cguccgcgcc caagaccgcu acuacuccuc cagcuggagc 960

gaaugggcau ccguccccug cuccgggagu acgaguggga gugggaagcc ggggaguggg 1020

gaggggagua cgaaggggcg caaccucccc gucgccaccc ccgaccccgg cauguucccc 1080

ugccuccacc acucccaaaa ucuccuccgc gccgucucca acaugcucca aaaagcccgc 1140

caaacccucg aauucuaccc cugcacgucc gaagaaaucg accacgaaga caucaccaaa 1200

gacaaaaccu ccaccgucga agccugccuc ccccucgaac ucaccaaaaa cgaauccugc 1260

cucaacucac gcgaaaccuc cuucaucacc aacggcucau gccucgccuc acgaaaaacc 1320

uccuucauga uggccucug ccucuccuca aucuacgaag accucaaaau guaccaaguc 1380

1440

caaaacaugc ucgcagucau cgacgaacuc augcaagccc ucaacuucaa cuccgaaacc 1500

gucccccaaa aaucaucccu cgaagaacca gacuucuaca aaaccaaaau caaacucugc 1560

1620

aacgccuccu aa 1632

<210> 643

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 643

augugccauc aacaacuagu aauaucaugg uucucacuag uauucuuagc aaguccccua 60

guagcaauau gggaacuaaa aaaagacguc uacguuguag aauuagacug guacccagac 120

gcaccaggcg aaaugguagu auaacaugc gauacaccag aagaagacgg aauaacaugg 180

acacuagacc aaucaucaga aguucuagga ucaggaaaaa cauuaacaau acaaguaaaa 240

gaauucgggg acgcaggaca auauacaugc cacaaaggag gagaaguuuu aucacacuca 300

cuacuauuau uacacaaaaa agaagacgga auauggucaa cugacauacu aaaagaucaa 360

aaagaaccaa aaaacaaaac auucuuaaga ugugaagcaa aaaauuacag uggaagauuc 420

acaugcuggu ggcuaacaac aauaaguaca gaccuaacau uuucaguaaa aucaaguaga 480

ggaucaucag acccacaagg cguaacaugu ggagcagcaa cacuaucagc agaacgaguc 540

agaggagaca acaaagaaua cgaauacucc guagaaugcc aagaagacag ugcaugcccc 600

gcagccgaag acuaaaauac 660

gaaaacuaca caagcucauu cuuuauacga gauauaauaa aaccagaccc accaaaaaac 720

cuacacuaa aaccacuaaa aaacucacgc caaguagaag uauccuggga auacccagau 780

acauggucaa caccacacuc auauuucagc uuaacauucu guguacaagu acaaggaaaa 840

ucaaaaagag aaaaaaaaga uagaguauuc accgacaaga caagcgcaac aguaauuugu 900

agaaaaaacg caucaauuuc aguaaagca caagacagau acuacagcuc aagcugguca 960

gaaugggcaa guguaccaug uucaggaagu acaaguggaa guggaaaacc aggaagugga 1020

gaaggaagua caaaaggaag aaaccuacca guagcaacac ccgacccagg aauguuccca 1080

ugccuacacc acucacaaaa ccuacuacgc gcaguaucaa acauguuaca aaaagcacga 1140

1200

gacaaaacau ccaccguaga agcaugccuc ccacuagaac uaacaaaaaa cgaaucaugc 1260

1320

ucauucauga uggcacuaug ccuauccucc auauacgaag accuaaaaau guaccaagua 1380

1440

caaaacaugc ucgcaguaau agacgaacua augcaagcac uaaacuuuaa cucagaaaca 1500

1560

1620

aacgcaucau aa 1632

<210> 644

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12(IL12B-Linker-IL12A)

<400> 644

augugccacc aacaacuagu uauuuccugg uucucauuag uauuccuagc cucaccauua 60

guagcuauau gggaauuaaa aaaagaugua uacguaguag aacuagacug guacccagau 120

gcaccaggag aaaugguagu acuaccugc gacacaccag aagaagacgg aauaacaugg 180

acccuagacc aaucaucaga aguauuagga aguggaaaaa cacuaacaau acaaguaaaa 240

gaauucggag acgcaggaca auauacuugc cacaaaggag gagaaguauu aagucauuca 300

uuacuccuau uacacaaaaa agaagacgga auauggagca ccgacauacu aaaagaccaa 360

420

acaugcuggu ggcuaacaac aauaucaaca gaccuaaccu ucuccguuaa aaguucaaga 480

ggaaguucag auccacaagg aguaacaugu ggagcagcaa cacuaagcgc agaaagagua 540

agaggcgaca auaaagaaua ugaauacuca guagaaugcc aagaagauuc agcauguccc 600

gcggccgaag aaucacuacc aauagaagua augguagacg caguacacaa acucaaauau 660

gaaaacuaca caucaucauu cuuuauaaga gacauaauaa aaccagaccc accaaaaaau 720

cuacaacuaa aaccauuaaa aaacucaaga caaguugaag uaagcuggga auauccagac 780

acauggucaa caccacacuc auacuuuuca cuaacauuuu gcguacaagu acaagguaaa 840

ucaaaaagag aaaaaaaaga ucgaguauuu acagacaaaa caagugcaac agucaauaugu 900

agaaaaaacg caucaauuuc agucagagca caagacagau auuacaguag uucaugguca 960

gaaugggcaa gcguuccaug cucaggaagu acaaguggaa guggaaaacc aggaagugga 1020

gaaggaagua caaaaggaag aaaccuacca guagcaacac cagaccccgg aauguuccca 1080

ugccuccacc acucacaaaa ccuacuaaga gcaguaucaa acauguuaca aaaagccaga 1140

1200

gacaaaacau caacaguaga agcaugccua ccauuagaac uaaccaaaaa cgaaucaugc 1260

1320

ucauucauga uggcacuaug ccuaucaucc auauacgaag accuaaaaau guaccaagua 1380

1440

caaaauauugc ucgcaguaau agacgaauua augcaagcac uaaacuucaa cucagaaaca 1500

guaccacaaa aaucaucccu agaagaaccc gacuucuaca aaacaaaaau aaaacuaugc 1560

1620

aacgcaucau aa 1632

<210> 645

<211> 467

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab protein HC with signale peptide

<400> 645

Met Glu Leu Gly Leu Ser Trp Ile Phe Leu Leu Ala Ile Leu Lys Gly

1 5 10 15

Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

20 25 30

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

35 40 45

Ser Ser Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn

85 90 95

Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly

115 120 125

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

130 135 140

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

145 150 155 160

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

165 170 175

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

180 185 190

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

195 200 205

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

210 215 220

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

225 230 235 240

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

260 265 270

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

275 280 285

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

290 295 300

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

340 345 350

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

355 360 365

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

385 390 395 400

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

420 425 430

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

450 455 460

Pro Gly Lys

465

<210> 646

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 646

auggagcugg gccucagcug gaucuuccug cuggccaucc ucaagggggu gcagugccag 60

120

ugcgccgccu ccggcuucac cuucagcucc uacaccaugc acuggguccg ccaggcgccg 180

gggaagggcc uggagugggu gacguucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacuccguga aggggcgguu caccaucagc cgcgacaacu ccaagaacac ccucuaccug 300

cagaugaaca gccugcgggc cgaggacacc gccaucuacu acugcgcccg cacgggcugg 360

cucgggcccu ucgacuacug gggccagggg acccugguca ccguguccag cgcguccacc 420

aagggcccca gcguguuccc ccuggccccg uccagcaagu ccacgagcgg cgggaccgcc 480

gccuccggcu gccuggucaa gacuacuuc cccgagcccg ugaccguguc cuggaacagc 540

ggggcgcuga ccagcggcgu ccacacguuc cccgccgugc uccaguccag cggccuguac 600

ucccuagcu ccguggucac cgugccgagc uccagccucg ggacccagac cuacaucugc 660

aacgugaacc acaagcccuc caacacgaag gucgacaagc ggguggagcc caagagcugc 720

gacaagaccc acacgugccc gcccugcccc gcccccgagc ugcugggcgg gcccuccgug 780

uuccucuucc cgcccaagcc caaggacacc cugaugauca gccgcacccc cgaggugacc 840

ugcgucgugg ucgacguguc ccacgaggac ccggagguca aguucaacug guacguggac 900

ggcguggagg uccacaacgc caagaccaag ccccgggagg agcaguacaa cagcaccuac 960

cgcguggugu ccguccugac ggugcuccac caggacuggc ugaacgggaa ggaguacaag 1020

ugcaagguga gcaacaaggc ccugcccgcg cccaucgaga agaccaucuc caaggccaag 1080

ggccagccgc gggagcccca ggucuacacc cucccgccca gccgcgacga gcugaccaag 1140

aaccaggugu cccugacgug ccucgugaag ggcuucuacc ccagcgacau cgccgucgag 1200

ugggagagca acgggcagcc cgagaacaac uacaagacca cgcccccggu gcuggacucc 1260

gacggcagcu ucuuccugua cuccaagcuc accguggaca agagccggug gcagcagggg 1320

1380

cugagccucu cccccggcaa guga 1404

<210> 647

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 647

auggagcucg gccucuccug gaucuuccuc cucgccaucc ucaagggcgu ccagugccag 60

guccagcucg ucgaguccgg cggcggcguc guccagcccg gccgcucccu ccgccucucc 120

ugcgccgccu ccggcuucac cuucuccucc uacaccaugc acuggguccg ccaggccccc 180

ggcaagggcc ucgaggggu caccuucauc uccuacgacg gcaacaacaa guacuacgcc 240

gacuccguca agggccgcuu caccaucucc cgcgacaacu ccaagaacac ccucuaccuc 300

cagaugaacu cccuccgcgc cgaggacacc gccaucuacu acugcgcccg caccggcugg 360

cucggccccu ucgacuacug gggccagggc acccucguca ccgucuccuc cgccuccacc 420

aagggcccccu ccgucuuccc ccucgccccc uccuccaagu ccaccuccgg cggcaccgcc 480

gccuccggcu gccucgucaa gacuacuuc cccgagcccg ucaccgucuc cuggaacucc 540

ggcgcccuca ccuccggcgu ccacaccuuc cccgccgucc uccaguccuc cggccucuac 600

ucccucuccu ccgucgucac cguccccucc uccucccucg gcacccagac cuacaucugc 660

aacgucaacc acaagcccuc caacaccaag gucgacaagc gcgucgagcc caaguccugc 720

gacaagaccc acaccugccc ccccugcccc gcccccgagc uccucggcgg ccccuccguc 780

uuccucuucc cccccaagcc caaggacacc cucaugaucu cccgcacccc cgaggucacc 840

ugcgucgucg ucgacgucuc ccacgaggac cccgagguca aguucaacug guacgucgac 900

ggcgucgagg uccacaacgc caagaccaag ccccgcgagg agcaguacaa cuccaccuac 960

cgcgucgucu ccguccucac cguccuccac caggacuggc ucaacggcaa ggaguacaag 1020

ugcaaggucu ccaacaaggc ccuccccgcc cccaucgaga agaccaucuc caaggccaag 1080

ggccagcccc gcgagcccca ggucuacacc cucccccccu cccgcgacga gcucaccaag 1140

aaccaggucu cccucaccug ccucgucaag ggcuucuacc ccuccgacau cgccgucgag 1200

ugggagucca acggccagcc cgagaacaac uacaagacca ccccccccgu ccucgacucc 1260

gacggcuccu ucuuccucua cuccaagcuc accgucgaca agucccgcug gcagcagggc 1320

1380

cuccccucu cccccggcaa guga 1404

<210> 648

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 648

auggagcugg gccucagcug gaucuuccuu cuggccauuu ugaagggggu gcagugccaa 60

guccaguuag uugaauccgg agguggcgug guacagcccg ggagaucucu gaggcuauca 120

ugugcugcaa guggauuuac cuucagcucc uacacaaugc acugggugcg gcaggccccu 180

ggcaaagguc ucgagugggu cacuuuuaua ucuuaugacg ggaacaauaa guacuaugcg 240

gauucgguga aaggacgcuu cacgaucuca cgagacaaca gcaagaauac ccuguaccuu 300

caaaugaaca gucugcgugc ugaagauaca gccauuuauu acugcgcaag aacuggcugg 360

uugggcccau uugacuauug ggggcaggga acccucguua caguguccuc ugccagcacc 420

aaagguccgu ccgucuuccc ccuggcuccu ucaaguaaga gcacuucugg cgggacagca 480

gcccugggau gucucgugaa ggauuacuuu cgagcccg uaaccguuuc cuggaacuca 540

ggcgcuuuaa cgagcggugu gcauacuuuc ccugccgucc ugcagaguuc ugggcuuuac 600

uccuugagcu cgguggugac cgucccaucu uccucacugg gaacacagac uuauaucugc 660

aauguuaauc acaaacccag uaacaccaag guggacaaaa ggguagaacc uaaagcugu 720

gauaaaacac auaccugccc accguguccc gcgccugagc uacucggcgg cccauccgug 780

uuucuguuuc ccccuaagcc aaaggacacg cuuaugauuu cucggacucc cgaggucaca 840

ugcgugguug uggaugucag ccacgaagac ccggagguga aauuuaauug guacguagau 900

gggguugaag ugcauaacgc aaagaccaaa ccucgcgagg agcaauauaa uucaacuuac 960

agagucguga guguccugac aguguugcac caggacuggc ucaacggaaa ggaauauuaaa 1020

uguaagguuu ccaauaaagc ccugcccgcu ccaaucgaga agaccauaag caaggccaaa 1080

ggucagccua gggaacccca gguguacacg uuaccacccu cucgggauga gcugaccaag 1140

aaccaaguau cacucacaug ccuugucaaa ggcuucuauc cuagugacau cgcaguggaa 1200

ugggagagca augggcagcc agagaacaac uacaagacua ccccgcccgu ucuggacucc 1260

1320

1380

cucucucuga gcccugguaa auga 1404

<210> 649

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 649

auggagcugg gccugagcug gaucuuccug cuggccaucc ugaagggcgu gcagugccag 60

gugcagcugg uggagagcgg cggcggcgug gugcagcccg gcagaagccu gagacugagc 120

ugcgccgcca gcggcuucac cuucagcagc uacaccaugc acugggugag acaggccccc 180

ggcaagggcc uggagugggu gaccuucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacagcguga agggcagauu caccaucagc agagacaaca gcaagaacac ccuguaccug 300

cagaugaaca gccugagagc cgaggacacc gccaucuacu acugcgccag aaccggcugg 360

cugggccccu ucgacuacug gggccagggc acccugguga cggugagcag cgccagcacc 420

aagggcccca gcguguuccc ccuggccccc agcagcaaga gcaccagcgg cggcaccgcc 480

gcccugggcu gccuggugaa gacuacuuc cccgagcccg ugaccgugag cuggaacagc 540

ggcgcccuga ccagcggcgu gcacaccuuc cccgccgugc ugcagagcag cggccuguac 600

agccugagca gcguggugac cgugcccagc agcagccugg gcacccagac cuacaucugc 660

aacgugaacc acaagcccag caacaccaag guggacaaga gaguggagcc caagagcugc 720

gacaagaccc acaccugccc ccccugcccc gcccccgagc ugcugggcgg ccccagcgug 780

uuccuguucc cccccaagcc caaggacacc cugaugauca gcagaacccc cgaggugacc 840

ugcguggugg uggacgugag cccgaggac cccgagguga aguucaacug guacguggac 900

ggcguggagg ugcacaacgc caagaccaag cccagagagg agcaguacaa cagcaccuac 960

agagugguga gcgugcugac cgugcugcac caggacuggc ugaacggcaa ggaguacaag 1020

ugcaagguga gcaacaaggc ccugcccgcc cccaucgaga agaccaucag caaggccaag 1080

ggccagccca gagagcccca gguguacacc cugcccccca gcagagacga gcugaccaag 1140

aaccagguga gccugaccug ccuggugaag ggcuucuacc ccagcgacau cgccguggag 1200

ugggagagca acggccagcc cgagaacaac uacaagacca ccccccccgu gcuggacagc 1260

gacggcagcu ucuuccugua cagcaagcug accguggaca agagcagaug gcagcagggc 1320

1380

cugagccuga gccccggcaa guga 1404

<210> 650

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 650

auggagcugg gccucagcug gaucuuccug cuugccauuc ugaagggggu gcagugccaa 60

guccagcucg uugaauccgg aggcggggug gugcagcccg gaagaucucu gcggcuuagc 120

ugugcugccu ccggcuuuac cuucucuagc uacacaaugc acuggguccg ccaggcgccu 180

gggaaaggac uggagugggu gacguuuauc uccuaugacg gcaacaauaa guacuaugcu 240

gauucuguua aaggcagauu caccauuagc cgggacaacu ccaagaauac acucuaccug 300

caaaugaaca gccugcgcgc cgaagauacc gccaucuauu acugcgcuag aacagggugg 360

cucggaccgu uugacuauug gggccagggg acccugguga cagucucuuc cgccagcacc 420

aaaggacccu cuguguuccc ucuugcuccc uccagcaagu cuacguccgg cgggaccgcc 480

gcgcugggau gucucguuaa ggauuacuuu ccugagccg ugacagucag cuggaacucc 540

ggcgcccuga ccucuggcgu gcauacauuc ccugcugugc uucagagcuc cgggcuguac 600

agccucucuu ccgucguuac cgugccgagc ucuagccugg gaacgcagac auauauuugc 660

aaugugaauc acaaacccuc caacaccaag gucgacaaac ggguggaacc uaagucuugu 720

gauaaaacac auaccugucc cccuugcccc gccccggagc ugcucggcgg gccuagcguu 780

uuucuguuuc ccccuaagcc caaggacacc cuuaugaucu cccgcacacc cgaggugacg 840

ugcgucgugg uugaugugag ccacgaagac ccugagguca aauucaauug guacguggau 900

ggagucgaag ugcauaacgc uaagaccaaa ccgagagagg agcaauauaa uucuacauac 960

cggguugugu ccguccugac cgugcuccac caggacuggc ugaacggcaa ggaauauaaa 1020

uguaagguua gcaauaaagc ccuucccgcg ccuaucgaga agacaauuuc uaaggccaaa 1080

gggcagcccc gcgaaccuca gguguacacc cugcccccgu ccagagauga gcucacgaag 1140

aaccaaguca gccugacaug ccuggugaaa ggauucuauc cuuccgacau cgcuguggaa 1200

ugggagucua auggccagcc cgagaacaac uacaagacca ccccucccgu ucucgacagc 1260

1320

1380

cucuccuga gcccuggaaa auga 1404

<210> 651

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 651

auggaauuag guuuauccug gaucuuucuc cuagcaauac ucaaaggagu acaaugccaa 60

guacaauuag uggaauccgg aggaggugua guacaaccag gaagaucacu aagacuauca 120

ugcgcagcau caggauuuac auucucauca uacacaaugc acuggguaag acaagcccca 180

ggaaaaggau uagaaugggu uacauuuaua uccuacgacg gaaacaauaa auacuacgca 240

gacucaguca aaggaagauu cacuauauca agagacaauu cuaaaaacac acuauaccua 300

caaaugaacu cucuccgagc agaagauaca gccauauaacu acugcgcaag aacaggaugg 360

uuaggaccuu ucgacuacug gggacaagga acucuaguaa cugucucauc ugccucaaca 420

aaaggcccau caguauuucc acuagcccca ucaucuaaau cuacaucagg uggaaccgcu 480

gcauuaggau gcuuaguaaa agacuauuuu cccgaaccag uaacuguauc uuggaacucc 540

ggagcacuua cuucuggugu acacacauuc ccagcaguuu uacaaagcuc aggacuauac 600

ucucuaagcu caguaguaac ugucccauca ucaucccuug gcacccaaac auacauaugu 660

720 aacguaaauc acaaacccag uaauaccaaa

gauaaaacac acacaugccc ccccugccca gcaccugaac uucuaggagg accaucugua 780

uuccucuucc cuccaaaacc aaaagauacu cucaugauau cacgcacacc cgaaguaacu 840

ugugucguag uagacguauc acacgaagac ccagaaguua aauucaacug guauguagac 900

ggaguagaag uccacaacgc aaaaacaaaa ccacgagaag aacaauacaa cuccaccuau 960

1020

1080

ggucaaccac gagaacccca aguauauaca cuuccaccau caagagacga acuuaccaaa 1140

1200

ugggaaucca auggacaacc agaaaauaau uacaaaacca caccaccugu acuagauuca 1260

1320

1380

cuaucacuau cccccggcaa auga 1404

<210> 652

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 652

auggagcugg gccucagcug gaucuuccug uuggccauuc ugaagggggu gcagugccaa 60

guccagcucg uggaauccgg uggcggggua gugcagcccg gcaggagucu gcgguugagc 120

ugugcagccu ccgguuuuac cuucaguagc uacacuaugc acuggguccg ccaggcgcca 180

gggaaaggcc uggagugggu gaccuuuauc uccuaugacg gcaacaauaa guacuaugcc 240

gauagcguga aagggagguu cacgauuucc cgggacaaca guaagaauac ucucuaccug 300

caaaugaaca gccugcgcgc agaagauacc gccaucuauu acugcgcaag gaccgguugg 360

cucgcccgu uugacuauug ggggcagggc acucugguca ccguguccag cgccaguacg 420

aaaggucccu ccguauuccc auuggcgccc agcuccaaga guacuagcgg gggcaccgcc 480

gcacugggcu gucucgugaa ggauuacuuu ccagagcccg ucacuguguc cuggaauagc 540

ggggcccuga ccaguggugu gcauaccuuc ccagccgucc ugcaguccag cggcuuguac 600

agucucucca gcgugguaac ggugccgagc uccagucugg ggacucagac cuauauuugc 660

aacgucaauc acaaacccag caacacuaag guggacaaac ggguggaacc aaaguccugu 720

gauaaaaccc auaccugucc cccaugcccc gcaccggagc ugcucggcgg ucccagcguc 780

uuucuguucc cacccaagcc aaaagacacu uugaugauca gucgcacgcc cgaggugacc 840

ugcguagugg ucgauguguc ccacgaagac ccagagguca aguuuaauug guacguggau 900

ggcguggaag uacauaacgc caagacuaaa ccgagggagg agcaauauaa uagcaccuac 960

1020

uguaagguga guaauaaagc gcugcccgcc ccaaucgaga agacuauuag caaggcaaaa 1080

ggccagcccc gcgaaccaca gguguacacg uugcccccgu ccagggauga gcucaccaag 1140

aaccaaguaa gccugacuug ccggugaaa ggguucuauc caagugacau cgccgucgaa 1200

ugggagucca auggucagcc cgagaacaac uacaagacca cucccccagu gcucgacagc 1260

gauggcuccu ucuuucugua caguaaauug accgucgaca agagccggug gcagcaaggg 1320

1380

cucucccuga gccccggcaa auga 1404

<210> 653

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 653

auggaacucg gccuaagcug gaucuuccuc cuggccaucc ucaaaggcgu acagugccag 60

guccaacucg uagaauccgg aggcggcguc guacaacccg gccgcucccu ccgccuaucc 120

ugcgcagcuu ccggcuucac auucaguuca uacaccaugc acuggguccg acaagccccc 180

ggcaaaggac ucgaaugggu cacuuuuauc ucuuacgacg gcaacaauaa auacuacgca 240

gacuccguca aaggccgcuu uacaaucuca cgugacaacu ccaaaaacac ccuauaccuc 300

caaaugaacu cccuacgcgc ugaagacacc gccauuuacu auugcgcccg cacaggcugg 360

cuuggaccau ucgacuacug gggacaagga acccuuguca ccgucuccuc ugccagcacc 420

aaaggccccu ccgucuuccc ccucgcuccc agcuccaaau ccacgucagg cggcacugca 480

gccuccggau gccuagucaa agacuacuuc cccgaacccg ucacagucuc auggaacucc 540

ggagcccuca cuucaggcgu ccacaccuuc cccgcaguac uacaaucuuc aggccuauac 600

ucccuaagcu ccgucgucac cguacccucc ucaucccucg gaacacaaac cuacauauugc 660

aacgucaacc acaaacccuc aaacacaaaa guagacaaac gcgucgaacc caaauccugc 720

gacaaaaccc auaccugccc acccugcccc gccccggaac uccuaggcgg ccccagcguc 780

uucuuauucc cacccaaacc caaagacacg cucaugauaa guagaacccc cgaagugacc 840

ugcgucgucg ucgacgucuc ccacgaagac ccugaaguua aauucaacug guacgucgac 900

ggcgucgaag uucacaacgc caaaaccaaa ccccgagaag aacaauacaa cuccaccuac 960

1020

1080

1140

aaucagguca gccuaaccug ccucgucaaa ggauucuacc ccuccgacau cgccgucgaa 1200

ugggaaagca acggccaacc cgaaaacaac uacaaaacca ccccacccgu acucgacucc 1260

gacggcuccu ucuuccucua cuccaagcuc accgucgaca aaucccgcug gcaacaggga 1320

aacguauucu ccugcuccgu caugcacgaa gcccuccaca accacuauac ccaaaaauca 1380

cucucccuau cacccggaaa auaa 1404

<210> 654

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 654

auggaacuag gccuaucaug gaucuuccuc cucgccaucc ucaaaggcgu ccaaugccag 60

guccaacucg ucgaauccgg cggaggcguc guccaacccg gccgaucacu ccgccucucc 120

ugcgccgccu ccggcuucac uuucuccucc uacacaaugc acuggguacg ccaagcccca 180

ggaaaaggac ucgaaugggu caccuucauc uccuacgacg gaaacaacaa auacuacgcc 240

gacagcguua aaggacgauu cacaaucucc cgcgacaacu cuaaaaacac ccuauaaccuc 300

caaaugaacu cccuccgcgc cgaagacaca gcaaucuacu acugcgccag aaccgggaugg 360

cuaggccccu ucgacuacug gggccaagga acccucguca caguauccuc cgccuccacc 420

aaaggcccuu ccguauuucc ccuggccccc ucauccaaau ccaccagcgg cggaaccgcc 480

gcacuuggcu gccucguaaa agacuacuuc cccgaacccg uaaccgucuc cuggaacagc 540

ggcgcccuaa cgucaggcgu acacaccuuc cccgcagucc uccaauccuc cggacuauau 600

agccucucca gcguaguaac aguacccucc agcucucucg gcacacaaac cuauauucugc 660

aacguaaacc acaaacccag caacaccaaa guugacaaac gcguugaacc caaauccugc 720

gacaaaaccc acacaugccc acccugcccc gcccccgaac uccucggcgg ucccucaguc 780

uuccucuucc caccaaaacc uaaagacacu cuaaugauau cccgcacccc agaagugacc 840

ugcgucguag ucgacgucuc ccacgaagac cccgaaguca aauucaacug guacgucgac 900

ggcgucgaag uacacaacgc caaaaccaaa ccccgagaag aacaauacaa cucaaccuac 960

agagucguca gcguccucac cguccuccau caggacuggc ucaacggaaa agaauacaaa 1020

1080

ggccaaccac gcgaacccca aguauacaca cucccacccu cacgagacga acucaccaag 1140

aaccaaguau cuuuaaccug ccuugucaaa ggcuucuacc ccuccgacau cgccguggaa 1200

ugggaaucca acggacaacc cgaaaacaac uacaagacca caccacccgu ccuugacuca 1260

1320

1380

cucucccugu ccccgggaaa auga 1404

<210> 655

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 655

auggaacuug gccuuuccug gaucuuccuc cucgccauac ucaaaggcgu ccaaugccaa 60

guucagcuag ucgaauccgg uggcggcgua guccaacccg gacgcagccu ccgacuaucc 120

ugcgccgccu ccggauucac cuucuccuca uacaccaugc acuggguccg ccaagccccc 180

ggcaaaggcc ucgaaugggu cacauucauc uccuacgaug gaaacaacaa auacuacgcc 240

gacucaguca aaggccgcuu cacaaucucc cgagacaacu ccaaaaacac ccuauaccuc 300

caaaugaacu cacuuagagc cgaagacaca gcaauauacu acugcgcccg caccggaugg 360

cuaggacccu ucgacuacug gggccaaggg acccucguca ccguuagcuc cgccuccaca 420

aaaggacccu ccguauuccc ccucgcccca uccuccaaau ccacaucugg cggcaccgcc 480

gcacucggau gccucguaaa agacuacuuc cccgaacccg ucacagucag cuggaacuca 540

ggcgcucuca ccuccggcgu ccacacauuc ccggcagucc ugcaaagcag cggccucuac 600

ucccuaucau cuguagucac cgucccaucc ucuucccucg gcacccaaac cuacaucugc 660

aacguaaacc acaaacccag caacaccaaa guggauaaac gaguagaacc caaaucuugc 720

gacaaaaccc acacuugccc acccugcccc gccccagaac uucuaggcgg acccuccguc 780

uuccucuucc cacccaaacc caaagacacc cucaugaucu cacgcacccc cgagguaacc 840

ugcguugucg ucgacguguc ccacgaagac ccugaaguca aguucaacug guacgucgac 900

ggcgucgaag ugcacaacgc caaaacaaaa ccacgcgaag aacaauauaa cucaaccuac 960

1020

uguaaaguau ccaauaaagc acuccccgcc cccauagaga aaacgaucuc caaggccaaa 1080

1140

1200

ugggaaucca acggccaacc agaaaacaac uacaagacaa caccucccgu ccucgacucc 1260

gacggauccu ucuucuuaua cucaaaacua accgucgaca aaucuagaug gcaacaaggc 1320

1380

cuccccucu cccccggcaa auga 1404

<210> 656

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 656

auggaacuag gacucucaug gauauuuuua cuagccauac ucaaaggcgu ccaaugucaa 60

guacaaccuag uagaaucagg cggaggaguu guccaacccg gccgaucccu ccgcuuauca 120

ugugcagcau cuggauucac auuuucauca uacacaaugc acugggucag acaagcccca 180

ggaaaagguu uagaaugggu aacauuuaua ucauacgacg guaacaacaa auacuaugca 240

gacucaguaa aaggaagauu uacaaucagc agagacaaua gcaaaaacac acuauaccua 300

caaaugaacu cccuacgagc agaagacaca gccaucuauu acugugcacg aacaggaugg 360

cuaggaccau ucgauuacug gggccaagga acauuaguca ccguaucuuc ugcauccaca 420

aaagguccuu caguauuucc auuagcaccc agcuccaaau cuacaucugg cggaacagcc 480

gccuuaggau gcuuaguuaa agauuacuuu ccagaaccag uaacaguuuc auggaacuca 540

ggagcucuaa caucuggagu acacacauuu ccagcagucc uacaaucauc cggacuauau 600

ucacuaucau caguaguaac uguccccuca ucauuuag gcacacaaac uuauauuugc 660

aauguaaacc auaaaccauc aaauacaaaa gucgacaaaa gaguagaacc aaaaucaugc 720

gacaaaaccc acacaugucc acccugcccc gccccagaau uauuaggagg accaucuguc 780

uuccuuuucc caccaaaacc aaaagacacc uuaaugauau cucgaacucc agaaguaaca 840

uguguaguug uagauguuuc acaugaagac ccagaaguaa aauucaacug guacgucgac 900

ggaguagaag uacacaaugc aaaaacaaaa ccccgagaag aacaauacaa cuccacauac 960

agaguagucu caguacuaac aguacuccau caagacuggc uaaacggaaa agaauacaaa 1020

1080

1140

aaccaaguaa gucuaacaug uuuaguaaaa ggauucuauc ccagcgacau agcagucgaa 1200

ugggaaucaa auggacaacc agaaaacaac uauaaaacca caccaccagu auuagauuca 1260

gacggaucau uuuuccuuua cucaaaauua acaguagaca aauccagaug gcaacaaggc 1320

1380

cuaucacucu caccaggcaa auga 1404

<210> 657

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 657

auggaacuag gacuauccug gauauuucua cuagccaucc uaaaaggagu acaaugucaa 60

guacaauuag uagaauccgg aggcggagua guccaacccg gaagaucacu aagacucagu 120

ugugcagcau caggauucac auuuucauca uauacaaugc acuggguuag acaagcaccc 180

ggaaaaggac ucgaaugggu aaccuuuauc uccuacgaug gaaacaauaa auauuacgca 240

gauucuguaa aaggccgauu cacaauauca agagacaacu cuaaaaauac auuauaacua 300

caaaugaacu cuuuaagagc agaagacaca gcaauauauu acugugcaag aacaggaugg 360

cucggaccau ucgacuauug gggacaagga accuuaguaa caguauccag cgcuagcaca 420

aaaggcccuu cugucuuccc auuagcacca uccucaaaau caacuucugg cggaacagca 480

gcucuaggau gcuuaguaaa agauuauuuu ccagaaccag uuacuguauc cuggaacuca 540

ggagcacuaa ccaguggagu ucacacauuu ccagccguau uacaaucauc cggauuauau 600

ucauuaucau ccgucguaac cguaccaagc ucauauuag gaacacaaac auacauaugc 660

aacguaaauc acaaaccauc cauacaaaa guagauaaaa gaguagaacc uaaauccugu 720

gauaaaacac acacaugccc accaugccca gcaccagaau uacuaggagg accaucagua 780

uuccuauucc caccaaaacc aaaagauaca cuaaugauau caagaacacc agaaguaacu 840

uguguagucg uagacgucuc acaugaagac ccagaaguaa aauuuaauug guauguugac 900

ggagucgaag uacacaacgc caaaacaaaa ccacgagaag aacaauacaa cucaacauau 960

agaguaguau cuguauuaac aguauuacau caagauuggu uaaacggaaa agaauacaaa 1020

uguaaaguau caaauaaagc ucuaccagca ccaauagaaa agacaaucuc aaaagcaaaa 1080

ggccaaccuc gagaaccaca aguauacaca cuaccaccau caagagacga auuaaccaaa 1140

1200

ugggaaucaa acggucaacc ugaaaacaac uauaaaacaa caccaccagu uuuagacuca 1260

1320

1380

cucucacuau cacccgguaa auaa 1404

<210> 658

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 658

auggagcugg gccucagcug gaucuuccug cuggccaucc ucaagggggu gcagugccag 60

120

ugcgccgccu ccggcuucac cuucagcucc uacaccaugc acuggguccg ccaggcgccg 180

gggaagggcc uggagugggu gacguucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacuccguga aggggcgguu caccaucagc cgcgacaacu ccaagaacac ccucuaccug 300

cagaugaaca gccugcgggc cgaggacacc gccaucuacu acugcgcccg cacgggcugg 360

cucgggcccu ucgacuacug gggccagggg acccugguca ccguguccag cgcguccacc 420

aagggcccca gcguguuccc ccuggccccg uccagcaagu ccacgagcgg cgggaccgcc 480

gccuccggcu gccuggucaa gacuacuuc cccgagcccg ugaccguguc cuggaacagc 540

ggggcgcuga ccagcggcgu ccacacguuc cccgccgugc uccaguccag cggccuguac 600

ucccuagcu ccguggucac cgugccgagc uccagccucg ggacccagac cuacaucugc 660

aacgugaacc acaagcccuc caacacgaag gucgacaagc ggguggagcc caagagcugc 720

gacaagaccc acacgugccc gcccugcccc gcccccgagc ugcugggcgg cccgagcgug 780

uuccucuucc cgcccaagcc caaggacacc cugaugauca gccgcacccc cgaggucacg 840

ugcguggugg ucgacgugag ccacgaggac cccgagguga aguucaacug guacgucgac 900

ggggugggagg ugcacaacgc caagaccaag ccccgggagg agcaguacaa cagcaccuac 960

cgcgucguga gcgugcugac cguccuccac caggacuggc ugaacggcaa ggaguacaag 1020

ugcaaggugu cgaacaaggc ccugccggcc cccaucgaga agacgaucag caaggcgaag 1080

ggccagccgc gggagcccca ggucuacacc cucccgccca gccgcgacga gcugaccaag 1140

aaccaggugu cccugacgug ccucgugaag ggcuucuacc ccagcgacau cgccgucgag 1200

ugggagagca acgggcagcc cgagaacaac uacaagacca cgcccccggu gcuggacucc 1260

gacggcagcu ucuuccugua cuccaagcuc accguggaca agagccggug gcagcagggg 1320

1380

cugagccucu cccccggcaa guga 1404

<210> 659

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 659

auggagcugg gccucagcug gaucuuccuu cuggccauuu ugaagggggu gcagugccaa 60

guccaguuag uugaauccgg agguggcgug guacagcccg ggagaucucu gaggcuauca 120

ugugcugcaa guggauuuac cuucagcucc uacacaaugc acugggugcg gcaggccccu 180

ggcaaagguc ucgagugggu cacuuuuaua ucuuaugacg ggaacaauaa guacuaugcg 240

gauucgguga aaggacgcuu cacgaucuca cgagacaaca gcaagaauac ccuguaccuu 300

caaaugaaca gucugcgugc ugaagauaca gccauuuauu acugcgcaag aacuggcugg 360

uugggcccau uugacuauug ggggcaggga acccucguua caguguccuc ugccagcacc 420

aaagguccgu ccgucuuccc ccuggcuccu ucaaguaaga gcacuucugg cgggacagca 480

gcccugggau gucucgugaa ggauuacuuu cgagcccg uaaccguuuc cuggaacuca 540

ggcgcuuuaa cgagcggugu gcauacuuuc ccugccgucc ugcagaguuc ugggcuuuac 600

uccuugagcu cgguggugac cgucccaucu uccucacugg gaacacagac uuauaucugc 660

aauguuaauc acaaacccag uaacaccaag guggacaaaa ggguagaacc uaaagcugu 720

gauaaaacac auaccugccc accguguccc gcccccgagc ugcugggcgg cccgagcgug 780

uuccucuucc cgcccaagcc caaggacacc cugaugauca gccgcacccc cgaggucacg 840

ugcguggugg ucgacgugag ccacgaggac cccgagguga aguucaacug guacgucgac 900

ggggugggagg ugcacaacgc caagaccaag ccccgggagg agcaguacaa cagcaccuac 960

cgcgucguga gcgugcugac cguccuccac caggacuggc ugaacggcaa ggaguacaag 1020

ugcaaggugu cgaacaaggc ccugccggcc cccaucgaga agacgaucag caaggcgaag 1080

ggucagccua gggaacccca gguguacacg uuaccacccu cucgggauga gcugaccaag 1140

aaccaaguau cacucacaug ccuugucaaa ggcuucuauc cuagugacau cgcaguggaa 1200

ugggagagca augggcagcc agagaacaac uacaagacua ccccgcccgu ucuggacucc 1260

1320

1380

cucucucuga gcccugguaa auga 1404

<210> 660

<211> 1404

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 660

auggagcugg gccugagcug gaucuuccug cuggccaucc ugaagggcgu gcagugccag 60

gugcagcugg uggagagcgg cggcggcgug gugcagcccg gcagaagccu gagacugagc 120

ugcgccgcca gcggcuucac cuucagcagc uacaccaugc acugggugag acaggccccc 180

ggcaagggcc uggagugggu gaccuucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacagcguga agggcagauu caccaucagc agagacaaca gcaagaacac ccuguaccug 300

cagaugaaca gccugagagc cgaggacacc gccaucuacu acugcgccag aaccggcugg 360

cugggccccu ucgacuacug gggccagggc acccugguga cggugagcag cgccagcacc 420

aagggcccca gcguguuccc ccuggccccc agcagcaaga gcaccagcgg cggcaccgcc 480

gcccugggcu gccuggugaa gacuacuuc cccgagcccg ugaccgugag cuggaacagc 540

ggcgcccuga ccagcggcgu gcacaccuuc cccgccgugc ugcagagcag cggccuguac 600

agccugagca gcguggugac cgugcccagc agcagccugg gcacccagac cuacaucugc 660

aacgugaacc acaagcccag caacaccaag guggacaaga gaguggagcc caagagcugc 720

780

uuccucuucc cgcccaagcc caaggacacc cugaugauca gccgcacccc cgaggucacg 840

ugcguggugg ucgacgugag ccacgaggac cccgagguga aguucaacug guacgucgac 900

ggggugggagg ugcacaacgc caagaccaag ccccgggagg agcaguacaa cagcaccuac 960

cgcgucguga gcgugcugac cguccuccac caggacuggc ugaacggcaa ggaguacaag 1020

ugcaaggugu cgaacaaggc ccugccggcc cccaucgaga agacgaucag caaggcgaag 1080

ggccagccca gagagcccca gguguacacc cugcccccca gcagagacga gcugaccaag 1140

aaccagguga gccugaccug ccuggugaag ggcuucuacc ccagcgacau cgccguggag 1200

ugggagagca acggccagcc cgagaacaac uacaagacca ccccccccgu gcuggacagc 1260

gacggcagcu ucuuccugua cagcaagcug accguggaca agagcagaug gcagcagggc 1320

1380

cugagccuga gccccggcaa guga 1404

<210> 661

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab protein HC without signale peptide

<400> 661

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

115 120 125

Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly

130 135 140

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

145 150 155 160

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

165 170 175

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

180 185 190

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

195 200 205

Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr

210 215 220

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

260 265 270

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 662

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 662

caggugcagc uggucgagag cggcgggggc guggugcagc ccgggcgcuc ccuccggcug 60

agcugcgccg ccuccggcuu caccuucagc uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gccuggagug ggugacguuc aucagcuacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc agccgcgaca acuccaagaa cacccucuac 240

cugcagauga acagccugcg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggacccugg ucaccguguc cagcgcgucc 360

accaagggcc cggcguguu cccccuggcc ccguccagca aguccacgag cggcgggacc 420

gccgcccucg gcugccuggu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

agcggggcgc ugaccagcgg cguccacacg uuccccgccg ugcuccaguc cagcggccug 540

uacucccuga gcuccguggu caccgugccg agcuccagcc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagagc 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg agcugcuggg cgggcccucc 720

guguuccucu ucccgcccaa gcccaaggac acccugauga ucagccgcac ccccgaggug 780

accugcgucg uggucgacgu guccicgag gacccgggagg ucaaguucaa cugguacgug 840

gacggcgugg agguccacaa cgccaagacc aagccccggg aggagcagua caacagcacc 900

uaccgcgugg uguccguccu gacggugcuc caccaggacu ggcugaacgg gaaggaguac 960

1020

aagggccagc cgcgggagcc ccaggucuac acccuccgc ccagccgcga cgagcugacc 1080

aagaaccagg ugucccugac gugccucgug aagggcuucu accccagcga caucgccguc 1140

gagugggaga gcaacgggca gcccgagaac aacuacaaga ccacgccccc ggugcuggac 1200

uccgacggca gcuucuuccu guacuccaag cucaccgugg acaagagccg guggcagcag 1260

gggaacgucu ucuccugcag cgugaugcac gaggcccugc acaaccacua cacccagaag 1320

ucccugagcc ucucccccgg caaguga 1347

<210> 663

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 663

cagguccagc ucgucgaguc cggcggcggc gucguccagc ccggccgcuc ccuccgccuc 60

uccugcgccg ccuccggcuu caccuucucc uccuacacca ugcacugggu ccgccaggcc 120

cccggcaagg gccucgagug ggucaccuuc aucuccuacg acggcaacaa caaguacuac 180

gccgacuccg ucaagggccg cuucaccauc ucccgcgaca acuccaagaa cacccucuac 240

cuccagauga acucccuccg cgccgaggac accgccaucu acuacugcgc ccgcaccggc 300

uggcucggcc ccuucgacua cuggggccag ggcacccucg ucaccgucuc cuccgccucc 360

accaagggcc ccuccgucuu cccccucgcc cccuccucca aguccaccuc cggcggcacc 420

gccgcccucg gcugccucgu caaggacuac uuccccgagc ccgucaccgu cuccuggaac 480

uccggcgccc ucaccuccgg cguccacacc uuccccgccg uccuccaguc cuccggccuc 540

uuccccucu ccuccgucgu caccgucccc uccuccuccc ucggcaccca gaccuacauc 600

ugcaacguca accacaagcc cuccaacacc aaggucgaca agcgcgucga gcccaagucc 660

ugcgacaaga cccacaccug cccccccugc cccgcccccg agcuccucgg cggccccucc 720

gucuuccucu ucccccccaa gcccaaggac acccucauga ucucccgcac ccccgagguc 780

accugcgucg ucgucgacgu cucccgag gaccccgagg ucaaguucaa cugguacguc 840

gacggcgucg agguccacaa cgccaagacc aagccccgcg aggagcagua caacuccacc 900

uaccgcgucg ucuccguccu caccguccuc caccaggacu ggcucaacgg caaggaguac 960

1020

aagggccagc ccgcgagcc ccaggucuac acccuccccc ccucccgcga cgagcucacc 1080

aagaaccagg ucucccucac cugccucguc aagggcuucu accccuccga caucgccguc 1140

gagugggagu ccaacggcca gcccgagaac aacuacaaga ccaccccccc cguccucgac 1200

uccgacggcu ccuucuuccu cuacuccaag cucaccgucg acaagucccg cuggcagcag 1260

ggcaacgucu ucuccugcuc cgucaugcac gaggcccucc acaaccacua cacccagaag 1320

ucccuccccc ucucccccgg caaguga 1347

<210> 664

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 664

caggugcaac uggucgagag cggcggggga guugugcagc ccgguagauc ccucaggcuu 60

ucuugcgccg cuucaggcuu caccuuuagu agcuacacaa ugcacugggu acggcaggca 120

ccugggaagg gacuggaaug ggugacuuuc aucuccuaug acggcaacaa uaaauacuau 180

gccgauucug ucaagggucg cuuuacgauu ucgcgagaca acagcaaaaa uaccuuguac 240

uuacagauga acucacugcg ugcggaggau acagcuauau auuacugugc cagaacuggg 300

uggcuaggac cauucgacua uuggggccaa ggcacccucg ugacaguuag uuccgcaucu 360

accaaggggc cgagcguguu ucccggggcc ccuuccucaa aaaguacuag cggagguaca 420

gcugcacuug gcugccuggu caaggauuac uucccagaac ccgugaccgu aucuuggaac 480

uccggggccu ugacgucagg aguucauacu uuuccugcug ugcuccagag caguggccug 540

uacucucugu ccagcgucgu gaccgugcca ucgucuuccc ucgguacaca gacuuauauc 600

uguaauguca aucacaagcc cucaaacacc aaaguugaca agagggugga gccuaaaagu 660

ugcgauaaga cacauaccug uccaccgugc cccgccccug aauuacuugg gggaccaagc 720

guauuccugu uucccccuaa accaaaggac acguugauga uuucccggac ucccgaggug 780

840

gauggcguag agguucauaa cgcgaaaacc aagccucgcg aagaacagua uaauagcacu 900

uacagagugg ucucagugcu gacaguccua caccaagacu ggcucaacgg caaagaguau 960

aagugcaaag ugaguaauaa ggcacugccc gccccaaucg agaaaaccau uuccaaggcu 1020

aaggggcagc cuagggagcc ccagguuuac acgcuuccac ccagccggga ugaacugacc 1080

aaaaaccagg ugucuuugac augucucgua aagggauuuu auccuucaga caucgccguc 1140

gagugggaaa guaaugguca accagagaac aacuacaaaa cuaccccgcc cgugcuggac 1200

agcgauggcu ccuucuuuuu auacucuaag cugacaguug acaaaucgcg cuggcagcag 1260

gggaaugugu ucagcugcuc cgucaugcac gaggcacucc auaaccacua uacucaaaag 1320

ucacuuaguc ugucuccugg aaaguga 1347

<210> 665

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 665

caggugcagc ugguggagag cggcggcggc guggugcagc ccggcagaag ccugagacug

agcugcgccg ccagcggcuu caccuucagc agcuacacca ugcacugggu gagacaggcc 120

cccggcaagg gccuggagug ggugaccuuc aucagcuacg acggcaacaa caaguacuac 180

gccgacagcg ugaagggcag auucaccauc agcagagaca acagcaagaa cacccuguac 240

cugcagauga acagccugag agccgaggac accgccaucu acuacugcgc cagaaccggc 300

uggcugggcc ccuucgacua cuggggccag ggcacccugg ugaccgugag cagcgccagc 360

accaagggcc cggcguguu cccccggcc cccagcagca agagcaccag cggcggcacc 420

gccgcccugg gcugccuggu gaaggacuac uuccccgagc ccgugaccgu gagcuggaac 480

agcggcgccg ugaccagcgg cgugcacacc uuccccgccg ugcugcagag cagcggccug 540

uacagccuga gcagcguggu gaccgugccc agcagcagcc ugggcaccca gaccuacuc 600

ugcaacguga accacaagcc cagcaacacc aagguggaca agagagugga gcccaagagc 660

ugcgacaaga cccacaccug cccccccugc cccgcccccg agcugcuggg cggccccagc 720

guguuccugu ucccccccaa gcccaaggac acccugauga ucagcagaac ccccgaggug 780

accugcgugg ugguggacgu gagccacgag gaccccgagg ugaaguucaa cugguacgug 840

gacggcgugg aggugcacaa cgccaagacc aagccgag aggagcagua caacagcacc 900

uacagagugg ugagcgugcu gaccgugcug caccaggacu ggcugaacgg caaggaguac 960

1020

aagggccagc ccagagagcc ccagguguac acccugcccc ccagcagaga cgagcugacc 1080

aagaaccagg ugagccugac cugccuggug aagggcuucu accccagcga caugccgug 1140

gagugggaga gcaacggcca gcccgagaac aacuacaaga cccaccccccc cgugcuggac 1200

agcgacggca gcuucuuccu guacagcaag cugaccgugg acaagagcag auggcagcag 1260

ggcaacgugu ucagcugcag cgugaugcac gaggcccugc acaaccacua cacccagaag 1320

agccugagcc ugagccccgg caaguga 1347

<210> 666

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 666

caggugcaac uggucgagag cggcggggga guugugcagc ccggcagauc ccuccggcug 60

ucuugcgccg cuagcggguu caccuuuucc ucuuacacaa ugcacugggu gcgccaggcc 120

ccuggaaagg gccuugaaug ggucacguuc aucagcuaug acgggaacaa uaaauacuau 180

gcggauuccg ugaagggaag auuuaccauu ucucgggaca acagcaaaaa uacacuguac 240

cuccagauga acucccugcg cgcugaggau accgccaucu auuacugugc cagaacaggc 300

uggcuuggcc cguucgacua uugggggcaa ggaacccugg uuacagugag cucugcuucc 360

accaagggcc ccagcgucuu uccucucgcc cccucuucca aaagcacguc ugggggaacc 420

gcugcccugg gcugccuggu gaaggauuac uucccugaac ccguuacagu guccuggaau 480

agcggggcgc ucaccuccgg aguccauaca uuuccugccg ugcugcaguc uagcggccuu 540

uacucccuga gcucuguggu caccguuccg uccagcucuc ucggcacgca gacauauauuu 600

uguaacguga aucacaagcc cagcaacacc aaaguggaca agcgggucga gccuaaaucc 660

ugcgauaaga cacauaccug uccccccuugc cccgcuccgg aacugcuugg gggaccuucu 720

guguuccugu uucccccuaa acccaaggac acccucauga ucagccgcac acccgagguu 780

acgugugugg ucguggaugu uucccgag gacccugaag ugaaguucaa uugguacguc 840

gauggcgugg agguccauaa cgccaaaacc aagccgagag aagaacagua uaauagcaca 900

uaccgggugg uuucugugcu gaccguccug caccaagacu ggcucaacgg gaaagaguau 960

1020

aagggacagc cccgcgagcc ucagguuuac acccuucccc cgucuagaga ugaacugacg 1080

aaaaaccagg ugucccucac augucugguc aagggcuuuu auccuagcga caucgccgug 1140

gagugggaau ccaaugggca acccgagaac aacuacaaaa ccaccccucc cgugcuugac 1200

ucugauggca gcuucuuucu guacuccaag cucacaguug acaaaucucg guggcagcag 1260

ggaaaugucu ucagcugcuc cgugaugcac gaggcucugc auaaccacua uacccaaaag 1320

agccugucuc ucuccccugg caaguga 1347

<210> 667

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 667

caaguucaac uaguagaauc aggaggagga gucguccaac caggcagauc acuaagacua 60

ucaugugcag ccucuggcuu cacauucucu ucuuauacaa ugcacugggu aagacaagca 120

cggaaaag gacuagaaug gguaacauuc auaucuuuacg acggaaauaa caaauauuac 180

gcugauucug uaaaagguag auucacaauu ucuagagaca auaguaaaaa uacauuauac 240

cuccaaauga auagucuuag agcagaagau acagcaauau acuauugugc acgaacagga 300

ugguuaggac cauucgauua cuggggucaa ggaacauuag uaacaguauc aucugcauca 360

acaaaagguc cuucaguauu cccacucgca ccaucaucaa aauccacauc aggaggaacu 420

gcagcccucg gaugccuagu caaagacuac uucccagaac caguaaccgu aucuuggaac 480

uccggagcau uaacaucugg aguacauaca uucccugcag uacuccaauc aucagacua 540

uacucacuau ccuccguagu aaccgucccu ucaucaucuc uagguacaca aacuuacaua 600

ugcaacguaa aucacaaacc aucuaauaca aaaguagaca aaagagucga accaaaauca 660

ugcgacaaaa cccacacaug ccccccaugc ccagcacccg aacuacucgg aggaccauca 720

guauuucuau uuccaccaaa accaaaagau acacuaauga

accuguguug ucgucgacgu aucgcacgaa gacccagaag uaaaauuuaa uugguacgua 840

900

uuuugaguag uuucugucuu aaccgucuua caccaagauu gguuaaacgg uaaagaauau 960

aaaugcaaag uaucuaauaa agcucuaccc gccccaaucg aaaaaacaau aucaaaagcc 1020

aaaggccaac cucgagaacc acaaguauac acacuacccc

aaaaaccaag uaagccuaac augccuagua aaaggcuuuu auccaucaga cauagcagua 1140

gaaugggaau cuaacgguca accugaaaau aacuauaaaa caacaccacc aguacuagac 1200

ucagauggau cauucuuucu auacucaaaa uuaacaguag auaaaucaag auggcaacaa 1260

1320

ucucucagcc uaucacccgg aaaauga 1347

<210> 668

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 668

caggugcaac uggucgagag cggcgggggu gugguacagc ccggcagguc ccuccggcug 60

aguugcgccg caagcggguu caccuuuucc aguuacacua ugcacugggu gcgccaggcc 120

ccaggcaagg guuuggaaug ggucaccuuc aucagcuaug acgggaacaa uaaauacuau 180

gcggauuccg ugaagggcag guuuacgauu agccgggaca acuccaaaaa uacucuguac 240

cuccagauga acagucugcg cgccgaggau accgcaaucu auuacugugc caggaccggc 300

ugguuggggc cguucgacua uuggggucaa ggcacucugg ugaccgucag cuccgcaagc 360

acgaaggggc ccaguguguu uccacucgcc cccuccagca aauccaccag uggcgguacc 420

gcggcccugg ggugccuggu aaaggauuac uucccagaac ccgugacugu cagcuggaac 480

uccggcgcac ucaccagcgg cgugcauacc uuuccagccg ugcugcagag uuccggguug 540

uacagccuga guuccgucgu gacgguaccg agcagcuccc ucgguacuca gaccuauauuu 600

uguaauguga aucacaagcc caguaacacu aaagucgaca agcggggugga gccaaaaagc 660

ugcgauaaga cccauaccug ucccccaugc cccgccccgg aacugcuggg cgggcccucc 720

guguucuugu uuccacccaa accaaaggac acucucauga ucagccgcac gcccgagguc 780

accugugugg uaguggaugu cagucacgag gacccagaag ugaaauucaa uugguacguc 840

gauggcgugg aggugcauaa cgcaaagacu aagccgagg aagaacagua uaauuccacc 900

uaccggguag ugagcguccu gaccgugcug caccaagacu ggcucaacgg uaaagaguau 960

1020

aagggccagc cccgcgagcc acagguguac acguugcccc cgagcaggga ugaacugacc 1080

aaaaaccagg ugucccucac uugucuggua aagggguuuu auccaagcga caucgcagug 1140

gagugggaaa guaauggcca acccgagaac aacuacaaaa ccacuccccc aguccuggac 1200

uccgauggga gcuucuucuu guacuccaag cucacugugg acaaaagucg guggcagcag 1260

1320

agccugaguc ucucccccgg caaguga 1347

<210> 669

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 669

caaguccagc uaguagaauc cggcgggaggc gucguccaac caggacgcuc gcuaagacuc 60

agcugcgccg caucuggcuu cacauucagc ucauacacaa ugcacugggu cagacaagcu 120

ccaggcaaag gccucgaaug ggucacauuc auaucauacg acggcaacaa caaauacuac 180

gccgacuccg uaaaaggccg cuucaccauc uccagagaca acuccaaaaa cacccuauac 240

cuccaaauga acucacucag agccgaagac accgcaaucu acuacugcgc aagaaccggc 300

uggcuuggcc ccuucgauua cuggggacaa ggcacccucg ucaccgucuc auccgcaucc 360

accaaaggcc cauccgucuu cccccucgca ccaucaucca aauccaccag cggagguacc 420

gccgcacucg gcugccuagu caaagacuac uuccccgaac cugucacagu cuccuggaac 480

uccggagccc ugacaucggg cguccacaca uuccccgccg uccuacaaag cuccggccuc 540

uacagccucu ccucagucgu caccguaccc uccuccagcc ucggaacaca aaccuacauc 600

ugcaacguua accacaaacc uuccaacacc aaagucgaca aacgagucga acccaaaucg 660

ugcgacaaaa cccauaccug cccacccugc cccgcccccg aacuccucgg cggcccaucc 720

gucuuccuau ucccacccaa accaaaggac acacucauga uaucacgaac cccugaaguc 780

acgugcgucg ucgucgacgu uucacacgaa gaccccgaag ucaaauucaa cugguacgua 840

gacggagucg aaguccacaa cgccaaaacc aaaccccgag aagaacaaua caacucuacc 900

uaccgcgucg uauccguccu caccguccuc caccaagacu ggcuaaacgg caaagaauac 960

aagugcaaag uuucgaacaa agcccucccc gcacccaucg agaaaaccau cuccaaagcc 1020

1080

aaaaaucaag ucucucuaac cugccucgua aaaggcuucu accccuccga cauagcagua 1140

gaaugggaau cuaacggcca gcccgaaaac aacuacaaaa caaccccacc cguacucgac 1200

uccgacggcu cauucuuccu cuacucaaaa cucaccgucg auaaaucccg cuggcaacaa 1260

ggcaaugucu ucucaugcag cgucaugcac gaagcacucc acaaccacua cacacaaaag 1320

agccucuccc uaucccccgg caaauga 1347

<210> 670

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 670

caaguccagc uagucgaauc aggcgggaggc gucguccaac ccggacgguc ccuacgacuc 60

agcugugcug ccagcggcuu caccuucucg uccuacacaa ugcacugggu ccggcaagca 120

cccggcaaag gucucgaaug ggucaccuuc auauccuaug acggcaacaa caaauacuac

gccgacuccg ucaaaggccg cuucacaauc ucaagagaca acuccaaaaa cacccucuac 240

cuccaaauga acucgcuaag agcagaagac accgccaucu acuacugcgc ccgcaccgga 300

uggcucggcc ccuucgacua cuggggccaa ggcacccuag ucacaguauc auccgccucu 360

acaaagggac cauccgucuu cccccucgcc ccauccucca aauccaccuc uggaggcacc 420

gccgcacucg gaugccucgu caaagacuac uuccccgaac ccgucacagu cuccuggaac 480

uccggcgccc uaaccuccgg aguccacaca uucccugcug uccuacaauc cucgggccua 540

uacucccucu caucuguagu caccgucccc ucauccuccc uuggaaccca aacguacaua 600

ugcaacguca accacaaacc uuccaacaca aaagucgaca aacguguaga gccaaagucc 660

ugugacaaaa cacacacaug cccaccaugu cccgcgcccg aacuacucgg cggacccuca 720

gucuuccucu uucccccgaa acccaaagac acccucauga uaucacgcac ccccgaaguu 780

accugcgucg ucgucgacgu cucccacgaa gaccccgaag ucaaauucaa cugguacguc 840

gacggcguag aaguccacaa cgccaaaacc aaaccacggg aagaacaaua caacuccaca 900

uaccgcgucg ucagcguacu caccguccua caucaagacu ggcuaaacgg caaagaauac 960

1020

aaaggccaac cccgggaacc acaaguauau acccucccac cgaacagaga cgaacucacc 1080

aaaaaccaag uuucacucac augccucgua aaaggauucu accccucuga cauugcuguc 1140

gaaugggaau ccaacggaca acccgaaaac aacuacaaaa ccaccccgcc cguccucgac 1200

uccgacggcu cauucuuccu auacuccaaa cucaccguag acaaaucccg auggcagcaa 1260

ggcaacgucu ucuccugcag cguaaugcac gaagcacucc acaaccacua uacccaaaaa 1320

ucccucuccc ugucccccgg aaaguaa 1347

<210> 671

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 671

caaguacaac ucgucgaauc cggcggcggc guaguccaac caggcagauc ccuacgccuc 60

uccugcgccg cauccggauu caccuucucc uccuacacca ugcacugggu acgccaagcc 120

cccggcaagg gccucgaaug ggucacguuc aucucuuacg acggcaacaa caaauacuac 180

gccgacuccg uaaaaggucg uuucaccauc ucccgcgaca acagcaaaaa cacccuauac 240

cuucaaauga acucccuccg cgccgaagac accgccaucu acuacugugc ccgcaccggu 300

uggcucggcc ccuucgacua cuggggucaa ggaacccuag uuaccguauc auccgcaucu 360

accaaaggcc ccuccguauu cccacuagcc ccaucgucca aaucaacauc aggcggcaca 420

gccgcccucg gaugccuagu caaagacuac uuccccgaac ccgucaccgu cucauggaac 480

uccggagccc uaaccucggg aguccacacc uucccagcgg uacuacaauuc auccggacuu 540

uacucccuau cauccgucgu cacaguacca uccucauccc ucgggaccca aaccuacaua 600

ugcaacguca accacaaacc auccaacacc aaagucgaca aaagagucga accaaaaucc 660

ugcgacaaaa cccacacaug cccacccugc ccagcccccg aacuccucgg cggccccucc 720

guauuccucu ucccacccaa acccaaggac acccucauga uaucccgcac cccagaagua 780

accugcguag uagucgacgu uucacacgaa gaccccgaag ucaaauucaa cugguacgua 840

gacggcgucg agguccacaa cgccaaaacc aaaccucgcg aagaacaaua caacagcaca 900

uaccgcgucg ucuccguccu aaccguacua caccaagacu ggcuaaacgg caaagaauac 960

1020

aaaggucaac ccgcgaacc ccaaguauac acccuacccc caucccgcga cgagcucacc 1080

aaaaaccaag uaucccuaac cugccucguc aaaggcuucu accccuccga cauagccguc 1140

gaaugggaaa gcaauggcca gcccgaaaac aacuacaaaa caaccccacc cguccucgac 1200

uccgacggcu cuuucuuccu cuacucaaaa cucacagucg acaaaucacg auggcaacaa 1260

ggcaacgucu ucuccugcag cguaaugcac gaagcccucc acaaccacua cacccaaaaa 1320

ucacucagcc uaagccccgg caaguaa 1347

<210> 672

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 672

caaguccaac uagucgaauc aggaggaggc guaguacaac caggaagauc cuuaagacuu 60

ucaugugcag caucuggauu uaccuucuca ucauacacaa ugcacugggu cagacaagcc 120

ccgggaaaag gacuagaaug gguaacauuu auaucauaug auggaaauaa caaauauuac 180

gcagauucug uaaaaggaag auucaccauc ucaagagaua auucaaaaaa cacacuauac 240

cuacaaauga acucacucag agcugaagac accgcaauau acuauugcgc aagaacagga 300

ugguuaggac cuuucgauua cuggggacaa ggaacacuag uuaccgucuc cuccgcaagu 360

accaaaggac caucuguauu cccauuagca ccaucaucca aaucaacauc aggaggaacc 420

gcagcauuag gaugcuuagu aaaagacuac uuuccugaac ccguaacagu aucauggaau 480

uccggagcac uaacaucagg aguacauacc uuuccagcag uacuccaauc aucaggauua 540

uauuccuuau cuucaguagu aacaguccca ucaucuucac uagguacaca aaccuacauc 600

ugcaauguaa accacaaacc aucaaauaca aaagucgaca aaagaguuga accaaaauca 660

ugugacaaaa cucacacaug cccaccaugu ccagccccag aauuacuagg aggaccauca 720

guauuccuuu ucccaccaaa accaaaagau acucuaauga uaucccguac cccagaagua 780

acaugcgucg uaguagacgu aucacacgaa gaccccgaag uaaaauucaa uugguacguc 840

900

uaccguguag uaucaguauu aacagucuua caccaagacu ggcuaaacgg aaaagaauac 960

1020

1080

aaaaaccaag uaucccuaac augccuagua aaaggauucu acccuucaga caucgcagua 1140

gaaugggaau ccaacggaca accugaaaac aacuauaaaa caacaccacc aguauuagau 1200

1260

1320

ucacuaucau uaucaccagg aaaauaa 1347

<210> 673

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 673

caaguucaau uaguagaauc uggaggagga guaguccaac caggacguuc acuaagacuc 60

ucuugugcag cuucaggauu uacguucuca agcuauacca ugcacugggu aagacaagcc 120

cggaaaag gauuagaaug gguaacauuu auaucuuuacg acggcaauaa caaauauuau 180

240

cuacaaauga auagccuaag agcagaagau acagcaauau auuacugugc acguacagga 300

ugguuagguc cuuucgauua cuggggacaa gguacucuag uuacaguaag cagcgcaucu 360

accaaaggac caagcguauu cccucuugcu ccaucaagca aauccacauc aggcggaaca 420

gcugcauuag gaugcuuagu aaaagacuau uucccagaac ccguaacggu aucuuggaac 480

agcggcgcau uaacaucagg aguacauacu uuuccugcag uacuacaaag cuccggauua 540

uacucuuuau caucaguagu aacaguacca uccucaucac uaggaacaca aacauauaua 600

uguaacguaa aucauaaacc aucaaacacc aaaguagaca aaagaguaga accaaaauca 660

ugugauaaaa cucacaccug uccuccaugu ccagcacccg aauuauuagg agguccaagu 720

780

acauguguag uaguagacgu cucacacgaa gacccagaag uaaaauucaa cugguacgua 840

900

uacagaguag ugucaguauu aacaguauua caccaagacu ggcuaaaugg aaaagaauac 960

aaauguaaag uaucaaauaa agcacuacca gcaccaaucg 1020

1080

aaaaaccaag uaagcuuaac augucuagua aaaggauucu auccauccga cauagcagua 1140

gaaugggaau caaauggguca accagaaaac aacuacaaaa caacaccacc aguucucgau 1200

ucagauggau cauuuuuucu auauagcaaa uuaacuguag acaaaucuag auggcaacaa 1260

gaagcacucc acaaucauua cacacaaaaa 1320

aguuuaaguu uauccccagg caaauaa 1347

<210> 674

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 674

caggugcagc uggucgagag cggcgggggc guggugcagc ccgggcgcuc ccuccggcug 60

agcugcgccg ccuccggcuu caccuucagc uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gccuggagug ggugacguuc aucagcuacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc agccgcgaca acuccaagaa cacccucuac 240

cugcagauga acagccugcg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggacccugg ucaccguguc cagcgcgucc 360

accaagggcc cggcguguu cccccuggcc ccguccagca aguccacgag cggcgggacc 420

gccgcccucg gcugccuggu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

agcggggcgc ugaccagcgg cguccacacg uuccccgccg ugcuccaguc cagcggccug 540

uacucccuga gcuccguggu caccgugccg agcuccagcc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagagc 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg agcugcuggg cggcccgagc 720

guguuccucu ucccgcccaa gcccaaggac acccugauga ucagccgcac ccccgagguc 780

acgugcgugg uggucgacgu gagccacgag gaccccgagg ugaaguucaa cugguacguc 840

gacgggggg aggugcacaa cgccaagacc aagccccggg aggagcagua caacagcacc 900

uaccgcgucg ugagcgugcu gaccguccuc caccaggacu ggcugaacgg caaggaguac 960

1020

aagggccagc cgcgggagcc ccaggucuac acccuccgc ccagccgcga cgagcugacc 1080

aagaaccagg ugucccugac gugccucgug aagggcuucu accccagcga caucgccguc 1140

gagugggaga gcaacgggca gcccgagaac aacuacaaga ccacgccccc ggugcuggac 1200

uccgacggca gcuucuuccu guacuccaag cucaccgugg acaagagccg guggcagcag 1260

gggaacgucu ucuccugcag cgugaugcac gaggcccugc acaaccacua cacccagaag 1320

ucccugagcc ucucccccgg caaguga 1347

<210> 675

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 675

caggugcaac uggucgagag cggcggggga guugugcagc ccgguagauc ccucaggcuu 60

ucuugcgccg cuucaggcuu caccuuuagu agcuacacaa ugcacugggu acggcaggca 120

ccugggaagg gacuggaaug ggugacuuuc aucuccuaug acggcaacaa uaaauacuau 180

gccgauucug ucaagggucg cuuuacgauu ucgcgagaca acagcaaaaa uaccuuguac 240

uuacagauga acucacugcg ugcggaggau acagcuauau auuacugugc cagaacuggg 300

uggcuaggac cauucgacua uuggggccaa ggcacccucg ugacaguuag uuccgcaucu 360

accaaggggc cgagcguguu ucccggggcc ccuuccucaa aaaguacuag cggagguaca 420

gcugcacuug gcugccuggu caaggauuac uucccagaac ccgugaccgu aucuuggaac 480

uccggggccu ugacgucagg aguucauacu uuuccugcug ugcuccagag caguggccug 540

uacucucugu ccagcgucgu gaccgugcca ucgucuuccc ucgguacaca gacuuauauc 600

uguaauguca aucacaagcc cucaaacacc aaaguugaca agagggugga gccuaaaagu 660

ugcgauaaga cacauaccug uccaccgugc cccgcccccg agcugcuggg cggcccgagc 720

guguuccucu ucccgcccaa gcccaaggac acccugauga ucagccgcac ccccgagguc 780

acgugcgugg uggucgacgu gagccacgag gaccccgagg ugaaguucaa cugguacguc 840

gacgggggg aggugcacaa cgccaagacc aagccccggg aggagcagua caacagcacc 900

uaccgcgucg ugagcgugcu gaccguccuc caccaggacu ggcugaacgg caaggaguac 960

1020

aaggggcagc cuagggagcc ccagguuuac acgcuuccac ccagccggga ugaacugacc 1080

aaaaaccagg ugucuuugac augucucgua aagggauuuu auccuucaga caucgccguc 1140

gagugggaaa guaaugguca accagagaac aacuacaaaa cuaccccgcc cgugcuggac 1200

agcgauggcu ccuucuuuuu auacucuaag cugacaguug acaaaucgcg cuggcagcag 1260

gggaaugugu ucagcugcuc cgucaugcac gaggcacucc auaaccacua uacucaaaag 1320

ucacuuaguc ugucuccugg aaaguga 1347

<210> 676

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 676

caggugcagc ugguggagag cggcggcggc guggugcagc ccggcagaag ccugagacug

agcugcgccg ccagcggcuu caccuucagc agcuacacca ugcacugggu gagacaggcc 120

cccggcaagg gccuggagug ggugaccuuc aucagcuacg acggcaacaa caaguacuac 180

gccgacagcg ugaagggcag auucaccauc agcagagaca acagcaagaa cacccuguac 240

cugcagauga acagccugag agccgaggac accgccaucu acuacugcgc cagaaccggc 300

uggcugggcc ccuucgacua cuggggccag ggcacccugg ugaccgugag cagcgccagc 360

accaagggcc cggcguguu cccccggcc cccagcagca agagcaccag cggcggcacc 420

gccgcccugg gcugccuggu gaaggacuac uuccccgagc ccgugaccgu gagcuggaac 480

agcggcgccg ugaccagcgg cgugcacacc uuccccgccg ugcugcagag cagcggccug 540

uacagccuga gcagcguggu gaccgugccc agcagcagcc ugggcaccca gaccuacuc 600

ugcaacguga accacaagcc cagcaacacc aagguggaca agagagugga gcccaagagc 660

ugcgacaaga cccacaccug cccccccugc cccgcccccg agcugcuggg cggcccgagc 720

guguuccucu ucccgcccaa gcccaaggac acccugauga ucagccgcac ccccgagguc 780

acgugcgugg uggucgacgu gagccacgag gaccccgagg ugaaguucaa cugguacguc 840

gacgggggg aggugcacaa cgccaagacc aagccccggg aggagcagua caacagcacc 900

uaccgcgucg ugagcgugcu gaccguccuc caccaggacu ggcugaacgg caaggaguac 960

1020

aagggccagc ccagagagcc ccagguguac acccugcccc ccagcagaga cgagcugacc 1080

aagaaccagg ugagccugac cugccuggug aagggcuucu accccagcga caugccgug 1140

gagugggaga gcaacggcca gcccgagaac aacuacaaga cccaccccccc cgugcuggac 1200

agcgacggca gcuucuuccu guacagcaag cugaccgugg acaagagcag auggcagcag 1260

ggcaacgugu ucagcugcag cgugaugcac gaggcccugc acaaccacua cacccagaag 1320

agccugagcc ugagccccgg caaguga 1347

<210> 677

<211> 235

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab protein LC with signale peptide

<400> 677

Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro

1 5 10 15

Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser

20 25 30

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

35 40 45

Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro

65 70 75 80

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

85 90 95

Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr

100 105 110

Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

130 135 140

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

165 170 175

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

180 185 190

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230 235

<210> 678

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 678

auggagaccc ccgcccagcu gcucuuccug cugcuccugu ggcugccggga caccacgggc 60

gagaucgugc ugacccagag ccccggcacc cucucccuga gcccggggga gcgcgccacg 120

cuguccugcc gggccagcca guccgucggc agcuccuacc ucgcguggua ccagcagaag 180

cccggggcagg cgccccgccu gcugaucuac ggcgccuuca gccgggccac cgggaucccc 240

gaccgcuucu ccggcagcgg cuccgggacc gacuucaccc ucacgaucag ccggcuggag 300

ccggaggacu ucgccgugua cuacugccag caguacggcu ccagccccug gaccuucggg 360

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 420

cccagcgacg agcagcugaa guccgggacg gccagcgugg ucugccuccu gaacaacuuc 480

uacccccggg aggccaaggu gcaguggaag guggacaacg cgcugcaguc cggcaacagc 540

caggagagcg ucaccgagca ggacuccaag gacagcaccu acucccucag cuccacccug 600

acgcugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu gacccaccag 660

ggccucucca gccccgucac caaguccuuc aaccgcgggg agugcuga 708

<210> 679

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 679

auggagaccc ccgcccagcu ccucuuccuc cuccuccucu ggcuccccga caccaccggc 60

gagaucgucc ucacccaguc ccccggcacc cucucccucu cccccggcga gcgcgccacc 120

cucuccugcc gcgccuccca guccgucggc uccuccuacc ucgccuggua ccagcagaag 180

cccggccagg ccccccgccu ccucaucuac ggcgccuucu cccgcgccac cggcaucccc 240

gaccgcuucu ccggcuccgg cuccggcacc gacuucaccc ucaccaucuc ccgccucgag 300

cccgaggacu ucgccgucua cuacugccag caguacggcu ccucccccug gaccuucggc 360

cagggcacca aggucgagau caagcgcacc gucgccgccc ccuccgucuu caucuucccc 420

cccuccgacg agcagcucaa guccggcacc gccuccgucg ucugccuccu caacaacuuc 480

uacccccgcg aggccaaggu ccaguggaag gucgacaacg cccuccaguc cggcaacucc 540

caggaguccg ucaccgagca ggacuccaag gacuccaccu acucccucuc cuccacccuc 600

acccucucca aggccgacua cgagaagcac aaggucuacg ccugcgaggu cacccaccag 660

ggccucuccu cccccgucac caaguccuuc aaccgcggcg agugcuga 708

<210> 680

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 680

auggagaccc ccgcccagcu ucucuuccuu cuguuguuau ggcugccuga cacaacuggc 60

gaaaucgugc uaacgcaaag cccagggacc cucucccugu cuccgggaga gagagcuaca 120

cuuucaugca gggcaaguca gagcgucggu uccucuuacc uggccuggua ucagcagaag 180

cccggccaag cgccucgguu gcucauuuac ggggcuuuuu cgcgcgccaac uggaauacca 240

gaucgauucu caggcagcgg uagugggacc gacuuuacac ugaccaucuc ccgucuggaa 300

cccgaggauu ucgcaguuua uuacugucag caguauggau cuagcccuug gacuuuuggc 360

cagggcacaa aaguggaaau uaagagaacc guagccgcuc cauccguguu caucuuuccc 420

ccuucagacg agcaacuca aagugggacg gcaagcgucg ugugcuuacu gaacaauuuc 480

uacccaaggg aggccaaggu ucaguggaaa guggauaacg cucugcaguc uggaaauucc 540

caggaaucag ucacugagca agacagcaag gauaguaccu auucuuuguc cagcacacug 600

acucuaucga aggccgacua cgaaaaacac aagguguacg cgugugaggu aacccaucag 660

ggucucucuu ccccgguuac aaaaucauuu aaccggggcg agugcuga 708

<210> 681

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 681

auggagaccc ccgcccagcu gcuguuccug cugcugcugu ggcugcccga caccaccggc 60

gagaucgugc ugacccagag ccccggcacc cugagccuga gccccggcga gagagccacc 120

180

cccggccagg cccccagacu gcugaucuac ggcgccuuca gcagagccac cggcaucccc 240

gacagauuca gcggcagcgg cagcggcacc gacuucaccc ugaccaucag cagacuggag 300

cccgaggacu ucgccgugua cuacugccag caguacggca gcagccccug gaccuucggc 360

cagggcacca agguggagau caagagaacc guggccgccc ccagcguguu caucuucccc 420

cccagcgacg agcagcugaa gagcggcacc gccagcgugg ugugccugcu gaacaacuuc 480

uaccccagag aggccaaggu gcaguggaag guggacaacg cccugcagag cggcaacagc 540

caggagagcg ugaccgagca ggacagcaag gacagcaccu acagccugag cagcacccug 600

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu gacccaccag 660

ggccugagca gccccgugac caagagcuuc aacagaggcg agugcuga 708

<210> 682

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 682

auggagaccc ccgcccagcu ccuguuccug cuucugcucu ggcugccuga cacaacggggc 60

gaaaucgugc uuacccaaag cccggggaca cugucccucu cucccggaga gagagcuacc 120

cugagcugcc gggccuccca gucugucggc agcuccuacc uggcguggua ucagcagaaa 180

ccugggcaag cuccccgccu ccugauuuac ggagccuuuu cuagagccac aggcaucccu 240

gaucgguuca gcggguccgg aagcggcacc gacuuuuacac uuaccauuuc ucgccuggaa 300

cccgaggauu ucgcuguuua uuacugucag caguauggcu ccagcccuug gacguuuggg 360

cagggaacca aaguggaaau caagagaaca guggccgcuc cgucugucuu cauuuuuccc 420

ccuuccgacg agcaacucaa aagcggcacc gccucugugg uuugccugcu uaacaauuuc 480

uacccccggg aggcgaaggu gcaguggaaa gucgauaacg cccugcaguc cgggaauagc 540

caggaauccg ugacagagca agacucuaag gauagcaccu auucccucag cucuacgcug 600

acacugucca aggcugacua cgaaaaacac aagguuuacg ccugugaggu gacccaucag 660

ggacucagcu cuccugucac aaagagcuuu aaccgcggcg agugcuga 708

<210> 683

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 683

auggaaacac cagcacaacu acuauucuua cuauuacuau ggcuaccaga cacaacagga 60

120

cuaucaugca gagcauccca aucaguugga ucuuccuacc uagccuggua ucaacaaaaa 180

ccaggacaag caccaagauu acuaauauac ggagcauucu caagagcaac uggaauccca 240

gauagauucu caggaucagg aucaggaaca gacuucacau uaacaauuuc acgacuagaa 300

ccagaagacu ucgcaguaua cuacugucaa caauacggau ccucaccaug gaccuucggc 360

caaggaacaa aaguagaaau aaaaagaaca guagcagccc caucuguauu cauauuccca 420

ccaucagaug aacaacuaaa aucaggaaca gcaucaguag uaugcuuacu aaacaacuuc 480

uacccaagag aagccaaagu acaauggaaa guagacaacg cacuacaauc aggaaauucc 540

caagaaucag uaacagaaca agacucaaaa gacuccacau acucauuauc aucaacauua 600

acacuaucaa aagcagacua cgaaaaacac aaaguauacg

ggacuaucau caccaguaac aaaaucauuc aaccgaggag aaugcuga 708

<210> 684

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 684

auggagaccc ccgcccagcu ccuguuccug uugcugcucu ggcugccaga cacuaccggc 60

gaaaucgugu ugacgcaaag cccggggacu cugucccuca gucccgguga gagggcaacc 120

cugagcugcc gggccuccca gagugucggc agcuccuacc uggcguggua ucagcagaag 180

ccagggcaag caccccgccu ccugauuuac ggcgccuuua gcagggccac cgguauccca 240

300

360

cagggcacca aaguagaaau caagggacu guggccgcgc cguccgucuu cauuuuuccc 420

ccaagcgacg agcaacucaa auccgggacc gccagugugg ugugccugcu gaacaauuuc 480

uacccccggg aggcaaaggu ccaguggaaa guggauaacg ccuugcagag cggcaauucc 540

caggaaagcg uaaccgagca agacaguaag gauuccacgu auagccucag uuccacucug 600

acccugagca aggccgacua cgaaaaacac aagguguacg caugugaggu cacucaucag 660

ggucucagcu ccccagugac caaaaguuuu aaccgcgggg agugcuga 708

<210> 685

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 685

auggaaaccc ccgcccaacu ccucuuccua uuacuccucu ggcuacccga caccaccggc 60

gaaaucgucc ucacccaauc cccaggcacc cucucucucu cccccggaga acgcgcaaca 120

cucuccugcc gugcauccca auccgucgga ucuuccuacc ucgccuggua ccaacaaaaa 180

240

gaccguuucu caggauccgg cuccggcacc gauuucacac ucaccaucuc ccgccuagaa 300

ccagaagacu ucgccguaua cuacugccag caauacggau cuucccccug gacauucggc 360

caaggcacca aagucgaaau caaacgcacc gucgcagccc ccuccgucuu caucuuccca 420

cccuccgacg aacaacuaaa aucuggcaca gcauccgucg ucugccuccu aaacaacuuc 480

uacccccgcg aagccaaagu ccaauggaaa gucgacaacg cacuccaauc uggcaacuca 540

caagaauccg ucacagaaca agacuccaaa gacucaaccu acucccucuc cucaacccuc 600

acccucucca aagccgacua cgaaaaacac aaggucuacg caugcgaagu cacccaucaa 660

ggacucuccu cccccgucac caaauccuuc aaccgcggcg aaugcuaa 708

<210> 686

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 686

auggaaacac ccgcccaacu ccucuuccuc cuccuccucu ggcuacccga caccaccggc 60

gaaaucgucc ucacccaauc ccccggcacc cuaucccucu cccccggcga acgcgccacc 120

cuauccugcc gcgcauccca auccguagga uccuccuacc ucgccuggua ccaacaaaaa 180

cccggccaag caccccgccu ccucaucuac ggagccuucu cccgcgccaac cggcaucccu 240

gaccgcuucu ccggcucagg cucaggcacc gacuucaccc ucaccaucuc ucgccuagaa 300

cccgaagacu ucgccguaua cuauugccaa caauacggcu ccuccccuug gaccuucggc 360

caaggaaca aagucgaaau caaacgaacc gucgccgccc ccucagucuu caucuuccca 420

cccuccgacg aacaacucaa auccgguacc gccuccgucg ucugccuucu caacaacuuc 480

uacccccgag aagccaaagu acaauggaaa gucgacaacg cacuacaauc aggcaacucc 540

caagaauccg ucaccgaaca agauuccaaa gacucaaccu acucacucuc cuccacacuc 600

acccucucca aagccgacua cgaaaaacac aaagucuacg ccugcgaagu cacccaccaa 660

ggacucucca gccccgucac caaauccuuc aaccgcggcg aaugcuaa 708

<210> 687

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 687

auggaaacuc ccgcccaacu acucuuccuc cuccuccucu ggcuccccga caccaccggc 60

gaaaucgucc uuacccaguc ccccggcacc cucucacucu cccccggcga acgcgccacc 120

cuauccuguc gcgccuccca aucagucggc ucaucauacc ucgccuggua ccaacaaaaa 180

240

gaccgauucu ccggcuccgg cuccggcacu gacuucaccc ucaccauauc ccgccucgaa 300

cccgaagacu ucgcagucua cuacugccaa caauacggau cuucccccug gaccuucggc 360

caaggcacca aagucgaaau caaacgcacc gucgccgccc ccuccgucuu cauauuccca 420

cccucagacg aacaacucaa aucaggcacc gcauccgucg ucugccuccu caacaacuuc 480

uacccccgcg aagccaaagu ccaauggaaa gucgacaacg cccuccaauc aggcaacuca 540

caagaauccg ucacagaaca agacuccaaa gacucaaccu acucccucuc cucaacccuc 600

acacucucca aagccgacua cgaaaaacac aaagucuacg ccugcgaagu cacccaccaa 660

ggacuuuccu cacccgucac caaauccuuc aaccgcggcg aaugcuaa 708

<210> 688

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 688

auggaaacac cagcacaacu auuauuccua uuacuucuau ggcuaccaga cacaacagga 60

120

cucucaugcc gagcauccca auccgucgga ucaucauauc uagcauggua ccaacaaaaa 180

ccaggacaag cacccagacu acuaauauac ggagcauuuu caagagccac aggaauccca 240

gacagauuuu caggaucagg aucaggaaca gacuucacau uaacaauuuc acgauuagaa 300

360 cccgaagacu ucgcaguaua cuacugccaa caauacggau caucucccug

caaggcacaa aaguagaaau aaaacgaaca gucgcagcac caucaguauu cauauuccca 420

ccaucagacg aacaacuaaa aucaggaaca gcaucaguag uaugccuauu aaauaacuuc 480

uacccaagag aagcaaaagu ccaauggaaa guagauaacg cacuacaauc aggaaacucu 540

caagaaucag uaaccgaaca agacucaaaa gauucaaccu acucauuauc aucaacauua 600

acacuaucaa aagcagacua cgaaaaacac aaaguauacg caugcgaagu aacccaccaa660

ggccuaucau caccaguaac aaaaucauuc aacagaggag aaugcuga 708

<210> 689

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 689

auggaaaccc cugcccaauu acuauucuua uuauuacucu ggcuaccaga cacaacagga 60

120

180

ccgggacaag caccaagauu auuaauauau ggagcauucu cacgagcaac cggaauacca 240

gauagauucu caggaucagg aagcggcacc

ccagaagauu ucgcaguaua cuacugccaa caauauggau cuucaccaug gacauucgga 360

caaggaaca aaguugaaau aaaaagaaca guagcagcac caucaguauu cauauuccca 420

ccaucagacg aacaauuaaa aucaggaaca gccucuguag uaugccuauu aaacaacuuuu 480

uacccaagag aagcaaaagu ucauggaaa guagacaaug cacuacaauc aggcaacuca 540

caagaaucag uaacagaaca agacucuaaa gacucaacau auagccuauc aucaacacuc 600

acccuaucaa aagcagacua cgaaaaacac aaaguauacg caugugaagu aacacaccaa 660

ggacuaucau caccaguaac aaaaucauuc aacagaggag aaugcuaa 708

<210> 690

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 690

auggagaccc ccgcccagcu gcucuuccug cugcuccugu ggcugccggga caccacgggc 60

gagaucgugc ugacccagag ccccggcacc cucucccuga gcccggggga gcgcgccacg 120

cuguccugcc gggccagcca guccgucggc agcuccuacc ucgcguggua ccagcagaag 180

cccggggcagg cgccccgccu gcugaucuac ggcgccuuca gccgggccac cgggaucccc 240

gaccgcuucu ccggcagcgg cuccgggacc gacuucaccc ucacgaucag ccggcuggag 300

ccggaggacu ucgccgugua cuacugccag caguacggcu ccagccccug gaccuucggg 360

cagggcacca agguggagau caagcgcacc guggcggccc ccagcguguu caucuucccg 420

cccagcgacg agcagcugaa gagcgggacc gccucggucg ugugccuccu gaacaacuuc 480

uacccccggg aggccaaggu gcaguggaag gucgacaacg cgcugcagag cggcaacagc 540

caggagagcg ugacggagca ggacagcaag gacagcaccu acucgcucag cagcacccug 600

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu cacgcaccag 660

gggcucagcu cgcccgugac caagagcuuc aaccgcgggg agugcuga 708

<210> 691

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 691

auggagaccc ccgcccagcu ucucuuccuu cuguuguuau ggcugccuga cacaacuggc 60

gaaaucgugc uaacgcaaag cccagggacc cucucccugu cuccgggaga gagagcuaca 120

cuuucaugca gggcaaguca gagcgucggu uccucuuacc uggccuggua ucagcagaag 180

cccggccaag cgccucgguu gcucauuuac ggggcuuuuu cgcgcgccaac uggaauacca 240

gaucgauucu caggcagcgg uagugggacc gacuuuacac ugaccaucuc ccgucuggaa 300

cccgaggauu ucgcaguuua uuacugucag caguauggau cuagcccuug gacuuuuggc 360

cagggcacaa aaguggaaau uaagagaacc guggcggccc ccagcguguu caucuucccg 420

cccagcgacg agcagcugaa gagcgggacc gccucggucg ugugccuccu gaacaacuuc 480

uacccccggg aggccaaggu gcaguggaag gucgacaacg cgcugcagag cggcaacagc 540

caggagagcg ugacggagca ggacagcaag gacagcaccu acucgcucag cagcacccug 600

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu cacgcaccag 660

gggcucagcu cgcccgugac caagagcuuc aaccgcggcg agugcuga 708

<210> 692

<211> 708

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 692

auggagaccc ccgcccagcu gcuguuccug cugcugcugu ggcugcccga caccaccggc 60

gagaucgugc ugacccagag ccccggcacc cugagccuga gccccggcga gagagccacc 120

180

cccggccagg cccccagacu gcugaucuac ggcgccuuca gcagagccac cggcaucccc 240

gacagauuca gcggcagcgg cagcggcacc gacuucaccc ugaccaucag cagacuggag 300

cccgaggacu ucgccgugua cuacugccag caguacggca gcagccccug gaccuucggc 360

cagggcacca agguggagau caagagaacc guggcggccc ccagcguguu caucuucccg 420

cccagcgacg agcagcugaa gagcgggacc gccucggucg ugugccuccu gaacaacuuc 480

uacccccggg aggccaaggu gcaguggaag gucgacaacg cgcugcagag cggcaacagc 540

caggagagcg ugacggagca ggacagcaag gacagcaccu acucgcucag cagcacccug 600

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu cacgcaccag 660

gggcucagcu cgcccgugac caagagcuuc aaccgcggcg agugcuga 708

<210> 693

<211> 215

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab protein LC without signale peptide

<400> 693

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala

100 105 110

Ala Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser

115 120 125

Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu

130 135 140

Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser

145 150 155 160

Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu

165 170 175

Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val

180 185 190

Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys

195 200 205

Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 694

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 694

gagaucgugc ugacccagag ccccggcacc cucucccuga gcccggggga gcgcgccacg 60

cuguccugcc gggccagcca guccgucggc agcuccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgccu gcugaucuac ggcgccuuca gccggggccac cgggaucccc 180

gaccgcuucu ccggcagcgg cuccgggacc gacuucaccc ucacgaucag ccggcuggag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccagccccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 360

cccagcgacg agcagcugaa guccgggacg gccagcgugg ucugccuccu gaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag guggacaacg cgcugcaguc cggcaacagc 480

caggagagcg ucaccgagca ggacuccaag gacagcaccu acucccucag cuccacccug 540

acgcugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu gacccaccag 600

ggccucucca gccccgucac caaguccuuc aaccgcgggg agugcuga 648

<210> 695

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 695

gagaucgucc ucacccaguc ccccggcacc cucucccucu cccccggcga gcgcgccacc 60

cucuccugcc gcgccuccca guccgucggc uccuccuacc ucgccuggua ccagcagaag 120

cccggccagg ccccccgccu ccucaucuac ggcgccuucu cccgcgccac cggcaucccc 180

gaccgcuucu ccggcuccgg cuccggcacc gacuucaccc ucaccaucuc ccgccucgag 240

cccgaggacu ucgccgucua cuacugccag caguacggcu ccucccccug gaccuucggc 300

cagggcacca aggucgagau caagcgcacc gucgccgccc ccuccgucuu caucuucccc 360

cccuccgacg agcagcucaa guccggcacc gccuccgucg ucugccuccu caacaacuuc 420

uacccccgcg aggccaaggu ccaguggaag gucgacaacg cccuccaguc cggcaacucc 480

caggaguccg ucaccgagca ggacuccaag gacuccaccu acucccucuc cuccacccuc 540

acccucucca aggccgacua cgagaagcac aaggucuacg ccugcgaggu cacccaccag 600

ggccucuccu cccccgucac caaguccuuc aaccgcggcg agugcuga 648

<210> 696

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 696

gagaucgugc ugacccagag ccccggcaca cucucccuuu cuccugggga aagagccacu 60

cugucaugca gggcuaguca aagcgucgga uccucuuacu uggcauggua ucagcagaag 120

ccaggucagg ccccgcgguu acugauuuac ggcgcguucu cgcgcgcuac ggggauaccc 180

gaccgauuuu caggaagcgg cagugguacc gauuucacac uaacuaucuc ccgucucgag 240

ccugaagacu uugccguuua uuacugucaa caguaugggu cuagcccaug gaccuucgga 300

cagggcacaa aaguggagau uaagagaacc guagcagccc ccuccguguu uaucuucccu 360

ccaucagaug aacagcugaa aaguggcacu gcuagcgucg ugugccuucu gaacaauuuu 420

uaccccaggg aggcaaaggu ucauggaaa guggacaacg ccuugcaguc uggaaauucc 480

caggagucag ucacagaaca ggauagcaag gacaguaccu auucucucuc cagcacgcug 540

acucugucga aggcugauua cgagaaacac aagguguacg ccugugaagu aacccaucaa 600

gggcucucuu ccccuguuac aaaaucauuc aaccggggug agugcuga 648

<210> 697

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 697

gagaucgugc ugacccagag ccccggcacc cugagccuga gccccggcga gagagccacc 60

120

cccggccagg cccccagacu gcugaucuac ggcgccuuca gcagagccac cggcaucccc 180

gacagauuca gcggcagcgg cagcggcacc gacuucaccc ugaccaucag cagacuggag 240

cccgaggacu ucgccgugua cuacugccag caguacggca gcagccccug gaccuucggc 300

cagggcacca agguggagau caagagaacc guggccgccc ccagcguguu caucuucccc 360

cccagcgacg agcagcugaa gagcggcacc gccagcgugg ugugccugcu gaacaacuuc 420

uaccccagag aggccaaggu gcaguggaag guggacaacg cccugcagag cggcaacagc 480

caggagagcg ugaccgagca ggacagcaag gacagcaccu acagccugag cagcacccug 540

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu gacccaccag 600

ggccugagca gccccgugac caagagcuuc aacagaggcg agugcuga 648

<210> 698

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 698

gagaucgugc ugacccagag ccccggcaca cucagccugu cuccugggga aagagccacg 60

cuuagcugcc gggcuuccca aucugucgga agcuccuacc uggccuggua ucagcagaag 120

ccggggccagg cgccccgccu ccugauuuac ggggcuuucu cuagagccac cggaaucccu 180

gaccgguuua gcggcuccgg gagcggaaca gauuucaccc uuacaauuuc ucgccuggag 240

cccgaagacu uugccguuua uuacugucaa caguauggcu ccagcccuug gaccuucggc 300

caggggacaa aaguggagau caagagaacc guggcugccc ccucugucuu uauuuucccu 360

ccguccgaug aacagcucaa aagcggaacg gcuucugugg uuugccugcu gaacaauuuu 420

uacccccggg aggccaaggu gcaauggaaa gucgacaacg cgcuccaguc cggcaauagc 480

caggaguccg ugaccgaaca ggauucuaag gacagcacau auucccugag cucuacccuu 540

acacugucca aggccgauua cgagaaacac aagguuuacg cuugugaagu gacccaucaa 600

gggcucagcu cuccugucac gaaauccuuc aaccgcggag agugcuga 648

<210> 699

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 699

gaaauaguac uaacacaacacacaggaacc

cuaagcugca gagccucaca aucagucgga ucaucauacc uagcauggua ccaacaaaaa 120

ccaggacaag cccccagauu acuaaucuac ggagcauucu cacgagcaac aggaauccca 180

gacagauucu cagguuccgg aucaggaaca gacuucacac uaacaauuuc cagauuagaa 240

ccagaagacu ucgcaguaua cuacugccaa caauacggau caucaccaug gacauuugga 300

caaggaacca aaguagaaau caaaagaaca guagcagccc caucaguauu uauauuccca 360

ccaucagacg aacaacuaaa aucaggcacc gcaucaguag uaugucuauu aaacaacuuc 420

uacccaagag aagcaaaagu acaauggaaa guagacaacg cacuacaauc aggaaacucc 480

caagaaucag ucacagaaca agacucaaaa gacucaacau acucacuauc aucaacacua 540

accuuaucaa aagcagacua cgaaaaacac aaaguauacg caugcgaagu aacacaccaa 600

ggauuaucau ccccaguaac aaaaucauuc aacagaggag aaugcuga 648

<210> 700

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 700

gagaucgugc ugacccagag ccccggcacu cucucccuga guccaggggga aagggccacc 60

uugagcugcc gggcauccca aagugucggu agcuccuacc uggccuggua ucagcagaag 120

ccggggccagg cgccccgccu ccugauuuac ggggccuuca gcagggcaac gggcauccca 180

gaccgguuuu ccgguagugg gagcggcacu gauuucaccu ugaccauuuc ccgccuggag 240

cccgaagacu uugccgugua uuacugucaa caguauggca gcaguccaug gacuuucggg 300

caggguacca aaguagagau caagaggacg guggcagccc ccuccgucuu uauuuuccca 360

ccgagcgaug aacagcucaa auccggcacu gcgagugugg ugugccugcu gaacaauuuuu 420

uacccccggg aggccaaggu ccaauggaaa guggacaacg cacuccagag cggcaauucc 480

caggagagcg uaaccgaaca ggauaguaag gacuccacuu auagccugag uuccaccuug 540

acccugagca aggccgauua cgagaaacac aagguguacg ccugugaagu cacgcaucaa 600

gggcucagcu ccccagugac uaaaaguuuc aaccgcggug agugcuga 648

<210> 701

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 701

gaaaucgucc uaacccaauc ccccggcaca cuaucucucu ccccaggcga acgcgcaaca 60

cuauccugcc gcgccucaca aucagucggc uccuccuacc uagccuggua ccaacaaaaa 120

cccggccaag caccccgacu ccucaucuac ggcgccuucu cccgcgccaac aggcauccca 180

gaccgcuucu ccggcuccgg cuccggcaca gacuucacac ucaccaucuc acgccucgaa 240

cccgaagacu ucgccgucua cuacugccaa caauacggau caucccccug gaccuucgga 300

caaggcacca aagucgaaau caaacgcacc gucgccgccc ccuccgucuu caucuuccca 360

cccucagacg aacaacuaaa auccggcacc gccucaguag ucugccuacu aaacaacuuc 420

uacccccgcg aagccaaagu ccaauggaaa gucgacaacg cccuccaauc cggcaacuca 480

caagaaucag ucaccgaaca agacucaaaa gacuccaccu acucccuauc cuccacccuc 540

acccuaucaa aagccgacua cgaaaaacac aaaguauacg cgugcgaagu aacccaccag 600

ggccuauccu cacccgucac aaaauccuuc aaccgcggcg aaugcuga 648

<210> 702

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 702

gaaaucguac uaacccaauc acccggcacc cucucccucu cccccggcga acgagccacc 60

cuaucaugcc gcgccuccca auccguaggc uccuccuacc uagccuggua ccaacaaaaa 120

ccaggccaag caccccgacu acucaucuac ggagccuucu cccgcgccac cggcaucccc 180

gaccgcuucu ccggcuccgg cuccggcacc gacuucaccc ucaccaucuc ccgccucgaa 240

cccgaagacu ucgccgucua cuacugccaa caauacggau caucccccug gaccuucggc 300

caaggcacca aagucgaaau caaacgcacc gucgccgccc ccuccgucuu cauauuccca 360

cccuccgacg aacaacuaaa aucaggaacc gccuccgucg ucugccuacu aaacaacuuc 420

uacccccgcg aagccaaagu acaauggaaa gucgacaacg cccuccaauc cggcaacucc 480

caagaauccg uaaccgaaca agacuccaaa gacucaaccu auucccucuc cuccacacuc 540

acacuaucca aagccgacua cgaaaaacac aaagucuacg ccugcgaagu aacccaccaa 600

ggccucucau cacccgucac caaauccuuc aaccgcggcg aaugcuaa 648

<210> 703

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 703

gaaaucgucc ucacccaauc ccccggcacc cuaucacucu cacccggcga acgcgcaacc 60

cucuccugcc gagccuccca auccgucggc uccucauacc ucgccuggua ccaacaaaaa 120

cccggccaag caccccgucu ccucaucuac ggcgccuucu cacgcgccac cggcaucccc 180

gaccgcuucu ccggcucugg cucaggcacc gacuucaccc ucaccaucuc ccgccucgaa 240

cccgaagacu ucgccgucua cuacugccaa caauacggau caucccccug gaccuucggc 300

caaggcacaa aagucgaaau caaacgcacc gucgccgccc cauccgucuu caucuuccca 360

cccuccgacg aacaacucaa auccggcacc gccuccgucg ucugccuccu caacaacuuc 420

uacccccgcg aagccaaagu ccaauggaaa gucgacaacg cccuccaauc cggcaacucc 480

caagaauccg ucaccgaaca agacuccaaa gacuccaccu acucacucuc cuccacccuu 540

acccucucca aagccgacua cgaaaaacac aaagucuacg ccugcgaagu cacccaccaa 600

ggccucuccu cccccgucac caaauccuuc aaccgcggcg aaugcuaa 648

<210> 704

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 704

60

uuauccugca gagcaucaca aucuguagga ucuucauacc uagcauggua ccaacaaaaa 120

ccaggacaag caccaagauu acuaauauau ggagcauuuu ccagagcaac aggcauacca 180

gacagauucu caggaucagg aucaggaacc gacuucacac uaacaauuuc aagacuagaa 240

ccagaagacu ucgcaguaua cuacugccaa caauacggau caucaccaug gacauucgga 300

caaggaacaa aaguagaaau aaaaagaaca gucgcagcac caucaguauu cauauuccca 360

ccaucagacg aacaauuaaa auccggaaca gcaucaguag uaugccuacu aaauaacuuc 420

uacccaagag aagcaaaagu acaauggaaa guagacaacg cauuacaauc aggaaacucc 480

caagaaucag uaacagaaca agacucuaaa gacucaacau acucccuauc aucaacacua 540

acacuaucaa aagcagacua ugaaaaacac aaaguauacg caugcgaagu cacacaucaa 600

ggacuaucau caccaguaac aaaaucauuu aacagaggag aaugcuaa 648

<210> 705

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 705

60

uuaucaugca gagcaucaca aucaguagga ucaucauacc uagccuggua ccaacaaaaa 120

cggagacaag ccccaagauu acuauauac ggagcauucu caagagcaac aggaauacca 180

gacagauucu cagguucugg cucaggcaca gacuucacac ucacaauuuc aagacuagaa 240

ccagaagacu ucgccguaua cuacugccaa caauacggau ccucaccaug gacauucgga 300

caucaguauu cauauuccca 360

ccaucagacg aacaauuaaa aucaggaaca gcaucaguag uaugccuauu aaacaacuuc 420

uacccacgag aagccaaagu ccaauggaaa guagauaacg cauuacaauc agguaacuca 480

caagaaucag uaacagaaca agacuccaaa gacucaacau acagccuauc aucaacacua 540

600

ggacuaucau caccaguaac aaaaucauuc aauagaggag aaugcuaa 648

<210> 706

<211> 215

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 706

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala

100 105 110

Ala Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser

115 120 125

Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu

130 135 140

Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser

145 150 155 160

Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu

165 170 175

Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val

180 185 190

Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys

195 200 205

Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 707

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 707

gagaucgugc ugacccagag ccccggcacc cucucccuga gcccggggga gcgcgccacg 60

cuguccugcc gggccagcca guccgucggc agcuccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgccu gcugaucuac ggcgccuuca gccggggccac cgggaucccc 180

gaccgcuucu ccggcagcgg cuccgggacc gacuucaccc ucacgaucag ccggcuggag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccagccccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc guggcggccc ccagcguguu caucuucccg 360

cccagcgacg agcagcugaa gagcgggacc gccucggucg ugugccuccu gaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag gucgacaacg cgcugcagag cggcaacagc 480

caggagagcg ugacggagca ggacagcaag gacagcaccu acucgcucag cagcacccug 540

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu cacgcaccag 600

gggcucagcu cgcccgugac caagagcuuc aaccgcgggg agugcuga 648

<210> 708

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 708

gagaucgugc ugacccagag ccccggcaca cucucccuuu cuccugggga aagagccacu 60

cugucaugca gggcuaguca aagcgucgga uccucuuacu uggcauggua ucagcagaag 120

ccaggucagg ccccgcgguu acugauuuac ggcgcguucu cgcgcgcuac ggggauaccc 180

gaccgauuuu caggaagcgg cagugguacc gauuucacac uaacuaucuc ccgucucgag 240

ccugaagacu uugccguuua uuacugucaa caguaugggu cuagcccaug gaccuucgga 300

cagggcacaa aaguggagau uaagagaacc guggcggccc ccagcguguu caucuucccg 360

cccagcgacg agcagcugaa gagcgggacc gccucggucg ugugccuccu gaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag gucgacaacg cgcugcagag cggcaacagc 480

caggagagcg ugacggagca ggacagcaag gacagcaccu acucgcucag cagcacccug 540

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu cacgcaccag 600

gggcucagcu cgcccgugac caagagcuuc aaccgcggug agugcuga 648

<210> 709

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 709

gagaucgugc ugacccagag ccccggcacc cugagccuga gccccggcga gagagccacc 60

120

cccggccagg cccccagacu gcugaucuac ggcgccuuca gcagagccac cggcaucccc 180

gacagauuca gcggcagcgg cagcggcacc gacuucaccc ugaccaucag cagacuggag 240

cccgaggacu ucgccgugua cuacugccag caguacggca gcagccccug gaccuucggc 300

cagggcacca agguggagau caagagaacc guggcggccc ccagcguguu caucuucccg 360

cccagcgacg agcagcugaa gagcgggacc gccucggucg ugugccuccu gaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag gucgacaacg cgcugcagag cggcaacagc 480

caggagagcg ugacggagca ggacagcaag gacagcaccu acucgcucag cagcacccug 540

acccugagca aggccgacua cgagaagcac aagguguacg ccugcgaggu cacgcaccag 600

gggcucagcu cgcccgugac caagagcuuc aaccgcggcg agugcuga 648

<210> 710

<211> 2791

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt1 IRES construct

<400> 710

auggagcugg gccucagcug gaucuuccug cuggccaucc ucaagggggu gcagugccag 60

120

ugcgccgccu ccggcuucac cuucagcucc uacaccaugc acuggguccg ccaggcgccg 180

gggaagggcc uggagugggu gacguucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacuccguga aggggcgguu caccaucagc cgcgacaacu ccaagaacac ccucuaccug 300

cagaugaaca gccugcgggc cgaggacacc gccaucuacu acugcgcccg cacgggcugg 360

cucgggcccu ucgacuacug gggccagggg acccugguca ccguguccag cgcguccacc 420

aagggcccca gcguguuccc ccuggccccg uccagcaagu ccacgagcgg cgggaccgcc 480

gccuccggcu gccuggucaa gacuacuuc cccgagcccg ugaccguguc cuggaacagc 540

ggggcgcuga ccagcggcgu ccacacguuc cccgccgugc uccaguccag cggccuguac 600

ucccuagcu ccguggucac cgugccgagc uccagccucg ggacccagac cuacaucugc 660

aacgugaacc acaagcccuc caacacgaag gucgacaagc ggguggagcc caagagcugc 720

gacaagaccc acacgugccc gcccugcccc gcccccgagc ugcugggcgg gcccuccgug 780

uuccucuucc cgcccaagcc caaggacacc cugaugauca gccgcacccc cgaggugacc 840

ugcgucgugg ucgacguguc ccacgaggac ccggagguca aguucaacug guacguggac 900

ggcguggagg uccacaacgc caagaccaag ccccgggagg agcaguacaa cagcaccuac 960

cgcguggugu ccguccugac ggugcuccac caggacuggc ugaacgggaa ggaguacaag 1020

ugcaagguga gcaacaaggc ccugcccgcg cccaucgaga agaccaucuc caaggccaag 1080

ggccagccgc gggagcccca ggucuacacc cucccgccca gccgcgacga gcugaccaag 1140

aaccaggugu cccugacgug ccucgugaag ggcuucuacc ccagcgacau cgccgucgag 1200

ugggagagca acgggcagcc cgagaacaac uacaagacca cgcccccggu gcuggacucc 1260

gacggcagcu ucuuccugua cuccaagcuc accguggaca agagccggug gcagcagggg 1320

1380

cugagccucu cccccggcaa gugaccaugc auuugaaagc cggggggggg agauccggau 1440

ugccagucug cucgauaucg caggcugggu ccgugacuac ccacuccccc uuuaauuccg 1500

ccccucuccc uccccccccc cuaacguuac uggccgaagc cgcuuggaau aaggccggug 1560

ugcguuuguc uauauguuau uuuccaccau auugccgucu uuuggcaaug ugagggccg 1620

gaaaccggc ccugucuucu ugacgagcau uccuaggggu cuuuccccuc ucgccaaagg 1680

aaugcaaggu cuguugaaug ucgugaagga agcaguuccu cuggaagcuu cuugaagaca 1740

aacaacgucu guagcgaccc uuugcaggca gcggaacccc ccaccuggcg acaggugccu 1800

cugcggccaa aagccacgug uauaagauac accugcaaag gcggcacaac cccagugcca 1860

cguugugagu uggauaguug uggaaagagu caaauggcuc uccucaagcg uauucaacaa 1920

ggggcugaag gaugcccaga agguacccca uuguauggga ucugaucugg ggccucggug 1980

cacaugcuuu acguguguuu agucgagguu aaaaaacguc uaggcccccc gaaccacgggg 2040

gacgugguuu uccuuugaaa aacacgauga uaauagaucu accauggaga cccccgccca 2100

gcugcucuuc cugcugcucc uguggcugcc ggacaccacg ggcgagaucg ugcugaccca 2160

gagccccggc acccucuccc ugagcccggg ggagcgcgcc acgcuguccu gccgggccag 2220

ccaguccguc ggcagcuccu accucgcgug guaccagcag aagcccggggc aggcgccccg 2280

ccugcugauc uacggcgccu ucagccgggc caccgggauc cccgaccgcu ucuccggcag 2340

cggcuccggg accgacuuca cccucacgau cagccggcug gagccgggagg acuucgccgu 2400

guacuacugc cagcaguacg gcuccagccc cuggaccuuc gggcagggca ccaaggugga 2460

gaucaagcgc accgucgccg cccccuccgu guucaucuuc ccgcccagcg acgagcagcu 2520

2580

ggugcagugg aagguggaca acgcgcugca guccggcaac agccaggaga gcgucaccga 2640

gcaggacucc aaggacagca ccuacucccu cagcuccacc cugacgcuga gcaaggccga 2700

cuacgagaag cacaaggugu acgccugcga ggugacccac cagggccucu ccagccccgu 2760

caccaagucc uucaaccgcg gggagugcug a 2791

<210> 711

<211> 2791

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt3 IRES construct

<400> 711

auggagcugg gccucagcug gaucuuccuu cuggccauuu ugaagggggu gcagugccaa 60

guccaguuag uugaauccgg agguggcgug guacagcccg ggagaucucu gaggcuauca 120

ugugcugcaa guggauuuac cuucagcucc uacacaaugc acugggugcg gcaggccccu 180

ggcaaagguc ucgagugggu cacuuuuaua ucuuaugacg ggaacaauaa guacuaugcg 240

gauucgguga aaggacgcuu cacgaucuca cgagacaaca gcaagaauac ccuguaccuu 300

caaaugaaca gucugcgugc ugaagauaca gccauuuauu acugcgcaag aacuggcugg 360

uugggcccau uugacuauug ggggcaggga acccucguua caguguccuc ugccagcacc 420

aaagguccgu ccgucuuccc ccuggcuccu ucaaguaaga gcacuucugg cgggacagca 480

gcccugggau gucucgugaa ggauuacuuu cgagcccg uaaccguuuc cuggaacuca 540

ggcgcuuuaa cgagcggugu gcauacuuuc ccugccgucc ugcagaguuc ugggcuuuac 600

uccuugagcu cgguggugac cgucccaucu uccucacugg gaacacagac uuauaucugc 660

aauguuaauc acaaacccag uaacaccaag guggacaaaa ggguagaacc uaaagcugu 720

gauaaaacac auaccugccc accguguccc gcgccugagc uacucggcgg cccauccgug 780

uuucuguuuc ccccuaagcc aaaggacacg cuuaugauuu cucggacucc cgaggucaca 840

ugcgugguug uggaugucag ccacgaagac ccggagguga aauuuaauug guacguagau 900

gggguugaag ugcauaacgc aaagaccaaa ccucgcgagg agcaauauaa uucaacuuac 960

agagucguga guguccugac aguguugcac caggacuggc ucaacggaaa ggaauauuaaa 1020

uguaagguuu ccaauaaagc ccugcccgcu ccaaucgaga agaccauaag caaggccaaa 1080

ggucagccua gggaacccca gguguacacg uuaccacccu cucgggauga gcugaccaag 1140

aaccaaguau cacucacaug ccuugucaaa ggcuucuauc cuagugacau cgcaguggaa 1200

ugggagagca augggcagcc agagaacaac uacaagacua ccccgcccgu ucuggacucc 1260

1320

1380

cucucucuga gcccugguaa augaccaugc auuugaaagc cggggggggg agauccggau 1440

ugccagucug cucgauaucg caggcugggu ccgugacuac ccacuccccc uuuaauuccg 1500

ccccucuccc uccccccccc cuaacguuac uggccgaagc cgcuuggaau aaggccggug 1560

ugcguuuguc uauauguuau uuuccaccau auugccgucu uuuggcaaug ugagggccg 1620

gaaaccggc ccugucuucu ugacgagcau uccuaggggu cuuuccccuc ucgccaaagg 1680

aaugcaaggu cuguugaaug ucgugaagga agcaguuccu cuggaagcuu cuugaagaca 1740

aacaacgucu guagcgaccc uuugcaggca gcggaacccc ccaccuggcg acaggugccu 1800

cugcggccaa aagccacgug uauaagauac accugcaaag gcggcacaac cccagugcca 1860

cguugugagu uggauaguug uggaaagagu caaauggcuc uccucaagcg uauucaacaa 1920

ggggcugaag gaugcccaga agguacccca uuguauggga ucugaucugg ggccucggug 1980

cacaugcuuu acguguguuu agucgagguu aaaaaacguc uaggcccccc gaaccacgggg 2040

gacgugguuu uccuuugaaa aacacgauga uaauagaucu accauggaga cccccgccca 2100

2160

aagcccaggg acccucuccc ugucuccggg agagagagcu acacuuucau gcagggcaag 2220

ucagagcguc gguuccucuu accuggccug guaucagcag aagcccggcc aagcgccucg 2280

guugcucauu uacggggcuu uuucgcgcgc

cgguaguggg accgacuuua cacugaccau cucccgucug gaacccgagg auuucgcagu 2400

uuauuacugu cagcaguaug gaucuagccc uuggacuuuu ggccagggca caaaagugga 2460

aauuaagaga accguagccg cuccauccgu guucaucuuu cccccuucag acgagcaacu 2520

caaaaguggg acggcaagcg ucgugugcuu acugaacaau uucuacccaa gggaggccaa 2580

2640

gcaagacagc aaggauagua ccuauucuuu guccagcaca cugacucuau cgaaggccga 2700

cuacgaaaaa cacaaggugu acgcguguga gguaacccau cagggucucu cuuccccggu 2760

uacaaaauca uuuaaccggg gcgagugcug a 2791

<210> 712

<211> 2791

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt4 IRES construct

<400> 712

auggagcugg gccugagcug gaucuuccug cuggccaucc ugaagggcgu gcagugccag 60

gugcagcugg uggagagcgg cggcggcgug gugcagcccg gcagaagccu gagacugagc 120

ugcgccgcca gcggcuucac cuucagcagc uacaccaugc acugggugag acaggccccc 180

ggcaagggcc uggagugggu gaccuucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacagcguga agggcagauu caccaucagc agagacaaca gcaagaacac ccuguaccug 300

cagaugaaca gccugagagc cgaggacacc gccaucuacu acugcgccag aaccggcugg 360

cugggccccu ucgacuacug gggccagggc acccugguga cggugagcag cgccagcacc 420

aagggcccca gcguguuccc ccuggccccc agcagcaaga gcaccagcgg cggcaccgcc 480

gcccugggcu gccuggugaa gacuacuuc cccgagcccg ugaccgugag cuggaacagc 540

ggcgcccuga ccagcggcgu gcacaccuuc cccgccgugc ugcagagcag cggccuguac 600

agccugagca gcguggugac cgugcccagc agcagccugg gcacccagac cuacaucugc 660

aacgugaacc acaagcccag caacaccaag guggacaaga gaguggagcc caagagcugc 720

gacaagaccc acaccugccc ccccugcccc gcccccgagc ugcugggcgg ccccagcgug 780

uuccuguucc cccccaagcc caaggacacc cugaugauca gcagaacccc cgaggugacc 840

ugcguggugg uggacgugag cccgaggac cccgagguga aguucaacug guacguggac 900

ggcguggagg ugcacaacgc caagaccaag cccagagagg agcaguacaa cagcaccuac 960

agagugguga gcgugcugac cgugcugcac caggacuggc ugaacggcaa ggaguacaag 1020

ugcaagguga gcaacaaggc ccugcccgcc cccaucgaga agaccaucag caaggccaag 1080

ggccagccca gagagcccca gguguacacc cugcccccca gcagagacga gcugaccaag 1140

aaccagguga gccugaccug ccuggugaag ggcuucuacc ccagcgacau cgccguggag 1200

ugggagagca acggccagcc cgagaacaac uacaagacca ccccccccgu gcuggacagc 1260

gacggcagcu ucuuccugua cagcaagcug accguggaca agagcagaug gcagcagggc 1320

1380

cugagccuga gccccggcaa gugaccaugc auuugaaagc cggggggggg agauccggau 1440

ugccagucug cucgauaucg caggcugggu ccgugacuac ccacuccccc uuuaauuccg 1500

ccccucuccc uccccccccc cuaacguuac uggccgaagc cgcuuggaau aaggccggug 1560

ugcguuuguc uauauguuau uuuccaccau auugccgucu uuuggcaaug ugagggccg 1620

gaaaccggc ccugucuucu ugacgagcau uccuaggggu cuuuccccuc ucgccaaagg 1680

aaugcaaggu cuguugaaug ucgugaagga agcaguuccu cuggaagcuu cuugaagaca 1740

aacaacgucu guagcgaccc uuugcaggca gcggaacccc ccaccuggcg acaggugccu 1800

cugcggccaa aagccacgug uauaagauac accugcaaag gcggcacaac cccagugcca 1860

cguugugagu uggauaguug uggaaagagu caaauggcuc uccucaagcg uauucaacaa 1920

ggggcugaag gaugcccaga agguacccca uuguauggga ucugaucugg ggccucggug 1980

cacaugcuuu acguguguuu agucgagguu aaaaaacguc uaggcccccc gaaccacgggg 2040

gacgugguuu uccuuugaaa aacacgauga uaauagaucu accauggaga cccccgccca 2100

gcugcuguuc cugcugcugc uguggcugcc cgacaccacc ggcgagaucg ugcugaccca 2160

gagccccggc acccugagcc ugagccccgg cgagagagcc acccugagcu gcagagccag 2220

ccagagcgug ggcagcagcu accuggccug guaccagcag aagcccggcc aggcccccag 2280

acugcugauc uacggcgccu ucagcagagc caccggcauc cccgacagau ucagcggcag 2340

cggcagcggc accgacuuca cccugaccau cagcagacug gagcccgagg acuucgccgu 2400

guacuacugc cagcaguacg gcagcagccc cuggaccuuc ggccagggca ccaaggugga 2460

gaucaagaga accguggccg cccccagcgu guucaucuuc ccccccagcg acgagcagcu 2520

gaagagcggc accgccagcg uggugugccu gcugaacaac uucuacccca gagaggccaa 2580

ggugcagugg aagguggaca acgcccugca gagcggcaac agccaggaga gcgugaccga 2640

gcaggacagc aaggacagca ccuacagccu gagcagcacc cugacccuga gcaaggccga 2700

cuacgagaag cacaaggugu acgccugcga ggugacccac cagggccuga gcagccccgu 2760

gaccaagagc uucaacagag gcgagugcug a 2791

<210> 713

<211> 2175

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt1 F2A construct

<400> 713

auggagcugg gccucagcug gaucuuccug cuggccaucc ucaagggggu gcagugccag 60

120

ugcgccgccu ccggcuucac cuucagcucc uacaccaugc acuggguccg ccaggcgccg 180

gggaagggcc uggagugggu gacguucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacuccguga aggggcgguu caccaucagc cgcgacaacu ccaagaacac ccucuaccug 300

cagaugaaca gccugcgggc cgaggacacc gccaucuacu acugcgcccg cacgggcugg 360

cucgggcccu ucgacuacug gggccagggg acccugguca ccguguccag cgcguccacc 420

aagggcccca gcguguuccc ccuggccccg uccagcaagu ccacgagcgg cgggaccgcc 480

gccuccggcu gccuggucaa gacuacuuc cccgagcccg ugaccguguc cuggaacagc 540

ggggcgcuga ccagcggcgu ccacacguuc cccgccgugc uccaguccag cggccuguac 600

ucccuagcu ccguggucac cgugccgagc uccagccucg ggacccagac cuacaucugc 660

aacgugaacc acaagcccuc caacacgaag gucgacaagc ggguggagcc caagagcugc 720

gacaagaccc acacgugccc gcccugcccc gcccccgagc ugcugggcgg gcccuccgug 780

uuccucuucc cgcccaagcc caaggacacc cugaugauca gccgcacccc cgaggugacc 840

ugcgucgugg ucgacguguc ccacgaggac ccggagguca aguucaacug guacguggac 900

ggcguggagg uccacaacgc caagaccaag ccccgggagg agcaguacaa cagcaccuac 960

cgcguggugu ccguccugac ggugcuccac caggacuggc ugaacgggaa ggaguacaag 1020

ugcaagguga gcaacaaggc ccugcccgcg cccaucgaga agaccaucuc caaggccaag 1080

ggccagccgc gggagcccca ggucuacacc cucccgccca gccgcgacga gcugaccaag 1140

aaccaggugu cccugacgug ccucgugaag ggcuucuacc ccagcgacau cgccgucgag 1200

ugggagagca acgggcagcc cgagaacaac uacaagacca cgcccccggu gcuggacucc 1260

gacggcagcu ucuuccugua cuccaagcuc accguggaca agagccggug gcagcagggg 1320

1380

cugagccucu cccccggcaa ggugaagcag acacucaauu ucgaccuucu gaaguuggcu 1440

ggagauguug agucuaaccc aggccccaug gagacccccg cccagcugcu cuuccugcug 1500

cuccuguggc ugccggacac cacgggcgag aucgugcuga cccagagccc cggcacccuc 1560

ucccugagcc cgggggagcg cgccacgcug uccugccggg ccagccaguc cgucggcagc 1620

uccuaccucg cgugguacca gcagaagccc gggcaggcgc cccgccugcu gaucuacggc 1680

gccuucagcc gggccaccgg gaucccgac cgcuucuccg gcagcggcuc cgggaccgac 1740

uucacccuca cgaucagccg gcuggagccg gaggacuucg ccguguacua cugccagcag 1800

uacggcucca gccccuggac cuucgggcag ggcaccaagg uggagaucaa gcgcaccguc 1860

gccgcccccu ccguguucau cuucccgccc agcgacgagc agcugaaguc cgggacggcc 1920

agcguggucu gccuccugaa caacuucuac ccccgggagg ccaaggugca guggaaggug 1980

gacaacgcgc ugcaguccgg caacagccag

agcaccuacu cccucagcuc cacccugacg cugagcaagg ccgacuacga gaagcacaag 2100

2160

cgcggggagu gcuga 2175

<210> 714

<211> 2175

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt3 F2A construct

<400> 714

auggagcugg gccucagcug gaucuuccuu cuggccauuu ugaagggggu gcagugccaa 60

guccaguuag uugaauccgg agguggcgug guacagcccg ggagaucucu gaggcuauca 120

ugugcugcaa guggauuuac cuucagcucc uacacaaugc acugggugcg gcaggccccu 180

ggcaaagguc ucgagugggu cacuuuuaua ucuuaugacg ggaacaauaa guacuaugcg 240

gauucgguga aaggacgcuu cacgaucuca cgagacaaca gcaagaauac ccuguaccuu 300

caaaugaaca gucugcgugc ugaagauaca gccauuuauu acugcgcaag aacuggcugg 360

uugggcccau uugacuauug ggggcaggga acccucguua caguguccuc ugccagcacc 420

aaagguccgu ccgucuuccc ccuggcuccu ucaaguaaga gcacuucugg cgggacagca 480

gcccugggau gucucgugaa ggauuacuuu cgagcccg uaaccguuuc cuggaacuca 540

ggcgcuuuaa cgagcggugu gcauacuuuc ccugccgucc ugcagaguuc ugggcuuuac 600

uccuugagcu cgguggugac cgucccaucu uccucacugg gaacacagac uuauaucugc 660

aauguuaauc acaaacccag uaacaccaag guggacaaaa ggguagaacc uaaagcugu 720

gauaaaacac auaccugccc accguguccc gcgccugagc uacucggcgg cccauccgug 780

uuucuguuuc ccccuaagcc aaaggacacg cuuaugauuu cucggacucc cgaggucaca 840

ugcgugguug uggaugucag ccacgaagac ccggagguga aauuuaauug guacguagau 900

gggguugaag ugcauaacgc aaagaccaaa ccucgcgagg agcaauauaa uucaacuuac 960

agagucguga guguccugac aguguugcac caggacuggc ucaacggaaa ggaauauuaaa 1020

uguaagguuu ccaauaaagc ccugcccgcu ccaaucgaga agaccauaag caaggccaaa 1080

ggucagccua gggaacccca gguguacacg uuaccacccu cucgggauga gcugaccaag 1140

aaccaaguau cacucacaug ccuugucaaa ggcuucuauc cuagugacau cgcaguggaa 1200

ugggagagca augggcagcc agagaacaac uacaagacua ccccgcccgu ucuggacucc 1260

1320

1380

cucucucuga gcccugguaa agugaagcag acacucaauu ucgaccuucu gaaguuggcu 1440

ggagauguug agucuaaccc aggccccaug gagacccccg cccagcuucu cuuccuucug 1500

uuguuauggc ugccugacac aacuggcgaa aucgugcuaa cgcaaagccc agggacccuc 1560

ucccugucuc cgggagagag agcuacacuu ucaugcaggg caagucucag cgucgguucc 1620

ucuuaccugg ccugguauca gcagaagccc ggccaagcgc cucgguugcu cauuuuacggg 1680

gcuuuuucgc gcgccacugg aauaccagau cgauucucag gcagcgguag ugggaccgac 1740

uuuuuauua cugucagcag 1800

uuuuggccag ggcacaaaag uggaaauuaa gagaaccgua 1860

gccgcuccau ccguguucau cuuucccccu ucagacgagc aacucaaaag ugggacggca 1920

agcgucgugu gcuuacugaa caauuucuac ccaagggagg ccaagguuca guggaaagug 1980

2040

aguaccuauu cuuuguccag cacacugacu cuaucgaagg ccgacuacga aaaacacaag 2100

guguacgcgu gugagguaac ccaucagggu cucucuuccc cgguuacaaa aucauuuaac 2160

cggggcgagu gcuga 2175

<210> 715

<211> 2175

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt4 F2A construct

<400> 715

auggagcugg gccugagcug gaucuuccug cuggccaucc ugaagggcgu gcagugccag 60

gugcagcugg uggagagcgg cggcggcgug gugcagcccg gcagaagccu gagacugagc 120

ugcgccgcca gcggcuucac cuucagcagc uacaccaugc acugggugag acaggccccc 180

ggcaagggcc uggagugggu gaccuucauc agcuacgacg gcaacaacaa guacuacgcc 240

gacagcguga agggcagauu caccaucagc agagacaaca gcaagaacac ccuguaccug 300

cagaugaaca gccugagagc cgaggacacc gccaucuacu acugcgccag aaccggcugg 360

cugggccccu ucgacuacug gggccagggc acccugguga cggugagcag cgccagcacc 420

aagggcccca gcguguuccc ccuggccccc agcagcaaga gcaccagcgg cggcaccgcc 480

gcccugggcu gccuggugaa gacuacuuc cccgagcccg ugaccgugag cuggaacagc 540

ggcgcccuga ccagcggcgu gcacaccuuc cccgccgugc ugcagagcag cggccuguac 600

agccugagca gcguggugac cgugcccagc agcagccugg gcacccagac cuacaucugc 660

aacgugaacc acaagcccag caacaccaag guggacaaga gaguggagcc caagagcugc 720

gacaagaccc acaccugccc ccccugcccc gcccccgagc ugcugggcgg ccccagcgug 780

uuccuguucc cccccaagcc caaggacacc cugaugauca gcagaacccc cgaggugacc 840

ugcguggugg uggacgugag cccgaggac cccgagguga aguucaacug guacguggac 900

ggcguggagg ugcacaacgc caagaccaag cccagagagg agcaguacaa cagcaccuac 960

agagugguga gcgugcugac cgugcugcac caggacuggc ugaacggcaa ggaguacaag 1020

ugcaagguga gcaacaaggc ccugcccgcc cccaucgaga agaccaucag caaggccaag 1080

ggccagccca gagagcccca gguguacacc cugcccccca gcagagacga gcugaccaag 1140

aaccagguga gccugaccug ccuggugaag ggcuucuacc ccagcgacau cgccguggag 1200

ugggagagca acggccagcc cgagaacaac uacaagacca ccccccccgu gcuggacagc 1260

gacggcagcu ucuuccugua cagcaagcug accguggaca agagcagaug gcagcagggc 1320

1380

cugagccuga gccccggcaa ggugaagcag acacucaauu ucgaccuucu gaaguuggcu 1440

ggagauguug agucuaaccc aggccccaug gagacccccg cccagcugcu guuccugcug 1500

1560

1620

agcuaccgg ccugguacca gcagaagccc ggccaggccc ccagacugcu gaucuacggc 1680

gccuucagca gagccaccgg cauccccgac agauucagcg gcagcggcag cggcaccgac 1740

uucacccuga ccaucagcag acuggagccc gaggacuucg ccguguacua cugccagcag 1800

uacggcagca gccccuggac cuucggccag ggcaccaagg uggagaucaa gagaaccgug 1860

gccgccccca gcguguucau cuuccccccc agcgacgagc agcugaagag cggcaccgcc 1920

agcguggugu gccugcugaa caacuucuac cccagagagg ccaaggugca guggaaggug 1980

2040

agcaccuaca gccugagcag cacccugacc cugagcaagg ccgacuacga gaagcacaag 2100

2160

agaggcgagu gcuga 2175

<210> 716

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 716

augugccacc agcagcuggu gaucagcugg uucagccugg uguuccuggc cagcccccug 60

guggccaucu gggagcugaa gaaggacgug uacguggugg agcuggacug guaccccgac 120

gcccccggcg agaugguggu gcugaccugc gacacccccg aggaggacgg caucaccugg 180

acccuggacc agagcagcga ggugcugggc agcggcaaga cccugaccau ccaggugaag 240

gaguucggcg acgccggcca guacaccugc cacaagggcg gcgaggugcu gagccacagc 300

cugcugcugc ugcacaagaa ggaggacggc aucuggagca ccgacauccu gaaggaccag 360

aaggagccca agaacaagac cuuccugaga ugcgaggcca agaacuacag cggcagauuc 420

accugcuggu ggcugaccac caucagcacc gaccugaccu ucagcgugaa gagcagcaga 480

ggcagcagcg acccccaggg cgugaccugc ggcgccgcca cccugagcgc cgagagagug 540

agaggcgaca acaaggagua cgaguacagc guggagugcc aggaggacag cgccugcccc 600

gccgccgagg agagccugcc caucgaggug augguggacg ccgugcacaa gcugaaguac 660

gagaacuaca ccagcagcuu cuucaucaga gacaucauca agcccgaccc ccccaagaac 720

cugcagcuga agccccugaa gaacagcaga caggugggagg ugagcuggga guaccccgac 780

accuggagca ccccccacag cuacuucagc cugaccuucu gcgugcaggu gcagggcaag 840

agcaagagag agaagaagga cagaguguuc accgacaaga ccagcgccac cgugaucugc 900

agaaagaacg ccagcaucag cgugagagcc caggacagau acuacagcag cagcuggagc 960

gagugggcca gcgugcccug cagcuag 987

<210> 717

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 717

augugccacc agcagcuggu gaucuccugg uucagccugg uguuccuggc cagcccccug 60

guggccaucu gggagcugaa gaaggaugug uauguggugg agcuggacug guacccagau 120

gccccggag agaugguggu gcugaccugu gacaccccag aagaagaugg caucaccugg 180

acccuggacc agagcagcga ggugcugggc agcggcaaga cccugaccau ccaggugaag 240

gaguuuggag augcuggcca guacaccugc cacaagggcg gggaggugcu gagccacagc 300

cugcugcugc ugcacaagaa ggaggauggc aucuggagca cagacauccu gaaggaccag 360

aaggaggcca agaacaagac cuuccugcgc ugugaggcca agaacuacag cggccgcuuc 420

accugcuggu ggcugaccac caucagcaca gaccugaccu ucucugugaa gagcagccgg 480

ggcagcagug acccccaggg cgugaccugu ggggccgcca cccugucugc ugagcgggug 540

cggggggacag cgccugccca 600

gcugcugagg agagccugcc caucgaggug agguggaug cugugcacaa gcugaaguau 660

gagaacuaca ccagcagcuu cuucauccgg gacaucauca agccagaccc ccccaagaac 720

cugcagcuga agccccugaa gaacagccgg cagguggagg uguccuggga guacccagac 780

accuggagca ccccccacag cuacuucagc cugaccuucu gugugcaggu gcagggcaag 840

agcaagcggg agaagaagga cagagucuuc acagacaaga ccagcgccac cgucaucugc 900

aggaagaaug ccagcaucuc ugugcggggcc caggaccgcu acuacagcag cuccuggagc 960

gaggggccu cugugcccug cagcuag 987

<210> 718

<211> 720

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 718

auguggcccc caggcagcgc cagccagccc ccacccagcc cugcugcugc caccggccug 60

cacccugcug cccggccugu gucccugcag ugccgccugu ccaugugccc agcccggagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag gaaccugccu 180

guggccaccc cagaccccgg cauguucccc ugccugcacc acagccagaa ccugcugcgg 240

gcugugagca acaugcugca gaaggcccgg cagacccugg aguucuaccc cugcaccagc 300

gaggagauug accacgagga caucaccaag gacaagacca gcacagugga ggccugccug 360

ccccuggagc ugaccaagaa uggcagcugc cuggccagca ggaagaccag cuucaugaug 420

gcccugugcc ugagcagcau cuaugaggac cugaagaugu accaggugga guucaagacc 480

augaaugcca agcugcugau ggaccccaag aggcagaucu uccuggacca gaacaugcug 540

gccgugauug augagcugau gcaggcccug aacuucaaca gcgagaccgu gccccagaag 600

agcagccugg aggagccaga cuucuacaag accaagauca agcugugcau ccugcugcac 660

gccuuccgca uccgggcugu gaccaucgac agagugauga gcuaccugaa ugccagcuag 720

<210> 719

<211> 720

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 719

auguggcccc caggcagcgc cagccagccc ccacccagcc cugcugcugc caccggccug 60

cacccugcug cccggccugu gucccugcag ugccgccugu ccaugugccc agcccggagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag gaaccugccu 180

guggccaccc cagaccccgg cauguucccc ugccugcacc acagccagaa ccugcugcgg 240

gcugugagca acaugcugca gaaggcccgg cagacccugg aguucuaccc cugcaccagc 300

gaggagauug accacgagga caucaccaag gacaagacca gcacagugga ggccugccug 360

ccccuggagc ugaccaagaa uggcagcugc cuggccagca ggaagaccag cuucaugaug 420

gcccugugcc ugagcagcau cuaugaggac cugaagaugu accaggugga guucaagacc 480

augaaugcca agcugcugau ggaccccaag aggcagaucu uccuggacca gaacaugcug 540

gccgugauug augagcugau gcaggcccug aacuucaaca gcgagaccgu gccccagaag 600

agcagccugg aggagccaga cuucuacaag accaagauca agcugugcau ccugcugcac 660

gccuuccgca uccgggcugu gaccaucgac agagugauga gcuaccugaa ugccagcuag 720

<210> 720

<211> 720

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 720

auguggcccc ccggcagcgc cagccagccc ccccccagcc ccgccgccgc caccggccug 60

caccccgccg ccagacccgu gagccugcag ugcagacuga gcaugugccc cgccagaagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag aaaccugccc 180

guggccaccc ccgaccccgg cauguucccc ugccugcacc acagccagaa ccugcugaga 240

gccgugagca acaugcugca gaaggccaga cagacccugg aguucuaccc cugcaccagc 300

gaggagaucg accacgagga caucaccaag gacaagacca gcaccgugga ggccugccug 360

ccccuggagc ugaccaagaa cggcagcugc cuggccagca gaaagaccag cuucaugaug 420

gcccugugcc ugagcagcau cuacgaggac cugaagaugu accaggugga guucaagacc 480

augaacgcca agcugcugau ggaccccaag agacagaucu uccuggacca gaacaugcug 540

gccgugaucg acgagcugau gcaggcccug aacuucaaca gcgagaccgu gccccagaag 600

agcagccugg aggacccga cuucuacaag accaagauca

gccuucagaa ucagagccgu gaccaucgac agagugauga gcuaccugaa cgccagcuag 720

<210> 721

<211> 720

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 721

auguggcccc ccggcagcgc cagccagccc ccccccagcc ccgccgccgc caccggccug 60

caccccgccg ccagacccgu gagccugcag ugcagacuga gcaugugccc cgccagaagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag aaaccugccc 180

guggccaccc ccgaccccgg cauguucccc ugccugcacc acagccagaa ccugcugaga 240

gccgugagca acaugcugca gaaggccaga cagacccugg aguucuaccc cugcaccagc 300

gaggagaucg accacgagga caucaccaag gacaagacca gcaccgugga ggccugccug 360

ccccuggagc ugaccaagaa cggcagcugc cuggccagca gaaagaccag cuucaugaug 420

gcccugugcc ugagcagcau cuacgaggac cugaagaugu accaggugga guucaagacc 480

augaacgcca agcugcugau ggaccccaag agacagaucu uccuggacca gaacaugcug 540

gccgugaucg acgagcugau gcaggcccug aacuucaaca gcgagaccgu gccccagaag 600

agcagccugg aggacccga cuucuacaag accaagauca

gccuucagaa ucagagccgu gaccaucgac agagugauga gcuaccugaa cgccagcuag 720

<210> 722

<211> 762

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 722

auguggcccc caggcagcgc cagccagccc ccacccagcc cugcugcugc caccggccug 60

cacccugcug cccggccugu gucccugcag ugccgccugu ccaugugccc agcccggagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag gaaccugccu 180

guggccaccc cagaccccgg cauguucccc ugccugcacc acagccagaa ccugcugcgg 240

gcugugagca acaugcugca gaaggcccgg cagacccugg aguucuaccc cugcaccagc 300

gaggagauug accacgagga caucaccaag gacaagacca gcacagugga ggccugccug 360

ccccuggagc ugaccaagaa ugaaagcugc cugaacagcc gggagaccag cuucaucacc 420

aacggcagcu gccuggccag caggaagacc agcuucauga uggcccugug ccuagcagc 480

aucuaugagg accugaagau guaccaggug gaguucaaga ccaugaaugc caagcugcug 540

aggacccca agaggcagau cuuccuggac cagaacaugc uggccgugau ugaugagcug 600

augcaggccc ugaacuucaa cagcgagacc gugccccaga agagcagccu ggaggagcca 660

gacuucuaca agaccaagau caagcugugc auccugcugc acgccuuccg cauccgggcu 720

gugaccaucg acagagugau gagcuaccug aaugccagcu ag 762

<210> 723

<211> 762

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 723

auguggcccc caggcagcgc cagccagccc ccacccagcc cugcugcugc caccggccug 60

cacccugcug cccggccugu gucccugcag ugccgccugu ccaugugccc agcccggagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag gaaccugccu 180

guggccaccc cagaccccgg cauguucccc ugccugcacc acagccagaa ccugcugcgg 240

gcugugagca acaugcugca gaaggcccgg cagacccugg aguucuaccc cugcaccagc 300

gaggagauug accacgagga caucaccaag gacaagacca gcacagugga ggccugccug 360

ccccuggagc ugaccaagaa ugaaagcugc cugaacagcc gggagaccag cuucaucacc 420

aacggcagcu gccuggccag caggaagacc agcuucauga uggcccugug ccuagcagc 480

aucuaugagg accugaagau guaccaggug gaguucaaga ccaugaaugc caagcugcug 540

aggacccca agaggcagau cuuccuggac cagaacaugc uggccgugau ugaugagcug 600

augcaggccc ugaacuucaa cagcgagacc gugccccaga agagcagccu ggaggagcca 660

gacuucuaca agaccaagau caagcugugc auccugcugc acgccuuccg cauccgggcu 720

gugaccaucg acagagugau gagcuaccug aaugccagcu ag 762

<210> 724

<211> 762

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 724

auguggcccc ccggcagcgc cagccagccc ccccccagcc ccgccgccgc caccggccug 60

caccccgccg ccagacccgu gagccugcag ugcagacuga gcaugugccc cgccagaagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag aaaccugccc 180

guggccaccc ccgaccccgg cauguucccc ugccugcacc acagccagaa ccugcugaga 240

gccgugagca acaugcugca gaaggccaga cagacccugg aguucuaccc cugcaccagc 300

gaggagaucg accacgagga caucaccaag gacaagacca gcaccgugga ggccugccug 360

ccccuggagc ugaccaagaa cgagagcugc cugaacagca gagagaccag cuucaucacc 420

aacggcagcu gccuggccag cagaaagacc agcuucauga uggcccugug ccuagcagc 480

aucuacgagg accugaagau guaccaggug gaguucaaga ccaugaacgc caagcugcug 540

auggaccca agagacagau cuuccuggac cagaacaugc uggccgugau cgacgagcug 600

augcaggccc ugaacuucaa cagcgagacc gugccccaga agagcagccu ggaggagccc 660

720

gugaccaucg acagagugau gagcuaccug aacgccagcu ag 762

<210> 725

<211> 762

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 725

auguggcccc ccggcagcgc cagccagccc ccccccagcc ccgccgccgc caccggccug 60

caccccgccg ccagacccgu gagccugcag ugcagacuga gcaugugccc cgccagaagc 120

cugcugcugg uggccacccu ggugcugcug gaccaccuga gccuggccag aaaccugccc 180

guggccaccc ccgaccccgg cauguucccc ugccugcacc acagccagaa ccugcugaga 240

gccgugagca acaugcugca gaaggccaga cagacccugg aguucuaccc cugcaccagc 300

gaggagaucg accacgagga caucaccaag gacaagacca gcaccgugga ggccugccug 360

ccccuggagc ugaccaagaa cgagagcugc cugaacagca gagagaccag cuucaucacc 420

aacggcagcu gccuggccag cagaaagacc agcuucauga uggcccugug ccuagcagc 480

aucuacgagg accugaagau guaccaggug gaguucaaga ccaugaacgc caagcugcug 540

auggaccca agagacagau cuuccuggac cagaacaugc uggccgugau cgacgagcug 600

augcaggccc ugaacuucaa cagcgagacc gugccccaga agagcagccu ggaggagccc 660

720

gugaccaucg acagagugau gagcuaccug aacgccagcu ag 762

<210> 726

<211> 2761

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12 construct

<400> 726

gggcauacag uuguuccauc ccgacaugaa cucagccucc cgucugaccg ccccuuggcc 60

uuccuucuuc cucgaucugu ggaacccagg gaaucugccu agugcugucu ccaagcaccu 120

uggccaugau guaaacccag agaaauuagc aucuccaucu ccuuccuuau uccccaccca 180

aaagucauuu ccucuuaguu cauuaccugg gauuuugaug ucuauguucc cuccucguua 240

uugauacaca cacagagaga gacaaacaaa aaaggaacuu cuugaaauuc ccccagaagg 300

360

aggaguagag uauauaaguu ccaguaccag caacagcagc agaagaaaca acaucuguuu 420

cagggccauu ggacucuccg uccugcccag agcaagaugu gucaccagca guuggucauc 480

ucuugguuuu cccugguuuu ucuggcaucu ccccucgugg ccauauggga acugaagaaa 540

600 gauguuuaug ucguagaauu ggauugguau ccggaugccc

accugugaca ccccugaaga agaugguauc accuggaccu uggaccagag cagugagguc 660

uuaggcucug gcaaaacccu gaccauccaa gucaaagagu uuggagaugc uggccaguac 720

accugucaca aaggaggcga gguucuaagc cauucgcucc ugcugcuuca caaaaaggaa 780

guggaauuu gguccacuga uauuuuaaag gaccagaaag aacccaaaaa uaagaccuuuu 840

cuaagaugcg aggccaagaa uuauucugga cguuucaccu gcugguggcu gacgacaauc 900

aguacugauu ugacauucag ugucaaaagc agcagaggcu cuucugaccc ccaaggggug 960

acgugcggag cugcuacacu cucugcagag agagucagag gggacaacaa ggaguaugag 1020

uacucagugg agugccagga ggacagugcc ugcccagcug cugaggagag ucugcccauu 1080

1140

aucagggaca ucaucaaacc ugacccaccc aagaacuugc agcugaagcc auuaaagaau 1200

ucucggcagg uggaggucag cugggaguac ccugacaccu ggaguacucc acauuccuac 1260

uucucccuga cauucugcgu ucagguccag ggcaagagca agagagaaaa gaaagauaga 1320

1380

cgggcccagg accgcuacua uagcucaucu uggagcgaau gggcaucugu gcccugcagu 1440

uagguucuga uccaggauga 1500

1560

1620

1680

1740

ucugccagga uguauggaau guuucauacu cuuaugaccu gauccaucag gaucaguccc 1800

uauuaugcaa aaugugaauu uaauuuuauu uguacugaca acuuuucaag caaggcugca 1860

aguacaucag uuuuaugaca aucaggaaga augcaguguu cugauaccag ugccaucaua 1920

cacuugugau ggaugggaac gcaagagaua cuuacaugga aaccugacaa ugcaaaccug 1980

uugagaagau ccaggagaac aagaugcuag uucccauguc ugugaagacu uccggagau 2040

gguguugaua aagcaauuua gggccacuua cacuucuaag caaguuuaau cuuuggaugc 2100

cugaauuuua aaagggcuag aaaaaaauga uugaccagcc ugggaaacau aacaagaccc 2160

cgucucuaca aaaaaaauuu aaaauuagcc aggcguggug gcucaugcuu guggucccag 2220

2280

ccgugauugu gccacugcau accagccuag gugacagaau gagacccugu cucaaaaaaa 2340

aaaugauug aaauuaaaau ucagcuuuag cuuccauggc aguccucacc cccaccucuc 2400

uaaaagacac aggaggauga cacagaaaca ccguaagugu cuggaaggca aaaagaucuu 2460

aagauucaag agagaggaca aguaguuaug gcuaaggaca ugaaauuguc agaauggcag 2520

2580

cucauuagca ugaaugaacc ugauacacaa uuaugaccag aaaauauggc uccaugaagg 2640

2700

uuauuuauuu auuuauuuuu gcauucugag gcugaacuaa uaaaaacucu ucuuuguaau 2760

c 2761

<210> 727

<211> 591

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12A

<400> 727

60

uuggccagaa accuccccgu ggccacucca gaccaggaa uguucccaug ccuucaccac 120

ucccaaaacc ugcugagggc cgucagcaac augcuccaga agaaugagag uugccuaaau 180

uccagagaga ccucuuucau aacuaauggg aguugccugg ccuccagaaa gaccucuuuu 240

augauggccc ugugccuuag uaguauuuau gaagacuuga agauguacca gguggaguuc 300

aagaccauga augcaaagcu ucugauggau ccuaagaggc agaucuuucu agaucaaaac 360

augcuggcag uuauugauga gcugaugcag gcccugaauu ucaacaguga gacugugcca 420

caaaaauccu cccuugaaga accggauuuu uauaaaacua aaaucaagcu cugcauacuu 480

cuucaugcuu ucagaauucg ggcagugacu auugauagag ugaugagcua ucugaaugcu 540

uccuaaaaag cgaggucccu ccaaaccguu gucauuuuua uaaaacuuug a 591

<210> 728

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 728

augaucgaga cauauaacca gaccucccca agauccgcag cuaccgggcu gccuaucagc 60

augaaaaucu uuauguacuu guuaacggug uuuuugauca

cucuuugcag uguaucugca uagaaggcuu gacaaaauug aagaugagag aaaucugcac 180

gaagacuucg uguuuaugaa aaccauccaa cgguguaaca ccggggagcg gucucuuagc 240

cugcugaauu gcgaagagau uaagagccaa uuugaggguu uugugaaaga caucaugcug 300

aacaaagagg aaaccaagaa agaaaacucu uucgagaugc agaaagguga ccagaacccu 360

cagaucgccg cccacgugau cucugaggcc aguuccaaga cuacaucugu gcuccaaugg 420

gccgaaaaag gcuacuacac uauguccaau aacuugguga cccuagagaa cggaaagcaa 480

cugaccguga aacggcaggg acuguacuac auuuacgccc aggugacguu cugcuccaac 540

cgcgaagcca guucucaggc uccuuuuauc gccagucuuu gccucaaaag cccggggcga 600

uucgaaagaa uccuguugag ggcagcaaac acacacucau ccgcuaaacc uugcgggcag 660

caaucgaucc aucuuggcgg agucuuugaa cugcagcccg gcgccucugu auucgugaac 720

gucacggacc caagccaggu gagccaugga acaggguuua caucauuugg acugcuaaag 780

cuguag 786

<210> 729

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 729

augaucgaga ccuacacca gaccagcccc agaagcgccg ccaccggccu gcccaucagc 60

augaagaucu ucauguaccu gcugaccgug uuccugauca cccagaugau cggcagcgcc 120

cuguucgccg uguaccugca cagaagacug gacaagaucg aggacgagag aaaccugcac 180

gaggacuucg uguucaugaa gaccauccag agaugcaaca ccggcgagag aagccugagc 240

cugcugaacu gcgaggagau caaggccag uucgagggcu ucgugaagga caucaugcug 300

aacaaggagg agaccaagaa ggagaacagc uucgagaugc agaagggcga ccagaacccc 360

cagaucgccg cccacgugau cagcgaggcc agcagcaaga ccaccagcgu gcugcagugg 420

gccgagaagg gcuacuacac caugagcaac aaccugguga cccuggagaa cggcaagcag 480

cugaccguga aggacaggg ccuguacuac aucuacgccc aggugaccuu cugcagcaac 540

agagaggcca gcagccaggc ccccuucauc gccagccugu gccugaagag ccccggcaga 600

uucgagagaa uccugcugag agccgccaac acccacagca gcgccaagcc cugcggccag 660

cagagcaucc accugggcgg cguguucgag cugcagcccg gcgccagcgu guucgugaac 720

780

cuguag 786

<210> 730

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 730

augauugaga ccuacacca gaccagcccc aggucugcug ccaccggccu gcccaucucc 60

augaagaucu ucauguaccu gcugacugug uuccugauca cccagaugau uggcagcgcc 120

cuguuugcug uguaccugca ccggcggcug gacaagauug aagaugaaag aaaccugcau 180

240

cugcugaacu gugaggagau caagagccag uuugagggcu uugugaagga caucaugcug 300

aacaaggagg agaccaagaa ggagaacagc uuugagaugc agaaggggga ccagaacccc 360

cagauugcug cccacgugau cagcgaggcc agcagcaaga ccaccucugu gcugcagugg 420

gccgagaagg gcuacuacac caugagcaac aaccugguga cccuggagaa uggcaagcag 480

cugacuguga aggcaggg ccuguacuac aucuaugccc aggugaccuu cugcagcaac 540

cgggaggcca gcagccaggc ccccuucauc gccagccugu gccugaagag cccuggccgc 600

uuugagcgca uccugcugcg ggccgccaac acccacagca gcgccaagcc cuguggccag 660

cagagcaucc accugggcgg cguguuugag cugcagcccg gggccucugu guuugugaau 720

gugacagacc ccagccaggu gucccaugga acaggcuuca ccagcuuugg ccugcugaag 780

cuguag 786

<210> 731

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 731

augauugaga ccuacacca gaccagcccc aggucugcug ccaccggccu gcccaucucc 60

augaagaucu ucauguaccu gcugacugug uuccugauca cccagaugau uggcagcgcc 120

cuguuugcug uguaccugca ccggcggcug gacaagauug aagaugaaag aaaccugcau 180

240

cugcugaacu gugaggagau caagagccag uuugagggcu uugugaagga caucaugcug 300

aacaaggagg agaccaagaa ggagaacagc uuugagaugc agaaggggga ccagaacccc 360

cagauugcug cccacgugau cagcgaggcc agcagcaaga ccaccucugu gcugcagugg 420

gccgagaagg gcuacuacac caugagcaac aaccugguga cccuggagaa uggcaagcag 480

cugacuguga aggcaggg ccuguacuac aucuaugccc aggugaccuu cugcagcaac 540

cgggaggcca gcagccaggc ccccuucauc gccagccugu gccugaagag cccuggccgc 600

uuugagcgca uccugcugcg ggccgccaac acccacagca gcgccaagcc cuguggccag 660

cagagcaucc accugggcgg cguguuugag cugcagcccg gggccucugu guuugugaau 720

gugacagacc ccagccaggu gucccaugga acaggcuuca ccagcuuugg ccugcugaag 780

cuguag 786

<210> 732

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 732

augauugaga cguacaauca gacaagcccc cgaagcgcag cgaccggacu ucccauaagu 60

augaaaaucu uuauguaucu gcugaccgug uuucuuauca cccaaaugau aggcuccgcu 120

cuauuugccg uguaucucca ucgcaggcua gauaaaaucg aagaugagcg aaaccugcau 180

240

cugcugaauu gugaagaaau caagucccag uuugagggcu ucgucaagga uauaaugcug 300

aacaaagagg agaccaagaa ggagaacagc uucgaaaugc aaaagggaga ccagaaccca 360

caaaucgcag cucacgucau aucagaggcc ucaucaaaaa caacaucggu ucugcaaugg 420

gcuugaaaagg gcuauuauac cauguucuaac aauuugguga ccuuggaaaa ugguaaacag 480

cucaccguga agcggcaggg ccuuuacuac auauacgcuc aggugacuuu uugcucuaau 540

cgggaagcca gcagucaggc accauucauu gcuucgcucu gccugaaaag cccagggaga 600

uuugaacgca uuuuuacugcg cgcugcaaac acccacucua gcgcuaagcc auguggccaa 660

caguccauac acuuaggcgg aguauucgaa uuacagccug gcgcuagugu cuucguuaau 720

guaacagauc caucccaagu gagucacggc accggcuuca ccucuuuugg ucuguugaag 780

cuguag 786

<210> 733

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 733

augaucgaga ccuacacca gaccagcccc cggagcgccg ccaccgguuu gccuaucucu 60

augaagaucu ucauguaccu ucucacuguu uuucugauua cccagaugau cgguucugcc 120

cuguucgcag uguacuugca ccgucgucug gauaaaaucg aagacgagcg gaaucuccau 180

gaggauuucg uguuuaugaa gacaauacag cgcugcaaca ccggcgaaag aagucucagc 240

uugcucaacu gcgaagagau caaaagccag uuugaggggu ucgugaaaga caucaugcuc 300

360

cagaucgcgg cacaugugau uucugaagcc uccaguaaga cuaccucagu guugcagugg 420

480

uugacaguua agagacaggg ccuguacuac auuuaugccc agguacguu cugcuccaau 540

cgugaagcua gcagccaggc cccguuuauc gcuucucuau gccugaaaag uccuggaagg 600

uuugagcgaa uucugcucag agcagcgaau acccacagca gugccaaacc cugugggcag 660

cagucuauuc accuuggcgg cguguucgag cugcagccgg gcgcauccgu guucgugaau 720

guaacagacc cgagucaagu gagucacggc accgguuuua ccaguuuugg gcuuuugaaa 780

uuguag 786

<210> 734

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 734

augauugaga cguacaauca gacaagcccc cgaagcgcag cgaccggacu ucccauaagu 60

augaaaaucu uuauguaucu gcugaccgug uuucuuauca cccaaaugau aggcuccgcu 120

cuauuugccg uguaucucca ucgcaggcua gauaaaaucg aagaugagcg aaaccugcau 180

240

cugcugaauu gugaagaaau caagucccag uuugagggcu ucgucaagga uauaaugcug 300

aacaaagagg agaccaagaa ggagaacagc uucgaaaugc aaaagggaga ccagaaccca 360

caaaucgcag cucacgucau aucagaggcc ucaucaaaaa caacaucggu ucugcaaugg 420

gcuugaaaagg gcuauuauac cauguucuaac aauuugguga ccuuggaaaa ugguaaacag 480

cucaccguga agcggcaggg ccuuuacuac auauacgcuc aggugacuuu uugcucuaau 540

cgggaagcca gcagucaggc accauucauu gcuucgcucu gccugaaaag cccagggaga 600

uuugaacgca uuuuuacugcg cgcugcaaac acccacucua gcgcuaagcc auguggccaa 660

caguccauac acuuaggcgg aguauucgaa uuacagccug gcgcuagugu cuucguuaau 720

guaacagauc caucccaagu gagucacggc accggcuuca ccucuuuugg ucuguugaag 780

cuguag 786

<210> 735

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 735

augaucgaga ccuacacca gaccagcccc cggagcgccg ccaccgguuu gccuaucucu 60

augaagaucu ucauguaccu ucucacuguu uuucugauua cccagaugau cgguucugcc 120

cuguucgcag uguacuugca ccgucgucug gauaaaaucg aagacgagcg gaaucuccau 180

gaggauuucg uguuuaugaa gacaauacag cgcugcaaca ccggcgaaag aagucucagc 240

uugcucaacu gcgaagagau caaaagccag uuugaggggu ucgugaaaga caucaugcuc 300

360

cagaucgcgg cacaugugau uucugaagcc uccaguaaga cuaccucagu guugcagugg 420

480

uugacaguua agagacaggg ccuguacuac auuuaugccc agguacguu cugcuccaau 540

cgugaagcua gcagccaggc cccguuuauc gcuucucuau gccugaaaag uccuggaagg 600

uuugagcgaa uucugcucag agcagcgaau acccacagca gugccaaacc cugugggcag 660

cagucuauuc accuuggcgg cguguucgag cugcagccgg gcgcauccgu guucgugaau 720

guaacagacc cgagucaagu gagucacggc accgguuuua ccaguuuugg gcuuuugaaa 780

uuguag 786

<210> 736

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 736

augaucgaga ccuacacca gaccagcccc cggagcgccg ccaccgguuu gccuaucucu 60

augaagaucu ucauguaccu ucucacuguu uuucugauua cccagaugau cgguucugcc 120

cuguucgcag uguacuugca ccgucgucug gauaaaaucg aagacgagcg gaaucuccau 180

gaggauuucg uguuuaugaa gacaauacag cgcugcaaca ccggcgaaag aagucucagc 240

uugcucaacu gcgaagagau caaaagccag uuugaggggu ucgugaaaga caucaugcuc 300

360

cagaucgcgg cacaugugau uucugaagcc uccaguaaga cuaccucagu guugcagugg 420

480

uugacaguua agagacaggg ccuguacuac auuuaugccc agguacguu cugcuccaau 540

cgugaagcua gcagccaggc cccguuuauc gcuucucuau gccugaaaag uccuggaagg 600

uuugagcgaa uucugcucag agcagcgaau acccacagca gugccaaacc cugugggcag 660

cagucuauuc accuuggcgg cguguucgag cugcagccgg gcgcauccgu guucgugaau 720

guaacagacc cgagucaagu gagucacggc accgguuuua ccaguuuugg gcuuuugaaa 780

uuguag 786

<210> 737

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 737

augaucgaga ccuacacca gaccagcccc agaagcgccg ccaccggccu gcccaucagc 60

augaagaucu ucauguaccu gcugaccgug uuccugauca cccagaugau cggcagcgcc 120

cuguucgccg uguaccugca cagaagacug gacaagaucg aggacgagag aaaccugcac 180

gaggacuucg uguucaugaa gaccauccag agaugcaaca ccggcgagag aagccugagc 240

cugcugaacu gcgaggagau caaggccag uucgagggcu ucgugaagga caucaugcug 300

aacaaggagg agaccaagaa ggagaacagc uucgagaugc agaagggcga ccagaacccc 360

cagaucgccg cccacgugau cagcgaggcc agcagcaaga ccaccagcgu gcugcagugg 420

gccgagaagg gcuacuacac caugagcaac aaccugguga cccuggagaa cggcaagcag 480

cugaccguga aggacaggg ccuguacuac aucuacgccc aggugaccuu cugcagcaac 540

agagaggcca gcagccaggc ccccuucauc gccagccugu gccugaagag ccccggcaga 600

uucgagagaa uccugcugag agccgccaac acccacagca gcgccaagcc cugcggccag 660

cagagcaucc accugggcgg cguguucgag cugcagcccg gcgccagcgu guucgugaac 720

780

cuguag 786

<210> 738

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 738

augaucgaga cauauaacca gaccucccca agauccgcag cuaccgggcu gccuaucagc 60

augaaaaucu uuauguacuu guuaacggug uuuuugauca

cucuuugcag uguaucugca uagaaggcuu gacaaaauug aagaugagag aaaucugcac 180

gaagacuucg uguuuaugaa aaccauccaa cgguguaaca ccggggagcg gucucuuagc 240

cugcugaauu gcgaagagau uaagagccaa uuugaggguu uugugaaaga caucaugcug 300

aacaaagagg aaaccaagaa agaaaacucu uucgagaugc agaaagguga ccagaacccu 360

cagaucgccg cccacgugau cucugaggcc aguuccaaga cuacaucugu gcuccaaugg 420

gccgaaaaag gcuacuacac uauguccaau aacuugguga cccuagagaa cggaaagcaa 480

cugaccguga aacggcaggg acuguacuac auuuacgccc aggugacguu cugcuccaac 540

cgcgaagcca guucucaggc uccuuuuauc gccagucuuu gccucaaaag cccggggcga 600

uucgaaagaa uccuguugag ggcagcaaac acacacucau ccgcuaaacc uugcgggcag 660

caaucgaucc aucuuggcgg agucuuugaa cugcagcccg gcgccucugu auucgugaac 720

gucacggacc caagccaggu gagccaugga acaggguuua caucauuugg acugcuaaag 780

cuguag 786

<210> 739

<211> 24

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HLA-A2-SP

<400> 739

Met Ala Val Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala

1 5 10 15

Leu Ala Leu Thr Gln Thr Trp Ala

twenty

<210> 740

<211> 25

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HLA-A2-SP

<400> 740

Met Ala Val Met Ala Pro Arg Thr Leu Val Leu Leu Leu Ser Gly Ala

1 5 10 15

Leu Ala Leu Thr Gln Thr Trp Ala Gly

20 25

<210> 741

<211> 23

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 741

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly

1 5 10 15

Ala Val Phe Val Ser Pro Ser

twenty

<210> 742

<211> 21

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 742

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly

1 5 10 15

Ala Val Phe Val Ser

twenty

<210> 743

<211> 22

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 743

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly

1 5 10 15

Ala Val Phe Val Ser Pro

twenty

<210> 744

<211> 27

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsEPO

<400> 744

Met Gly Val His Glu Cys Pro Ala Trp Leu Trp Leu Leu Leu Ser Leu

1 5 10 15

Leu Ser Leu Pro Leu Gly Leu Pro Val Leu Gly

20 25

<210> 745

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsALB

<400> 745

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala

1 5 10 15

Tyr Ser

<210> 746

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - IgE

<400> 746

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val

1 5 10 15

His Ser

<210> 747

<211> 24

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsCD5

<400> 747

Met Pro Met Gly Ser Leu Gln Pro Leu Ala Thr Leu Tyr Leu Leu Gly

1 5 10 15

Met Leu Val Ala Ser Cys Leu Gly

twenty

<210> 748

<211> 20

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsIL2

<400> 748

Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu

1 5 10 15

Val Thr Asn Ser

twenty

<210> 749

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsCTRB2

<400> 749

Met Ala Phe Leu Trp Leu Leu Ser Cys Trp Ala Leu Leu Gly Thr Thr

1 5 10 15

Phe Gly

<210> 750

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - immunoglobulin (IgG heavy chain)

<400> 750

Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Phe Arg Gly

1 5 10 15

Val Gln Cys

<210> 751

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - human immunoglobulin heavy chain

<400> 751

Met Asp Trp Thr Trp Arg Val Phe Cys Leu Leu Ala Val Thr Pro Gly

1 5 10 15

Ala His Pro

<210> 752

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - human immunoglobulin light chain

<400> 752

Met Ala Trp Ser Pro Leu Phe Leu Thr Leu Ile Thr His Cys Ala Gly

1 5 10 15

Ser Trp Ala

<210> 753

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - GpLuc

<400> 753

Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu

1 5 10 15

Ala

<210> 754

<211> 21

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - MmIgkappa

<400> 754

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro

1 5 10 15

Gly Ser Thr Gly Asp

twenty

<210> 755

<211> 26

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - NrChit1

<400> 755

Met Lys Thr His Tyr Ser Ser Ala Ile Leu Pro Ile Leu Thr Leu Phe

1 5 10 15

Val Phe Leu Ser Ile Asn Pro Ser His Gly

20 25

<210> 756

<211> 21

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - ClLp1.1

<400> 756

Met Gly Met Arg Met Met Phe Ile Met Phe Met Leu Val Val Leu Ala

1 5 10 15

Thr Thr Val Val Ser

twenty

<210> 757

<211> 24

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - NgNep1

<400> 757

Met Ala Ser Ser Leu Tyr Ser Phe Leu Leu Ala Leu Ser Ile Val Tyr

1 5 10 15

Ile Phe Val Ala Pro Thr His Ser

twenty

<210> 758

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsAzu1

<400> 758

Met Thr Arg Leu Thr Val Leu Ala Leu Leu Ala Gly Leu Leu Ala Ser

1 5 10 15

Ser Arg Ala

<210> 759

<211> 16

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsCD33

<400> 759

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala

1 5 10 15

<210> 760

<211> 19

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - VcCtxB

<400> 760

Met Ile Lys Leu Lys Phe Gly Val Phe Phe Thr Val Leu Leu Ser Ser

1 5 10 15

Ala Tyr Ala

<210> 761

<211> 20

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsCST4

<400> 761

Met Ala Arg Pro Leu Cys Thr Leu Leu Leu Leu Met Ala Thr Leu Ala

1 5 10 15

Gly Ala Leu Ala

twenty

<210> 762

<211> 24

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsIns-iso1

<400> 762

Met Ala Leu Trp Met Arg Leu Leu Pro Leu Leu Ala Leu Leu Ala Leu

1 5 10 15

Trp Gly Pro Asp Pro Ala Ala Ala

twenty

<210> 763

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - HsSPARC

<400> 763

Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu

1 5 10 15

Ala

<210> 764

<211> 17

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - H1N1(Netherlands2009)-HA

<400> 764

Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn

1 5 10 15

Ala

<210> 765

<211> 30

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - YFV

<400> 765

Met Arg Gly Leu Ser Ser Arg Lys Arg Arg Ser His Asp Val Leu Thr

1 5 10 15

Val Gln Phe Leu Ile Leu Gly Met Leu Leu Met Thr Gly Gly

20 25 30

<210> 766

<211> 25

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - MHCII

<400> 766

Met Ala Ile Ser Gly Val Pro Val Leu Gly Phe Phe Ile Ile Ala Val

1 5 10 15

Leu Met Ser Ala Gln Glu Ser Trp Ala

20 25

<210> 767

<211> 24

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 767

Met Gly Lys Arg Ser Ala Gly Ser Ile Met Trp Leu Ala Ser Leu Ala

1 5 10 15

Val Val Ile Ala Cys Ala Gly Ala

twenty

<210> 768

<211> 30

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 768

Met Gly Arg Lys Gln Asn Lys Arg Gly Gly Asn Glu Gly Ser Ile Met

1 5 10 15

Trp Leu Ala Ser Leu Ala Val Val Ile Ala Cys Ala Gly Ala

20 25 30

<210> 769

<211> 21

<212> PRT

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 769

Met Asn Glu Gly Ser Ile Met Trp Leu Ala Ser Leu Ala Val Val Ile

1 5 10 15

Ala Cys Ala Gly Ala

twenty

<210> 770

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HLA-A2-SP

<400> 770

auggccguca uggcgccccg aacccucguc cugcuacucu cggggggcucu ggcccugacc 60

cagaccugg cg 72

<210> 771

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HLA-A2-SP

<400> 771

auggccguca uggcgccccg aacccucguc cugcuacucu cggggggcucu ggcccugacc 60

cagaccuggg cgggc 75

<210> 772

<211> 69

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 772

auggaugcaa ugaagagg gcucugcugu gugcugcugc uguguggagc agucuucguu 60

ucgcccagc 69

<210> 773

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 773

auggaugcaa ugaagagg gcucugcugu gugcugcugc uguguggagc agucuucguu 60

ucg63

<210> 774

<211> 66

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 774

auggaugcaa ugaagagg gcucugcugu gugcugcugc uguguggagc agucuucguu 60

ucgccc 66

<210> 775

<211> 81

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsEPO

<400> 775

augggggugc acgaaugucc ugccuggcug uggcuucucc ugucccugcu gucgcucccu 60

cugggccucc caguccigg c 81

<210> 776

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsALB

<400> 776

augaaguggg uaaccuuuau uucccuucuu uuucucuuua gcucggcuua uucc 54

<210> 777

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - IgE

<400> 777

auggacugga ccuggauccu guuccucgug gccgccgcga cccgcgucca cagc 54

<210> 778

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCD5

<400> 778

augcccaugg ggucucugca accgcuggcc accuuguacc ugcuggggau gcuggucgcu 60

uccugccucg ga 72

<210> 779

<211> 60

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsIL2

<400> 779

60

<210> 780

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCTRB2

<400> 780

auggcuuucc ucuggcuccu cuccigcugg gcccuccugg guaccaccuu cggc 54

<210> 781

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - immunoglobulin (IgG heavy chain)

<400> 781

auggaguuug ggcugagcug gguuuuccuc guugcucuuu uuagaggugu ccagugu 57

<210> 782

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - human immunoglobulin heavy chain

<400> 782

auggacugga ccuggagggu cuucuguuug cuggcuguaa cuccaggcgc ccacccc 57

<210> 783

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - human immunoglobulin light chain

<400> 783

auggccuggu ccccucucuu ccucacccuc aucacucacu gugcaggguc cugggcc 57

<210> 784

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - GpLuc

<400> 784

augggaguga aaguucuuuu ugcccuuauu uguauugcug uggccgaggc c 51

<210> 785

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - MmIgkappa

<400> 785

60

gac 63

<210> 786

<211> 78

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - NrChit1

<400> 786

augaagaccc auuauucauc agcaauucuc ccgauccuca cccucuucgu cuuucucucg 60

aucaauccau cccauggc 78

<210> 787

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - ClLp1.1

<400> 787

augggcaugc ggaugauguu cauguguuu augcugguug ucuuggcaac cacugucguu

ucc 63

<210> 788

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - NgNep1

<400> 788

auggccucgu cgcuguauuc uuucuuacuc gcauuaucga uaguuuacau cuuuguugcc 60

ccaacacauu cu 72

<210> 789

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsAzu1

<400> 789

augacccggc ugacaguccu ggcccugcug gcuggucugc uggcguccuc gagggcc 57

<210> 790

<211> 48

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCD33

<400> 790

augccgcugc ugcuacugcu gccccugcug ugggcagggg cccuggcu 48

<210> 791

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - VcCtxB

<400> 791

augauuaaau uaaaauuugg uguuuuuuuu acaguuuuac uaucuucagc auaugca 57

<210> 792

<211> 60

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCST4

<400> 792

auggcccggc cucuguguac ccugcuacuc cugauggcua cccuggcugg ggcucuggcc 60

<210> 793

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsIns-iso1

<400> 793

auggcccugu ggaugcgccu ccugccccug cuggcgcugc uggcccucug gggaccugac 60

ccagccgcag cc 72

<210> 794

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsSPARC

<400> 794

augagggccu ggaucuucuu ucuccuuugc cuggccggga gggcucuggc a 51

<210> 795

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - H1N1(Netherlands2009)-HA

<400> 795

augaaggcaa uacuaguagu ucugcuauau acauuugcaa ccgcaaaugc a 51

<210> 796

<211> 90

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - YFV

<400> 796

augagaggau uguccucaag gaaacgccgu ucccaugaug uucugacugu gcaauuccua 60

auuuugggaa ugcuguugau gacgggugga 90

<210> 797

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - MHCII

<400> 797

auggccauaa guggaguccc ugugcuagga uuuuucauca uagcugugcu gaugagcgcu 60

caggaaucaau gggcu 75

<210> 798

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 798

auggguaaac ggagcgcugg cucaaucaug uggcucgcga gcuuggcagu ugucauagcu 60

ugugcaggag cc 72

<210> 799

<211> 90

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 799

augggcagaa agcaaaacaa aagaggagga aaugaaggcu caaucaugug gcucgcgagc 60

uuggcaguug ucauagcuug ugcaggagcc 90

<210> 800

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 800

augaaugaag gcucaaucau guggcucgcg agcuuggcag uugucauagc uugugcagga 60

gcc63

<210> 801

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HLA-A2-SP

<400> 801

auggccguga uggccccgcg gacccugguc cuccugcuga gcggcgcgcu cgcccugacc 60

cagacguggg cc 72

<210> 802

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HLA-A2-SP

<400> 802

auggccguga uggccccgcg gacccugguc cuccugcuga gcggcgcgcu cgcccugacc 60

cagacguggg ccggg 75

<210> 803

<211> 69

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 803

auggacgcca ugaagcgcgg ccugugcugc gugcuccugc ugugcggggc cgucuucgug 60

agcccccc 69

<210> 804

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 804

auggacgcca ugaagcgcgg ccugugcugc gugcuccugc ugugcggggc cgucuucgug 60

agc63

<210> 805

<211> 66

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsPLAT

<400> 805

auggacgcca ugaagcgcgg ccugugcugc gugcuccugc ugugcggggc cgucuucgug 60

agcccc 66

<210> 806

<211> 81

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsEPO

<400> 806

augggcgugc acgagugccc cgccuggcug uggcuccugc ugagccuccu gucccugccg 60

ccggggcugc ccgucciggg c 81

<210> 807

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsALB

<400> 807

augaaguggg ugaccuucau cagccugcuc uuccuguucu ccagcgccua cucc 54

<210> 808

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - IgE

<400> 808

auggacugga ccuggauccu guuccucgug gccgccgcga cccgcgucca cagc 54

<210> 809

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCD5

<400> 809

augcccaugg gcagccugca gccgcucgcc acccuguacc ugcucgggau gcugguggcc 60

uccuggcugg gc 72

<210> 810

<211> 60

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsIL2

<400> 810

60

<210> 811

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCTRB2

<400> 811

auggccuucc uguggcuccu gagcugcugg gcccugcucg gcaccaccuu cggg 54

<210> 812

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - immunoglobulin (IgG heavy chain)

<400> 812

auggaguucg gccugagcug gguguuccuc gucgcccugu uccgcggggu gcagugc 57

<210> 813

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - human immunoglobulin heavy chain

<400> 813

auggacugga ccuggcgcgu guucugccug cucgccguca cccccggcgc ccacccg 57

<210> 814

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - human immunoglobulin light chain

<400> 814

auggcugga gcccccuguu ccucacccug aucacccacu gcgccggcuc cugggcg 57

<210> 815

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - GpLuc

<400> 815

augggcguga agguccuguu cgcccucauc ugcaucgccg uggcggaggc c 51

<210> 816

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - MmIgkappa

<400> 816

auggagaccg acacccugcu ccugugggug cugcuccugu ggguccccgg cagcacgggg 60

gac 63

<210> 817

<211> 78

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - NrChit1

<400> 817

augaagaccc acuacagcuc cgccauccug cccauccuca cccuguucgu guuccugagc 60

aucaacccgu cccacggc 78

<210> 818

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - ClLp1.1

<400> 818

augggcaugc gcaugauguu caucauguuc augcuggugg uccucgccac caccguggug 60

agc63

<210> 819

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - NgNep1

<400> 819

auggccagcu cccuguacag cuuccuccug gcccugucca ucguguacau cuucgucgcg 60

cccacccaca gc 72

<210> 820

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsAzu1

<400> 820

augacccgcc ugaccgcu cgcccugcug gccggccucc uggcgagcuc cggggcc 57

<210> 821

<211> 48

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCD33

<400> 821

augccccugc uccugcugcu cccgcugcug ugggccggcg cccucgcg 48

<210> 822

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - VcCtxB

<400> 822

augaucaagc ugaaguucgg cguguucuuc accguccucc ugagcuccgc cuacgcc 57

<210> 823

<211> 60

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsCST4

<400> 823

auggcccgcc cccugugcac ccuccugcug

<210> 824

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsIns-iso1

<400> 824

auggcccugu ggaugcgccu ccugccccug cucgcccugc uggcgcucug gggcccggac 60

cccgccgccg cc 72

<210> 825

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - HsSPARC

augcgcgccu ggaucuucuu ccugcucugc cuggccggcc gggcccuggc c 51

<210> 826

<211> 51

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - H1N1(Netherlands2009)-HA

<400> 826

augaaggcca uccgguggu ccuccuguac accuucgcca ccgcgaacgc c 51

<210> 827

<211> 90

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - YFV

<400> 827

augcggggcc ugagcucccg caagcggcgc agccacgacg ugcucaccgu ccaguuccug 60

auccugggga ugcuccugau gaccggcggg 90

<210> 828

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - MHCII

<400> 828

auggccauca gcggcgugcc cguccugggg uucuucauca ucgccgugcu cauguccgcg 60

caggagagcu gggcc 75

<210> 829

<211> 72

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 829

augggcaagc gcagcgccgg guccaucaug uggcuggcca gccucgcggu ggucaucgcc 60

ugcgccggcg cc 72

<210> 830

<211> 90

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 830

augggccgga agcagaacaa gcgcggggggc aacgagggga gcaucaugug gcuggccucc

cucgccgugg ucaucgcgug cgccggcgcc 90

<210> 831

<211> 63

<212>RNA

<213> Artificial Sequence

<220>

<223> signal peptide - JEV

<400> 831

augaacgagg gcagcaucau guggcuggcc ucccucgccg uggucaucgc gugcgccggg 60

gcc63

<210> 832

<211> 467

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 832

Met Glu Leu Gly Leu Ser Trp Ile Phe Leu Leu Ala Ile Leu Lys Gly

1 5 10 15

Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

20 25 30

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

35 40 45

Ser Ser Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn

85 90 95

Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly

115 120 125

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

130 135 140

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

145 150 155 160

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

165 170 175

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

180 185 190

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

195 200 205

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

210 215 220

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

225 230 235 240

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

260 265 270

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

275 280 285

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

290 295 300

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

340 345 350

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

355 360 365

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

385 390 395 400

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

420 425 430

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

450 455 460

Pro Gly Lys

465

<210> 833

<211> 448

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 833

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

115 120 125

Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly

130 135 140

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

145 150 155 160

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

165 170 175

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

180 185 190

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

195 200 205

Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr

210 215 220

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

260 265 270

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 834

<211> 235

<212> PRT

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 834

Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro

1 5 10 15

Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser

20 25 30

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

35 40 45

Val Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro

65 70 75 80

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

85 90 95

Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr

100 105 110

Gly Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

130 135 140

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

165 170 175

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

180 185 190

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230 235

<210> 835

<211> 386

<212> PRT

<213> Artificial Sequence

<220>

<223> Ovalbumin Ova

<400> 835

Met Gly Ser Ile Gly Ala Ala Ser Met Glu Phe Cys Phe Asp Val Phe

1 5 10 15

Lys Glu Leu Lys Val His His Ala Asn Glu Asn Ile Phe Tyr Cys Pro

20 25 30

Ile Ala Ile Met Ser Ala Leu Ala Met Val Tyr Leu Gly Ala Lys Asp

35 40 45

Ser Thr Arg Thr Gln Ile Asn Lys Val Val Arg Phe Asp Lys Leu Pro

50 55 60

Gly Phe Gly Asp Ser Ile Glu Ala Gln Cys Gly Thr Ser Val Asn Val

65 70 75 80

His Ser Ser Leu Arg Asp Ile Leu Asn Gln Ile Thr Lys Pro Asn Asp

85 90 95

Val Tyr Ser Phe Ser Leu Ala Ser Arg Leu Tyr Ala Glu Glu Arg Tyr

100 105 110

Pro Ile Leu Pro Glu Tyr Leu Gln Cys Val Lys Glu Leu Tyr Arg Gly

115 120 125

Gly Leu Glu Pro Ile Asn Phe Gln Thr Ala Ala Asp Gln Ala Arg Glu

130 135 140

Leu Ile Asn Ser Trp Val Glu Ser Gln Thr Asn Gly Ile Ile Arg Asn

145 150 155 160

Val Leu Gln Pro Ser Ser Val Asp Ser Gln Thr Ala Met Val Leu Val

165 170 175

Asn Ala Ile Val Phe Lys Gly Leu Trp Glu Lys Ala Phe Lys Asp Glu

180 185 190

Asp Thr Gln Ala Met Pro Phe Arg Val Thr Glu Gln Glu Ser Lys Pro

195 200 205

Val Gln Met Met Tyr Gln Ile Gly Leu Phe Arg Val Ala Ser Met Ala

210 215 220

Ser Glu Lys Met Lys Ile Leu Glu Leu Pro Phe Ala Ser Gly Thr Met

225 230 235 240

Ser Met Leu Val Leu Leu Pro Asp Glu Val Ser Gly Leu Glu Gln Leu

245 250 255

Glu Ser Ile Ile Asn Phe Glu Lys Leu Thr Glu Trp Thr Ser Ser Asn

260 265 270

Val Met Glu Glu Arg Lys Ile Lys Val Tyr Leu Pro Arg Met Lys Met

275 280 285

Glu Glu Lys Tyr Asn Leu Thr Ser Val Leu Met Ala Met Gly Ile Thr

290 295 300

Asp Val Phe Ser Ser Ser Ala Asn Leu Ser Gly Ile Ser Ser Ala Glu

305 310 315 320

Ser Leu Lys Ile Ser Gln Ala Val His Ala Ala His Ala Glu Ile Asn

325 330 335

Glu Ala Gly Arg Glu Val Val Gly Ser Ala Glu Ala Gly Val Asp Ala

340 345 350

Ala Ser Val Ser Glu Glu Phe Arg Ala Asp His Pro Phe Leu Phe Cys

355 360 365

Ile Lys His Ile Ala Thr Asn Ala Val Leu Phe Phe Gly Arg Cys Val

370 375 380

Ser Pro

385

<210> 836

<211> 1543

<212>RNA

<213> Artificial Sequence

<220>

<223> OVA RNAactive

<400> 836

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugggca 60

gcaucggggc cgcgucgaug gaguucugcu ucgacguguu caaggagcug aagguccacc 120

acgccaacga gaacaucuuc uacugcccga ucgccaucau gagcgcgcuc gccauggugu 180

accugggcgc caaggacagc acccggacgc agaucaacaa ggugguccgc uucgacaagc 240

ugcccggcuu cggggacucg aucgaggcgc agugcggcac cagcgugaac gugcacagcu 300

cgcuccggga cauccugaac cagaucacca agccgaacga cgucuacagc uucagccugg 360

ccucgcggcu cuacgccgag gagcgcuacc cgauccugcc cgaguaccug cagugcguga 420

aggagcucua ccggggcggg cuggagccga ucaacuucca gacggcggcc gaccaggccc 480

gggagcugau caacagcugg guggagagcc agaccaacgg caucauccgc aacguccucc 540

agccgucgag cguggacagc cagaccgcga uggugcuggu caacgccauc guguucaagg 600

gccuguggga gaagacguuc aaggacgagg acacccaggc caugcccuuc cgggugaccg 660

agcaggaguc gaagccgguc cagaugaugu accagaucgg gcucuuccgg guggcgagca 720

uggccagcga gaagaugaag auccuggagc ugccguucgc cucgggcacg augagcaugc 780

ucgugcugcu gcccgacgag gucagcggcc ucgagcagcu ggagucgauc aucaacuucg 840

agaagcugac cgaguggacc agcagcaacg ugauggagga gcgcaagauc aagguguacc 900

ucccgcggau gaagauggag gagaaguaca accugacguc gguccugaug gcgaugggga 960

ucaccgacgu guucagcagc ucggccaacc ucagcggcau cagcucggcc gagagccuga 1020

agaucagcca ggcggugcac gccgcccacg cggagaucaa cgaggccggc cgggaggucg 1080

uggggucggc cgaggcgggc guggacgccg ccagcgucag cgaggaguuc cgcgcggacc 1140

acccguuccu guucugcauc aagcacaucg ccaccaacgc cgugcucuuc uucggccggu 1200

gcgugucgcc cugaccacua gugcaucaca uuuaaaagca ucucagccua ccaugagaau 1260

1320

1380

1440

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaau gcauccccc cccccccccc 1500

cccccccccc cccccaaagg cucuuuucag agccaccaga auu 1543

<210> 837

<211> 1857

<212>RNA

<213> Artificial Sequence

<220>

<223> ppLuc

<400> 837

gggagaaagc uugagggaugg aggacgccaa gaacaucaag aagggccgg cgcccuucua 60

cccgcuggag gacgggaccg ccggcgagca gcuccacaag gccaugaagc gguacgcccu 120

ggugccgggc acgaucgccu ucaccgacgc ccacaucgag gucgacauca ccuacgcgga 180

guacuucgag augagcgugc gccuggccga ggccaugaag cgguacggcc ugaacaccaa 240

ccaccggauc guggugugcu cggagaacag ccugcaguuc uucaugccgg ugcugggcgc 300

ccucuucauc ggcguggccg ucgccccggc gaacgacauc uacaacgagc gggagcugcu 360

gaacagcaug gggaucagcc agccgaccgu gguguucgug agcaagaagg gccugcagaa 420

gauccugaac gugcagaaga agcugcccau cauccagaag aucaucauca uggacagcaa 480

gaccgacuac cagggcuucc agucgaugua cacguucgug accagccacc ucccgccggg 540

cuucaacgag uacgacuucg ucccggagag cuucgaccgg gacaagacca ucgcccugau 600

caugaacagc agcggcagca ccggccugcc gaagggggug gcccugccgc accggaccgc 660

cugcgugcgc uucucgcacg cccgggaccc caucuucggc aaccagauca ucccggacac 720

cgccauccug agcguggugc cguuccacca cggcuucggc auguucacga cccugggcua 780

840

gagccugcag gacuacaaga uccagagcgc gcugcucgug ccgacccugu ucagcuucuu 900

cgccaagagc acccugaucg acaaguacga ccugucgaac cugcacgaga ucgccagcgg 960

gggcgccccg cugagcaagg aggugggcga ggccguggcc aagcgguucc accucccgggg 1020

cauccgccag ggcuacggcc ugaccgagac cacgagcgcg

ggacgacaag ccgggcgccg ugggcaaggu ggucccguuc uucgaggcca agguggugga 1140

ccuggacacc ggcaagaccc ugggcgugaa ccagcggggc gagcugugcg ugcgggggcc 1200

1260

cggcuggcug cacagcggcg acaucgccua cugggacgag gacgagcacu ucuucaucgu 1320

cgaccggcug aagucgcuga ucaaguacaa gggcuaccag guggcgccgg ccgagcugga 1380

gagcauccug cuccagcacc ccaacaucuu cgacgccggc guggccggggc ugccggacga 1440

cgacgccggc gagcugccgg ccgcgguggu ggugcuggag cacggcaaga ccaugacgga 1500

gaaggagauc gucgacuacg uggccagcca ggugaccacc gccaagaagc ugcggggcgg 1560

cgugguguuc guggacgagg ucccgaaggg ccugaccggg aagcucgacg ccggaagau 1620

ccgcgagauc cugaucaagg ccaagaaggg cggcaagauc gccguguaag acuaguuaua 1680

agacugacua gcccgauggg ccucccaacg ggcccuccuc cccuccuugc accgagauua 1740

1800

aaaaaauauuu cccccccccc cccccccccc cccccccccc ucuagacaau uggaauu 1857

<210> 838

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Mp68 (2010107E04Rik) 5-UTR

<400> 838

ctttcccatt ctgtagcaga atttggtgtt gcctgtggtc ttggtcccgc ggag 54

<210> 839

<211> 54

<212>RNA

<213> Artificial Sequence

<220>

<223> Mp68 (2010107E04Rik) 5-UTR

<400> 839

cuuucccauu cuguagcaga auuugguguu gccugugguc uuggucccgc ggag 54

<210> 840

<211> 108

<212> DNA

<213> Artificial Sequence

<220>

<223> Nosip 5-UTR

<400> 840

ctcctgtcgg gcggaagtag gaggagtaga gtttaaaaac agtactcttt ttccggttcg 60

ggacgtagtt gaagcaacga caagccggat aaccgctctt gagacagg 108

<210> 841

<211> 108

<212>RNA

<213> Artificial Sequence

<220>

<223> Nosip 5-UTR

<400> 841

cuccugucgg gcggaaguag gaggaguaga guuuaaaaac aguacucuuu uuccgguucg 60

ggacguaguu gaagcaacga caagccggau aaccgcucuu gagacagg 108

<210> 842

<211> 62

<212> DNA

<213> Artificial Sequence

<220>

<223> HSD17B4 5-UTR

<400> 842

gtcccgcagt cggcgtccag cggctctgct tgttcgtgtg tgtgtcgttg caggccttat 60

tc62

<210> 843

<211> 62

<212>RNA

<213> Artificial Sequence

<220>

<223> HSD17B4 5-UTR

<400> 843

gucccgcagu cggcguccag cggcucugcu uguucgugug ugugucguug caggccuuau 60

uc62

<210> 844

<211> 84

<212> DNA

<213> Artificial Sequence

<220>

<223> Rpl31 5-UTR

<400> 844

cccgtgaccc ggaagttgta cggctacgcg actttccctc ccacaaaccc tcgcgccctt 60

cctttcctac ttgggcccgg caga 84

<210> 845

<211> 84

<212>RNA

<213> Artificial Sequence

<220>

<223> Rpl31 5-UTR

<400> 845

cccgugaccc ggaaguugua cggcuacgcg acuuucccuc ccacaaaccc ucgcgcccuu 60

ccuuuccuac uugggcccgg caga 84

<210> 846

<211> 102

<212> DNA

<213> Artificial Sequence

<220>

<223> TUBB4B 5-UTR

<400> 846

atataagcgt tggcggagcg tcggttgtag cactctgcgc gcccgctctt ctgctgctgt 60

ttgtctactt ccctcctgctt ccccgccgcc gccgccgcca tc 102

<210> 847

<211> 102

<212>RNA

<213> Artificial Sequence

<220>

<223> TUBB4B 5-UTR

<400> 847

auauaagcgu uggcggagcg ucgguuguag cacucugcgc gcccgcucuu cugcugcugu 60

uugucuacuu ccccugcuu ccccgccgcc gccgccgcca uc 102

<210> 848

<211> 75

<212> DNA

<213> Artificial Sequence

<220>

<223> ATP5A1 5-UTR

<400> 848

gcggctcggc cattttgtcc cagtcagtcc ggaggctgcg gctgcagaag taccgcctgc 60

ggagtaactg caaag 75

<210> 849

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> ATP5A1 5-UTR

<400> 849

gcggcucggc cauuuugucc cagucagucc ggaggcugcg gcugcagaag uaccgccugc 60

ggaguaacug caaag 75

<210> 850

<211> 81

<212> DNA

<213> Artificial Sequence

<220>

<223> Ndufa4 5-UTR

<400> 850

gtccgctcag ccaggttgca gaagcggctt agcgtgtgtc ctaatcttct ctctgcgtgt 60

aggtagggcct gtgccgcaaa c 81

<210> 851

<211> 81

<212>RNA

<213> Artificial Sequence

<220>

<223> Ndufa4 5-UTR

<400> 851

guccgcucag ccagguugca gaagcggcuu agcguguguc cuaaucuucu cucugcgugu 60

agguaggccu gugccgcaaa c 81

<210> 852

<211> 70

<212> DNA

<213> Artificial Sequence

<220>

<223> RPS9 3-UTR

<400> 852

gtccacctgt ccctcctggg ctgctggatt gtctcgtttt cctgccaaat aaacaggatc 60

agcgctttac 70

<210> 853

<211> 70

<212>RNA

<213> Artificial Sequence

<220>

<223> RPS9 3-UTR

<400> 853

guccaccugu cccuccuggg cugcuggauu gucucguuuu ccugccaaau aaacaggauc 60

agcgcuuuac 70

<210> 854

<211> 57

<212> DNA

<213> Artificial Sequence

<220>

<223> PSMB3 3-UTR

<400> 854

ccctgttccc agagccact ttttttttctt tttttgaaat aaaatagcct gtctttc 57

<210> 855

<211> 57

<212>RNA

<213> Artificial Sequence

<220>

<223> PSMB3 3-UTR

<400> 855

cccuguuccc agagcccacu uuuuuuucuu uuuuugaaau aaaauagccu gucuuuc 57

<210> 856

<211> 121

<212> DNA

<213> Artificial Sequence

<220>

<223> CASP1 3-UTR

<400> 856

aataaggaaa ctgtatgaat gtctgtggggc aggaagtgaa gagatccttc tgtaaaggtt 60

tttggaatta tgtctgctga ataataaact ttttgaaat aataaatctg gtagaaaaat 120

g 121

<210> 857

<211> 121

<212>RNA

<213> Artificial Sequence

<220>

<223> CASP1 3-UTR

<400> 857

aauaaggaaa cuguaugaau gucugugggc aggaagugaa gagauccuuc uguaaagguu 60

uuuggaauua ugucugcuga auaauaaacu uuuuugaaau aauaaaucug guagaaaaau 120

g 121

<210> 858

<211> 137

<212> DNA

<213> Artificial Sequence

<220>

<223> COX6B1 3-UTR

<400> 858

actggctgca tctccctttc ctctgtcctc catccttctc ccaggatggt gaagggggac 60

ctggtaccca gtgatcccca ccccaggatc ctaaatcatg acttacctgc taataaaaac 120

tcattggaaa agtgaga 137

<210> 859

<211> 137

<212>RNA

<213> Artificial Sequence

<220>

<223> COX6B1 3-UTR

<400> 859

acuggcugca ucucccuuuc cucuguccuc cauccuucuc cggauggu gaagggggac 60

120

ucauuggaaa agugaga 137

<210> 860

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 860

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 861

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 861

gggagaaagc uuaccaugga gcucggccuc uccuggaucu uccuccucgc cauccucaag 60

ggcguccagu gccaggucca gcucgucgag uccggcggcg gcgucgucca gcccggccgc 120

ucccuccgcc ucuccugcgc cgccuccggc uucaccuucu ccuccuacac caugcacugg 180

guccgccagg cccccggcaa gggccucgag ugggucaccu ucaucuccua cgacggcaac 240

aacaaguacu acgccgacuc cgucaagggc cgcuucacca ucucccgcga caacuccaag 300

aacacccucu accuccagau gaacucccuc cgcgccgagg acaccgccau cuacuacugc 360

gcccgcaccg gcuggcucgg ccccuucgac uacuggggcc agggcacccu cgucaccguc 420

uccuccgccu ccaccaaggg ccccuccguc uucccccucg cccccuccuc caaguccacc 480

uccggcggca ccgccgcccu cggcugccuc gucaaggacu acuuccccga gcccgucacc 540

gucuccugga acuccggcgc ccucaccucc ggcguccaca ccuuccccgc cguccuccag 600

uccuccggcc ucuacucccu cuccuccguc gucaccgucc ccuccuccuc ccucggcacc 660

cagaccuaca ucugcaacgu caaccacaag cccuccaaca ccaaggucga caagcgcguc 720

gagcccaagu ccugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcuccuc 780

ggcggccccu ccgucuuccu cuuccccccc aagcccaagg acacccucau gaucucccgc 840

acccccgagg ucaccugcgu cgucgucgac gucuccccg aggaccccga ggucaaguuc 900

aacugguacg ucgacggcgu cgagguccac aacgccaaga ccaagccccg cgaggagcag 960

uacaacucca ccuaccgcgu cgucuccguc cucaccgucc uccaccagga cuggcucaac 1020

ggcaaggagu acaagugcaa ggucuccaac aaggcccucc ccgcccccau cgagaagacc 1080

aucuccaagg ccaagggcca gccccgcgag ccccaggucu acacccuccc ccccucccgc 1140

gacgagcuca ccaagaacca ggucucccuc accugccucg ucaagggcuu cuaccccucc 1200

gacaucgccg ucgaguggga guccaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccguccucg acuccgacgg cuccuucuuc cucuacucca agcucaccgu cgacaagucc 1320

cgcuggcagc aggcaacgu cuucuccugc uccgucaugc acgaggcccu ccacaaccac 1380

uacacccaga agucccucuc ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 862

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 862

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcgcc ugagcuacuc 780

ggcggcccau ccguguuucu guuucccccu aagccaaagg acacgcuuau gauuucucgg 840

acucccgagg ucacaugcgu gguuguggau gucagccacg aagacccggga ggugaaauuu 900

aauugguacg uagauggggu ugaagugcau aacgcaaaga ccaaaccucg cgaggagcaa 960

uauaauucaa cuuacagagu cgugaguguc cugacagugu ugcaccagga cuggcucaac 1020

ggaaaggaau auaaauguaa gguuuccaau aaagcccugc ccgcuccaau cgagaagacc 1080

auaagcaagg ccaaagguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 863

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 863

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccca gcguguuccu guuccccccc aagcccaagg acacccugau gaucagcaga 840

acccccgagg ugaccugcgu ggugguggac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg uggacggcgu ggaggugcac aacgccaaga ccaagcccag agaggagcag 960

uacaacagca ccuacagagu ggugagcgug cugaccgugc ugcaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcccccau cgagaagacc 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 864

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 864

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuugc cauucugaag 60

ggggugcagu gccaagucca gcucguugaa uccggaggcg ggguggugca gccgggaaga 120

ucucugcggc uuagcugugc ugccuccggc uuuaccuucu cuagcuacac aaugcacugg 180

guccgccagg cgccugggaa aggacuggag ugggugacgu uuaucuccua ugacggcaac 240

aauaaguacu augcugauuc uguuaaaggc agauucacca uuagccggga caacuccaag 300

aauacacucu accugcaaau gaacagccug cgcgccgaag auaccgccau cuauuuacugc 360

gcuagaacag gguggcucgg accguuugac uauuggggcc aggggacccu ggugacaguc 420

ucuuccgcca gcaccaaagg acccucugug uucccucuug cucccuccag caagucuacg 480

uccggcggga ccgccgcgcu gggaugucuc guuaaggauu acuuuccuga gcccgugaca 540

gucagcugga acuccggcgc ccugaccucu ggcgugcaua cauucccugc ugugcuucag 600

660

cagacauaua uuugcaaugu gaaucacaaa cccuccaaca ccaaggucga caaacggggug 720

gaaccuaagu cuugugauaa aacacauacc ugucccccuu gccccgcccc ggagcugcuc 780

ggcggggccua gcguuuuucu guuucccccu aagcccaagg acacccuuau gaucucccgc 840

acacccgagg ugacgugcgu cgugguugau gugagccacg aagacccuga ggucaaauuc 900

aauugguacg uggauggagu cgaagugcau aacgcuaaga ccaaaccgag agaggagcaa 960

uauaauucua cauaccgggu uguguccguc cugaccgugc uccaccagga cuggcugaac 1020

ggcaaggaau auaaauguaa gguuagcaau aaagcccuuc ccgcgccuau cgagaagaca 1080

1140

gaugagcuca cgaagaacca agucagccug acaugccugg ugaaaggauu cuauccuucc 1200

1260

cccguucucg acagcgaugg cuccuuuuuc cuguacucua aacuuacagu cgacaagagc 1320

cgguggcagc aagggaaugu guucuccugu agcgugaugc acgaagcccu gcauaaccac 1380

uauacccaga agucucucuc ccugagcccu ggaaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 865

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 865

gggagaaagc uuaccaugga auuagguuua uccuggaucu uucuccuagc aauacucaaa 60

ggaguacaau gccaaguaca auuaguggaa uccggaggag guguaguaca accaggaaga 120

ucacuaagac uaucaugcgc agcaucagga uuuacauucu caucauacac aaugcacugg 180

guaagacaag cccggaaa aggauuagaa uggguuacau uuauauccua cgacggaaac 240

300

aacacacuau accuacaaau gaacucucuc cgagcagaag auacagccau auacuacugc 360

gcaagaacag gaugguuagg accuuucgac uacuggggac aaggaacucu aguaacuguc 420

ucaucugccu caacaaaagg cccaucagua uuuccacuag ccccaucauc uaaaucuaca 480

ucagguggaa ccgcugcauu aggaugcuua guaaaagacu auuuucccga accaguaacu 540

guaucuugga acuccggagc acuuacuucu gguguacaca cauucccagc aguuuuacaa 600

agcucaggac uauacucucu aagcucagua guaacugucc caucaucauc ccuuggcacc 660

caaacauaca uauguaacgu aaaucacaaa cccaguaaua ccaaaguaga caaaagagua 720

gaacccaaau caugugauaa aacacacaca ugcccccccu gcccagcacc ugaacuucua 780

ggaggaccau cuguauuccu cuucccucca aaaccaaaag auacucucau gauaucacgc 840

acacccgaag uaacuugugu cguaguagac guaucacacg aagacccaga aguuaaauuc 900

aacugguaug uagacggagu agaaguccac aacgcaaaaa caaaaccacg agaagaacaa 960

uacaacucca ccuaucgcgu aguuucagua cuuacaguuc uccaccaaga uuggcuaaac 1020

1080

auaaguaaag caaaagguca accacgagaa ccccaaguau auacacuucc accaucaaga 1140

gacgaacuua ccaaaaacca agucucacuc acaugcuuag uaaaaggauu uuacccauca 1200

1260

1320

cgauggcaac aaggcaaugu auucucuugu ucugucaugc augaagcacu acacaaccac 1380

uacacacaaa aaucacuauuc acuauccccc ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 866

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 866

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuguuggc cauucugaag 60

ggggugcagu gccaagucca gcucguggaa uccgguggcg ggguugugca gcccggcagg 120

agucugcggu ugagcugugc agccuccggu uuuaccuuca

guccgccagg cgccagggaa aggccuggag ugggugaccu uuaucuccua ugacggcaac 240

aauaaguacu augccgauag cgugaaaggg agguucacga uuucccggga caacaguaag 300

aauacucucu accugcaaau gaacagccug cgcgcagaag auaccgccau cuauuuacugc 360

gcaaggaccg guuggcucgg cccguuugac uauugggggc agggcacucu ggucaccgug 420

uccagcgcca guacgaaagg ucccuccgua uucccauugg cgccagcuc caagaguacu 480

agcgggggca ccgccgcacu gggcugucuc gugaaggauu acuuuccaga gcccgucacu 540

guguccugga auagcggggc ccugaccagu ggugugcaua ccuucccagc cguccugcag 600

uccagcggcu uguacagucu cuccagcgug guaacggugc cgagcuccag ucuggggacu 660

cagaccuaua uuugcaacgu caaucacaaa cccagcaaca cuaagggugga caaacggggug 720

gaaccaaagu ccugugauaa aacccauacc ugucccccau gccccgcacc ggagcugcuc 780

ggcgguccca gcgucuuucu guucccaccc aagccaaaag acacuuugau gaucagucgc 840

acgcccgagg ugaccugcgu aguggucgau gugucccg aagacccaga ggucaaguuu 900

aauugguacg uggauggcgu ggaaguacau aacgccaaga cuaaaccgag ggaggagcaa 960

uauaauagca ccuaccgggu ggucuccgug cugaccgucc uccaccagga cuggcugaac 1020

gggaaggaau auaaauguaa ggugaguaau aaagcgcugc ccgccccaau cgagaagacu 1080

auuagcaagg caaaaggcca gccccgcgaa ccacaggugu acacguugcc cccguccagg 1140

gaugagcuca ccaagaacca aguaagccug acuugccugg ugaaaggguu cuauccaagu 1200

gacaucgccg ucgaauggga guccaauggu cagcccgaga acaacuacaa gaccacuccc 1260

ccagugcucg acagcgaugg cuccuucuuu cuguacagua aauugaccgu cgacaagagc 1320

cgguggcagc aagggaaugu guucuccugc agcgugaugc acgaagcacu gcauaaccac 1380

uauacgcaga agagucucuc ccugagcccc ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 867

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 867

gggagaaagc uuaccaugga acucggccua agcuggaucu uccuccuggc cauccucaaa 60

ggcguacagu gccaggucca acucguagaa uccggaggcg gcgucguaca acccggccgc 120

ucccuccgcc uauccugcgc agcuuccggc uucacauuca guucauacac caugcacugg 180

guccgacaag cccccggcaa aggacucgaa ugggucacuu uuaucucuua cgacggcaac 240

aauaaauacu acgcagacuc cgucaaaggc cgcuuuacaa ucucacguga caacuccaaa 300

aacacccuau accuccaaau gaacucccua cgcgcugaag acaccgccau uuacuauugc 360

gcccgcacag gcuggcuugg accauucgac uacuggggac aaggaacccu ugucaccguc 420

uccucugcca gcaccaaagg ccccuccguc uucccccucg cucccagcuc caaauccacg 480

ucaggcggca cugcagcccu cggaugccua gucaaagacu acuuccccga acccgucaca 540

gucucaugga acuccggagc ccucacuuca ggcguccaca ccuuccccgc aguacuacaa 600

ucuucaggcc uauacucccu aagcuccguc gucaccguac ccuccucauc ccucggaaca 660

caaaccuaca uaugcaacgu caaccacaaa cccucaaaca caaaaguaga caaacgcguc 720

gaacccaaau ccugcgacaa aacccauacc ugcccacccu gccccgcccc ggaacuccua 780

ggcggcccca gcgucuucuu auucccaccc aaacccaaag acacgcucau gauaaguaga 840

acccccgaag ugaccugcgu cgucgucgac gucuccccg aagacccuga aguuaaauuc 900

aacugguacg ucgacggcgu cgaaguucac aacgccaaaa ccaaaccccg agaagaacaa 960

uacaacucca ccuaccgagu cgucucagua cuaacagucc uccaccaaga cuggcucaac 1020

ggaaaagaau acaaaugca agucuccaac aaagcacuac cugccccaau cgagaaaaca 1080

1140

gacgaacuca ccaaaaauca ggucagccua accugccucg ucaaaggauu cuaccccucc 1200

gacaucgccg ucgaauggga aagcaacggc caacccgaaa acaacuacaa aaccacccca 1260

cccguaacucg acuccgacgg cuccuucuuc cucuacucca agcucaccgu cgacaaaucc 1320

cgcuggcaac agggaaacgu auucuccugc uccgucaugc acgaagcccu ccacaaccac 1380

uauacccaaa aaucacucuc ccuaucaccc ggaaaauaag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 868

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 868

gggagaaagc uuaccaugga acuaggccua ucauggaucu uccuccucgc cauccucaaa 60

ggcguccaau gccaggucca acucgucgaa uccggcggag gcgucgucca acccggccga 120

uucaccgcc ucuccugcgc cgccuccggc uucacuuucu ccuccuacac aaugcacugg 180

guacgccaag ccccaggaaa aggacucgaa ugggucaccu ucaucuccua cgacggaaac 240

aacaaauacu acgccgacag cguuaaagga cgauucacaa ucucccgcga caacucuaaa 300

aacacccuau accuccaaau gaacucccuc cgcgccgaag acacagcaau cuacuacugc 360

gccagaaccg gauggcuagg ccccuucgac uacuggggcc aaggaacccu cgucacagua 420

uccuccgccu ccaccaaagg cccuuccgua uuuccccugg cccccucauc caaauccacc 480

agcggcggaa ccgccgcacu uggcugccuc guaaaagacu acuuccccga acccguaacc 540

gucucugga acagcggcgc ccuaacguca ggcguacaca ccuuccccgc aguccuccaa 600

uccuccggac uauauagccu cuccagcgua guaacaguac ccuccagcuc ucucggcaca 660

caaaccuaua ucugcaacgu aaaccacaaa cccagcaaca ccaaaguuga caaacgcguu 720

gaacccaaau ccugcgacaa aacccacaca ugcccacccu gccccgcccc cgaacuccuc 780

ggcggucccu cagucuuccu cuucccacca aaaccuaaag acacucuaau gauaucccgc 840

accccagaag ugaccugcgu cguagucgac gucuccccg aagaccccga agucaaauuc 900

aacugguacg ucgacggcgu cgaaguacac aacgccaaaa ccaaacccg agaagaacaa 960

uacaacucaa ccuacagagu cgucagcguc cucaccgucc uccaucagga cuggcucaac 1020

1080

1140

gacgaacuca ccaagaacca aguaucuuua accugccuug ucaaaggcuu cuaccccucc 1200

gacaucgccg uggaauggga auccaacggga caacccgaaa acaacuacaa gaccacacca 1260

cccguccuug acumagacgg cuccuucuuc cucuauucca aacuuaccgu cgacaaaucc 1320

cgauggcaac aaggcaacgu cuucuccugc ucaguaaugc acgaagcccu acacaaccac 1380

uacacgcaaa aaucacucuc ccuguccccc ggaaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 869

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 869

gggagaaagc uuaccaugga acuuggccuu uccuggaucu uccuccucgc cauacucaaa 60

ggcguccaau gccaaguuca gcuagucgaa uccgguggcg gcguagucca acccggacgc 120

agccuccgac uauccugcgc cgccuccggga uucaccuucu ccucauacac caugcacugg 180

guccgccaag cccccggcaa aggccucgaa ugggucacau ucaucuccua cgauggaaac 240

aacaaauacu acgccgacuc agucaaaggc cgcuucacaa ucucccgaga caacuccaaa 300

aacacccuau accuccaaau gaacucacuu agagccgaag acacagcaau auacuacugc 360

gcccgcaccg gauggcuagg acccuucgac uacuggggcc aagggacccu cgucaccguu 420

agcuccgccu ccacaaaagg acccuccgua uucccccucg ccccauccuc caaauccaca 480

ucuggcggca ccgccgcacu cggaugccuc guaaaagacu acuuccccga acccgucaca 540

gucagcugga acucaggcgc ucucaccucc ggcguccaca cauucccggc aguccugcaa 600

agcagcggcc ucuacucccu aucaucugua gucaccgucc cauccucuuc ccucggcacc 660

caaaccuaca ucugcaacgu aaaccacaaa cccagcaaca ccaaagugga uaaacgagua 720

gaacccaaau cuugcgacaa aacccacacu ugcccacccu gccccgcccc agaacuucua 780

ggcggacccu ccgucuuccu cuuccccc aaacccaaag acacccucau gaucucacgc 840

acccccgagg uaaccugcgu ugucgucgac gugucccacg aagacccuga agucaaguuc 900

aacugguacg ucgacggcgu cgaagugcac aacgccaaaa caaaaccacg cgaagaacaa 960

uauaacucaa ccuaccgcgu agucuccguc cuaaccgucc uccaccaaga cuggcuaaac 1020

ggcaaagaau acaaauguaa aguauccaau aaagcacucc ccgcccccaau agagaaaacg 1080

1140

gacgaacuca ccaaaaacca aguaucccua accugccuag ucaaaggcuu cuaccccucc 1200

gacaucgcag uagaauggga auccaacggc caaccagaaa acaacuacaa gacaacaccu 1260

cccguccucg acuccgacgg auccuucuuc uuauacucaa aacuaaccgu cgacaaaucu 1320

agauggcaac aaggcaacgu cuucucaugc uccguaaugc acgaagcucu ccacaaccac 1380

uacacccaaa aaucacucuc ccucuccccc ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 870

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 870

60

ggcguccaau gucaaguaca acuaguagaa ucaggcggag gaguugucca acccggccga 120

ucccuccgcu uaucaugugc agcaucugga uucacauuuu caucauacac aaugcacugg 180

gucagacaag cccggaaa agguuuagaa uggguaacau uuauaucaua cgacgguaac 240

aacaaauacu augcagacuc aguaaaagga agauuuacaa ucagcagaga caauagcaaa 300

aacacacuau accuacaaau gaacucccua cgagcagaag acacagccau cuauuacugu 360

gcacgaacag gauggcuagg accauucgau uacuggggcc aaggaacauu agucaccgua 420

ucuucugcau ccacaaaagg uccuucagua uuuccauuag cacccagcuc caaaucuaca 480

ucuggcggaa cagccgccuu aggaugcuua guuaaagauu acuuuccaga accaguaaca 540

guuucaugga acucaggagc ucuaacaucu ggaguacaca cauuuccagc aguccuacaa 600

ucauccggac uauauucacu aucaucagua guaacugucc ccucaucauc auuaggcaca 660

caaacuuaua uuugcaaugu aaaccauaaa ccaucaaaua caaaagucga caaaagagua 720

gaaccaaaau caugcgacaa aacccacaca uguccacccu gccccgcccc agaauuauua 780

ggaggaccau cugucuuccu uuucccacca aaaccaaaag acaccuuaau gauaucucga 840

acuccagaag uaacaugugu aguuguagau guuucacaug aagacccaga aguaaaauuc 900

aacugguacg ucgacggagu agaaguacac aaugcaaaaa caaaaccccg agaagaacaa 960

uacaacucca cauacagagu agucucagua cuaacaguac uccaucaaga cuggcuaaac 1020

ggaaaagaau acaaauguaa aguaaguaau aaagcacuac ccgcaccaau agaaaaaaca 1080

auaucaaaag caaaaggaca accaagagaa ccacaaguau auacacuacc uccauccaga 1140

gaugaauuaa caaaaaacca aguaagucua acauguuuag uaaaaggauu cuaucccagc 1200

gacauagcag ucgaauggga aucaaaugga caaccagaaa acaacuauaa aaccacacca 1260

ccaguauuag auucagacgg aucauuuuuc cuuuacucaa aauuaacagu agacaaaucc 1320

agauggcaac aaggcaaugu cuuuucaugc ucugucaugc acgaagcucu acauaaucac 1380

uacacucaaa aaucacuauuc acucucacca ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 871

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 871

60

ggaguacaau gucaaguaca auuaguagaa uccggaggcg gaguagucca acccggaaga 120

ucacuaagac ucaguugugc agcaucagga uucacauuuu caucauauac aaugcacugg 180

guuagacaag cacccggaaa aggacucgaa uggguaaccu uuaucuccua cgauggaaac 240

300

360

gcaagaacag gauggcucgg accauucgac uauuggggac aaggaaccuu aguaacagua 420

uccagcgcua gcacaaaagg cccuucuguc uucccauuag caccauccuc aaaaucaacu 480

ucuggcggaa cagcagcucu aggaugcuua guaaaagauu auuuuccaga accaguuacu 540

guauccugga acucaggagc acuaaccagu ggaguucaca cauuuccagc cguauuacaa 600

ucauccggau uauauucauu aucauccguc guaaccguac caagcucauc auuaggaaca 660

caaacauaca uaugcaacgu aaaucacaaa ccauccaaua caaaaguaga uaaaagagua 720

gaaccuaaau ccuugauaa aacacacaca ugcccaccau gcccagcacc agaauuacua 780

ggaggaccau caguauuccu auucccacca aaaccaaaag auacacuaau gauaucaaga 840

acaccagaag uaacuugugu agucguagac gucucacaug aagacccaga aguaaaauuuu 900

aauugguaug uugacggagu cgaaguacac aacgccaaaa caaaaccacg agaagaacaa 960

uacaacucaa cauauagagu aguaucugua uuaacaguau uacaucaaga uugguuaaac 1020

ggaaaagaau acaaauguaa aguaucaaau aaagcucuac cagcaccaau agaaaagaca 1080

1140

gacgaauuaa ccaaaaacca agucucauua acaugcuuag uuaaagguuu cuaccccagc 1200

gacaucgcag uugaauggga aucaaacggu caaccugaaa acaacuauaa aacaacacca 1260

ccaguuuuag acucagaugg auccuuuuuc uuauacucaa aauuaacagu ugacaaauca 1320

agauggcaac aaggaaaugu cuuuucaugu uccgucaugc augaagcacu acacaaccau 1380

uacacccaaa aaucacucuc acuaucaccc gguaaauaag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 872

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 872

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcggcccga gcguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ucacgugcgu gguggucgac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg ucgacggggu ggaggugcac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu cgugagcgug cugaccgucc uccaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugucgaac aaggcccugc cggcccccau cgagaagacg 1080

aucagcaagg cgaagggcca gccgcgggag ccccaggucu acacccuccc gccgccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 873

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 873

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcccc cgagcugcug 780

ggcggcccga gcguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ucacgugcgu gguggucgac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg ucgacggggu ggaggugcac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu cgugagcgug cugaccgucc uccaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugucgaac aaggcccugc cggcccccau cgagaagacg 1080

aucagcaagg cgaaggguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 874

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 874

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccga gcguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ucacgugcgu gguggucgac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg ucgacggggu ggaggugcac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu cgugagcgug cugaccgucc uccaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugucgaac aaggcccugc cggcccccau cgagaagacg 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 875

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 875

gggagaaagc uuacccaggu gcagcugguc gagagcggcg ggggcguggu gcagcccggg 60

cgcucccucc ggcugagcug cgccgccucc ggcuucaccu ucagcuccua caccaugcac 120

uggguccgcc aggcgccggg gaagggccug gaguggguga cguucaucag cuacgacggc 180

aacaacaagu acuacgccga cuccgugaag gggcgguuca ccaucagccg cgacaacucc 240

aagaacaccc ucuaccugca gaugaacagc cugcgggccg aggacaccgc caucuacuac 300

ugcgcccgca cgggcuggcu cgggcccuuc gacuacuggg gccaggggac ccuggucacc 360

guguccagcg cguccaccaa gggccccagc guguuccccc uggccccguc cagcaagucc 420

acgagcggcg ggaccgccgc ccucggcugc cuggucaagg acuacuuccc cgagcccgug 480

accguguccu ggaacagcgg ggcgcugacc agcggcgucc acacguuccc cgccgugcuc 540

caguccagcg gccuguacuc ccuagcucc guggucaccg ugccgagcuc cagccucggg 600

acccagaccu acaucugcaa cgugaaccac aagcccucca acacgaaggu cgacaagcgg 660

guggagccca agagcugcga caagacccac acgugcccgc ccugccccgc ccccgagcug 720

cugggcgggc ccuccguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggugaccug cgucgugguc gacguguccc acgaggaccc ggaggucaag 840

uucaacuggu acguggacgg cguggagguc cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca ggaccuaccg cgugggugucc guccugacgg ugcuccacca ggacuggcug 960

1020

accaucucca aggccaaggg ccagccgcgg gagccccagg ucuacacccu cccgcccagc 1080

cgcgacgagc ugaccaagaa ccaggugucc cugacgugcc ucgugaaggg cuucuacccc 1140

agcgacaucg ccgucgagug ggagagcaac gggcagcccg agaacaacua caagaccacg 1200

cccccggugc uggacuccga cggcagcuuc uuccuguacu ccaagcucac cguggacaag 1260

agccgguggc agcaggggaa cgucuucucc ugcagcguga ugcacgaggc ccugcacaac 1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 876

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 876

ggggagaaagc uuacccaggu ccagcucguc gaguccggcg gcggcgucgu ccagcccggc 60

cgcucccucc gccucuccug cgccgccucc ggcuucaccu ucuccuccua caccaugcac 120

uggguccgcc aggccccgg caagggccuc gaguggguca ccuucaucuc cuacgacggc 180

aacaacaagu acuacgccga cuccgucaag ggccgcuuca ccaucucccg cgacaacucc 240

aagaacaccc ucuaccucca gaugaacucc cuccgcgccg aggacaccgc caucuacuac 300

ugcgcccgca ccggcuggcu cggccccuuc gacuacuggg gccagggcac ccucgucacc 360

gucuccuccg ccuccaccaa gggccccucc gucuuccccc ucgcccccuc cuccaagucc 420

accuccggcg gcaccgccgc ccucggcugc cucgucaagg acuacuuccc cgagcccguc 480

accgucuccu ggaacuccgg cgcccucacc uccggcgucc acaccuuccc cgccguccuc 540

caguccuccg gccucuacuc ccucuccucc gucgucaccg uccccuccuc cucccucggc 600

acccagaccu acaucugcaa cgucaaccac aagcccucca acaccaaggu cgacaagcgc 660

gucgagccca aguccugcga caagacccac accugccccc ccugccccgc ccccgagcuc 720

cucggcggcc ccuccgucuu ccucuucccc cccaagccca aggacacccu caugaucucc 780

840

uucaacuggu acgucgacgg cgucgagguc cacaacgcca agaccaagcc ccgcgaggag 900

caguacaacu ccaccuaccg cgucgucucc guccucaccg uccuccacca ggacuggcuc 960

1020

accaucucca aggccaaggg ccagccccgc gagccccagg ucuacacccu cccccccucc 1080

cucaccugcc ucgucaaggg cuucuacccc 1140

uccgacaucg ccgucgagug ggaguccaac ggccagcccg agaacaacua caagaccacc 1200

ccccccgucc ucgacuccga cggcuccuuc uuccucuacu ccaagcucac cgucgacaag 1260

ucccgcuggc agcagggcaa cgucuucucc ugcuccguca ugcacgaggc ccuccacaac 1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 877

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 877

gggagaaagc uuacccaggu gcaacugguc gagagcggcg ggggaguugu gcagcccggu 60

agaucccuca ggcuuucuug cgccgcuuca ggcuucaccu uuaguagcua cacaaugcac 120

uggguacggc aggcaccugg gaagggacug gaauggguga cuuucaucuc cuaugacggc 180

aacaauaaau acuaugccga uucugucaag ggucgcuuua cgauuucgcg agacaacagc 240

aaaaauaccu uguacuuaca gaugaacuca cugcgugcgg aggauacagc uauauauuac 300

ugugccagaa cuggguggcu aggaccauuc gacuauuggg gccaaggcac ccucgugaca 360

guuaguuccg caucuaccaa ggggccgagc guguuucccc uggccccuuc cucaaaaaagu 420

acuagcggag guaacagcugc acuuggcugc cuggucaagg auuacuuccc agaacccgug 480

accguaucuu ggaacuccgg ggccuugacg ucaggaguuc auacuuuucc ugcugugcuc 540

cagagcagug gccuguacuc ucuguccagc gucgugaccg ugccaucguc uucccucggu 600

acacagacuu auaucuguaa ugucaaucac aagcccucaa acaccaaagu ugacaagagg 660

guggagccua aaaguugcga uaagacacau accuguccac cgugccccgc cccugaauua 720

cuugggggac caagcguauu ccuguuuccc ccuaaaccaa aggacacguu gaugauuucc 780

cggacucccg aggugacaug ugucgugguu gaugugucuc acgaggaccc ggaagucaag 840

uucaauuggu acguggaugg cguagagguu cauaacgcga aaaccaagcc ucgcgaagaa 900

caguauaaua gcacuuacag aguggucuca gugcugacag uccuacacca agacuggcuc 960

aacggcaaag aguauaagug caaagugagu aauaaggcac ugcccgcccc aaucgagaaa 1020

accauuucca aggcuaaggg gcagccuagg gagccccagg uuuacacgcu uccacccagc 1080

cgggaugaac ugaccaaaaa ccaggugucu uugacauguc ucguaaaggg auuuuauccu 1140

ucagacaucg ccgucgagug ggaaaguaau ggucaaccag agaacaacua caaaacuacc 1200

ccgcccgugc uggacagcga uggcuccuuc uuuuuauacu cuaagcugac aguugacaaa 1260

ucgcgcuggc agcaggggaa uguguucagc ugcuccguca ugcacgaggc acuccauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 878

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 878

gggagaaagc uuacccaggu gcagcuggug gagagcggcg gcggcguggu gcagcccggc 60

agaagccuga gacugagcug cgccgccagc ggcuucaccu ucagcagcua caccaugcac 120

ugggugagac aggccccgg caagggccug gaguggguga ccuucaucag cuacgacggc 180

aacaacaagu acuacgccga cagcgugaag ggcagauuca ccaucagcag agacaacagc 240

aagaacaccc uguaccugca gaugaacagc cugagagccg aggacaccgc caucuacuac 300

ugcgccagaa ccggcuggcu gggccccuuc gacuacuggg gccagggcac ccuggugacc 360

gugagcagcg ccagcaccaa gggccccagc guguuccccc uggcccccag cagcaagagc 420

accagcggcg gcaccgccgc ccugggcugc cuggugaagg acuacuuccc cgagcccgug 480

accgugagcu ggaacagcgg cgccugacc agcggcgugc acaccuuccc cgccgugcug 540

600

acccagaccu acaucugcaa cgugaaccac aagcccagca acaccaaggu ggacaagaga 660

guggagccca agagcugcga caagacccac accugccccc ccugccccgc ccccgagcug 720

cugggcggcc cggcguguu ccuguucccc cccaagccca aggacacccu gaugaucagc 780

agaacccccg aggugaccug cgugguggg gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acguggacgg cguggaggug cacaacgcca agaccaagcc cagagaggag 900

caguacaaca gcaccuacag aguggugagc gugcugaccg ugcugcacca ggacuggcug 960

1020

accaucagca aggccaaggg ccagcccaga gagccccagg uguacacccu gccccccagc 1080

agagacgagc ugaccaagaa ccaggugagc cugaccugcc uggugaaggg cuucuacccc 1140

agcgacaucg ccguggagug ggagagcaac ggccagcccg agaacaacua caagaccacc 1200

ccccccgugc uggacagcga cggcagcuuc uuccuguaca gcaagcugac cguggacaag 1260

1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 879

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 879

gggagaaagc uuacccaggu gcaacugguc gagagcggcg ggggaguugu gcagcccggc 60

agaucccucc ggcugucuug cgccgcuagc ggguucaccu uuuccucuua cacaaugcac 120

ugggugcgcc aggccccugg aaagggccuu gaauggguca cguucaucag cuaugacggg 180

aacaauaaau acuaugcgga uuccgugaag ggaagauuua ccauuucucg ggacaacagc 240

aaaaauacac uguaccucca gaugaacucc cugcgcgcug aggauaccgc caucuauuac 300

ugugccagaa caggcuggcu uggcccguuc gacuauuggg ggcaaggaac ccugguuaca 360

gugagcucug cuuccaccaa gggccccagc gucuuuccuc ucgcccccuc uuccaaaagc 420

acgucugggg gaaccgcugc ccugggcugc cuggugaagg auuacuuccc ugaacccguu 480

acaguguccu ggaauagcgg ggcgcucacc uccggagucc auacauuucc ugccgugcug 540

cagucuagcg gccuuuuacuc ccugagcucu guggucaccg uuccguccag cucucucggc 600

acgcagacau auauuuguaa cgugaaucac aagcccagca acaccaaagu ggacaagcgg 660

gucgagccua aauccugcga uaagacacau accugucccc cuugccccgc uccggaacug 720

cuugggggac cuucuguguu ccuguuuccc ccuaaaccca aggacacccu caugaucagc 780

cgcacacccg agguuacgug ugggucgug gauguuuccc acgaggaccc ugaagugaag 840

uucaauuggu acgucgaugg cguggagguc cauaacgcca aaaccaagcc gagagaagaa 900

caguauaaua gcacauaccg ggugguuucu gugcugaccg uccugcacca agacuggcuc 960

aacgggaaag aguauaagug caaagugucc aauaaggcuc ugcccgcccc uauugagaaa 1020

acaaucagca aggcgaaggg acagccccgc gagccucagg uuuacacccu ucccccgucu 1080

agagaugaac ugacgaaaaa ccaggugucc cucacauguc uggucaaggg cuuuuauccu 1140

agcgacaucg ccguggagug ggaauccaau gggcaacccg agaacaacua caaaaccacc 1200

ccucccgugc uugacucuga uggcagcuuc uuucuguacu ccaagcucac aguugacaaa 1260

ucucgguggc agcagggaaa ugucuucagc ugcuccguga ugcacgaggc ucugcauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 880

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 880

gggagaaagc uuacccaagu ucaacuagua gaaucaggag gaggagucgu ccaaccaggc 60

agaucacuaa gacuaucaug ugcagccucu ggcuucacau ucucuucuua uacaaugcac 120

uggguaagac aagcaccagg aaaaggacua gaauggguaa cauucauauuc uuacgacgga 180

auuacgcuga uucuguaaaa gguagauuca caauuucuag agacaauagu 240

aaaaauacau uauaccucca aaugaauagu cuuagagcag aagauacagc aauauacuau 300

ugugcacgaa caggaugguu aggaccauuc gauuacuggg gucaaggaac auuaguaaca 360

guaucaucug caucaacaaa agguccuuca guauucccac ucgcaccauc aucaaaaucc 420

acaucaggag gaacugcagc ccucggaugc cuagucaaag acuacuuccc agaaccagua 480

accguaucuu ggaacuccgg agcauuaaca ucuggaguac auacauuccc ugcaguacuc 540

caaucaucag gacuauacuc acuauccucc guaguaaccg ucccuucauc aucucuaggu 600

acacaaacuu acauaugcaa cguaaaucac aaaccaucua auacaaaagu agacaaaaga 660

gucgaaccaa aaucaugcga caaaacccac acaugccccc caugcccagc acccgaacua 720

cucggaggac caucaguauu ucuauuucca ccaaaaccaa aagauacacu augauauca 780

840

uuuaauuggu acguagacgg uguagaaguu cacaaugcaa aaacaaaacc aagagaagaa 900

caauacaacu caacauauag aguaguuucu gucuuaaccg ucuuacacca agauugguua 960

1020

acaauaucaa aagccaaagg ccaaccucga gaaccacaag uauacacacu acccccuuca 1080

agagaugaac uaacaaaaaa ccaaguaagc cuaacaugcc uaguaaaagg cuuuuaucca 1140

ucagacauag caguagaaug ggaaucuaac ggucaaccug aaaauaacua uaaaacaaca 1200

ccaccaguac uagacucaga uggauuc uuucuauacu caaaauuaac aguagauaaa 1260

ucaagauggc aacaaggaaa cguuuuuucu uguucuguaa ugcacgaagc acuacacaau 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 881

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 881

gggagaaagc uuacccaggu gcaacugguc gagagcggcg gggguguggu acagcccggc 60

aggucccucc ggcugaguug cgccgcaagc ggguucaccu uuuccaguua cacuaugcac 120

ugggugcgcc aggccccagg caaggguuug gaauggguca ccuucaucag cuaugacggg 180

aacaauaaau acuaugcgga uuccgugaag ggcagguuua cgauuagccg ggacaacucc 240

aaaaauacuc uguaccucca gaugaacagu cugcgcgccg aggauaccgc aaucuauuac 300

ugugccagga ccggcugguu ggggccguuc gacuauuggg gucaaggcac ucggugacc 360

gucagcuccg caagcacgaa ggggcccagu guguuuccac ucgcccccuc cagcaaaucc 420

accaguggcg guaccgcggc ccuggggugc cugguaaagg auuacuuccc agaacccgg 480

acugucagcu ggaacuccgg cgcacucacc agcggcgugc auaccuuucc agccgugcug 540

cagaguuccg gguuguacag ccugaguucc gucgugacgg uaccgagcag cucccucggu 600

acucagaccu auauuuguaa ugugaaucac aagcccagua acacuaaagu cgacaagcgg 660

guggagccaa aaagcugcga uaagacccau accugucccc caugccccgc ccgggaacug 720

cugggcgggc ccuccguguu cuuguuucca cccaaaccaa aggacacucu caugaucagc 780

840

uucaauuggu acgucgaugg cguggaggug cauaacgcaa agacuaagcc gagggaagaa 900

caguauaauu ccaccuaccg gguagugagc guccugaccg ugcugcacca agacuggcuc 960

1020 aacgguaaag aguauaagug caaagucucc aauaaggccc

acuaucagua aggccaaggg ccagccccgc gagccacagg uguacacguu gcccccgagc 1080

agggaugaac ugaccaaaaa ccaggugucc cucacuuguc ugguaaaggg guuuuaucca 1140

agcgacaucg caguggagug ggaaaguaau ggccaacccg agaacaacua caaaaccacu 1200

1260

1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 882

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 882

gggagaaagc uuacccaagu ccagcuagua gaauccggcg gaggcgucgu ccaaccagga 60

cgcucgcuaa gacucagcug cgccgcaucu ggcuucacau ucagcucaua cacaaugcac 120

ugggucagac aagcuccagg caaaggccuc gaauggguca cauucauauuc auacgacggc 180

aacaacaaau acuacgccga cuccguaaaa ggccgcuuca ccaucuccag agacaacucc 240

aaaaacaccc uauaccucca aaugaacuca cucagagccg aagacaccgc aaucuacuac 300

ugcgcaagaa ccggcuggcu uggccccuuc gauuacuggg gacaaggcac ccucgucacc 360

gucucauccg cauccaccaa aggcccaucc gucuuccccc ucgcaccauc auccaaaucc 420

accagcggag guaccgccgc acucggcugc cuagucaaag acuacuuccc cgaaccuguc 480

acagucuccu ggaacuccgg agcccucaca ucgggcgucc acacauuccc cgccguccua 540

caaagcuccg gccucuacag ccucuccuca gucgucaccg uacccuccuc cagccucgga 600

acacaaaccu acaucugcaa cguuaaccac aaaccuucca acaccaaagu cgacaaacga 660

gucgaaccca aaucgugcga caaaacccau accugcccac ccugccccgc ccccgaacuc 720

cucggcggcc cauccgucuu ccuauuccca cccaaaccaa aggacacacu caugauauca 780

cgaaccccug aagucacgug cgucgucguc gacguuucac acgaagaccc cgaagucaaa 840

uucaacuggu acguagacgg agucgaaguc cacaacgcca aaaccaaacc cggagaagaa 900

cauaccaacu cuaccuaccg cgucguaucc guccucaccg uccuccacca agacuggcua 960

1020

accaucucca aagccaaagg acaaccccgc gaaccccaag uguacacccu cccacccucg 1080

1140

uccgacauag caguagaaug ggaaucuaac ggccagcccg aaaacaacua caaaacaacc 1200

ccacccguac ucgacuccga cggcucauuc uuccucuacu caaaacucac cgucgauaaa 1260

ucccgcuggc aacaaggcaa ugucuucuca ugcagcguca ugcacgaagc acuccacaac 1320

cacuacacac aaaagagccu cucccuaucc cccggcaaau gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 883

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 883

gggagaaagc uuacccaagu ccagcuaguc gaaucaggcg gaggcgucgu ccaacccgga 60

cggucccuac gacucagcug ugcugccagc ggcuucaccu ucucguccua cacaaugcac 120

uggguccggc aagcacccgg caaaggucuc gaauggguca ccuucauauuc cuaugacggc 180

aacaacaaau acuacgccga cuccgucaaa ggccgcuuca caaucucaag agacaacucc 240

300

ugcgcccgca ccggauggcu cggccccuuc gacuacuggg gccaaggcac ccuagucaca 360

guaucauccg ccucuacaaa gggaccaucc gucuuccccc ucgccccauc cuccaaaucc 420

accucuggag gcaccgccgc acucggaugc cucgucaaag acuacuuccc cgaacccguc 480

acagucuccu ggaacuccgg cgcccuaacc uccggagagucc acacauuccc ugcuguccua 540

caauccucgg gccuauacuc ccucucaucu guagucaccg uccccucauc cucccuugga 600

acccaaacgu acauaugcaa cgucaaccac aaaccuucca acacaaaagu cgacaaacgu 660

guagagccaa aguccuguga caaaacacac acaugcccac caugucccgc gcccgaacua 720

cucggcggac ccucagucuu ccucuuuccc ccgaaaccca aagacacccu caugauauca 780

cgcacccccg aaguuaccug cgucgucguc gacgucuccc acgaagaccc cgaagucaaa 840

uucaacuggu acgucgacgg cguagaaguc cacaacgcca aaaccaaacc acgggaagaa 900

caauacaacu ccacauaccg cgucgucagc guacucaccg uccuacauca agacuggcua 960

1020

1080

agagacgaac ucaccaaaaa ccaaguuuca cucacaugcc ucguaaaagg auucuacccc 1140

ucugacauug cugucgaaug ggaauccaac ggacaacccg aaaacaacua caaaaccacc 1200

ccgcccgucc ucgacuccga cggcucauuc uuccuauacu ccaaacucac cguagacaaa 1260

ucccgauggc agcaaggcaa cgucuucucc ugcagcguaa ugcacgaagc acuccacaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 884

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 884

gggagaaagc uuacccaagu acaacucguc gaauccggcg gcggcguagu ccaaccaggc 60

agaucccuac gccucuccug cgccgcaucc ggauucaccu ucuccuccua caccaugcac 120

uggguacgcc aagccccgg caagggccuc gaauggguca cguucaucuc uuacgacggc 180

aacaacaaau acuacgccga cuccguaaaa ggucguuuca ccaucucccg cgacaacagc 240

aaaaacaccc uauaccuuca aaugaacucc cuccgcgccg aagacaccgc caucuacuac 300

ugugcccgca ccgguuggcu cggccccuuc gacuacuggg gucaaggaac ccuaguuacc 360

guaucauccg caucuaccaa aggccccucc guauucccac uagccccauc guccaaauca 420

acaucaggcg gcacagccgc ccucggaugc cuagucaaag acuacuuccc cgaacccguc 480

accgucucau ggaacuccgg agcccuaacc ucgggagucc acaccuuccc agcgguacua 540

caaucauccg gacuuuacuc ccuaucaucc gucgucacag uaccauccuc aucccucgggg 600

acccaaaccu acauaugcaa cgucaaccac aaaccaucca acaccaaagu cgacaaaaga 660

gucgaaccaa aauccugcga caaaacccac acaugcccac ccugcccagc ccccgaacuc 720

cucggcggcc ccuccguauu ccucuuccca cccaaaccca aggacacccu caugaauaucc 780

cgcaccccag aaguaaccug cguaguaguc gacguuucac acgaagaccc cgaagucaaa 840

uucaacuggu acguagacgg cgucgagguc cacaacgcca aaaccaaacc ucgcgaagaa 900

caauacaaca gcacauaccg cgucgucucc guccuaaccg uacuacacca agacuggcua 960

1020

accauaucca aagccaaagg ucaaccccgc gaaccccaag uauacacccu acccccaucc 1080

1140 cgcgacgagc ucaccaaaaa ccaaguaucc cuaaccugcc

uccgacauag ccgucgaaug ggaaagcaau ggccagcccg aaaacaacua caaaacaacc 1200

ccacccgucc ucgacuccga cggcucuuuc uuccucuacu caaaacucac agucgacaaa 1260

ucacgauggc aacaaggcaa cgucuucucc ugcagcguaa ugcacgaagc ccuccacaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 885

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 885

gggagaaagc uuacccaagu ccaacuaguc gaaucaggag gaggcguagu acaaccagga 60

agauccuuaa gacuuucaug ugcagcaucu ggauuuaccu ucucaucaua cacaaugcac 120

ugggucagac aagccccgg aaaaggacua gaauggguaa cauuuauauc auaugaugga 180

aauaacaaau auuacgcaga uucuguaaaa ggaagauuca ccaucucaag agauaauuca 240

aaaaacacac uauaccuaca aaugaacuca cucagagcug aagacaccgc aauauacuau 300

ugcgcaagaa caggaugguu aggaccuuuc gauuacuggg gacaaggaac acuaguuacc 360

gucuccuccg caaguaccaa aggaccaucu guauucccau uagcaccauc auccaaauca 420

acaucaggag gaaccgcagc auuaggaugc uuaguaaaag acuacuuucc ugaacccgua 480

acaguaucau ggaauuccgg agcacuaaca ucaggaguac auaccuuucc agcaguaacuc 540

600

acacaaaccu acaucugcaa uguaaaccac aaaccaucaa auacaaaagu cgacaaaaga 660

guugaaccaa aaucauguga caaaacucac acaugcccac cauguccagc cccagaauua 720

cuaggaggac caucaguauu ccuuuuccca ccaaaaccaa aagauacucu aaugauaucc 780

cguaccccag aaguaacaug cgucguagua gacguaucac acgaagaccc cgaaguaaaa 840

uucaauuggu acgucgacgg aguagaagua cacaacgcca aaacaaaacc ccgagaagaa 900

caauacaacu ccacauaccg uguaguauca guauuaacag ucuuacacca agacuggcua 960

1020

accauaucaa aagcaaaagg ccaacccaga gaaccccaag uuuauacacu accaccauca 1080

agagacgaau uaacaaaaaa ccaaguaucc cuaacaugcc uaguaaaagg auucuacccu 1140

ucagacaucg caguagaaug ggaauccaac ggacaaccug aaaacaacua uaaaacaaca 1200

ccaccaguau uagauagcga uggaucuuuc uucuuauauu caaaacuuac aguagacaaa 1260

ucucgauggc aacaaggaaa cguauucuca ugcuccguaa ugcacgaagc gcuacauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 886

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 886

gggagaaagc uuacccaagu ucaauuagua gaaucuggag gaggaguagu ccaaccagga 60

120

uggguaagac aagccccagg aaaaggauua gaauggguaa cauuuauauc uuacgacggc 180

aauaacaaau auuaugcaga cucaguuaaa gguagauuca caauaagccg agacaauuca 240

300

ugugcacgua caggaugguu agguccuuuc gauuacuggg gacaagguac ucuaguuaca 360

guaagcagcg caucuaccaa aggaccaagc guauucccuc uugcuccauc aagcaaaucc 420

acaucaggcg gaacagcugc auuaggaugc uuaguaaaag acuauuuccc agaacccgua 480

acgguaucuu ggaacagcgg cgcauuaaca ucaggaguac auacuuuucc ugcaguacua 540

caaagcuccg gauuauacuc uuuaucauca guaguaacag uaccauccuc aucacuagga 600

660

guagaaccaa aaucauguga uaaaacucac accuguccuc cauguccagc acccgaauua 720

uuaggagguc caaguguauu cuuauuucca ccaaaaccua aagauacccu augauauca 780

agaacaccag aaguaacaug uguaguagua gacgucucac acgaagaccc agaaguaaaa 840

uucaacuggu acguagacgg aguagaagua cauaacgcua aaacuaaacc acgagaagaa 900

caauacaaua guacauacag aguaguguca guauuaacag uauuacacca agacuggcua 960

1020

accaucucca aagccaaagg acaaccccgu gaaccucaag ucuauacccu accacccuca 1080

1140

uccgacauag caguagaaug ggaaucaaau ggucaaccag aaaacaacua caaaacaaca 1200

ccaccaguuc ucgauucaga uggauucauuu uuucuauaua gcaaauuaac uguagacaaa 1260

ucuagauggc aacaaggaaa uguauucuca uguucaguaa ugcaugaagc acuccacaau 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 887

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 887

gggagaaagc uuacccaggu gcagcugguc gagagcggcg ggggcguggu gcagcccggg 60

cgcucccucc ggcugagcug cgccgccucc ggcuucaccu ucagcuccua caccaugcac 120

uggguccgcc aggcgccggg gaagggccug gaguggguga cguucaucag cuacgacggc 180

aacaacaagu acuacgccga cuccgugaag gggcgguuca ccaucagccg cgacaacucc 240

aagaacaccc ucuaccugca gaugaacagc cugcgggccg aggacaccgc caucuacuac 300

ugcgcccgca cgggcuggcu cgggcccuuc gacuacuggg gccaggggac ccuggucacc 360

guguccagcg cguccaccaa gggccccagc guguuccccc uggccccguc cagcaagucc 420

acgagcggcg ggaccgccgc ccucggcugc cuggucaagg acuacuuccc cgagcccgug 480

accguguccu ggaacagcgg ggcgcugacc agcggcgucc acacguuccc cgccgugcuc 540

caguccagcg gccuguacuc ccuagcucc guggucaccg ugccgagcuc cagccucggg 600

acccagaccu acaucugcaa cgugaaccac aagcccucca acacgaaggu cgacaagcgg 660

guggagccca agagcugcga caagacccac acgugcccgc ccugccccgc ccccgagcug 720

cugggcggcc cgagcguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggucacgug cguggugguc gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acgucgacgg gguggaggug cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca gcaccuaccg cgucgugagc gugcugaccg uccuccacca ggacuggcug 960

aacggcaagg aguacaagug caaggugucg aacaaggccc ugccggcccc caucgagaag 1020

acgaucagca aggcgaaggg ccagccgcgg gagccccagg ucuacacccu cccgcccagc 1080

cgcgacgagc ugaccaagaa ccaggugucc cugacgugcc ucgugaaggg cuucuacccc 1140

agcgacaucg ccgucgagug ggagagcaac gggcagcccg agaacaacua caagaccacg 1200

cccccggugc uggacuccga cggcagcuuc uuccuguacu ccaagcucac cguggacaag 1260

agccgguggc agcaggggaa cgucuucucc ugcagcguga ugcacgaggc ccugcacaac 1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 888

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 888

gggagaaagc uuacccaggu gcaacugguc gagagcggcg ggggaguugu gcagcccggu 60

agaucccuca ggcuuucuug cgccgcuuca ggcuucaccu uuaguagcua cacaaugcac 120

uggguacggc aggcaccugg gaagggacug gaauggguga cuuucaucuc cuaugacggc 180

aacaauaaau acuaugccga uucugucaag ggucgcuuua cgauuucgcg agacaacagc 240

aaaaauaccu uguacuuaca gaugaacuca cugcgugcgg aggauacagc uauauauuac 300

ugugccagaa cuggguggcu aggaccauuc gacuauuggg gccaaggcac ccucgugaca 360

guuaguuccg caucuaccaa ggggccgagc guguuucccc uggccccuuc cucaaaaaagu 420

acuagcggag guaacagcugc acuuggcugc cuggucaagg auuacuuccc agaacccgug 480

accguaucuu ggaacuccgg ggccuugacg ucaggaguuc auacuuuucc ugcugugcuc 540

cagagcagug gccuguacuc ucuguccagc gucgugaccg ugccaucguc uucccucggu 600

acacagacuu auaucuguaa ugucaaucac aagcccucaa acaccaaagu ugacaagagg 660

guggagccua aaaguugcga uaagacacau accuguccac cgugccccgc ccccgagcug 720

cugggcggcc cgagcguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggucacgug cguggugguc gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acgucgacgg gguggaggug cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca gcaccuaccg cgucgugagc gugcugaccg uccuccacca ggacuggcug 960

aacggcaagg aguacaagug caaggugucg aacaaggccc ugccggcccc caucgagaag 1020

acgaucagca aggcgaaggg gcagccuagg gagccccagg uuuacacgcu uccacccagc 1080

cgggaugaac ugaccaaaaa ccaggugucu uugacauguc ucguaaaggg auuuuauccu 1140

ucagacaucg ccgucgagug ggaaaguaau ggucaaccag agaacaacua caaaacuacc 1200

ccgcccgugc uggacagcga uggcuccuuc uuuuuauacu cuaagcugac aguugacaaa 1260

ucgcgcuggc agcaggggaa uguguucagc ugcuccguca ugcacgaggc acuccauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 889

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 889

gggagaaagc uuacccaggu gcagcuggug gagagcggcg gcggcguggu gcagcccggc 60

agaagccuga gacugagcug cgccgccagc ggcuucaccu ucagcagcua caccaugcac 120

ugggugagac aggccccgg caagggccug gaguggguga ccuucaucag cuacgacggc 180

aacaacaagu acuacgccga cagcgugaag ggcagauuca ccaucagcag agacaacagc 240

aagaacaccc uguaccugca gaugaacagc cugagagccg aggacaccgc caucuacuac 300

ugcgccagaa ccggcuggcu gggccccuuc gacuacuggg gccagggcac ccuggugacc 360

gugagcagcg ccagcaccaa gggccccagc guguuccccc uggcccccag cagcaagagc 420

accagcggcg gcaccgccgc ccugggcugc cuggugaagg acuacuuccc cgagcccgug 480

accgugagcu ggaacagcgg cgccugacc agcggcgugc acaccuuccc cgccgugcug 540

600

acccagaccu acaucugcaa cgugaaccac aagcccagca acaccaaggu ggacaagaga 660

guggagccca agagcugcga caagacccac accugccccc ccugccccgc ccccgagcug 720

cugggcggcc cgagcguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggucacgug cguggugguc gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acgucgacgg gguggaggug cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca gcaccuaccg cgucgugagc gugcugaccg uccuccacca ggacuggcug 960

aacggcaagg aguacaagug caaggugucg aacaaggccc ugccggcccc caucgagaag 1020

acgaucagca aggcgaaggg ccagcccaga gagccccagg uguacacccu gccccccagc 1080

agagacgagc ugaccaagaa ccaggugagc cugaccugcc uggugaaggg cuucuacccc 1140

agcgacaucg ccguggagug ggagagcaac ggccagcccg agaacaacua caagaccacc 1200

ccccccgugc uggacagcga cggcagcuuc uuccuguaca gcaagcugac cguggacaag 1260

1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 890

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 890

gggagaaagc uuaccaugga gacccccgcc cagcugcucu uccugcugcu ccuguggcug 60

ccggacacca cgggcgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 120

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 180

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 240

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 300

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 360

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccgucgc cgcccccucc 420

guguucaucu ucccgcccag cgacgagcag cugaaguccg ggacggccag cguggucugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggugga caacgcgcug 540

caguccggca acagccagga gagcgucacc gagcaggacu ccaaggacag caccuacucc 600

cucagcucca cccugacgcu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggugaccc accagggccu cuccagcccc gucaccaagu ccuucaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 891

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 891

gggagaaagc uuaccaugga gacccccgcc cagcuccucu uccuccuccu ccucuggcuc 60

120

ggcgagcgcg ccaccucuc cugccgcgcc ucccaguccg ucggcuccuc cuaccucgcc 180

ugguaccagc agaagcccgg ccaggccccc cgccuccuca ucuacggcgc cuucucccgc 240

gccaccggca uccccgaccg cuucuccggc uccggcuccg gcaccgacuu cacccucacc 300

aucucccgcc ucgagcccga ggacuucgcc gucuacuacu gccagcagua cggcuccucc 360

cccuggaccu ucggccaggg caccaagguc gagaucaagc gcaccgucgc cgcccccucc 420

gucuucaucu ucccccccuc cgacgagcag cucaaguccg gcaccgccuc cgucgucugc 480

cuccucaaca acuucuaccc ccgcgaggcc aagguccagu ggaaggucga caacgcccuc 540

caguccggca acucccagga guccgucacc gagcaggacu ccaaggacuc caccuacucc 600

cucuccucca cccucacccu cuccaaggcc gacuacgaga agcacaaggu cuacgccugc 660

gaggucaccc accagggccu cuccuccccc gucaccaagu ccuucaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 892

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 892

gggagaaagc uuaccaugga gacccccgcc cagcuucucu uccuucuguu guuauggcug 60

ccugacacaa cuggcgaaau cgugcuaacg caaagcccag ggacccucuc ccugucuccg 120

ggagagagag cuacacuuuc augcagggca agucagagcg ucgguuccuc uuaccuggcc 180

ugguaucagc agaagcccgg ccaagcgccu cgguugcuca uuuacggggc uuuuucgcgc 240

gccacuggaa uaccagaucg auucucaggc agcgguagug ggaccgacuu uacacugacc 300

aucucccguc uggaacccga ggauuucgca guuuauuacu gucagcagua uggaucuagc 360

ccuuggacuu uuggcgggg cacaaaagug gaaauuaaga gaaccguagc cgcuccaucc 420

guguucaucu uucccccuuc agacgagcaa cucaaaagug ggacggcaag cgucgugugc 480

uuacugaaca auuucuaccc aagggaggcc aagguucagu ggaaagugga uaacgcucug 540

600

660

gagguaaccc aucagggucu cucuuccccg guuacaaaau cauuuaaccg gggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 893

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 893

gggagaaagc uuaccaugga gacccccgcc cagcugcugu uccugcugcu gcuguggcug 60

120

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 180

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 240

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 300

aucagcagac uggagcccga ggacuucgcc

cccuggaccu ucggccaggg caccaaggug gagaucaaga gaaccguggc cgcccccagc 420

guguucaucu ucccccccag cgacgagcag cugaagagcg gcaccgccag cguggugugc 480

cugcugaaca acuucuaccc cagagaggcc aaggugcagu ggaaggugga caacgcccug 540

cagagcggca acagccagga gagcgugacc gagcaggaca gcaaggacag caccuacagc 600

cugagcagca cccugacccu gagcaaggcc

gaggugaccc accagggccu gagcagcccc gugaccaaga gcuucaacag aggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 894

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 894

gggagaaagc uuaccaugga gacccccgcc cagcuccugu uccugcuucu gcucuggcug 60

ccugacacaa cgggcgaaau cgugcuuacc caaagcccgg ggacacuguc ccucucuccc 120

ggagagagag cuacccugag cugccggggcc ucccagucug ucggcagcuc cuaccuggcg 180

ugguaucagc agaaaccugg gcaagcuccc cgccuccuga uuuacggagc cuuuucuaga 240

gccacaggca ucccugaucg guucagcggg uccggaagcg gcaccgacuu uacacuuacc 300

auuucucgcc uggaacccga ggauuucgcu guuuauuacu gucagcagua uggcuccagc 360

ccuuggacgu uugggcaggg aaccaaagug gaaaucaaga gaacaguggc cgcuccgucu 420

gucuucauuu uucccccuuc cgacgagcaa cucaaaagcg gcaccgccuc ugugguuugc 480

cugcuuaaca auuucuaccc ccgggaggcg aaggugcagu ggaaagucga uaacgcccug 540

caguccggga auagcggga auccgugaca gagcaagacu cuaaggaauag caccuauucc 600

660

gaggugaccc aucagggacu cagcucuccu gucacaaaga gcuuuaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 895

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 895

gggagaaagc uuaccaugga aacaccagca caacuacuau ucuuacuauu acuauggcua 60

ccagacacaa caggagaaau aguacuaaca caaucaccag gaacacuaag ucauaucacca 120

ggagaaagag caacacuauc augcagagca ucccaaucag uuggaucuuc cuaccuagcc 180

ugguaucaac aaaaaccagg acaagcacca agauuacuaa uauacggagc auucucaaga 240

gcaacuggaa ucccagauag auucucagga ucaggaucag gaacagacuu cacauuaaca 300

auaucacgac uagaaccaga agacuucgca guauacuacu gucaacaaua cggauccuca 360

ccauggaccu ucggccaagg aacaaaagua gaaauaaaaa gaacaguagc agccccaucu 420

guauucauau ucccaccauc agaugaaca cuaaaaucag gaacagcauc aguaguaugc 480

uuacuaaaca acuucuaccc aagagaagcc aaaguacaau ggaaaguaga caacgcacua 540

600

660

gaaguaacac accaaggacu aucaucacca guaacaaaau cauucaaccg aggagaaugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 896

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 896

gggagaaagc uuaccaugga gacccccgcc cagcuccugu uccuguugcu gcucuggcug 60

ccagacacua ccggcgaaau cguguugacg caaagcccgg ggacucuguc ccucaguccc 120

ggugagaggg caacccugag cugccgggcc ucccagagug ucggcagcuc cuaccuggcg 180

ugguaucagc agaagccagg gcaagcaccc cgccuccuga uuuacggcgc cuuuagcagg 240

gccaccggua ucccagaucg guucuccggg aguggcagcg gcacugacuu uaccuugacg 300

360 auuucccgcc uggaacccga ggauuucgca

ccauggacuu uuggucaggg caccaaagua gaaaucaaga ggacuguggc cgcgccgucc 420

gucuucauuu uucccccaag cgacgagcaa cucaaauccg ggaccgccag uguggugugc 480

cugcugaaca auuucuaccc ccgggaggca aagguccagu ggaaagugga uaacgccuug 540

cagagcggca auucccagga aagcguaacc gagcaagaca guaaggauuc cacguauagc 600

cucaguucca cucugacccu gagcaaggcc gacuacgaaa aacacaaggu guacgcaugu 660

gaggucacuc aucagggucu cagcucccca gugaccaaaa guuuuaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 897

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 897

gggagaaagc uuaccaugga aacccccgcc caacuccucu uccuauuacu ccucuggcua 60

cccgacacca ccggcgaaau cguccucacc caauccccag gcacccucuc ucucuccccc 120

ggagaacgcg caacacucuc cugccggca ucccaauccg ucggaucuuc cuaccucgcc 180

ugguaccaac aaaaacccgg ccaagcccca cgccuccuca ucuacggcgc cuucucccgc 240

gccaccggca uuccagaccg uuucucagga uccggcuccg gcaccgauuu cacacucacc 300

aucucccgcc uagaaccaga agacuucgcc guauacuacu gccagcaaua cggaucuucc 360

cccuggacau ucggccaagg caccaaaguc gaaaucaaac gcaccgucgc agcccccucc 420

gucuucaucu ucccacccuc cgacgaacaa cuaaaaucug gcacagcauc cgucgucugc 480

cuccuaaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcacuc 540

caaucuggca acucacaaga auccgucaca gaacaagacu ccaaagacuc aaccuacucc 600

cucuccucaa cccucacccu cuccaaagcc gacuacgaaa aacacaaggu cuacgcaugc 660

gaagucaccc aucaaggacu cuccuccccc gucaccaaau ccuucaaccg cggcgaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 898

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 898

gggagaaagc uuaccaugga aacacccgcc caacuccucu uccuccuccu ccucuggcua 60

cccgacacca ccggcgaaau cguccucacc caaucccccg gcacccuauc ccucuccccc 120

ggcgaacgcg ccacccuauc cugccgcgca ucccaauccg uaggauccuc cuaccucgcc 180

ugguaccaac aaaaacccgg ccaagcaccc cgccuccuca ucuacggagc cuucucccgc 240

gccaccggca ucccugaccg cuucuccggc ucaggcucag gcaccgacuu cacccucacc 300

aucucucgcc uagaacccga agacuucgcc guauacuauu gccaacaaua cggcuccucc 360

ccuuggaccu ucggccaagg aacaaaaguc gaaaucaaac gaaccgucgc cgcccccuca 420

gucuucaucu ucccacccuc cgacgaacaa cucaaauccg guaccgccuc cgucgucugc 480

cuucucaaca acuucuaccc ccgagaagcc aaaguacaau ggaaagucga caacgcacua 540

caaucaggca acucccaaga auccgucacc gaacaagauu ccaaagacuc aaccuacuca 600

cucuccucca cacucacccu cuccaaagcc gacuacgaaa aacacaaagu cuacgccugc 660

gaagucaccc acccaaggacu cuccagcccc gucaccaaau ccuucaaccg cggcgaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 899

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 899

gggagaaagc uuaccaugga aacucccgcc caacuacucu uccuccuccu ccucuggcuc 60

cccgacacca ccggcgaaau cguccuuacc cagucccccg gcacccucuc acucuccccc 120

ggcgaacgcg ccacccuauc cugucgcgcc ucccaaucag ucggcucauc auaccucgcc 180

ugguaccaac aaaaacccgg ccaagccccu cgccuccuca uauacggcgc cuucucccgc 240

gccaccggca uccccgaccg auucuccggc uccggcuccg gcacugacuu cacccucacc 300

auaucccgcc ucgaacccga agacuucgca gucuacuacu gccaacaaua cggaucuucc 360

cccuggaccu ucggccaagg caccaaaguc gaaaucaaac gcaccgucgc cgcccccucc 420

gucuucauau ucccaccuc agacgaacaa cucaaaucag gcaccgcauc cgucgucugc 480

cuccucaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcccuc 540

caaucaggca acucacaaga auccgucaca gaacaagacu ccaaagacuc aaccuacucc 600

cucuccucaa cccucacacu cuccaaagcc gacuacgaaa aacacaaagu cuacgccugc 660

gaagucaccc acccaaggacu uuccucaccc gucaccaaau ccuucaaccg cggcgaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 900

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 900

gggagaaagc uuaccaugga aacaccagca caacuauuau uccuauuacu ucuauggcua 60

ccagacacaa caggagaaau aguauuaaca caaagcccag gaacacucuc auuaucacca 120

ggagaaagag caacacucuc augccgagca ucccaauccg ucggaucauc auaucuagca 180

ugguaccaac aaaaaccagg acaagcaccc agacuacuaa uauacggagc auuuucaaga 240

gccacaggaa ucccagacag auuuucagga ucaggaucag gaacagacuu cacauuaaca 300

auaucacgau uagaacccga agacuucgca guauacuacu gccaacaaua cggaucaucu 360

cccuggacau ucggacaagg cacaaaagua gaaauaaaac gaacagucgc agcaccauca 420

guauucauau ucccaccauc agacgaaca cuaaaaucag gaacagcauc aguaguaugc 480

cuauuuaaaua acuucuaccc aagagaagca aaaguccaau ggaaaguaga uaacgcacua 540

caaucaggaa acucucaaga aucaguaacc gaacaagacu caaaagauuc aaccuacuca 600

uuaucaucaa cauuaacacu aucaaaagca gacuacgaaa aacacaaagu auacgcaugc 660

gaaguaaccc accaaggccu aucaucacca guaacaaaau cauucaacag aggagaaugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 901

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 901

gggagaaagc uuaccaugga aaccccugcc caauuacuau ucuuauuauu acucuggcua 60

ccagacacaa caggagaaau aguuuuaaca caaucaccag gcacacuauuc acuaucacca 120

ggagaaagag caacacuauc augcagagcc uccacaaucag ucggaucauc auaccuagca 180

ugguaucaac aaaaacccgg acaagcacca agauuauuaa uauauggagc auucucacga 240

gcaaccggaa uaccagauag auucucagga ucaggaagcg gcaccgacuu cacauuaaca 300

360

ccauggacau ucggacaagg aacaaaaguu gaaauaaaaa gaacaguagc agcaccauca 420

guauucauau ucccaccauc agacgaacaa uuaaaaucag gaacagccuc uguaguaugc 480

cuauuaaaca acuuuuaccc aagagaagca aaaguucaau ggaaaguaga caaugcacua 540

caaucaggca acucacaaga aucaguaaca gaacaagacu cuaaagacuc aacauauagc 600

660

gaaguaacac accaaggacu aucaucacca guaacaaaau cauucaacag aggagaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 902

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 902

gggagaaagc uuaccaugga gacccccgcc cagcugcucu uccugcugcu ccuguggcug 60

ccggacacca cgggcgagau cgugcugacc cagagccccg gcacccucuc ccuagcccg 120

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 180

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 240

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 300

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 360

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccguggc ggcccccagc 420

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 540

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 600

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 903

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 903

gggagaaagc uuaccaugga gacccccgcc cagcuucucu uccuucuguu guuauggcug 60

ccugacacaa cuggcgaaau cgugcuaacg caaagcccag ggacccucuc ccugucuccg 120

ggagagagag cuacacuuuc augcagggca agucagagcg ucgguuccuc uuaccuggcc 180

ugguaucagc agaagcccgg ccaagcgccu cgguugcuca uuuacggggc uuuuucgcgc 240

gccacuggaa uaccagaucg auucucaggc agcgguagug ggaccgacuu uacacugacc 300

aucucccguc uggaacccga ggauuucgca guuuauuacu gucagcagua uggaucuagc 360

ccuuggacuu uuggcgggg cacaaaagug gaaauuaaga gaaccguggc ggcccccagc 420

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 540

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 600

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 904

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 904

gggagaaagc uuaccaugga gacccccgcc cagcugcugu uccugcugcu gcuguggcug 60

120

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 180

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 240

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 300

aucagcagac uggagcccga ggacuucgcc

cccuggaccu ucggccaggg caccaaggug gagaucaaga gaaccguggc ggcccccagc 420

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 540

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 600

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 905

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 905

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 60

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 120

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 180

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 240

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 300

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccgucgc cgcccccucc 360

guguucaucu ucccgcccag cgacgagcag cugaaguccg ggacggccag cguggucugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggugga caacgcgcug 480

caguccggca acagccagga gagcgucacc gagcaggacu ccaaggacag caccuacucc 540

cucagcucca cccugacgcu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggugaccc accagggccu cuccagcccc gucaccaagu ccuucaaccg cggggagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 906

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 906

gggagaaagc uuaccgagau cguccucacc cagucccccg gcacccucuc ccucuccccc 60

ggcgagcgcg ccaccucuc cugccgcgcc ucccaguccg ucggcuccuc cuaccucgcc 120

ugguaccagc agaagcccgg ccaggccccc cgccuccuca ucuacggcgc cuucucccgc 180

gccaccggca uccccgaccg cuucuccggc uccggcuccg gcaccgacuu cacccucacc 240

aucucccgcc ucgagcccga ggacuucgcc gucuacuacu gccagcagua cggcuccucc 300

cccuggaccu ucggccaggg caccaagguc gagaucaagc gcaccgucgc cgcccccucc 360

gucuucaucu ucccccccuc cgacgagcag cucaaguccg gcaccgccuc cgucgucugc 420

cuccucaaca acuucuaccc ccgcgaggcc aagguccagu ggaaggucga caacgcccuc 480

caguccggca acucccagga guccgucacc gagcaggacu ccaaggacuc caccuacucc 540

cucuccucca cccucacccu cuccaaggcc gacuacgaga agcacaaggu cuacgccugc 600

gaggucaccc accagggccu cuccuccccc gucaccaagu ccuucaaccg cggcgagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 907

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 907

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacacucuc ccuuucuccu 60

ggggaaagag ccacucuguc augcagggcu agucaaagcg ucggauccuc uuacuuggca 120

ugguaucagc agaagccagg ucaggccccg cgguuacuga uuuacggcgc guucucgcgc 180

gcuacgggga uacccgaccg auuuucagga agcggcagug guaccgauuu cacacuaacu 240

aucucccguc ucgagccuga agacuuugcc guuuauuacu gucaacagua ugggucuagc 300

ccauggaccu ucggacaggg cacaaaagug gagauuaaga gaaccguagc agcccccucc 360

guguuuaucu ucccuccauc agaugaacag cugaaaagug gcacugcuag cgucgugugc 420

cuucugaaca auuuuuaccc cagggaggca aagguucaau ggaaagugga caacgccuug 480

cagucuggaa auucccagga gucagucaca gaacaggaua gcaaggacag uaccuauucu 540

cucuccagca cgcugacucu gucgaaggcu gauuacgaga aacacaaggu guacgccugu 600

gaaguaaccc aucaagggcu cucuuccccu guuacaaaau cauucaaccg gggugagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 908

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 908

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccugag ccugagcccc 60

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 120

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 180

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 240

aucagcagac uggagcccga ggacuucgcc guguacuacu gccagcagua cggcagcagc 300

cccuggaccu ucggccaggg caccaaggug gagaucaaga gaaccguggc cgcccccagc 360

guguucaucu ucccccccag cgacgagcag cugaagagcg gcaccgccag cguggugugc 420

cugcugaaca acuucuaccc cagagaggcc aaggugcagu ggaaggugga caacgcccug 480

cagagcggca acagccagga gagcgugacc gagcaggaca gcaaggacag caccuacagc 540

cugagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggugaccc accagggccu gagcagcccc gugaccaaga gcuucaacag aggcgagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 909

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 909

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacacucag ccugucuccu 60

ggggaaagag ccacgcuuag cugccggggcu ucccaaucug ucggaagcuc cuaccuggcc 120

ugguaucagc agaagccggg ccaggcgccc cgccuccuga uuuacggggc uuucucuaga 180

gccaccggaa ucccugaccg guuuagcggc uccgggagcg gaacagauuu cacccuuaca 240

auuucucgcc uggagcccga agacuuugcc guuuauuacu gucaacagua uggcuccagc 300

ccuuggaccu ucggcgggg gacaaaagug gagaucaaga gaaccguggc ugcccccucu 360

gucuuuauuu ucccuccguc cgaugaacag cucaaaagcg gaacggcuuc ugugguuugc 420

cugcugaaca auuuuuaccc ccgggaggcc aaggugcaau ggaaagucga caacgcgcuc 480

caguccggca auagccagga guccgugacc gaacaggauu cuaaggacag cacauauucc 540

cugagcucua cccuuacacu guccaaggcc gauuacgaga aacacaaggu uuacgcuugu 600

gaagugaccc aucaagggcu cagcucuccu gucacgaaau ccuucaaccg cggagagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 910

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 910

gggagaaagc uuaccgaaau aguacuaaca caaucaccag gaacccucuc acuaucucca 60

ggagaaagag caacacuaag cugcagagcc uccacaaucag ucggaucauc auaccuagca 120

ugguaccaac aaaaaccagg acaagccccc agauuacuaa ucuacggagc auucucacga 180

240

auauccagau uagaaccaga agacuucgca guauacuacu gccaacaaua cggaucauca 300

ccauggacau uuggacaagg aaccaaagua gaaaucaaaa gaacaguagc agccccauca 360

guauuuauau ucccaccauc agacgaacaa cuaaaaucag gcaccgcauc aguaguaugu 420

cuauuaaaca acuucuaccc aagagaagca aaaguacaau ggaaaguaga caacgcacua 480

caaucaggaa acucccaaga aucagucaca gaacaagacu caaaagacuca aacauacuca 540

cuaucaucaa cacuaaccuu aucaaaagca gacuacgaaa aacacaaagu auacgcaugc 600

gaaguaacac accaaggauu aucaucccca guaacaaaau cauucaacag aggagaaugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 911

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 911

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacucucuc ccugagucca 60

ggggaaaggg ccaccuugag cugccggggca ucccaaagug ucgguagcuc cuaccuggcc 120

ugguaucagc agaagccggg ccaggcgccc cgccuccuga uuuacggggc cuucagcagg 180

gcaacgggca ucccagaccg guuuuccggu agugggagcg gcacugauuu caccuugacc 240

300 auuucccgcc uggagcccga agacuuugcc

ccauggacuu ucgggcaggg uaccaaagua gagaucaaga ggacgguggc agcccccucc 360

gucuuuauuu ucccaccgag cgaugaacag cucaaauccg gcacugcgag uguggugugc 420

cugcugaaca auuuuuaccc ccgggaggcc aagguccaau ggaaagugga caacgcacuc 480

cagagcggca auucccagga gagcguaacc gaacaggaua guaaggacuc cacuuauagc 540

cugaguucca ccuugacccu gagcaaggcc gauuacgaga aacacaaggu guacgccugu 600

gaagucacgc aucaagggcu cagcucccca gugacuaaaa guuucaaccg cggugagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 912

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 912

gggagaaagc uuaccgaaau cguccuaacc caaucccccg gcacacuauc ucucucccca 60

ggcgaacgcg caacacuauc cugccgcgcc ucacaaucag ucggcuccuc cuaccuagcc 120

ugguaccaac aaaaacccgg ccaagcaccc cgacuccuca ucuacggcgc cuucucccgc 180

gccacaggca ucccagaccg cuucuccggc uccggcuccg gcacagacuu cacacucacc 240

aucucacgcc ucgaacccga agacuucgcc gucuacuacu gccaacaaua cggaucaucc 300

cccuggaccu ucggacaagg caccaaaguc gaaaucaaac gcaccgucgc cgcccccucc 360

gucuucaucu ucccaccuc agacgaacaa cuaaaauccg gcaccgccuc aguagucugc 420

cuacuaaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcccuc 480

caauccggca acucacaaga aucagucacc gaacaagacu caaaagacuc caccuacucc 540

cuauccucca cccucacccu aucaaaagcc gacuacgaaa aacacaaagu auacgcgugc 600

gaaguaaccc accagggccu aucucaccc gucacaaaau ccuucaaccg cggcgaaugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 913

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 913

gggagaaagc uuaccgaaau cguacuaacc caaucacccg gcacccucuc ccucuccccc 60

ggcgaacgag ccacccuauc augccgcgcc ucccaauccg uaggcuccuc cuaccuagcc 120

ugguaccaac aaaaaccagg ccaagcaccc cgacuacuca ucuacggagc cuucucccgc 180

gccaccggca uccccgaccg cuucuccggc uccggcuccg gcaccgacuu cacccucacc 240

aucucccgcc ucgaacccga agacuucgcc gucuacuacu gccaacaaua cggaucaucc 300

cccuggaccu ucggccaagg caccaaaguc gaaaucaaac gcaccgucgc cgcccccucc 360

gucuucauau ucccacccuc cgacgaacaa cuaaaaucag gaaccgccuc cgucgucugc 420

cuacuaaaca acuucuaccc ccgcgaagcc aaaguacaau ggaaagucga caacgcccuc 480

caauccggca acucccaaga auccguaacc gaacaagacu ccaaagacuc aaccuauucc 540

cucuccucca cacucacacu auccaaagcc gacuacgaaa aacacaaagu cuacgccugc 600

gaaguaaccc accaaggccu cucaucaccc gucaccaaau ccuucaaccg cggcgaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 914

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 914

gggagaaagc uuaccgaaau cguccucacc caaucccccg gcacccuauc acucucaccc 60

ggcgaacgcg caacccucuc cugccgagcc ucccaauccg ucggcuccuc auaccucgcc 120

ugguaccaac aaaaacccgg ccaagcaccc cgucuccuca ucuacggcgc cuucucacgc 180

gccaccggca uccccgaccg cuucuccggc ucuggcucag gcaccgacuu cacccucacc 240

aucucccgcc ucgaacccga agacuucgcc gucuacuacu gccaacaaua cggaucaucc 300

cccuggaccu ucggccaagg cacaaaaguc gaaaucaaac gcaccgucgc cgccccaucc 360

gucuucaucu ucccacccuc cgacgaacaa cucaaauccg gcaccgccuc cgucgucugc 420

cuccucaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcccuc 480

caauccggca acucccaaga auccgucacc gaacaagacu ccaaagacuca caccuacuca 540

cucuccucca cccuuacccu cuccaaagcc gacuacgaaa aacacaaagu cuacgccugc 600

gaagucaccc accaaggccu cuccuccccc gucaccaaau ccuucaaccg cggcgaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 915

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 915

gggagaaagc uuaccgaaau aguacuaaca caaucaccag gaacacuauc acucucaccu 60

ggagaaagag caacauuauc cugcagagca ucacaaucug uaggaucuuc auaccuagca 120

ugguaccaac aaaaaccagg acaagcacca agauuacuaa uauauggagc auuuuccaga 180

240

auaucaagac uagaaccaga agacuucgca guauacuacu gccaacaaua cggaucauca 300

ccauggacau ucggacaagg aacaaaagua gaaauaaaaa gaacagucgc agcaccauca 360

guauucauau ucccaccauc agacgaaca uuaaaauccg gaacagcauc aguaguaugc 420

cuacuaaaua acuucuaccc aagagaagca aaaguacaau ggaaaguaga caacgcauua 480

caaucaggaa acucccaaga aucaguaaca gaacaagacu cuaaagacuc aacauacucc 540

cuaucaucaa cacuaacacu aucaaaagca gacuaugaaa aacacaaagu auacgcaugc 600

gaagucacac aucaaggacu aucaucacca guaacaaaau cauuuaacag aggagaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 916

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 916

gggagaaagc uuaccgaaau aguacuaaca caaucaccag gaacauuauc acuaucccca 60

ggagaaagag caacauuauc augcagagca ucacaaucag uaggaucauc auaccuagcc 120

ugguaccaac aaaaaccagg acaagcccca agauuacuaa uauacggagc auucucaaga 180

gcaacaggaa uaccagacag auucucaggu ucuggcucag gcacagacuu cacacucaca 240

auaucaagac uagaaccaga agacuucgcc guauacuacu gccaacaaua cggauccuca 300

ccauggacau ucggacaagg aacaaaagua gaaauaaaac gaacaguagc agcaccauca 360

guauucauau ucccaccauc agacgaaca uuaaaaucag gaacagcauc aguaguaugc 420

cuauuaaaca acuucuaccc acgagaagcc aaaguccaau ggaaaguaga uaacgcauua 480

caaucaggua acucacaaga aucaguaaca gaacaagacu ccaaagacuc aacauacagc 540

cuaucaucaa cacuaacauu aucaaaagca gacuaugaaa aacacaaagu auacgcaugc 600

gagguaacac accaaggacu aucaucacca guaacaaaau cauucaauag aggagaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 917

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 917

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 60

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 120

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 180

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 240

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 300

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccguggc ggcccccagc 360

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 480

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 540

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggggagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 918

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 918

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacacucuc ccuuucuccu 60

ggggaaagag ccacucuguc augcagggcu agucaaagcg ucggauccuc uuacuuggca 120

ugguaucagc agaagccagg ucaggccccg cgguuacuga uuuacggcgc guucucgcgc 180

gcuacgggga uacccgaccg auuuucagga agcggcagug guaccgauuu cacacuaacu 240

aucucccguc ucgagccuga agacuuugcc guuuauuacu gucaacagua ugggucuagc 300

ccauggaccu ucggacaggg cacaaaagug gagauuaaga gaaccguggc ggcccccagc 360

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 480

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 540

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggugagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 919

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 919

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccugag ccugagcccc 60

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 120

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 180

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 240

aucagcagac uggagcccga ggacuucgcc guguacuacu gccagcagua cggcagcagc 300

360

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 480

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 540

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggcgagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 920

<211> 3008

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt1 IRES construct

<400> 920

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugac caugcauuug aaagccgggg 1440

gugggagauc cggauugcca gucugcucga uaucgcaggc uggguccgug acuacccacu 1500

cccccuuuaa uuccgccccu cucccucccc ccccccuaac guuacuggcc gaagccgcuu 1560

ggaauaaggc cggugugcgu uugucuauau guuauuuucc accauauugc cgucuuuugg 1620

caaugugagg gccgggaaac cuggcccugu cuucuugacg agcauuccua ggggucuuuc 1680

cccucucgcc aaaggaaugc aaggucuguu gaaugucgug aaggaagcag uuccucugga 1740

agcuucuuga agacaaacaa cgucuguagc gacccuuugc aggcagcgga accccccacc 1800

uggcgacagg ugccucugcg gccaaaagcc acguguauaa gauacaccug caaaggcggc 1860

acaaccccag ugccacguug ugaguuggau aguuguggaa agagucaaau ggcucuccuc 1920

aagcguauuc aacaaggggc ugaaggaugc ccagaaggua ccccauugua ugggaucuga 1980

ucuggggccu cggugcacau gcuuuacgug uguuuagucg agguuaaaaa acgucuaggc 2040

cccccgaacc acggggacgu gguuuuccuu ugaaaaacac gaugauaaua gaucuaccau 2100

2160

gaucgugcug acccagagcc ccggcacccu cucccugagc ccgggggagc gcgccacgcu 2220

guccugccgg gccagccagu ccgucggcag cuccuaccuc gcgugguacc agcagaagcc 2280

2340

ccgcuucucc ggcagcggcu ccgggaccga cuucacccuc acgaucagcc ggcuggagcc 2400

ggaggacuuc gccguguacu acugccagca guacggcucc agcccugga ccuucgggca 2460

gggcaccaag guggagauca agcgcaccgu cgccgccccc uccguguuca ucuucccgcc 2520

2580

ccccggggag gccaaggugc aguggaaggu ggacaacgcg cugcaguccg gcaacagcca 2640

ggagagcguc accgagcagg acuccaagga cagcaccuac ucccucagcu ccacccugac 2700

gcugagcaag gccgacuacg agaagcacaa gguguacgcc ugcgagguga cccaccaggg 2760

ccucuccagc cccgucacca aguccuucaa ccgcggggag ugcugaggac uaguuauaag 2820

acugacuagc ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau 2880

2940

aaaaugcauc cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca 3000

ccagaauu 3008

<210> 921

<211> 3008

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt3 IRES construct

<400> 921

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcgcc ugagcuacuc 780

ggcggcccau ccguguuucu guuucccccu aagccaaagg acacgcuuau gauuucucgg 840

acucccgagg ucacaugcgu gguuguggau gucagccacg aagacccggga ggugaaauuu 900

aauugguacg uagauggggu ugaagugcau aacgcaaaga ccaaaccucg cgaggagcaa 960

uauaauucaa cuuacagagu cgugaguguc cugacagugu ugcaccagga cuggcucaac 1020

ggaaaggaau auaaauguaa gguuuccaau aaagcccugc ccgcuccaau cgagaagacc 1080

auaagcaagg ccaaagguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaugac caugcauuug aaagccgggg 1440

gugggagauc cggauugcca gucugcucga uaucgcaggc uggguccgug acuacccacu 1500

cccccuuuaa uuccgccccu cucccucccc ccccccuaac guuacuggcc gaagccgcuu 1560

ggaauaaggc cggugugcgu uugucuauau guuauuuucc accauauugc cgucuuuugg 1620

caaugugagg gccgggaaac cuggcccugu cuucuugacg agcauuccua ggggucuuuc 1680

cccucucgcc aaaggaaugc aaggucuguu gaaugucgug aaggaagcag uuccucugga 1740

agcuucuuga agacaaacaa cgucuguagc gacccuuugc aggcagcgga accccccacc 1800

uggcgacagg ugccucugcg gccaaaagcc acguguauaa gauacaccug caaaggcggc 1860

acaaccccag ugccacguug ugaguuggau aguuguggaa agagucaaau ggcucuccuc 1920

aagcguauuc aacaaggggc ugaaggaugc ccagaaggua ccccauugua ugggaucuga 1980

ucuggggccu cggugcacau gcuuuacgug uguuuagucg agguuaaaaa acgucuaggc 2040

cccccgaacc acggggacgu gguuuuccuu ugaaaaacac gaugauaaua gaucuaccau 2100

ggagacccccc gccagcuuc ucuuccuucu guuguuaugg cugccugaca caacuggcga 2160

2220

uucaugcagg gcaagucaga gcgucgguuc cucuuaccug gccugguauc agcagaagcc 2280

2340

ucgauucuca ggcagcggua gugggaccga cuuuacacug accaucuccc gucuggaacc 2400

cgaggauuuc gcaguuuauu acugucagca guauggaucu agcccuugga cuuuuggcca 2460

gggcacaaaa guggaaauua agagaaccgu agccgcucca uccguguuca ucuuuccccc 2520

uucagacgag caacucaaaa gugggacggc aagcgucgug ugcuuacuga acaauuucua 2580

2640

ggaaucaguc acugagcaag acagcaagga uaguaccuau ucuuugucca gcacacugac 2700

ucuaucgaag gccgacuacg aaaaacacaa gguguacgcg ugugagguaa cccaucaggg 2760

ucucucuucc ccgguuacaa aaucauuuaa ccggggcgag ugcugaggac uaguuauaag 2820

acugacuagc ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau 2880

2940

aaaaugcauc cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca 3000

ccagaauu 3008

<210> 922

<211> 3008

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt4 IRES construct

<400> 922

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccca gcguguuccu guuccccccc aagcccaagg acacccugau gaucagcaga 840

acccccgagg ugaccugcgu ggugguggac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg uggacggcgu ggaggugcac aacgccaaga ccaagcccag agaggagcag 960

uacaacagca ccuacagagu ggugagcgug cugaccgugc ugcaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcccccau cgagaagacc 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagugac caugcauuug aaagccgggg 1440

gugggagauc cggauugcca gucugcucga uaucgcaggc uggguccgug acuacccacu 1500

cccccuuuaa uuccgccccu cucccucccc ccccccuaac guuacuggcc gaagccgcuu 1560

ggaauaaggc cggugugcgu uugucuauau guuauuuucc accauauugc cgucuuuugg 1620

caaugugagg gccgggaaac cuggcccugu cuucuugacg agcauuccua ggggucuuuc 1680

cccucucgcc aaaggaaugc aaggucuguu gaaugucgug aaggaagcag uuccucugga 1740

agcuucuuga agacaaacaa cgucuguagc gacccuuugc aggcagcgga accccccacc 1800

uggcgacagg ugccucugcg gccaaaagcc acguguauaa gauacaccug caaaggcggc 1860

acaaccccag ugccacguug ugaguuggau aguuguggaa agagucaaau ggcucuccuc 1920

aagcguauuc aacaaggggc ugaaggaugc ccagaaggua ccccauugua ugggaucuga 1980

ucuggggccu cggugcacau gcuuuacgug uguuuagucg agguuaaaaa acgucuaggc 2040

cccccgaacc acggggacgu gguuuuccuu ugaaaaacac gaugauaaua gaucuaccau 2100

ggagaccccc gcccagcugc uguuccugcu gcugcugugg cugcccgaca ccaccggcga 2160

gaucgugcug acccagagcc ccggcacccu gagccugagc cccggcgaga gagccacccu 2220

gagcugcaga gccagccaga gcgugggcag cagcuaccug gccugguacc agcagaagcc 2280

2340

cagauucagc ggcagcggca gcggcaccga cuucacccug accaucagca gacuggagcc 2400

cgaggacuuc gccguguacu acugccagca guacggcagc agcccuggga ccuucggcca 2460

gggcaccaag guggagauca agagaaccgu ggccgccccc agcguguuca ucuucccccc 2520

cagcgacgag cagcugaaga gcggcaccgc cagcguggug ugccugcuga acaacuucua 2580

ccccagagag gccaaggugc aguggaaggu ggacaacgcc cugcagagcg gcaacagcca 2640

ggagagcgug accgagcagg acagcaagga cagcaccuac agccugagca gcacccugac 2700

ccugagcaag gccgacuacg agaagcacaa gguguacgcc ugcgagguga cccaccaggg 2760

ccugagcagc cccgugacca agagcuucaa cagaggcgag ugcugaggac uaguuauaag 2820

acugacuagc ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau 2880

2940

aaaaugcauc cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca 3000

ccagaauu 3008

<210> 923

<211> 2392

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt1 F2A construct

<400> 923

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagguga agcagacacu caauuucgac 1440

cuucugaagu uggcuggaga uguugagucu aacccaggcc ccauggagac ccccgcccag 1500

1560

agccccggca cccucucccu gagcccgggg gagcgcgcca cgcuguccug cggggccagc 1620

caguccgucg gcagcuccua ccucgcgugg uaccagcaga agcccggggca ggcgccccgc 1680

1740

ggcuccggga ccgacuucac ccucacgauc agccggcugg agccggagga cuucgccgug 1800

uacuacugcc agcaguacgg cuccagcccc uggaccuucg ggcagggcac caagguggag 1860

aucaagcgca ccgucgccgc ccccuccgug uucaucuucc cgcccagcga cgagcagcug 1920

aaguccggga cggccagcgu ggucugccuc cugaacaacu ucuacccccg ggaggccaag 1980

gugcagugga agguggacaa cgcgcugcag uccggcaaca gccaggagag cgucaccgag 2040

caggacucca aggacagcac cuacucccuc agcuccaccc ugacgcugag caaggccgac 2100

uacgagaagc acaaggugua cgccugcgag gugacccacc agggccucuc cagccccguc 2160

acccaaguccu ucaaccgcgg ggagugcuga ggacuaguua uaagacugac uagcccgaug 2220

ggccucccaa cggggcccucc uccccuccuu gcaccgagau uaauaaaaaa aaaaaaaaaa 2280

2340

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 2392

<210> 924

<211> 2392

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt3 F2A construct

<400> 924

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcgcc ugagcuacuc 780

ggcggcccau ccguguuucu guuucccccu aagccaaagg acacgcuuau gauuucucgg 840

acucccgagg ucacaugcgu gguuguggau gucagccacg aagacccggga ggugaaauuu 900

aauugguacg uagauggggu ugaagugcau aacgcaaaga ccaaaccucg cgaggagcaa 960

uauaauucaa cuuacagagu cgugaguguc cugacagugu ugcaccagga cuggcucaac 1020

ggaaaggaau auaaauguaa gguuuccaau aaagcccugc ccgcuccaau cgagaagacc 1080

auaagcaagg ccaaagguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaguga agcagacacu caauuucgac 1440

cuucugaagu uggcuggaga uguugagucu aacccaggcc ccauggagac ccccgcccag 1500

1560

agcccaggga cccucucccu gucuccggga gagagagcua cacuuucaug cagggcaagu 1620

cagagcgucg guuccucuua ccuggccugg uaucagcaga agcccggcca agcgccucgg 1680

uugcucauuu acggggcuuu uucgcgcgcc acuggaauac cagaucgauu cucaggcagc 1740

gguaguggga ccgacuuuac acugaccauc ucccgucugg aacccgagga uuucgcaguu 1800

uauuacuguc agcaguaugg aucuagcccu uggacuuuug gccagggcac aaaaguggaa 1860

auuaagagaa ccguagccgc uccauccgug uucaucuuuc ccccuucaga cgagcaacuc 1920

aaaagggga cggcaagcgu cgugugcuua cugaacaauu ucuacccaag ggaggccaag 1980

guucagugga aaguggauaa cgcucugcag

caagacagca aggauaguac cuauucuuug uccagcacac ugacuucuauc gaaggccgac 2100

uacgaaaaac acaaggugua cgcgugugag guaacccauc agggucucuc uuccccgguu 2160

acaaaaucau uuaaccgggg cgagugcuga ggacuaguua uaagacugac uagcccgaug 2220

ggccucccaa cggggcccucc uccccuccuu gcaccgagau uaauaaaaaa aaaaaaaaaa 2280

2340

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 2392

<210> 925

<211> 2392

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt4 F2A construct

<400> 925

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccca gcguguuccu guuccccccc aagcccaagg acacccugau gaucagcaga 840

acccccgagg ugaccugcgu ggugguggac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg uggacggcgu ggaggugcac aacgccaaga ccaagcccag agaggagcag 960

uacaacagca ccuacagagu ggugagcgug cugaccgugc ugcaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcccccau cgagaagacc 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagguga agcagacacu caauuucgac 1440

cuucugaagu uggcuggaga uguugagucu aacccaggcc ccauggagac ccccgcccag 1500

1560

agccccggca cccugagccu gagccccggc gagagagcca cccugagcug cagagccagc 1620

cagagcgugg gcagcagcua ccuggccugg uaccagcaga agcccggcca ggcccccaga 1680

cugcugaucu acggcgccuu cagcagagcc accggcaucc cgacagauu cagcggcagc 1740

ggcagcggca ccgacuucac ccugaccauc agcagacugg agcccgagga cuucgccgug 1800

uacuacugcc agcaguacgg cagcagcccc uggaccuucg gccagggcac caagguggag 1860

aucaagagaa ccguggccgc ccccagcgug uucaucuucc cccccagcga cgagcagcug 1920

aagagcggca ccgccagcgu ggugugccug cugaacaacu ucuaccccag agaggccaag 1980

2040

caggacagca aggacagcac cuacagccug agcagcaccc ugacccugag caaggccgac 2100

uacgagaagc acaaggugua cgccugcgag gugacccacc agggccugag cagccccgug 2160

accaagagcu ucaacagagg cgagugcuga ggacuaguua uaagacugac uagcccgaug 2220

ggccucccaa cggggcccucc uccccuccuu gcaccgagau uaauaaaaaa aaaaaaaaaa 2280

2340

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 2392

<210> 926

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 926

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 927

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 927

gggagaaagc uuaccaugga gcucggccuc uccuggaucu uccuccucgc cauccucaag 60

ggcguccagu gccaggucca gcucgucgag uccggcggcg gcgucgucca gcccggccgc 120

ucccuccgcc ucuccugcgc cgccuccggc uucaccuucu ccuccuacac caugcacugg 180

guccgccagg cccccggcaa gggccucgag ugggucaccu ucaucuccua cgacggcaac 240

aacaaguacu acgccgacuc cgucaagggc cgcuucacca ucucccgcga caacuccaag 300

aacacccucu accuccagau gaacucccuc cgcgccgagg acaccgccau cuacuacugc 360

gcccgcaccg gcuggcucgg ccccuucgac uacuggggcc agggcacccu cgucaccguc 420

uccuccgccu ccaccaaggg ccccuccguc uucccccucg cccccuccuc caaguccacc 480

uccggcggca ccgccgcccu cggcugccuc gucaaggacu acuuccccga gcccgucacc 540

gucuccugga acuccggcgc ccucaccucc ggcguccaca ccuuccccgc cguccuccag 600

uccuccggcc ucuacucccu cuccuccguc gucaccgucc ccuccuccuc ccucggcacc 660

cagaccuaca ucugcaacgu caaccacaag cccuccaaca ccaaggucga caagcgcguc 720

gagcccaagu ccugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcuccuc 780

ggcggccccu ccgucuuccu cuuccccccc aagcccaagg acacccucau gaucucccgc 840

acccccgagg ucaccugcgu cgucgucgac gucuccccg aggaccccga ggucaaguuc 900

aacugguacg ucgacggcgu cgagguccac aacgccaaga ccaagccccg cgaggagcag 960

uacaacucca ccuaccgcgu cgucuccguc cucaccgucc uccaccagga cuggcucaac 1020

ggcaaggagu acaagugcaa ggucuccaac aaggcccucc ccgcccccau cgagaagacc 1080

aucuccaagg ccaagggcca gccccgcgag ccccaggucu acacccuccc ccccucccgc 1140

gacgagcuca ccaagaacca ggucucccuc accugccucg ucaagggcuu cuaccccucc 1200

gacaucgccg ucgaguggga guccaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccguccucg acuccgacgg cuccuucuuc cucuacucca agcucaccgu cgacaagucc 1320

cgcuggcagc aggcaacgu cuucuccugc uccgucaugc acgaggcccu ccacaaccac 1380

uacacccaga agucccucuc ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 928

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 928

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcgcc ugagcuacuc 780

ggcggcccau ccguguuucu guuucccccu aagccaaagg acacgcuuau gauuucucgg 840

acucccgagg ucacaugcgu gguuguggau gucagccacg aagacccggga ggugaaauuu 900

aauugguacg uagauggggu ugaagugcau aacgcaaaga ccaaaccucg cgaggagcaa 960

uauaauucaa cuuacagagu cgugaguguc cugacagugu ugcaccagga cuggcucaac 1020

ggaaaggaau auaaauguaa gguuuccaau aaagcccugc ccgcuccaau cgagaagacc 1080

auaagcaagg ccaaagguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 929

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 929

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccca gcguguuccu guuccccccc aagcccaagg acacccugau gaucagcaga 840

acccccgagg ugaccugcgu ggugguggac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg uggacggcgu ggaggugcac aacgccaaga ccaagcccag agaggagcag 960

uacaacagca ccuacagagu ggugagcgug cugaccgugc ugcaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcccccau cgagaagacc 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 930

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 930

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuugc cauucugaag 60

ggggugcagu gccaagucca gcucguugaa uccggaggcg ggguggugca gccgggaaga 120

ucucugcggc uuagcugugc ugccuccggc uuuaccuucu cuagcuacac aaugcacugg 180

guccgccagg cgccugggaa aggacuggag ugggugacgu uuaucuccua ugacggcaac 240

aauaaguacu augcugauuc uguuaaaggc agauucacca uuagccggga caacuccaag 300

aauacacucu accugcaaau gaacagccug cgcgccgaag auaccgccau cuauuuacugc 360

gcuagaacag gguggcucgg accguuugac uauuggggcc aggggacccu ggugacaguc 420

ucuuccgcca gcaccaaagg acccucugug uucccucuug cucccuccag caagucuacg 480

uccggcggga ccgccgcgcu gggaugucuc guuaaggauu acuuuccuga gcccgugaca 540

gucagcugga acuccggcgc ccugaccucu ggcgugcaua cauucccugc ugugcuucag 600

660

cagacauaua uuugcaaugu gaaucacaaa cccuccaaca ccaaggucga caaacggggug 720

gaaccuaagu cuugugauaa aacacauacc ugucccccuu gccccgcccc ggagcugcuc 780

ggcggggccua gcguuuuucu guuucccccu aagcccaagg acacccuuau gaucucccgc 840

acacccgagg ugacgugcgu cgugguugau gugagccacg aagacccuga ggucaaauuc 900

aauugguacg uggauggagu cgaagugcau aacgcuaaga ccaaaccgag agaggagcaa 960

uauaauucua cauaccgggu uguguccguc cugaccgugc uccaccagga cuggcugaac 1020

ggcaaggaau auaaauguaa gguuagcaau aaagcccuuc ccgcgccuau cgagaagaca 1080

1140

gaugagcuca cgaagaacca agucagccug acaugccugg ugaaaggauu cuauccuucc 1200

1260

cccguucucg acagcgaugg cuccuuuuuc cuguacucua aacuuacagu cgacaagagc 1320

cgguggcagc aagggaaugu guucuccugu agcgugaugc acgaagcccu gcauaaccac 1380

uauacccaga agucucucuc ccugagcccu ggaaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 931

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 931

gggagaaagc uuaccaugga auuagguuua uccuggaucu uucuccuagc aauacucaaa 60

ggaguacaau gccaaguaca auuaguggaa uccggaggag guguaguaca accaggaaga 120

ucacuaagac uaucaugcgc agcaucagga uuuacauucu caucauacac aaugcacugg 180

guaagacaag cccggaaa aggauuagaa uggguuacau uuauauccua cgacggaaac 240

300

aacacacuau accuacaaau gaacucucuc cgagcagaag auacagccau auacuacugc 360

gcaagaacag gaugguuagg accuuucgac uacuggggac aaggaacucu aguaacuguc 420

ucaucugccu caacaaaagg cccaucagua uuuccacuag ccccaucauc uaaaucuaca 480

ucagguggaa ccgcugcauu aggaugcuua guaaaagacu auuuucccga accaguaacu 540

guaucuugga acuccggagc acuuacuucu gguguacaca cauucccagc aguuuuacaa 600

agcucaggac uauacucucu aagcucagua guaacugucc caucaucauc ccuuggcacc 660

caaacauaca uauguaacgu aaaucacaaa cccaguaaua ccaaaguaga caaaagagua 720

gaacccaaau caugugauaa aacacacaca ugcccccccu gcccagcacc ugaacuucua 780

ggaggaccau cuguauuccu cuucccucca aaaccaaaag auacucucau gauaucacgc 840

acacccgaag uaacuugugu cguaguagac guaucacacg aagacccaga aguuaaauuc 900

aacugguaug uagacggagu agaaguccac aacgcaaaaa caaaaccacg agaagaacaa 960

uacaacucca ccuaucgcgu aguuucagua cuuacaguuc uccaccaaga uuggcuaaac 1020

1080

auaaguaaag caaaagguca accacgagaa ccccaaguau auacacuucc accaucaaga 1140

gacgaacuua ccaaaaacca agucucacuc acaugcuuag uaaaaggauu uuacccauca 1200

1260

1320

cgauggcaac aaggcaaugu auucucuugu ucugucaugc augaagcacu acacaaccac 1380

uacacacaaa aaucacuauuc acuauccccc ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 932

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 932

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuguuggc cauucugaag 60

ggggugcagu gccaagucca gcucguggaa uccgguggcg ggguugugca gcccggcagg 120

agucugcggu ugagcugugc agccuccggu uuuaccuuca

guccgccagg cgccagggaa aggccuggag ugggugaccu uuaucuccua ugacggcaac 240

aauaaguacu augccgauag cgugaaaggg agguucacga uuucccggga caacaguaag 300

aauacucucu accugcaaau gaacagccug cgcgcagaag auaccgccau cuauuuacugc 360

gcaaggaccg guuggcucgg cccguuugac uauugggggc agggcacucu ggucaccgug 420

uccagcgcca guacgaaagg ucccuccgua uucccauugg cgccagcuc caagaguacu 480

agcgggggca ccgccgcacu gggcugucuc gugaaggauu acuuuccaga gcccgucacu 540

guguccugga auagcggggc ccugaccagu ggugugcaua ccuucccagc cguccugcag 600

uccagcggcu uguacagucu cuccagcgug guaacggugc cgagcuccag ucuggggacu 660

cagaccuaua uuugcaacgu caaucacaaa cccagcaaca cuaagggugga caaacggggug 720

gaaccaaagu ccugugauaa aacccauacc ugucccccau gccccgcacc ggagcugcuc 780

ggcgguccca gcgucuuucu guucccaccc aagccaaaag acacuuugau gaucagucgc 840

acgcccgagg ugaccugcgu aguggucgau gugucccg aagacccaga ggucaaguuu 900

aauugguacg uggauggcgu ggaaguacau aacgccaaga cuaaaccgag ggaggagcaa 960

uauaauagca ccuaccgggu ggucuccgug cugaccgucc uccaccagga cuggcugaac 1020

gggaaggaau auaaauguaa ggugaguaau aaagcgcugc ccgccccaau cgagaagacu 1080

auuagcaagg caaaaggcca gccccgcgaa ccacaggugu acacguugcc cccguccagg 1140

gaugagcuca ccaagaacca aguaagccug acuugccugg ugaaaggguu cuauccaagu 1200

gacaucgccg ucgaauggga guccaauggu cagcccgaga acaacuacaa gaccacuccc 1260

ccagugcucg acagcgaugg cuccuucuuu cuguacagua aauugaccgu cgacaagagc 1320

cgguggcagc aagggaaugu guucuccugc agcgugaugc acgaagcacu gcauaaccac 1380

uauacgcaga agagucucuc ccugagcccc ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 933

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 933

gggagaaagc uuaccaugga acucggccua agcuggaucu uccuccuggc cauccucaaa 60

ggcguacagu gccaggucca acucguagaa uccggaggcg gcgucguaca acccggccgc 120

ucccuccgcc uauccugcgc agcuuccggc uucacauuca guucauacac caugcacugg 180

guccgacaag cccccggcaa aggacucgaa ugggucacuu uuaucucuua cgacggcaac 240

aauaaauacu acgcagacuc cgucaaaggc cgcuuuacaa ucucacguga caacuccaaa 300

aacacccuau accuccaaau gaacucccua cgcgcugaag acaccgccau uuacuauugc 360

gcccgcacag gcuggcuugg accauucgac uacuggggac aaggaacccu ugucaccguc 420

uccucugcca gcaccaaagg ccccuccguc uucccccucg cucccagcuc caaauccacg 480

ucaggcggca cugcagcccu cggaugccua gucaaagacu acuuccccga acccgucaca 540

gucucaugga acuccggagc ccucacuuca ggcguccaca ccuuccccgc aguacuacaa 600

ucuucaggcc uauacucccu aagcuccguc gucaccguac ccuccucauc ccucggaaca 660

caaaccuaca uaugcaacgu caaccacaaa cccucaaaca caaaaguaga caaacgcguc 720

gaacccaaau ccugcgacaa aacccauacc ugcccacccu gccccgcccc ggaacuccua 780

ggcggcccca gcgucuucuu auucccaccc aaacccaaag acacgcucau gauaaguaga 840

acccccgaag ugaccugcgu cgucgucgac gucuccccg aagacccuga aguuaaauuc 900

aacugguacg ucgacggcgu cgaaguucac aacgccaaaa ccaaaccccg agaagaacaa 960

uacaacucca ccuaccgagu cgucucagua cuaacagucc uccaccaaga cuggcucaac 1020

ggaaaagaau acaaaugcaa agucuccaac aaagcacuac cugccccaau cgaaaaaca 1080

1140

gacgaacuca ccaaaaauca ggucagccua accugccucg ucaaaggauu cuaccccucc 1200

gacaucgccg ucgaauggga aagcaacggc caacccgaaa acaacuacaa aaccacccca 1260

cccguaacucg acuccgacgg cuccuucuuc cucuacucca agcucaccgu cgacaaaucc 1320

cgcuggcaac agggaaacgu auucuccugc uccgucaugc acgaagcccu ccacaaccac 1380

uauacccaaa aaucacucuc ccuaucaccc ggaaaauaag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 934

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 934

gggagaaagc uuaccaugga acuaggccua ucauggaucu uccuccucgc cauccucaaa 60

ggcguccaau gccaggucca acucgucgaa uccggcggag gcgucgucca acccggccga 120

uucaccgcc ucuccugcgc cgccuccggc uucacuuucu ccuccuacac aaugcacugg 180

guacgccaag ccccaggaaa aggacucgaa ugggucaccu ucaucuccua cgacggaaac 240

aacaaauacu acgccgacag cguuaaagga cgauucacaa ucucccgcga caacucuaaa 300

aacacccuau accuccaaau gaacucccuc cgcgccgaag acacagcaau cuacuacugc 360

gccagaaccg gauggcuagg ccccuucgac uacuggggcc aaggaacccu cgucacagua 420

uccuccgccu ccaccaaagg cccuuccgua uuuccccugg cccccucauc caaauccacc 480

agcggcggaa ccgccgcacu uggcugccuc guaaaagacu acuuccccga acccguaacc 540

gucucugga acagcggcgc ccuaacguca ggcguacaca ccuuccccgc aguccuccaa 600

uccuccggac uauauagccu cuccagcgua guaacaguac ccuccagcuc ucucggcaca 660

caaaccuaua ucugcaacgu aaaccacaaa cccagcaaca ccaaaguuga caaacgcguu 720

gaacccaaau ccugcgacaa aacccacaca ugcccacccu gccccgcccc cgaacuccuc 780

ggcggucccu cagucuuccu cuucccacca aaaccuaaag acacucuaau gauaucccgc 840

accccagaag ugaccugcgu cguagucgac gucuccccg aagaccccga agucaaauuc 900

aacugguacg ucgacggcgu cgaaguacac aacgccaaaa ccaaacccg agaagaacaa 960

uacaacucaa ccuacagagu cgucagcguc cucaccgucc uccaucagga cuggcucaac 1020

1080

1140

gacgaacuca ccaagaacca aguaucuuua accugccuug ucaaaggcuu cuaccccucc 1200

gacaucgccg uggaauggga auccaacggga caacccgaaa acaacuacaa gaccacacca 1260

cccguccuug acumagacgg cuccuucuuc cucuauucca aacuuaccgu cgacaaaucc 1320

cgauggcaac aaggcaacgu cuucuccugc ucaguaaugc acgaagcccu acacaaccac 1380

1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 935

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 935

gggagaaagc uuaccaugga acuuggccuu uccuggaucu uccuccucgc cauacucaaa 60

ggcguccaau gccaaguuca gcuagucgaa uccgguggcg gcguagucca acccggacgc 120

agccuccgac uauccugcgc cgccuccggga uucaccuucu ccucauacac caugcacugg 180

guccgccaag cccccggcaa aggccucgaa ugggucacau ucaucuccua cgauggaaac 240

aacaaauacu acgccgacuc agucaaaggc cgcuucacaa ucucccgaga caacuccaaa 300

aacacccuau accuccaaau gaacucacuu agagccgaag acacagcaau auacuacugc 360

gcccgcaccg gauggcuagg acccuucgac uacuggggcc aagggacccu cgucaccguu 420

agcuccgccu ccacaaaagg acccuccgua uucccccucg ccccauccuc caaauccaca 480

ucuggcggca ccgccgcacu cggaugccuc guaaaagacu acuuccccga acccgucaca 540

gucagcugga acucaggcgc ucucaccucc ggcguccaca cauucccggc aguccugcaa 600

agcagcggcc ucuacucccu aucaucugua gucaccgucc cauccucuuc ccucggcacc 660

caaaccuaca ucugcaacgu aaaccacaaa cccagcaaca ccaaagugga uaaacgagua 720

gaacccaaau cuugcgacaa aacccacacu ugcccacccu gccccgcccc agaacuucua 780

ggcggacccu ccgucuuccu cuuccccc aaacccaaag acacccucau gaucucacgc 840

acccccgagg uaaccugcgu ugucgucgac gugucccacg aagacccuga agucaaguuc 900

aacugguacg ucgacggcgu cgaagugcac aacgccaaaa caaaaccacg cgaagaacaa 960

uauaacucaa ccuaccgcgu agucuccguc cuaaccgucc uccaccaaga cuggcuaaac 1020

ggcaaagaau acaaauguaa aguauccaau aaagcacucc ccgcccccaau agagaaaacg 1080

1140

gacgaacuca ccaaaaacca aguaucccua accugccuag ucaaaggcuu cuaccccucc 1200

gacaucgcag uagaauggga auccaacggc caaccagaaa acaacuacaa gacaacaccu 1260

cccguccucg acuccgacgg auccuucuuc uuauacucaa aacuaaccgu cgacaaaucu 1320

agauggcaac aaggcaacgu cuucucaugc uccguaaugc acgaagcucu ccacaaccac 1380

uacacccaaa aaucacucuc ccucuccccc ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

auccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 936

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 936

60

ggcguccaau gucaaguaca acuaguagaa ucaggcggag gaguugucca acccggccga 120

ucccuccgcu uaucaugugc agcaucugga uucacauuuu caucauacac aaugcacugg 180

gucagacaag cccggaaa agguuuagaa uggguaacau uuauaucaua cgacgguaac 240

aacaaauacu augcagacuc aguaaaagga agauuuacaa ucagcagaga caauagcaaa 300

aacacacuau accuacaaau gaacucccua cgagcagaag acacagccau cuauuacugu 360

gcacgaacag gauggcuagg accauucgau uacuggggcc aaggaacauu agucaccgua 420

ucuucugcau ccacaaaagg uccuucagua uuuccauuag cacccagcuc caaaucuaca 480

ucuggcggaa cagccgccuu aggaugcuua guuaaagauu acuuuccaga accaguaaca 540

guuucaugga acucaggagc ucuaacaucu ggaguacaca cauuuccagc aguccuacaa 600

ucauccggac uauauucacu aucaucagua guaacugucc ccucaucauc auuaggcaca 660

caaacuuaua uuugcaaugu aaaccauaaa ccaucaaaua caaaagucga caaaagagua 720

gaaccaaaau caugcgacaa aacccacaca uguccacccu gccccgcccc agaauuauua 780

ggaggaccau cugucuuccu uuucccacca aaaccaaaag acaccuuaau gauaucucga 840

acuccagaag uaacaugugu aguuguagau guuucacaug aagacccaga aguaaaauuc 900

aacugguacg ucgacggagu agaaguacac aaugcaaaaa caaaaccccg agaagaacaa 960

uacaacucca cauacagagu agucucagua cuaacaguac uccaucaaga cuggcuaaac 1020

ggaaaagaau acaaauguaa aguaaguaau aaagcacuac ccgcaccaau agaaaaaaca 1080

auaucaaaag caaaaggaca accaagagaa ccacaaguau auacacuacc uccauccaga 1140

gaugaauuaa caaaaaacca aguaagucua acauguuuag uaaaaggauu cuaucccagc 1200

gacauagcag ucgaauggga aucaaaugga caaccagaaa acaacuauaa aaccacacca 1260

ccaguauuag auucagacgg aucauuuuuc cuuuacucaa aauuaacagu agacaaaucc 1320

agauggcaac aaggcaaugu cuuuucaugc ucugucaugc acgaagcucu acauaaucac 1380

uacacucaaa aaucacuauuc acucucacca ggcaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 937

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC with signale peptide

<400> 937

60

ggaguacaau gucaaguaca auuaguagaa uccggaggcg gaguagucca acccggaaga 120

ucacuaagac ucaguugugc agcaucagga uucacauuuu caucauauac aaugcacugg 180

guuagacaag cacccggaaa aggacucgaa uggguaaccu uuaucuccua cgauggaaac 240

300

360

gcaagaacag gauggcucgg accauucgac uauuggggac aaggaaccuu aguaacagua 420

uccagcgcua gcacaaaagg cccuucuguc uucccauuag caccauccuc aaaaucaacu 480

ucuggcggaa cagcagcucu aggaugcuua guaaaagauu auuuuccaga accaguuacu 540

guauccugga acucaggagc acuaaccagu ggaguucaca cauuuccagc cguauuacaa 600

ucauccggau uauauucauu aucauccguc guaaccguac caagcucauc auuaggaaca 660

caaacauaca uaugcaacgu aaaucacaaa ccauccaaua caaaaguaga uaaaagagua 720

gaaccuaaau ccuugauaa aacacacaca ugcccaccau gcccagcacc agaauuacua 780

ggaggaccau caguauuccu auucccacca aaaccaaaag auacacuaau gauaucaaga 840

acaccagaag uaacuugugu agucguagac gucucacaug aagacccaga aguaaaauuuu 900

aauugguaug uugacggagu cgaaguacac aacgccaaaa caaaaccacg agaagaacaa 960

uacaacucaa cauauagagu aguaucugua uuaacaguau uacaucaaga uugguuaaac 1020

ggaaaagaau acaaauguaa aguaucaaau aaagcucuac cagcaccaau agaaaagaca 1080

1140

gacgaauuaa ccaaaaacca agucucauua acaugcuuag uuaaagguuu cuaccccagc 1200

gacaucgcag uugaauggga aucaaacggu caaccugaaa acaacuauaa aacaacacca 1260

ccaguuuuag acucagaugg auccuuuuuc uuauacucaa aauuaacagu ugacaaauca 1320

agauggcaac aaggaaaugu cuuuucaugu uccgucaugc augaagcacu acacaaccau 1380

uacacccaaa aaucacucuc acuaucaccc gguaaauaag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 938

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 938

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcggcccga gcguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ucacgugcgu gguggucgac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg ucgacggggu ggaggugcac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu cgugagcgug cugaccgucc uccaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugucgaac aaggcccugc cggcccccau cgagaagacg 1080

aucagcaagg cgaagggcca gccgcgggag ccccaggucu acacccuccc gccgccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 939

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 939

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcccc cgagcugcug 780

ggcggcccga gcguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ucacgugcgu gguggucgac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg ucgacggggu ggaggugcac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu cgugagcgug cugaccgucc uccaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugucgaac aaggcccugc cggcccccau cgagaagacg 1080

aucagcaagg cgaaggguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 940

<211> 1621

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC with signale peptide

<400> 940

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccga gcguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ucacgugcgu gguggucgac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg ucgacggggu ggaggugcac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu cgugagcgug cugaccgucc uccaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugucgaac aaggcccugc cggcccccau cgagaagacg 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagugag gacuaguuau aagacugacu 1440

agcccgaugg gccucccaac gggcccuccu ccccuccuug caccgagauu aauaaaaaaa 1500

1560

aucccccccc cccccccccc cccccccccc cccaaaggcu cuuuucagag ccaccagaau 1620

u 1621

<210> 941

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 941

gggagaaagc uuacccaggu gcagcugguc gagagcggcg ggggcguggu gcagcccggg 60

cgcucccucc ggcugagcug cgccgccucc ggcuucaccu ucagcuccua caccaugcac 120

uggguccgcc aggcgccggg gaagggccug gaguggguga cguucaucag cuacgacggc 180

aacaacaagu acuacgccga cuccgugaag gggcgguuca ccaucagccg cgacaacucc 240

aagaacaccc ucuaccugca gaugaacagc cugcgggccg aggacaccgc caucuacuac 300

ugcgcccgca cgggcuggcu cgggcccuuc gacuacuggg gccaggggac ccuggucacc 360

guguccagcg cguccaccaa gggccccagc guguuccccc uggccccguc cagcaagucc 420

acgagcggcg ggaccgccgc ccucggcugc cuggucaagg acuacuuccc cgagcccgug 480

accguguccu ggaacagcgg ggcgcugacc agcggcgucc acacguuccc cgccgugcuc 540

caguccagcg gccuguacuc ccuagcucc guggucaccg ugccgagcuc cagccucggg 600

acccagaccu acaucugcaa cgugaaccac aagcccucca acacgaaggu cgacaagcgg 660

guggagccca agagcugcga caagacccac acgugcccgc ccugccccgc ccccgagcug 720

cugggcgggc ccuccguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggugaccug cgucgugguc gacguguccc acgaggaccc ggaggucaag 840

uucaacuggu acguggacgg cguggagguc cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca ggaccuaccg cgugggugucc guccugacgg ugcuccacca ggacuggcug 960

1020

accaucucca aggccaaggg ccagccgcgg gagccccagg ucuacacccu cccgcccagc 1080

cgcgacgagc ugaccaagaa ccaggugucc cugacgugcc ucgugaaggg cuucuacccc 1140

agcgacaucg ccgucgagug ggagagcaac gggcagcccg agaacaacua caagaccacg 1200

cccccggugc uggacuccga cggcagcuuc uuccuguacu ccaagcucac cguggacaag 1260

agccgguggc agcaggggaa cgucuucucc ugcagcguga ugcacgaggc ccugcacaac 1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 942

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 942

ggggagaaagc uuacccaggu ccagcucguc gaguccggcg gcggcgucgu ccagcccggc 60

cgcucccucc gccucuccug cgccgccucc ggcuucaccu ucuccuccua caccaugcac 120

uggguccgcc aggccccgg caagggccuc gaguggguca ccuucaucuc cuacgacggc 180

aacaacaagu acuacgccga cuccgucaag ggccgcuuca ccaucucccg cgacaacucc 240

aagaacaccc ucuaccucca gaugaacucc cuccgcgccg aggacaccgc caucuacuac 300

ugcgcccgca ccggcuggcu cggccccuuc gacuacuggg gccagggcac ccucgucacc 360

gucuccuccg ccuccaccaa gggccccucc gucuuccccc ucgcccccuc cuccaagucc 420

accuccggcg gcaccgccgc ccucggcugc cucgucaagg acuacuuccc cgagcccguc 480

accgucuccu ggaacuccgg cgcccucacc uccggcgucc acaccuuccc cgccguccuc 540

caguccuccg gccucuacuc ccucuccucc gucgucaccg uccccuccuc cucccucggc 600

acccagaccu acaucugcaa cgucaaccac aagcccucca acaccaaggu cgacaagcgc 660

gucgagccca aguccugcga caagacccac accugccccc ccugccccgc ccccgagcuc 720

cucggcggcc ccuccgucuu ccucuucccc cccaagccca aggacacccu caugaucucc 780

840

uucaacuggu acgucgacgg cgucgagguc cacaacgcca agaccaagcc ccgcgaggag 900

caguacaacu ccaccuaccg cgucgucucc guccucaccg uccuccacca ggacuggcuc 960

1020

accaucucca aggccaaggg ccagccccgc gagccccagg ucuacacccu cccccccucc 1080

cucaccugcc ucgucaaggg cuucuacccc 1140

uccgacaucg ccgucgagug ggaguccaac ggccagcccg agaacaacua caagaccacc 1200

ccccccgucc ucgacuccga cggcuccuuc uuccucuacu ccaagcucac cgucgacaag 1260

ucccgcuggc agcagggcaa cgucuucucc ugcuccguca ugcacgaggc ccuccacaac 1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 943

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 943

gggagaaagc uuacccaggu gcaacugguc gagagcggcg ggggaguugu gcagcccggu 60

agaucccuca ggcuuucuug cgccgcuuca ggcuucaccu uuaguagcua cacaaugcac 120

uggguacggc aggcaccugg gaagggacug gaauggguga cuuucaucuc cuaugacggc 180

aacaauaaau acuaugccga uucugucaag ggucgcuuua cgauuucgcg agacaacagc 240

aaaaauaccu uguacuuaca gaugaacuca cugcgugcgg aggauacagc uauauauuac 300

ugugccagaa cuggguggcu aggaccauuc gacuauuggg gccaaggcac ccucgugaca 360

guuaguuccg caucuaccaa ggggccgagc guguuucccc uggccccuuc cucaaaaaagu 420

acuagcggag guaacagcugc acuuggcugc cuggucaagg auuacuuccc agaacccgug 480

accguaucuu ggaacuccgg ggccuugacg ucaggaguuc auacuuuucc ugcugugcuc 540

cagagcagug gccuguacuc ucuguccagc gucgugaccg ugccaucguc uucccucggu 600

acacagacuu auaucuguaa ugucaaucac aagcccucaa acaccaaagu ugacaagagg 660

guggagccua aaaguugcga uaagacacau accuguccac cgugccccgc cccugaauua 720

cuugggggac caagcguauu ccuguuuccc ccuaaaccaa aggacacguu gaugauuucc 780

cggacucccg aggugacaug ugucgugguu gaugugucuc acgaggaccc ggaagucaag 840

uucaauuggu acguggaugg cguagagguu cauaacgcga aaaccaagcc ucgcgaagaa 900

caguauaaua gcacuuacag aguggucuca gugcugacag uccuacacca agacuggcuc 960

aacggcaaag aguauaagug caaagugagu aauaaggcac ugcccgcccc aaucgagaaa 1020

accauuucca aggcuaaggg gcagccuagg gagccccagg uuuacacgcu uccacccagc 1080

cgggaugaac ugaccaaaaa ccaggugucu uugacauguc ucguaaaggg auuuuauccu 1140

ucagacaucg ccgucgagug ggaaaguaau ggucaaccag agaacaacua caaaacuacc 1200

ccgcccgugc uggacagcga uggcuccuuc uuuuuauacu cuaagcugac aguugacaaa 1260

ucgcgcuggc agcaggggaa uguguucagc ugcuccguca ugcacgaggc acuccauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 944

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 944

gggagaaagc uuacccaggu gcagcuggug gagagcggcg gcggcguggu gcagcccggc 60

agaagccuga gacugagcug cgccgccagc ggcuucaccu ucagcagcua caccaugcac 120

ugggugagac aggccccgg caagggccug gaguggguga ccuucaucag cuacgacggc 180

aacaacaagu acuacgccga cagcgugaag ggcagauuca ccaucagcag agacaacagc 240

aagaacaccc uguaccugca gaugaacagc cugagagccg aggacaccgc caucuacuac 300

ugcgccagaa ccggcuggcu gggccccuuc gacuacuggg gccagggcac ccuggugacc 360

gugagcagcg ccagcaccaa gggccccagc guguuccccc uggcccccag cagcaagagc 420

accagcggcg gcaccgccgc ccugggcugc cuggugaagg acuacuuccc cgagcccgug 480

accgugagcu ggaacagcgg cgccugacc agcggcgugc acaccuuccc cgccgugcug 540

600

acccagaccu acaucugcaa cgugaaccac aagcccagca acaccaaggu ggacaagaga 660

guggagccca agagcugcga caagacccac accugccccc ccugccccgc ccccgagcug 720

cugggcggcc cggcguguu ccuguucccc cccaagccca aggacacccu gaugaucagc 780

agaacccccg aggugaccug cgugguggg gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acguggacgg cguggaggug cacaacgcca agaccaagcc cagagaggag 900

caguacaaca gcaccuacag aguggugagc gugcugaccg ugcugcacca ggacuggcug 960

1020

accaucagca aggccaaggg ccagcccaga gagccccagg uguacacccu gccccccagc 1080

agagacgagc ugaccaagaa ccaggugagc cugaccugcc uggugaaggg cuucuacccc 1140

agcgacaucg ccguggagug ggagagcaac ggccagcccg agaacaacua caagaccacc 1200

ccccccgugc uggacagcga cggcagcuuc uuccuguaca gcaagcugac cguggacaag 1260

1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 945

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 945

gggagaaagc uuacccaggu gcaacugguc gagagcggcg ggggaguugu gcagcccggc 60

agaucccucc ggcugucuug cgccgcuagc ggguucaccu uuuccucuua cacaaugcac 120

ugggugcgcc aggccccugg aaagggccuu gaauggguca cguucaucag cuaugacggg 180

aacaauaaau acuaugcgga uuccgugaag ggaagauuua ccauuucucg ggacaacagc 240

aaaaauacac uguaccucca gaugaacucc cugcgcgcug aggauaccgc caucuauuac 300

ugugccagaa caggcuggcu uggcccguuc gacuauuggg ggcaaggaac ccugguuaca 360

gugagcucug cuuccaccaa gggccccagc gucuuuccuc ucgcccccuc uuccaaaagc 420

acgucugggg gaaccgcugc ccugggcugc cuggugaagg auuacuuccc ugaacccguu 480

acaguguccu ggaauagcgg ggcgcucacc uccggagucc auacauuucc ugccgugcug 540

cagucuagcg gccuuuuacuc ccugagcucu guggucaccg uuccguccag cucucucggc 600

acgcagacau auauuuguaa cgugaaucac aagcccagca acaccaaagu ggacaagcgg 660

gucgagccua aauccugcga uaagacacau accugucccc cuugccccgc uccggaacug 720

cuugggggac cuucuguguu ccuguuuccc ccuaaaccca aggacacccu caugaucagc 780

cgcacacccg agguuacgug ugggucgug gauguuuccc acgaggaccc ugaagugaag 840

uucaauuggu acgucgaugg cguggagguc cauaacgcca aaaccaagcc gagagaagaa 900

caguauaaua gcacauaccg ggugguuucu gugcugaccg uccugcacca agacuggcuc 960

aacgggaaag aguauaagug caaagugucc aauaaggcuc ugcccgcccc uauugagaaa 1020

acaaucagca aggcgaaggg acagccccgc gagccucagg uuuacacccu ucccccgucu 1080

agagaugaac ugacgaaaaa ccaggugucc cucacauguc uggucaaggg cuuuuauccu 1140

agcgacaucg ccguggagug ggaauccaau gggcaacccg agaacaacua caaaaccacc 1200

ccucccgugc uugacucuga uggcagcuuc uuucuguacu ccaagcucac aguugacaaa 1260

ucucgguggc agcagggaaa ugucuucagc ugcuccguga ugcacgaggc ucugcauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 946

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 946

gggagaaagc uuacccaagu ucaacuagua gaaucaggag gaggagucgu ccaaccaggc 60

agaucacuaa gacuaucaug ugcagccucu ggcuucacau ucucuucuua uacaaugcac 120

uggguaagac aagcaccagg aaaaggacua gaauggguaa cauucauauuc uuacgacgga 180

auuacgcuga uucuguaaaa gguagauuca caauuucuag agacaauagu 240

aaaaauacau uauaccucca aaugaauagu cuuagagcag aagauacagc aauauacuau 300

ugugcacgaa caggaugguu aggaccauuc gauuacuggg gucaaggaac auuaguaaca 360

guaucaucug caucaacaaa agguccuuca guauucccac ucgcaccauc aucaaaaucc 420

acaucaggag gaacugcagc ccucggaugc cuagucaaag acuacuuccc agaaccagua 480

accguaucuu ggaacuccgg agcauuaaca ucuggaguac auacauuccc ugcaguacuc 540

caaucaucag gacuauacuc acuauccucc guaguaaccg ucccuucauc aucucuaggu 600

acacaaacuu acauaugcaa cguaaaucac aaaccaucua auacaaaagu agacaaaaga 660

gucgaaccaa aaucaugcga caaaacccac acaugccccc caugcccagc acccgaacua 720

cucggaggac caucaguauu ucuauuucca ccaaaaccaa aagauacacu augauauca 780

840

uuuaauuggu acguagacgg uguagaaguu cacaaugcaa aaacaaaacc aagagaagaa 900

caauacaacu caacauauag aguaguuucu gucuuaaccg ucuuacacca agauugguua 960

1020

acaauaucaa aagccaaagg ccaaccucga gaaccacaag uauacacacu acccccuuca 1080

agagaugaac uaacaaaaaa ccaaguaagc cuaacaugcc uaguaaaagg cuuuuaucca 1140

ucagacauag caguagaaug ggaaucuaac ggucaaccug aaaauaacua uaaaacaaca 1200

ccaccaguac uagacucaga uggauuc uuucuauacu caaaauuaac aguagauaaa 1260

ucaagauggc aacaaggaaa cguuuuuucu uguucuguaa ugcacgaagc acuacacaau 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 947

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 947

gggagaaagc uuacccaggu gcaacugguc gagagcggcg gggguguggu acagcccggc 60

aggucccucc ggcugaguug cgccgcaagc ggguucaccu uuuccaguua cacuaugcac 120

ugggugcgcc aggccccagg caaggguuug gaauggguca ccuucaucag cuaugacggg 180

aacaauaaau acuaugcgga uuccgugaag ggcagguuua cgauuagccg ggacaacucc 240

aaaaauacuc uguaccucca gaugaacagu cugcgcgccg aggauaccgc aaucuauuac 300

ugugccagga ccggcugguu ggggccguuc gacuauuggg gucaaggcac ucggugacc 360

gucagcuccg caagcacgaa ggggcccagu guguuuccac ucgcccccuc cagcaaaucc 420

accaguggcg guaccgcggc ccuggggugc cugguaaagg auuacuuccc agaacccgg 480

acugucagcu ggaacuccgg cgcacucacc agcggcgugc auaccuuucc agccgugcug 540

cagaguuccg gguuguacag ccugaguucc gucgugacgg uaccgagcag cucccucggu 600

acucagaccu auauuuguaa ugugaaucac aagcccagua acacuaaagu cgacaagcgg 660

guggagccaa aaagcugcga uaagacccau accugucccc caugccccgc ccgggaacug 720

cugggcgggc ccuccguguu cuuguuucca cccaaaccaa aggacacucu caugaucagc 780

840

uucaauuggu acgucgaugg cguggaggug cauaacgcaa agacuaagcc gagggaagaa 900

caguauaauu ccaccuaccg gguagugagc guccugaccg ugcugcacca agacuggcuc 960

1020 aacgguaaag aguauaagug caaagucucc aauaaggccc

acuaucagua aggccaaggg ccagccccgc gagccacagg uguacacguu gcccccgagc 1080

agggaugaac ugaccaaaaa ccaggugucc cucacuuguc ugguaaaggg guuuuaucca 1140

agcgacaucg caguggagug ggaaaguaau ggccaacccg agaacaacua caaaaccacu 1200

1260

1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 948

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 948

gggagaaagc uuacccaagu ccagcuagua gaauccggcg gaggcgucgu ccaaccagga 60

cgcucgcuaa gacucagcug cgccgcaucu ggcuucacau ucagcucaua cacaaugcac 120

ugggucagac aagcuccagg caaaggccuc gaauggguca cauucauauuc auacgacggc 180

aacaacaaau acuacgccga cuccguaaaa ggccgcuuca ccaucuccag agacaacucc 240

aaaaacaccc uauaccucca aaugaacuca cucagagccg aagacaccgc aaucuacuac 300

ugcgcaagaa ccggcuggcu uggccccuuc gauuacuggg gacaaggcac ccucgucacc 360

gucucauccg cauccaccaa aggcccaucc gucuuccccc ucgcaccauc auccaaaucc 420

accagcggag guaccgccgc acucggcugc cuagucaaag acuacuuccc cgaaccuguc 480

acagucuccu ggaacuccgg agcccucaca ucgggcgucc acacauuccc cgccguccua 540

caaagcuccg gccucuacag ccucuccuca gucgucaccg uacccuccuc cagccucgga 600

acacaaaccu acaucugcaa cguuaaccac aaaccuucca acaccaaagu cgacaaacga 660

gucgaaccca aaucgugcga caaaacccau accugcccac ccugccccgc ccccgaacuc 720

cucggcggcc cauccgucuu ccuauuccca cccaaaccaa aggacacacu caugauauca 780

cgaaccccug aagucacgug cgucgucguc gacguuucac acgaagaccc cgaagucaaa 840

uucaacuggu acguagacgg agucgaaguc cacaacgcca aaaccaaacc cggagaagaa 900

cauaccaacu cuaccuaccg cgucguaucc guccucaccg uccuccacca agacuggcua 960

1020

accaucucca aagccaaagg acaaccccgc gaaccccaag uguacacccu cccacccucg 1080

1140

uccgacauag caguagaaug ggaaucuaac ggccagcccg aaaacaacua caaaacaacc 1200

ccacccguac ucgacuccga cggcucauuc uuccucuacu caaaacucac cgucgauaaa 1260

ucccgcuggc aacaaggcaa ugucuucuca ugcagcguca ugcacgaagc acuccacaac 1320

cacuacacac aaaagagccu cucccuaucc cccggcaaau gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 949

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 949

gggagaaagc uuacccaagu ccagcuaguc gaaucaggcg gaggcgucgu ccaacccgga 60

cggucccuac gacucagcug ugcugccagc ggcuucaccu ucucguccua cacaaugcac 120

uggguccggc aagcacccgg caaaggucuc gaauggguca ccuucauauuc cuaugacggc 180

aacaacaaau acuacgccga cuccgucaaa ggccgcuuca caaucucaag agacaacucc 240

300

ugcgcccgca ccggauggcu cggccccuuc gacuacuggg gccaaggcac ccuagucaca 360

guaucauccg ccucuacaaa gggaccaucc gucuuccccc ucgccccauc cuccaaaucc 420

accucuggag gcaccgccgc acucggaugc cucgucaaag acuacuuccc cgaacccguc 480

acagucuccu ggaacuccgg cgcccuaacc uccggagagucc acacauuccc ugcuguccua 540

caauccucgg gccuauacuc ccucucaucu guagucaccg uccccucauc cucccuugga 600

acccaaacgu acauaugcaa cgucaaccac aaaccuucca acacaaaagu cgacaaacgu 660

guagagccaa aguccuguga caaaacacac acaugcccac caugucccgc gcccgaacua 720

cucggcggac ccucagucuu ccucuuuccc ccgaaaccca aagacacccu caugauauca 780

cgcacccccg aaguuaccug cgucgucguc gacgucuccc acgaagaccc cgaagucaaa 840

uucaacuggu acgucgacgg cguagaaguc cacaacgcca aaaccaaacc acgggaagaa 900

caauacaacu ccacauaccg cgucgucagc guacucaccg uccuacauca agacuggcua 960

1020

1080

agagacgaac ucaccaaaaa ccaaguuuca cucacaugcc ucguaaaagg auucuacccc 1140

ucugacauug cugucgaaug ggaauccaac ggacaacccg aaaacaacua caaaaccacc 1200

ccgcccgucc ucgacuccga cggcucauuc uuccuauacu ccaaacucac cguagacaaa 1260

ucccgauggc agcaaggcaa cgucuucucc ugcagcguaa ugcacgaagc acuccacaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 950

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 950

gggagaaagc uuacccaagu acaacucguc gaauccggcg gcggcguagu ccaaccaggc 60

agaucccuac gccucuccug cgccgcaucc ggauucaccu ucuccuccua caccaugcac 120

uggguacgcc aagccccgg caagggccuc gaauggguca cguucaucuc uuacgacggc 180

aacaacaaau acuacgccga cuccguaaaa ggucguuuca ccaucucccg cgacaacagc 240

aaaaacaccc uauaccuuca aaugaacucc cuccgcgccg aagacaccgc caucuacuac 300

ugugcccgca ccgguuggcu cggccccuuc gacuacuggg gucaaggaac ccuaguuacc 360

guaucauccg caucuaccaa aggccccucc guauucccac uagccccauc guccaaauca 420

acaucaggcg gcacagccgc ccucggaugc cuagucaaag acuacuuccc cgaacccguc 480

accgucucau ggaacuccgg agcccuaacc ucgggagucc acaccuuccc agcgguacua 540

caaucauccg gacuuuacuc ccuaucaucc gucgucacag uaccauccuc aucccucgggg 600

acccaaaccu acauaugcaa cgucaaccac aaaccaucca acaccaaagu cgacaaaaga 660

gucgaaccaa aauccugcga caaaacccac acaugcccac ccugcccagc ccccgaacuc 720

cucggcggcc ccuccguauu ccucuuccca cccaaaccca aggacacccu caugaauaucc 780

cgcaccccag aaguaaccug cguaguaguc gacguuucac acgaagaccc cgaagucaaa 840

uucaacuggu acguagacgg cgucgagguc cacaacgcca aaaccaaacc ucgcgaagaa 900

caauacaaca gcacauaccg cgucgucucc guccuaaccg uacuacacca agacuggcua 960

1020

accauaucca aagccaaagg ucaaccccgc gaaccccaag uauacacccu acccccaucc 1080

1140 cgcgacgagc ucaccaaaaa ccaaguaucc cuaaccugcc

uccgacauag ccgucgaaug ggaaagcaau ggccagcccg aaaacaacua caaaacaacc 1200

ccacccgucc ucgacuccga cggcucuuuc uuccucuacu caaaacucac agucgacaaa 1260

ucacgauggc aacaaggcaa cgucuucucc ugcagcguaa ugcacgaagc ccuccacaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 951

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 951

gggagaaagc uuacccaagu ccaacuaguc gaaucaggag gaggcguagu acaaccagga 60

agauccuuaa gacuuucaug ugcagcaucu ggauuuaccu ucucaucaua cacaaugcac 120

ugggucagac aagccccgg aaaaggacua gaauggguaa cauuuauauc auaugaugga 180

aauaacaaau auuacgcaga uucuguaaaa ggaagauuca ccaucucaag agauaauuca 240

aaaaacacac uauaccuaca aaugaacuca cucagagcug aagacaccgc aauauacuau 300

ugcgcaagaa caggaugguu aggaccuuuc gauuacuggg gacaaggaac acuaguuacc 360

gucuccuccg caaguaccaa aggaccaucu guauucccau uagcaccauc auccaaauca 420

acaucaggag gaaccgcagc auuaggaugc uuaguaaaag acuacuuucc ugaacccgua 480

acaguaucau ggaauuccgg agcacuaaca ucaggaguac auaccuuucc agcaguaacuc 540

600

acacaaaccu acaucugcaa uguaaaccac aaaccaucaa auacaaaagu cgacaaaaga 660

guugaaccaa aaucauguga caaaacucac acaugcccac cauguccagc cccagaauua 720

cuaggaggac caucaguauu ccuuuuccca ccaaaaccaa aagauacucu aaugauaucc 780

cguaccccag aaguaacaug cgucguagua gacguaucac acgaagaccc cgaaguaaaa 840

uucaauuggu acgucgacgg aguagaagua cacaacgcca aaacaaaacc ccgagaagaa 900

caauacaacu ccacauaccg uguaguauca guauuaacag ucuuacacca agacuggcua 960

1020

accauaucaa aagcaaaagg ccaacccaga gaaccccaag uuuauacacu accaccauca 1080

agagacgaau uaacaaaaaa ccaaguaucc cuaacaugcc uaguaaaagg auucuacccu 1140

ucagacaucg caguagaaug ggaauccaac ggacaaccug aaaacaacua uaaaacaaca 1200

ccaccaguau uagauagcga uggaucuuuc uucuuauauu caaaacuuac aguagacaaa 1260

ucucgauggc aacaaggaaa cguauucuca ugcuccguaa ugcacgaagc gcuacauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 952

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab HC without signale peptide

<400> 952

gggagaaagc uuacccaagu ucaauuagua gaaucuggag gaggaguagu ccaaccagga 60

120

uggguaagac aagccccagg aaaaggauua gaauggguaa cauuuauauc uuacgacggc 180

aauaacaaau auuaugcaga cucaguuaaa gguagauuca caauaagccg agacaauuca 240

300

ugugcacgua caggaugguu agguccuuuc gauuacuggg gacaagguac ucuaguuaca 360

guaagcagcg caucuaccaa aggaccaagc guauucccuc uugcuccauc aagcaaaucc 420

acaucaggcg gaacagcugc auuaggaugc uuaguaaaag acuauuuccc agaacccgua 480

acgguaucuu ggaacagcgg cgcauuaaca ucaggaguac auacuuuucc ugcaguacua 540

caaagcuccg gauuauacuc uuuaucauca guaguaacag uaccauccuc aucacuagga 600

660

guagaaccaa aaucauguga uaaaacucac accuguccuc cauguccagc acccgaauua 720

uuaggagguc caaguguauu cuuauuucca ccaaaaccua aagauacccu augauauca 780

agaacaccag aaguaacaug uguaguagua gacgucucac acgaagaccc agaaguaaaa 840

uucaacuggu acguagacgg aguagaagua cauaacgcua aaacuaaacc acgagaagaa 900

caauacaaua guacauacag aguaguguca guauuaacag uauuacacca agacuggcua 960

1020

accaucucca aagccaaagg acaaccccgu gaaccucaag ucuauacccu accacccuca 1080

1140

uccgacauag caguagaaug ggaaucaaau ggucaaccag aaaacaacua caaaacaaca 1200

ccaccaguuc ucgauucaga uggauucauuu uuucuauaua gcaaauuaac uguagacaaa 1260

ucuagauggc aacaaggaaa uguauucuca uguucaguaa ugcaugaagc acuccacaau 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 953

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 953

gggagaaagc uuacccaggu gcagcugguc gagagcggcg ggggcguggu gcagcccggg 60

cgcucccucc ggcugagcug cgccgccucc ggcuucaccu ucagcuccua caccaugcac 120

uggguccgcc aggcgccggg gaagggccug gaguggguga cguucaucag cuacgacggc 180

aacaacaagu acuacgccga cuccgugaag gggcgguuca ccaucagccg cgacaacucc 240

aagaacaccc ucuaccugca gaugaacagc cugcgggccg aggacaccgc caucuacuac 300

ugcgcccgca cgggcuggcu cgggcccuuc gacuacuggg gccaggggac ccuggucacc 360

guguccagcg cguccaccaa gggccccagc guguuccccc uggccccguc cagcaagucc 420

acgagcggcg ggaccgccgc ccucggcugc cuggucaagg acuacuuccc cgagcccgug 480

accguguccu ggaacagcgg ggcgcugacc agcggcgucc acacguuccc cgccgugcuc 540

caguccagcg gccuguacuc ccuagcucc guggucaccg ugccgagcuc cagccucggg 600

acccagaccu acaucugcaa cgugaaccac aagcccucca acacgaaggu cgacaagcgg 660

guggagccca agagcugcga caagacccac acgugcccgc ccugccccgc ccccgagcug 720

cugggcggcc cgagcguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggucacgug cguggugguc gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acgucgacgg gguggaggug cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca gcaccuaccg cgucgugagc gugcugaccg uccuccacca ggacuggcug 960

aacggcaagg aguacaagug caaggugucg aacaaggccc ugccggcccc caucgagaag 1020

acgaucagca aggcgaaggg ccagccgcgg gagccccagg ucuacacccu cccgcccagc 1080

cgcgacgagc ugaccaagaa ccaggugucc cugacgugcc ucgugaaggg cuucuacccc 1140

agcgacaucg ccgucgagug ggagagcaac gggcagcccg agaacaacua caagaccacg 1200

cccccggugc uggacuccga cggcagcuuc uuccuguacu ccaagcucac cguggacaag 1260

agccgguggc agcaggggaa cgucuucucc ugcagcguga ugcacgaggc ccugcacaac 1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 954

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 954

gggagaaagc uuacccaggu gcaacugguc gagagcggcg ggggaguugu gcagcccggu 60

agaucccuca ggcuuucuug cgccgcuuca ggcuucaccu uuaguagcua cacaaugcac 120

uggguacggc aggcaccugg gaagggacug gaauggguga cuuucaucuc cuaugacggc 180

aacaauaaau acuaugccga uucugucaag ggucgcuuua cgauuucgcg agacaacagc 240

aaaaauaccu uguacuuaca gaugaacuca cugcgugcgg aggauacagc uauauauuac 300

ugugccagaa cuggguggcu aggaccauuc gacuauuggg gccaaggcac ccucgugaca 360

guuaguuccg caucuaccaa ggggccgagc guguuucccc uggccccuuc cucaaaaaagu 420

acuagcggag guaacagcugc acuuggcugc cuggucaagg auuacuuccc agaacccgug 480

accguaucuu ggaacuccgg ggccuugacg ucaggaguuc auacuuuucc ugcugugcuc 540

cagagcagug gccuguacuc ucuguccagc gucgugaccg ugccaucguc uucccucggu 600

acacagacuu auaucuguaa ugucaaucac aagcccucaa acaccaaagu ugacaagagg 660

guggagccua aaaguugcga uaagacacau accuguccac cgugccccgc ccccgagcug 720

cugggcggcc cgagcguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggucacgug cguggugguc gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acgucgacgg gguggaggug cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca gcaccuaccg cgucgugagc gugcugaccg uccuccacca ggacuggcug 960

aacggcaagg aguacaagug caaggugucg aacaaggccc ugccggcccc caucgagaag 1020

acgaucagca aggcgaaggg gcagccuagg gagccccagg uuuacacgcu uccacccagc 1080

cgggaugaac ugaccaaaaa ccaggugucu uugacauguc ucguaaaggg auuuuauccu 1140

ucagacaucg ccgucgagug ggaaaguaau ggucaaccag agaacaacua caaaacuacc 1200

ccgcccgugc uggacagcga uggcuccuuc uuuuuauacu cuaagcugac aguugacaaa 1260

ucgcgcuggc agcaggggaa uguguucagc ugcuccguca ugcacgaggc acuccauaac 1320

1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 955

<211> 1564

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab HC without signale peptide

<400> 955

gggagaaagc uuacccaggu gcagcuggug gagagcggcg gcggcguggu gcagcccggc 60

agaagccuga gacugagcug cgccgccagc ggcuucaccu ucagcagcua caccaugcac 120

ugggugagac aggccccgg caagggccug gaguggguga ccuucaucag cuacgacggc 180

aacaacaagu acuacgccga cagcgugaag ggcagauuca ccaucagcag agacaacagc 240

aagaacaccc uguaccugca gaugaacagc cugagagccg aggacaccgc caucuacuac 300

ugcgccagaa ccggcuggcu gggccccuuc gacuacuggg gccagggcac ccggugacc 360

gugagcagcg ccagcaccaa gggccccagc guguuccccc uggcccccag cagcaagagc 420

accagcggcg gcaccgccgc ccugggcugc cuggugaagg acuacuuccc cgagcccgug 480

accgugagcu ggaacagcgg cgcccugacc agcggcgugc acaccuuccc cgccgugcug 540

600

acccagaccu acaucugcaa cgugaaccac aagcccagca acaccaaggu ggacaagaga 660

guggagccca agagcugcga caagacccac accugccccc ccugccccgc ccccgagcug 720

cugggcggcc cgagcguguu ccucuucccg cccaagccca aggacacccu gaugaucagc 780

cgcacccccg aggucacgug cguggugguc gacgugagcc acgaggaccc cgaggugaag 840

uucaacuggu acgucgacgg gguggaggug cacaacgcca agaccaagcc ccgggaggag 900

caguacaaca gcaccuaccg cgucgugagc gugcugaccg uccuccacca ggacuggcug 960

aacggcaagg aguacaagug caaggugucg aacaaggccc ugccggcccc caucgagaag 1020

acgaucagca aggcgaaggg ccagcccaga gagccccagg uguacacccu gccccccagc 1080

agagacgagc ugaccaagaa ccaggugagc cugaccugcc uggugaaggg cuucuacccc 1140

agcgacaucg ccguggagug ggagagcaac ggccagcccg agaacaacua caagaccacc 1200

ccccccgugc uggacagcga cggcagcuuc uuccuguaca gcaagcugac cguggacaag 1260

1320

cccggcaagu gaggacuagu uauaagacug 1380

1440

1500

ugcauccccc cccccccccc cccccccccc ccccccaaag gcucuuuuca gagccaccag 1560

1564

<210> 956

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 956

gggagaaagc uuaccaugga gacccccgcc cagcugcucu uccugcugcu ccuguggcug 60

ccggacacca cgggcgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 120

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 180

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 240

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 300

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 360

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccgucgc cgcccccucc 420

guguucaucu ucccgcccag cgacgagcag cugaaguccg ggacggccag cguggucugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggugga caacgcgcug 540

caguccggca acagccagga gagcgucacc gagcaggacu ccaaggacag caccuacucc 600

cucagcucca cccugacgcu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggugaccc accagggccu cuccagcccc gucaccaagu ccuucaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 957

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 957

gggagaaagc uuaccaugga gacccccgcc cagcuccucu uccuccuccu ccucuggcuc 60

120

ggcgagcgcg ccaccucuc cugccgcgcc ucccaguccg ucggcuccuc cuaccucgcc 180

ugguaccagc agaagcccgg ccaggccccc cgccuccuca ucuacggcgc cuucucccgc 240

gccaccggca uccccgaccg cuucuccggc uccggcuccg gcaccgacuu cacccucacc 300

aucucccgcc ucgagcccga ggacuucgcc gucuacuacu gccagcagua cggcuccucc 360

cccuggaccu ucggccaggg caccaagguc gagaucaagc gcaccgucgc cgcccccucc 420

gucuucaucu ucccccccuc cgacgagcag cucaaguccg gcaccgccuc cgucgucugc 480

cuccucaaca acuucuaccc ccgcgaggcc aagguccagu ggaaggucga caacgcccuc 540

caguccggca acucccagga guccgucacc gagcaggacu ccaaggacuc caccuacucc 600

cucuccucca cccucacccu cuccaaggcc gacuacgaga agcacaaggu cuacgccugc 660

gaggucaccc accagggccu cuccuccccc gucaccaagu ccuucaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 958

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 958

gggagaaagc uuaccaugga gacccccgcc cagcuucucu uccuucuguu guuauggcug 60

ccugacacaa cuggcgaaau cgugcuaacg caaagcccag ggacccucuc ccugucuccg 120

ggagagagag cuacacuuuc augcagggca agucagagcg ucgguuccuc uuaccuggcc 180

ugguaucagc agaagcccgg ccaagcgccu cgguugcuca uuuacggggc uuuuucgcgc 240

gccacuggaa uaccagaucg auucucaggc agcgguagug ggaccgacuu uacacugacc 300

aucucccguc uggaacccga ggauuucgca guuuauuacu gucagcagua uggaucuagc 360

ccuuggacuu uuggcgggg cacaaaagug gaaauuaaga gaaccguagc cgcuccaucc 420

guguucaucu uucccccuuc agacgagcaa cucaaaagug ggacggcaag cgucgugugc 480

uuacugaaca auuucuaccc aagggaggcc aagguucagu ggaaagugga uaacgcucug 540

600

660

gagguaaccc aucagggucu cucuuccccg guuacaaaau cauuuaaccg gggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 959

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 959

gggagaaagc uuaccaugga gacccccgcc cagcugcugu uccugcugcu gcuguggcug 60

120

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 180

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 240

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 300

aucagcagac uggagcccga ggacuucgcc

cccuggaccu ucggccaggg caccaaggug gagaucaaga gaaccguggc cgcccccagc 420

guguucaucu ucccccccag cgacgagcag cugaagagcg gcaccgccag cguggugugc 480

cugcugaaca acuucuaccc cagagaggcc aaggugcagu ggaaggugga caacgcccug 540

cagagcggca acagccagga gagcgugacc gagcaggaca gcaaggacag caccuacagc 600

cugagcagca cccugacccu gagcaaggcc

gaggugaccc accagggccu gagcagcccc gugaccaaga gcuucaacag aggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 960

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 960

gggagaaagc uuaccaugga gacccccgcc cagcuccugu uccugcuucu gcucuggcug 60

ccugacacaa cgggcgaaau cgugcuuacc caaagcccgg ggacacuguc ccucucuccc 120

ggagagagag cuacccugag cugccggggcc ucccagucug ucggcagcuc cuaccuggcg 180

ugguaucagc agaaaccugg gcaagcuccc cgccuccuga uuuacggagc cuuuucuaga 240

gccacaggca ucccugaucg guucagcggg uccggaagcg gcaccgacuu uacacuuacc 300

auuucucgcc uggaacccga ggauuucgcu guuuauuacu gucagcagua uggcuccagc 360

ccuuggacgu uugggcaggg aaccaaagug gaaaucaaga gaacaguggc cgcuccgucu 420

gucuucauuu uucccccuuc cgacgagcaa cucaaaagcg gcaccgccuc ugugguuugc 480

cugcuuaaca auuucuaccc ccgggaggcg aaggugcagu ggaaagucga uaacgcccug 540

caguccggga auagcggga auccgugaca gagcaagacu cuaaggaauag caccuauucc 600

660

gaggugaccc aucagggacu cagcucuccu gucacaaaga gcuuuaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 961

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 961

gggagaaagc uuaccaugga aacaccagca caacuacuau ucuuacuauu acuauggcua 60

ccagacacaa caggagaaau aguacuaaca caaucaccag gaacacuaag ucauaucacca 120

ggagaaagag caacacuauc augcagagca ucccaaucag uuggaucuuc cuaccuagcc 180

ugguaucaac aaaaaccagg acaagcacca agauuacuaa uauacggagc auucucaaga 240

gcaacuggaa ucccagauag auucucagga ucaggaucag gaacagacuu cacauuaaca 300

auaucacgac uagaaccaga agacuucgca guauacuacu gucaacaaua cggauccuca 360

ccauggaccu ucggccaagg aacaaaagua gaaauaaaaa gaacaguagc agccccaucu 420

guauucauau ucccaccauc agaugaaca cuaaaaucag gaacagcauc aguaguaugc 480

uuacuaaaca acuucuaccc aagagaagcc aaaguacaau ggaaaguaga caacgcacua 540

600

660

gaaguaacac accaaggacu aucaucacca guaacaaaau cauucaaccg aggagaaugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 962

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 962

gggagaaagc uuaccaugga gacccccgcc cagcuccugu uccuguugcu gcucuggcug 60

ccagacacua ccggcgaaau cguguugacg caaagcccgg ggacucuguc ccucaguccc 120

ggugagaggg caacccugag cugccgggcc ucccagagug ucggcagcuc cuaccuggcg 180

ugguaucagc agaagccagg gcaagcaccc cgccuccuga uuuacggcgc cuuuagcagg 240

gccaccggua ucccagaucg guucuccggg aguggcagcg gcacugacuu uaccuugacg 300

360 auuucccgcc uggaacccga ggauuucgca

ccauggacuu uuggucaggg caccaaagua gaaaucaaga ggacuguggc cgcgccgucc 420

gucuucauuu uucccccaag cgacgagcaa cucaaauccg ggaccgccag uguggugugc 480

cugcugaaca auuucuaccc ccgggaggca aagguccagu ggaaagugga uaacgccuug 540

cagagcggca auucccagga aagcguaacc gagcaagaca guaaggauuc cacguauagc 600

cucaguucca cucugacccu gagcaaggcc gacuacgaaa aacacaaggu guacgcaugu 660

gaggucacuc aucagggucu cagcucccca gugaccaaaa guuuuaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 963

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 963

gggagaaagc uuaccaugga aacccccgcc caacuccucu uccuauuacu ccucuggcua 60

cccgacacca ccggcgaaau cguccucacc caauccccag gcacccucuc ucucuccccc 120

ggagaacgcg caacacucuc cugccggca ucccaauccg ucggaucuuc cuaccucgcc 180

ugguaccaac aaaaacccgg ccaagcccca cgccuccuca ucuacggcgc cuucucccgc 240

gccaccggca uuccagaccg uuucucagga uccggcuccg gcaccgauuu cacacucacc 300

aucucccgcc uagaaccaga agacuucgcc guauacuacu gccagcaaua cggaucuucc 360

cccuggacau ucggccaagg caccaaaguc gaaaucaaac gcaccgucgc agcccccucc 420

gucuucaucu ucccacccuc cgacgaacaa cuaaaaucug gcacagcauc cgucgucugc 480

cuccuaaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcacuc 540

caaucuggca acucacaaga auccgucaca gaacaagacu ccaaagacuc aaccuacucc 600

cucuccucaa cccucacccu cuccaaagcc gacuacgaaa aacacaaggu cuacgcaugc 660

gaagucaccc aucaaggacu cuccuccccc gucaccaaau ccuucaaccg cggcgaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 964

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 964

gggagaaagc uuaccaugga aacacccgcc caacuccucu uccuccuccu ccucuggcua 60

cccgacacca ccggcgaaau cguccucacc caaucccccg gcacccuauc ccucuccccc 120

ggcgaacgcg ccacccuauc cugccgcgca ucccaauccg uaggauccuc cuaccucgcc 180

ugguaccaac aaaaacccgg ccaagcaccc cgccuccuca ucuacggagc cuucucccgc 240

gccaccggca ucccugaccg cuucuccggc ucaggcucag gcaccgacuu cacccucacc 300

aucucucgcc uagaacccga agacuucgcc guauacuauu gccaacaaua cggcuccucc 360

ccuuggaccu ucggccaagg aacaaaaguc gaaaucaaac gaaccgucgc cgcccccuca 420

gucuucaucu ucccacccuc cgacgaacaa cucaaauccg guaccgccuc cgucgucugc 480

cuucucaaca acuucuaccc ccgagaagcc aaaguacaau ggaaagucga caacgcacua 540

caaucaggca acucccaaga auccgucacc gaacaagauu ccaaagacuc aaccuacuca 600

cucuccucca cacucacccu cuccaaagcc gacuacgaaa aacacaaagu cuacgccugc 660

gaagucaccc acccaaggacu cuccagcccc gucaccaaau ccuucaaccg cggcgaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 965

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 965

gggagaaagc uuaccaugga aacucccgcc caacuacucu uccuccuccu ccucuggcuc 60

cccgacacca ccggcgaaau cguccuuacc cagucccccg gcacccucuc acucuccccc 120

ggcgaacgcg ccacccuauc cugucgcgcc ucccaaucag ucggcucauc auaccucgcc 180

ugguaccaac aaaaacccgg ccaagccccu cgccuccuca uauacggcgc cuucucccgc 240

gccaccggca uccccgaccg auucuccggc uccggcuccg gcacugacuu cacccucacc 300

auaucccgcc ucgaacccga agacuucgca gucuacuacu gccaacaaua cggaucuucc 360

cccuggaccu ucggccaagg caccaaaguc gaaaucaaac gcaccgucgc cgcccccucc 420

gucuucauau ucccaccuc agacgaacaa cucaaaucag gcaccgcauc cgucgucugc 480

cuccucaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcccuc 540

caaucaggca acucacaaga auccgucaca gaacaagacu ccaaagacuc aaccuacucc 600

cucuccucaa cccucacacu cuccaaagcc gacuacgaaa aacacaaagu cuacgccugc 660

gaagucaccc acccaaggacu uuccucaccc gucaccaaau ccuucaaccg cggcgaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 966

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 966

gggagaaagc uuaccaugga aacaccagca caacuauuau uccuauuacu ucuauggcua 60

ccagacacaa caggagaaau aguauuaaca caaagcccag gaacacucuc auuaucacca 120

ggagaaagag caacacucuc augccgagca ucccaauccg ucggaucauc auaucuagca 180

ugguaccaac aaaaaccagg acaagcaccc agacuacuaa uauacggagc auuuucaaga 240

gccacaggaa ucccagacag auuuucagga ucaggaucag gaacagacuu cacauuaaca 300

auaucacgau uagaacccga agacuucgca guauacuacu gccaacaaua cggaucaucu 360

cccuggacau ucggacaagg cacaaaagua gaaauaaaac gaacagucgc agcaccauca 420

guauucauau ucccaccauc agacgaaca cuaaaaucag gaacagcauc aguaguaugc 480

cuauuuaaaua acuucuaccc aagagaagca aaaguccaau ggaaaguaga uaacgcacua 540

caaucaggaa acucucaaga aucaguaacc gaacaagacu caaaagauuc aaccuacuca 600

uuaucaucaa cauuaacacu aucaaaagca gacuacgaaa aacacaaagu auacgcaugc 660

gaaguaaccc accaaggccu aucaucacca guaacaaaau cauucaacag aggagaaugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 967

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC with signale peptide

<400> 967

gggagaaagc uuaccaugga aaccccugcc caauuacuau ucuuauuauu acucuggcua 60

ccagacacaa caggagaaau aguuuuaaca caaucaccag gcacacuauuc acuaucacca 120

ggagaaagag caacacuauc augcagagcc uccacaaucag ucggaucauc auaccuagca 180

ugguaucaac aaaaacccgg acaagcacca agauuauuaa uauauggagc auucucacga 240

gcaaccggaa uaccagauag auucucagga ucaggaagcg gcaccgacuu cacauuaaca 300

360

ccauggacau ucggacaagg aacaaaaguu gaaauaaaaa gaacaguagc agcaccauca 420

guauucauau ucccaccauc agacgaacaa uuaaaaucag gaacagccuc uguaguaugc 480

cuauuaaaca acuuuuaccc aagagaagca aaaguucaau ggaaaguaga caaugcacua 540

caaucaggca acucacaaga aucaguaaca gaacaagacu cuaaagacuc aacauauagc 600

660

gaaguaacac accaaggacu aucaucacca guaacaaaau cauucaacag aggagaaugc 720

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 968

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 968

gggagaaagc uuaccaugga gacccccgcc cagcugcucu uccugcugcu ccuguggcug 60

ccggacacca cgggcgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 120

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 180

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 240

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 300

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 360

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccguggc ggcccccagc 420

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 540

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 600

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggggagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 969

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 969

gggagaaagc uuaccaugga gacccccgcc cagcuucucu uccuucuguu guuauggcug 60

ccugacacaa cuggcgaaau cgugcuaacg caaagcccag ggacccucuc ccugucuccg 120

ggagagagag cuacacuuuc augcagggca agucagagcg ucgguuccuc uuaccuggcc 180

ugguaucagc agaagcccgg ccaagcgccu cgguugcuca uuuacggggc uuuuucgcgc 240

gccacuggaa uaccagaucg auucucaggc agcgguagug ggaccgacuu uacacugacc 300

aucucccguc uggaacccga ggauuucgca guuuauuacu gucagcagua uggaucuagc 360

ccuuggacuu uuggcgggg cacaaaagug gaaauuaaga gaaccguggc ggcccccagc 420

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 540

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 600

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 970

<211> 925

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC with signale peptide

<400> 970

gggagaaagc uuaccaugga gacccccgcc cagcugcugu uccugcugcu gcuguggcug 60

120

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 180

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 240

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 300

aucagcagac uggagcccga ggacuucgcc

cccuggaccu ucggccaggg caccaaggug gagaucaaga gaaccguggc ggcccccagc 420

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 480

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 540

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 600

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 660

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggcgagugc 720

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 780

840

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 900

ggcucuuuuc agagccacca gaauu 925

<210> 971

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 971

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 60

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 120

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 180

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 240

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 300

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccgucgc cgcccccucc 360

guguucaucu ucccgcccag cgacgagcag cugaaguccg ggacggccag cguggucugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggugga caacgcgcug 480

caguccggca acagccagga gagcgucacc gagcaggacu ccaaggacag caccuacucc 540

cucagcucca cccugacgcu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggugaccc accagggccu cuccagcccc gucaccaagu ccuucaaccg cggggagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 972

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 972

gggagaaagc uuaccgagau cguccucacc cagucccccg gcacccucuc ccucuccccc 60

ggcgagcgcg ccaccucuc cugccgcgcc ucccaguccg ucggcuccuc cuaccucgcc 120

ugguaccagc agaagcccgg ccaggccccc cgccuccuca ucuacggcgc cuucucccgc 180

gccaccggca uccccgaccg cuucuccggc uccggcuccg gcaccgacuu cacccucacc 240

aucucccgcc ucgagcccga ggacuucgcc gucuacuacu gccagcagua cggcuccucc 300

cccuggaccu ucggccaggg caccaagguc gagaucaagc gcaccgucgc cgcccccucc 360

gucuucaucu ucccccccuc cgacgagcag cucaaguccg gcaccgccuc cgucgucugc 420

cuccucaaca acuucuaccc ccgcgaggcc aagguccagu ggaaggucga caacgcccuc 480

caguccggca acucccagga guccgucacc gagcaggacu ccaaggacuc caccuacucc 540

cucuccucca cccucacccu cuccaaggcc gacuacgaga agcacaaggu cuacgccugc 600

gaggucaccc accagggccu cuccuccccc gucaccaagu ccuucaaccg cggcgagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 973

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 973

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacacucuc ccuuucuccu 60

ggggaaagag ccacucuguc augcagggcu agucaaagcg ucggauccuc uuacuuggca 120

ugguaucagc agaagccagg ucaggccccg cgguuacuga uuuacggcgc guucucgcgc 180

gcuacgggga uacccgaccg auuuucagga agcggcagug guaccgauuu cacacuaacu 240

aucucccguc ucgagccuga agacuuugcc guuuauuacu gucaacagua ugggucuagc 300

ccauggaccu ucggacaggg cacaaaagug gagauuaaga gaaccguagc agcccccucc 360

guguuuaucu ucccuccauc agaugaacag cugaaaagug gcacugcuag cgucgugugc 420

cuucugaaca auuuuuaccc cagggaggca aagguucaau ggaaagugga caacgccuug 480

cagucuggaa auucccagga gucagucaca gaacaggaua gcaaggacag uaccuauucu 540

cucuccagca cgcugacucu gucgaaggcu gauuacgaga aacacaaggu guacgccugu 600

gaaguaaccc aucaagggcu cucuuccccu guuacaaaau cauucaaccg gggugagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 974

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 974

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccugag ccugagcccc 60

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 120

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 180

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 240

aucagcagac uggagcccga ggacuucgcc guguacuacu gccagcagua cggcagcagc 300

cccuggaccu ucggccaggg caccaaggug gagaucaaga gaaccguggc cgcccccagc 360

guguucaucu ucccccccag cgacgagcag cugaagagcg gcaccgccag cguggugugc 420

cugcugaaca acuucuaccc cagagaggcc aaggugcagu ggaaggugga caacgcccug 480

cagagcggca acagccagga gagcgugacc gagcaggaca gcaaggacag caccuacagc 540

cugagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggugaccc accagggccu gagcagcccc gugaccaaga gcuucaacag aggcgagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 975

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 975

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacacucag ccugucuccu 60

ggggaaagag ccacgcuuag cugccggggcu ucccaaucug ucggaagcuc cuaccuggcc 120

ugguaucagc agaagccggg ccaggcgccc cgccuccuga uuuacggggc uuucucuaga 180

gccaccggaa ucccugaccg guuuagcggc uccgggagcg gaacagauuu cacccuuaca 240

auuucucgcc uggagcccga agacuuugcc guuuauuacu gucaacagua uggcuccagc 300

ccuuggaccu ucggcgggg gacaaaagug gagaucaaga gaaccguggc ugcccccucu 360

gucuuuauuu ucccuccguc cgaugaacag cucaaaagcg gaacggcuuc ugugguuugc 420

cugcugaaca auuuuuaccc ccgggaggcc aaggugcaau ggaaagucga caacgcgcuc 480

caguccggca auagccagga guccgugacc gaacaggauu cuaaggacag cacauauucc 540

cugagcucua cccuuacacu guccaaggcc gauuacgaga aacacaaggu uuacgcuugu 600

gaagugaccc aucaagggcu cagcucuccu gucacgaaau ccuucaaccg cggagagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 976

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 976

gggagaaagc uuaccgaaau aguacuaaca caaucaccag gaacccucuc acuaucucca 60

ggagaaagag caacacuaag cugcagagcc uccacaaucag ucggaucauc auaccuagca 120

ugguaccaac aaaaaccagg acaagccccc agauuacuaa ucuacggagc auucucacga 180

240

auauccagau uagaaccaga agacuucgca guauacuacu gccaacaaua cggaucauca 300

ccauggacau uuggacaagg aaccaaagua gaaaucaaaa gaacaguagc agccccauca 360

guauuuauau ucccaccauc agacgaacaa cuaaaaucag gcaccgcauc aguaguaugu 420

cuauuaaaca acuucuaccc aagagaagca aaaguacaau ggaaaguaga caacgcacua 480

caaucaggaa acucccaaga aucagucaca gaacaagacu caaaagacuca aacauacuca 540

cuaucaucaa cacuaaccuu aucaaaagca gacuacgaaa aacacaaagu auacgcaugc 600

gaaguaacac accaaggauu aucaucccca guaacaaaau cauucaacag aggagaaugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 977

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 977

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacucucuc ccugagucca 60

ggggaaaggg ccaccuugag cugccggggca ucccaaagug ucgguagcuc cuaccuggcc 120

ugguaucagc agaagccggg ccaggcgccc cgccuccuga uuuacggggc cuucagcagg 180

gcaacgggca ucccagaccg guuuuccggu agugggagcg gcacugauuu caccuugacc 240

300 auuucccgcc uggagcccga agacuuugcc

ccauggacuu ucgggcaggg uaccaaagua gagaucaaga ggacgguggc agcccccucc 360

gucuuuauuu ucccaccgag cgaugaacag cucaaauccg gcacugcgag uguggugugc 420

cugcugaaca auuuuuaccc ccgggaggcc aagguccaau ggaaagugga caacgcacuc 480

cagagcggca auucccagga gagcguaacc gaacaggaua guaaggacuc cacuuauagc 540

cugaguucca ccuugacccu gagcaaggcc gauuacgaga aacacaaggu guacgccugu 600

gaagucacgc aucaagggcu cagcucccca gugacuaaaa guuucaaccg cggugagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 978

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 978

gggagaaagc uuaccgaaau cguccuaacc caaucccccg gcacacuauc ucucucccca 60

ggcgaacgcg caacacuauc cugccgcgcc ucacaaucag ucggcuccuc cuaccuagcc 120

ugguaccaac aaaaacccgg ccaagcaccc cgacuccuca ucuacggcgc cuucucccgc 180

gccacaggca ucccagaccg cuucuccggc uccggcuccg gcacagacuu cacacucacc 240

aucucacgcc ucgaacccga agacuucgcc gucuacuacu gccaacaaua cggaucaucc 300

cccuggaccu ucggacaagg caccaaaguc gaaaucaaac gcaccgucgc cgcccccucc 360

gucuucaucu ucccaccuc agacgaacaa cuaaaauccg gcaccgccuc aguagucugc 420

cuacuaaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcccuc 480

caauccggca acucacaaga aucagucacc gaacaagacu caaaagacuc caccuacucc 540

cuauccucca cccucacccu aucaaaagcc gacuacgaaa aacacaaagu auacgcgugc 600

gaaguaaccc accagggccu aucucaccc gucacaaaau ccuucaaccg cggcgaaugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 979

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 979

gggagaaagc uuaccgaaau cguacuaacc caaucacccg gcacccucuc ccucuccccc 60

ggcgaacgag ccacccuauc augccgcgcc ucccaauccg uaggcuccuc cuaccuagcc 120

ugguaccaac aaaaaccagg ccaagcaccc cgacuacuca ucuacggagc cuucucccgc 180

gccaccggca uccccgaccg cuucuccggc uccggcuccg gcaccgacuu cacccucacc 240

aucucccgcc ucgaacccga agacuucgcc gucuacuacu gccaacaaua cggaucaucc 300

cccuggaccu ucggccaagg caccaaaguc gaaaucaaac gcaccgucgc cgcccccucc 360

gucuucauau ucccacccuc cgacgaacaa cuaaaaucag gaaccgccuc cgucgucugc 420

cuacuaaaca acuucuaccc ccgcgaagcc aaaguacaau ggaaagucga caacgcccuc 480

caauccggca acucccaaga auccguaacc gaacaagacu ccaaagacuc aaccuauucc 540

cucuccucca cacucacacu auccaaagcc gacuacgaaa aacacaaagu cuacgccugc 600

gaaguaaccc accaaggccu cucaucaccc gucaccaaau ccuucaaccg cggcgaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 980

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 980

gggagaaagc uuaccgaaau cguccucacc caaucccccg gcacccuauc acucucaccc 60

ggcgaacgcg caacccucuc cugccgagcc ucccaauccg ucggcuccuc auaccucgcc 120

ugguaccaac aaaaacccgg ccaagcaccc cgucuccuca ucuacggcgc cuucucacgc 180

gccaccggca uccccgaccg cuucuccggc ucuggcucag gcaccgacuu cacccucacc 240

aucucccgcc ucgaacccga agacuucgcc gucuacuacu gccaacaaua cggaucaucc 300

cccuggaccu ucggccaagg cacaaaaguc gaaaucaaac gcaccgucgc cgccccaucc 360

gucuucaucu ucccacccuc cgacgaacaa cucaaauccg gcaccgccuc cgucgucugc 420

cuccucaaca acuucuaccc ccgcgaagcc aaaguccaau ggaaagucga caacgcccuc 480

caauccggca acucccaaga auccgucacc gaacaagacu ccaaagacuca caccuacuca 540

cucuccucca cccuuacccu cuccaaagcc gacuacgaaa aacacaaagu cuacgccugc 600

gaagucaccc accaaggccu cuccuccccc gucaccaaau ccuucaaccg cggcgaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 981

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 981

gggagaaagc uuaccgaaau aguacuaaca caaucaccag gaacacuauc acucucaccu 60

ggagaaagag caacauuauc cugcagagca ucacaaucug uaggaucuuc auaccuagca 120

ugguaccaac aaaaaccagg acaagcacca agauuacuaa uauauggagc auuuuccaga 180

240

auaucaagac uagaaccaga agacuucgca guauacuacu gccaacaaua cggaucauca 300

ccauggacau ucggacaagg aacaaaagua gaaauaaaaa gaacagucgc agcaccauca 360

guauucauau ucccaccauc agacgaaca uuaaaauccg gaacagcauc aguaguaugc 420

cuacuaaaua acuucuaccc aagagaagca aaaguacaau ggaaaguaga caacgcauua 480

caaucaggaa acucccaaga aucaguaaca gaacaagacu cuaaagacuc aacauacucc 540

cuaucaucaa cacuaacacu aucaaaagca gacuaugaaa aacacaaagu auacgcaugc 600

gaagucacac aucaaggacu aucaucacca guaacaaaau cauuuaacag aggagaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 982

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab LC without signale peptide

<400> 982

gggagaaagc uuaccgaaau aguacuaaca caaucaccag gaacauuauc acuaucccca 60

ggagaaagag caacauuauc augcagagca ucacaaucag uaggaucauc auaccuagcc 120

ugguaccaac aaaaaccagg acaagcccca agauuacuaa uauacggagc auucucaaga 180

gcaacaggaa uaccagacag auucucaggu ucuggcucag gcacagacuu cacacucaca 240

auaucaagac uagaaccaga agacuucgcc guauacuacu gccaacaaua cggauccuca 300

ccauggacau ucggacaagg aacaaaagua gaaauaaaac gaacaguagc agcaccauca 360

guauucauau ucccaccauc agacgaaca uuaaaaucag gaacagcauc aguaguaugc 420

cuauuaaaca acuucuaccc acgagaagcc aaaguccaau ggaaaguaga uaacgcauua 480

caaucaggua acucacaaga aucaguaaca gaacaagacu ccaaagacuc aacauacagc 540

cuaucaucaa cacuaacauu aucaaaagca gacuaugaaa aacacaaagu auacgcaugc 600

gagguaacac accaaggacu aucaucacca guaacaaaau cauucaauag aggagaaugc 660

uaaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 983

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 983

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccucuc ccugagcccg 60

ggggagcgcg ccacgcuguc cugccgggcc agccaguccg ucggcagcuc cuaccucgcg 120

ugguaccagc agaagcccgg gcaggcgccc cgccugcuga ucuacggcgc cuucagccgg 180

gccaccggga uccccgaccg cuucuccggc agcggcuccg ggaccgacuu cacccucacg 240

aucagccggc uggagccgga ggacuucgcc guguacuacu gccagcagua cggcuccagc 300

cccuggaccu ucgggcaggg caccaaggug gagaucaagc gcaccguggc ggcccccagc 360

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 480

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 540

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggggagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 984

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 984

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacacucuc ccuuucuccu 60

ggggaaagag ccacucuguc augcagggcu agucaaagcg ucggauccuc uuacuuggca 120

ugguaucagc agaagccagg ucaggccccg cgguuacuga uuuacggcgc guucucgcgc 180

gcuacgggga uacccgaccg auuuucagga agcggcagug guaccgauuu cacacuaacu 240

aucucccguc ucgagccuga agacuuugcc guuuauuacu gucaacagua ugggucuagc 300

ccauggaccu ucggacaggg cacaaaagug gagauuaaga gaaccguggc ggcccccagc 360

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 480

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 540

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggugagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 985

<211> 865

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab backbone Rituximab LC without signale peptide

<400> 985

gggagaaagc uuaccgagau cgugcugacc cagagccccg gcacccugag ccugagcccc 60

ggcgagagg ccacccugag cugcagagcc agccagagcg ugggcagcag cuaccuggcc 120

ugguaccagc agaagcccgg ccaggccccc agacugcuga ucuacggcgc cuucagcaga 180

gccaccggca uccccgacag auucagcggc agcggcagcg gcaccgacuu cacccugacc 240

aucagcagac uggagcccga ggacuucgcc guguacuacu gccagcagua cggcagcagc 300

360

guguucaucu ucccgcccag cgacgagcag cugaagagcg ggaccgccuc ggucgugugc 420

cuccugaaca acuucuaccc ccgggaggcc aaggugcagu ggaaggucga caacgcgcug 480

cagagcggca acagccagga gagcgugacg gagcaggaca gcaaggacag caccuacucg 540

cucagcagca cccugacccu gagcaaggcc gacuacgaga agcacaaggu guacgccugc 600

gaggucacgc accaggggcu cagcucgccc gugaccaaga gcuucaaccg cggcgagugc 660

ugaggacuag uuauaagacu gacuagcccg augggccucc caacgggccc uccuccccuc 720

780

aaaaaaaaaa aaaaaaaaaa augcauccccc cccccccccc cccccccccc cccccccaaa 840

ggcucuuuuc agagccacca gaauu 865

<210> 986

<211> 3008

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt1 IRES construct

<400> 986

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagugac caugcauuug aaagccgggg 1440

gugggagauc cggauugcca gucugcucga uaucgcaggc uggguccgug acuacccacu 1500

cccccuuuaa uuccgccccu cucccucccc ccccccuaac guuacuggcc gaagccgcuu 1560

ggaauaaggc cggugugcgu uugucuauau guuauuuucc accauauugc cgucuuuugg 1620

caaugugagg gccgggaaac cuggcccugu cuucuugacg agcauuccua ggggucuuuc 1680

cccucucgcc aaaggaaugc aaggucuguu gaaugucgug aaggaagcag uuccucugga 1740

agcuucuuga agacaaacaa cgucuguagc gacccuuugc aggcagcgga accccccacc 1800

uggcgacagg ugccucugcg gccaaaagcc acguguauaa gauacaccug caaaggcggc 1860

acaaccccag ugccacguug ugaguuggau aguuguggaa agagucaaau ggcucuccuc 1920

aagcguauuc aacaaggggc ugaaggaugc ccagaaggua ccccauugua ugggaucuga 1980

ucuggggccu cggugcacau gcuuuacgug uguuuagucg agguuaaaaa acgucuaggc 2040

cccccgaacc acggggacgu gguuuuccuu ugaaaaacac gaugauaaua gaucuaccau 2100

2160

gaucgugcug acccagagcc ccggcacccu cucccugagc ccgggggagc gcgccacgcu 2220

guccugccgg gccagccagu ccgucggcag cuccuaccuc gcgugguacc agcagaagcc 2280

2340

ccgcuucucc ggcagcggcu ccgggaccga cuucacccuc acgaucagcc ggcuggagcc 2400

ggaggacuuc gccguguacu acugccagca guacggcucc agcccugga ccuucgggca 2460

gggcaccaag guggagauca agcgcaccgu cgccgccccc uccguguuca ucuucccgcc 2520

2580

ccccggggag gccaaggugc aguggaaggu ggacaacgcg cugcaguccg gcaacagcca 2640

ggagagcguc accgagcagg acuccaagga cagcaccuac ucccucagcu ccacccugac 2700

gcugagcaag gccgacuacg agaagcacaa gguguacgcc ugcgagguga cccaccaggg 2760

ccucuccagc cccgucacca aguccuucaa ccgcggggag ugcugaggac uaguuauaag 2820

acugacuagc ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau 2880

2940

aaaaugcauc cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca 3000

ccagaauu 3008

<210> 987

<211> 3008

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt3 IRES construct

<400> 987

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcgcc ugagcuacuc 780

ggcggcccau ccguguuucu guuucccccu aagccaaagg acacgcuuau gauuucucgg 840

acucccgagg ucacaugcgu gguuguggau gucagccacg aagacccggga ggugaaauuu 900

aauugguacg uagauggggu ugaagugcau aacgcaaaga ccaaaccucg cgaggagcaa 960

uauaauucaa cuuacagagu cgugaguguc cugacagugu ugcaccagga cuggcucaac 1020

ggaaaggaau auaaauguaa gguuuccaau aaagcccugc ccgcuccaau cgagaagacc 1080

auaagcaagg ccaaagguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaugac caugcauuug aaagccgggg 1440

gugggagauc cggauugcca gucugcucga uaucgcaggc uggguccgug acuacccacu 1500

cccccuuuaa uuccgccccu cucccucccc ccccccuaac guuacuggcc gaagccgcuu 1560

ggaauaaggc cggugugcgu uugucuauau guuauuuucc accauauugc cgucuuuugg 1620

caaugugagg gccgggaaac cuggcccugu cuucuugacg agcauuccua ggggucuuuc 1680

cccucucgcc aaaggaaugc aaggucuguu gaaugucgug aaggaagcag uuccucugga 1740

agcuucuuga agacaaacaa cgucuguagc gacccuuugc aggcagcgga accccccacc 1800

uggcgacagg ugccucugcg gccaaaagcc acguguauaa gauacaccug caaaggcggc 1860

acaaccccag ugccacguug ugaguuggau aguuguggaa agagucaaau ggcucuccuc 1920

aagcguauuc aacaaggggc ugaaggaugc ccagaaggua ccccauugua ugggaucuga 1980

ucuggggccu cggugcacau gcuuuacgug uguuuagucg agguuaaaaa acgucuaggc 2040

cccccgaacc acggggacgu gguuuuccuu ugaaaaacac gaugauaaua gaucuaccau 2100

ggagacccccc gccagcuuc ucuuccuucu guuguuaugg cugccugaca caacuggcga 2160

2220

uucaugcagg gcaagucaga gcgucgguuc cucuuaccug gccugguauc agcagaagcc 2280

2340

ucgauucuca ggcagcggua gugggaccga cuuuacacug accaucuccc gucuggaacc 2400

cgaggauuuc gcaguuuauu acugucagca guauggaucu agcccuugga cuuuuggcca 2460

gggcacaaaa guggaaauua agagaaccgu agccgcucca uccguguuca ucuuuccccc 2520

uucagacgag caacucaaaa gugggacggc aagcgucgug ugcuuacuga acaauuucua 2580

2640

ggaaucaguc acugagcaag acagcaagga uaguaccuau ucuuugucca gcacacugac 2700

ucuaucgaag gccgacuacg aaaaacacaa gguguacgcg ugugagguaa cccaucaggg 2760

ucucucuucc ccgguuacaa aaucauuuaa ccggggcgag ugcugaggac uaguuauaag 2820

acugacuagc ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau 2880

2940

aaaaugcauc cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca 3000

ccagaauu 3008

<210> 988

<211> 3008

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt4 IRES construct

<400> 988

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccca gcguguuccu guuccccccc aagcccaagg acacccugau gaucagcaga 840

acccccgagg ugaccugcgu ggugguggac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg uggacggcgu ggaggugcac aacgccaaga ccaagcccag agaggagcag 960

uacaacagca ccuacagagu ggugagcgug cugaccgugc ugcaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcccccau cgagaagacc 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagugac caugcauuug aaagccgggg 1440

gugggagauc cggauugcca gucugcucga uaucgcaggc uggguccgug acuacccacu 1500

cccccuuuaa uuccgccccu cucccucccc ccccccuaac guuacuggcc gaagccgcuu 1560

ggaauaaggc cggugugcgu uugucuauau guuauuuucc accauauugc cgucuuuugg 1620

caaugugagg gccgggaaac cuggcccugu cuucuugacg agcauuccua ggggucuuuc 1680

cccucucgcc aaaggaaugc aaggucuguu gaaugucgug aaggaagcag uuccucugga 1740

agcuucuuga agacaaacaa cgucuguagc gacccuuugc aggcagcgga accccccacc 1800

uggcgacagg ugccucugcg gccaaaagcc acguguauaa gauacaccug caaaggcggc 1860

acaaccccag ugccacguug ugaguuggau aguuguggaa agagucaaau ggcucuccuc 1920

aagcguauuc aacaaggggc ugaaggaugc ccagaaggua ccccauugua ugggaucuga 1980

ucuggggccu cggugcacau gcuuuacgug uguuuagucg agguuaaaaa acgucuaggc 2040

cccccgaacc acggggacgu gguuuuccuu ugaaaaacac gaugauaaua gaucuaccau 2100

ggagaccccc gcccagcugc uguuccugcu gcugcugugg cugcccgaca ccaccggcga 2160

gaucgugcug acccagagcc ccggcacccu gagccugagc cccggcgaga gagccacccu 2220

gagcugcaga gccagccaga gcgugggcag cagcuaccug gccugguacc agcagaagcc 2280

2340

cagauucagc ggcagcggca gcggcaccga cuucacccug accaucagca gacuggagcc 2400

cgaggacuuc gccguguacu acugccagca guacggcagc agcccuggga ccuucggcca 2460

gggcaccaag guggagauca agagaaccgu ggccgccccc agcguguuca ucuucccccc 2520

cagcgacgag cagcugaaga gcggcaccgc cagcguggug ugccugcuga acaacuucua 2580

ccccagagag gccaaggugc aguggaaggu ggacaacgcc cugcagagcg gcaacagcca 2640

ggagagcgug accgagcagg acagcaagga cagcaccuac agccugagca gcacccugac 2700

ccugagcaag gccgacuacg agaagcacaa gguguacgcc ugcgagguga cccaccaggg 2760

ccugagcagc cccgugacca agagcuucaa cagaggcgag ugcugaggac uaguuauaag 2820

acugacuagc ccgaugggcc ucccaacggg cccuccuccc cuccuugcac cgagauuaau 2880

2940

aaaaugcauc cccccccccc cccccccccc cccccccccc aaaggcucuu uucagagcca 3000

ccagaauu 3008

<210> 989

<211> 2392

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt1 F2A construct

<400> 989

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccugcuggc cauccucaag 60

ggggugcagu gccaggugca gcuggucgag agcggcgggg gcguggugca gcccggggcgc 120

ucccuccggc ugagcugcgc cgccuccggc uucaccuuca gcuccuacac caugcacugg 180

guccgccagg cgccggggaa gggccuggag ugggugacgu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacuc cgugaagggg cgguucacca ucagccgcga caacuccaag 300

aacacccucu accugcagau gaacagccug cgggccgagg acaccgccau cuacuacugc 360

gcccgcacgg gcuggcucgg gcccuucgac uacuggggcc aggggacccu ggucaccgug 420

uccagcgcgu ccaccaaggg ccccagcgug uucccccugg ccccguccag caaguccacg 480

agcggcggga ccgccgcccu cggcugccug gucaaggacu acuuccccga gcccgugacc 540

guguccugga acagcggggc gcugaccagc ggcguccaca cguuccccgc cgugcuccag 600

uccagcggcc uguacucccu gagcuccgug gucaccgugc cgagcuccag ccucgggacc 660

cagaccuaca ucugcaacgu gaaccacaag cccuccaaca cgaaggucga caagcggggug 720

gagcccaaga gcugcgacaa gacccacacg ugcccgcccu gccccgcccc cgagcugcug 780

ggcgggcccu ccguguuccu cuucccgccc aagcccaagg acacccugau gaucagccgc 840

acccccgagg ugaccugcgu cguggucgac guguccccg aggacccggga ggucaaguuc 900

aacugguacg uggacggcgu ggagguccac aacgccaaga ccaagccccg ggaggagcag 960

uacaacagca ccuaccgcgu gguguccguc cugacggugc uccaccagga cuggcugaac 1020

gggaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcgcccau cgagaagacc 1080

aucuccaagg ccaagggcca gccgcgggag ccccaggucu acacccuccc gccagccgc 1140

gacgagcuga ccaagaacca ggugucccug acgugccucg ugaagggcuu cuaccccagc 1200

gacaucgccg ucgagggga gagcaacggg cagcccgaga acaacuacaa gaccacgccc 1260

ccggugcugg acuccgacgg cagcuucuuc cuguacucca agcucaccgu ggacaagagc 1320

1380

uacacccaga agucccugag ccucuccccc ggcaagguga agcagacacu caauuucgac 1440

cuucugaagu uggcuggaga uguugagucu aacccaggcc ccauggagac ccccgcccag 1500

1560

agccccggca cccucucccu gagcccgggg gagcgcgcca cgcuguccug cggggccagc 1620

caguccgucg gcagcuccua ccucgcgugg uaccagcaga agcccggggca ggcgccccgc 1680

1740

ggcuccggga ccgacuucac ccucacgauc agccggcugg agccggagga cuucgccgug 1800

uacuacugcc agcaguacgg cuccagcccc uggaccuucg ggcagggcac caagguggag 1860

aucaagcgca ccgucgccgc ccccuccgug uucaucuucc cgcccagcga cgagcagcug 1920

aaguccggga cggccagcgu ggucugccuc cugaacaacu ucuacccccg ggaggccaag 1980

gugcagugga agguggacaa cgcgcugcag uccggcaaca gccaggagag cgucaccgag 2040

caggacucca aggacagcac cuacucccuc agcuccaccc ugacgcugag caaggccgac 2100

uacgagaagc acaaggugua cgccugcgag gugacccacc agggccucuc cagccccguc 2160

acccaaguccu ucaaccgcgg ggagugcuga ggacuaguua uaagacugac uagcccgaug 2220

ggccucccaa cggggcccucc uccccuccuu gcaccgagau uaauaaaaaa aaaaaaaaaa 2280

2340

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 2392

<210> 990

<211> 2392

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt3 F2A construct

<400> 990

gggagaaagc uuaccaugga gcugggccuc agcuggaucu uccuucuggc cauuuugaag 60

ggggugcagu gccaagucca guuaguugaa uccggaggug gcgugguaca gcccgggaga 120

ucucugaggc uaucaugugc ugcaagugga uuuaccuuca gcuccuacac aaugcacugg 180

gugcggcagg ccccuggcaa aggucucgag ugggucacuu uuauaucuua ugacgggaac 240

aauaaguacu augcggauuc ggugaaagga cgcuucacga ucucacgaga caacagcaag 300

aauacccugu accuucaaau gaacagucug cgugcugaag auacagccau uuauuuacugc 360

gcaagaacug gcugguuggg cccauuugac uauugggggc agggaacccu cguuacagug 420

uccucugcca gcaccaaagg uccguccguc uucccccugg cuccuucaag uaaagcacu 480

ucuggcggga cagcagcccu gggaugucuc gugaaggauu acuuuccaga gcccguaacc 540

guuuccugga acucaggcgc uuuaacgagc ggugugcaua cuuucccugc cguccugcag 600

aguucugggc uuuacuccuu gagcucggug gugaccgucc caucuuccuc acugggaaca 660

cagacuuaua ucugcaaugu uaaucacaaa cccaguaaca ccaaggugga caaaagggua 720

gaaccuaaga gcugugauaa aacacauacc ugcccaccgu gucccgcgcc ugagcuacuc 780

ggcggcccau ccguguuucu guuucccccu aagccaaagg acacgcuuau gauuucucgg 840

acucccgagg ucacaugcgu gguuguggau gucagccacg aagacccggga ggugaaauuu 900

aauugguacg uagauggggu ugaagugcau aacgcaaaga ccaaaccucg cgaggagcaa 960

uauaauucaa cuuacagagu cgugaguguc cugacagugu ugcaccagga cuggcucaac 1020

ggaaaggaau auaaauguaa gguuuccaau aaagcccugc ccgcuccaau cgagaagacc 1080

auaagcaagg ccaaagguca gccuagggaa ccccaggugu acacguuacc acccucucgg 1140

1200

gacaucgcag uggaauggga gagcaauggg cagccagaga acaacuacaa gacuacccg 1260

cccguucugg acuccgaugg aucuuucuuc uuguacucga aacuaacagu ggacaagagc 1320

cgcuggcagc aaggcaaugu cuucuccugu ucagugaugc acgaagcucu gcauaaccac 1380

uauacucaga agagucucuc ucugagcccu gguaaaguga agcagacacu caauuucgac 1440

cuucugaagu uggcuggaga uguugagucu aacccaggcc ccauggagac ccccgcccag 1500

1560

agcccaggga cccucucccu gucuccggga gagagagcua cacuuucaug cagggcaagu 1620

cagagcgucg guuccucuua ccuggccugg uaucagcaga agcccggcca agcgccucgg 1680

uugcucauuu acggggcuuu uucgcgcgcc acuggaauac cagaucgauu cucaggcagc 1740

gguaguggga ccgacuuuac acugaccauc ucccgucugg aacccgagga uuucgcaguu 1800

uauuacuguc agcaguaugg aucuagcccu uggacuuuug gccagggcac aaaaguggaa 1860

auuaagagaa ccguagccgc uccauccgug uucaucuuuc ccccuucaga cgagcaacuc 1920

aaaagggga cggcaagcgu cgugugcuua cugaacaauu ucuacccaag ggaggccaag 1980

guucagugga aaguggauaa cgcucugcag

caagacagca aggauaguac cuauucuuug uccagcacac ugacuucuauc gaaggccgac 2100

uacgaaaaac acaaggugua cgcgugugag guaacccauc agggucucuc uuccccgguu 2160

acaaaaucau uuaaccgggg cgagugcuga ggacuaguua uaagacugac uagcccgaug 2220

ggccucccaa cggggcccucc uccccuccuu gcaccgagau uaauaaaaaa aaaaaaaaaa 2280

2340

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 2392

<210> 991

<211> 2392

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab opt4 F2A construct

<400> 991

gggagaaagc uuaccaugga gcugggccug agcuggaucu uccugcuggc cauccugaag 60

ggcgugcagu gccaggugca gcugguggag agcggcggcg gcguggugca gcccggcaga 120

agccugagac ugagcugcgc cgccagcggc uucaccuuca gcagcuacac caugcacugg 180

gugagacagg cccccggcaa gggccuggag ugggugaccu ucaucagcua cgacggcaac 240

aacaaguacu acgccgacag cgugaagggc agauucacca ucagcagaga caacagcaag 300

aacacccugu accugcagau gaacagccug agagccgagg acaccgccau cuacuacugc 360

gccagaaccg gcuggcuggg ccccuucgac uacuggggcc agggcacccu ggugaccgug 420

agcagcgcca gcaccaaggg ccccagcgug uucccccugg cccccagcag caagagcacc 480

agcggcggca ccgccgcccu gggcugccug gugaaggacu acuuccccga gcccgugacc 540

gugagcugga acagcggcgc ccugaccagc ggcgugcaca ccuuccccgc cgugcugcag 600

660

cagaccuaca ucugcaacgu gaaccacaag cccagcaaca ccaaggugga caagagagug 720

gagcccaaga gcugcgacaa gacccacacc ugcccccccu gccccgcccc cgagcugcug 780

ggcggcccca gcguguuccu guuccccccc aagcccaagg acacccugau gaucagcaga 840

acccccgagg ugaccugcgu ggugguggac gugagccacg aggaccccga ggugaaguuc 900

aacugguacg uggacggcgu ggaggugcac aacgccaaga ccaagcccag agaggagcag 960

uacaacagca ccuacagagu ggugagcgug cugaccgugc ugcaccagga cuggcugaac 1020

ggcaaggagu acaagugcaa ggugagcaac aaggcccugc ccgcccccau cgagaagacc 1080

1140

gacgagcuga ccaagaacca ggugagccug accugccugg ugaagggcuu cuaccccagc 1200

gacaucgccg uggaguggga gagcaacggc cagcccgaga acaacuacaa gaccaccccc 1260

cccgugcugg acagcgacgg cagcuucuuc cuguacagca agcugaccgu ggacaagagc 1320

agauggcagc agggcaacgu guucagcugc agcgugaugc acgaggcccu gcacaaccac 1380

uacacccaga agagccugag ccugagcccc ggcaagguga agcagacacu caauuucgac 1440

cuucugaagu uggcuggaga uguugagucu aacccaggcc ccauggagac ccccgcccag 1500

1560

agccccggca cccugagccu gagccccggc gagagagcca cccugagcug cagagccagc 1620

cagagcgugg gcagcagcua ccuggccugg uaccagcaga agcccggcca ggcccccaga 1680

cugcugaucu acggcgccuu cagcagagcc accggcaucc cgacagauu cagcggcagc 1740

ggcagcggca ccgacuucac ccugaccauc agcagacugg agcccgagga cuucgccgug 1800

uacuacugcc agcaguacgg cagcagcccc uggaccuucg gccagggcac caagguggag 1860

aucaagagaa ccguggccgc ccccagcgug uucaucuucc cccccagcga cgagcagcug 1920

aagagcggca ccgccagcgu ggugugccug cugaacaacu ucuaccccag agaggccaag 1980

2040

caggacagca aggacagcac cuacagccug agcagcaccc ugacccugag caaggccgac 2100

uacgagaagc acaaggugua cgccugcgag gugacccacc agggccugag cagccccgug 2160

accaagagcu ucaacagagg cgagugcuga ggacuaguua uaagacugac uagcccgaug 2220

ggccucccaa cggggcccucc uccccuccuu gcaccgagau uaauaaaaaa aaaaaaaaaa 2280

2340

cccccccccc cccccccccc ccccaaaggc ucuuuucaga gccaccagaa uu 2392

<210> 992

<211> 1849

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12_opt1_gen4

<400> 992

gggagaaagc uuaccaugug ccaccagcag cuggugauca gcugguucuc ccucgucuuc 60

cuggccagcc cccugguggc caucugggag cucaagaagg acguguacgu cguggagcug 120

gacugguacc cggacgcgcc cggcgagaug gugguccuga ccugcgacac ccccgaggag 180

gacgggauca cguggacccu cgaccagucc agcgaggugc ugggcuccgg gaagacccug 240

accauccagg ugaaggaguu cggcgacgcc gggcaguaca cgugccacaa gggcggcgag 300

guccucagcc acucccugcu gcuccugcac aagaaggagg acgggaucug gagcaccgac 360

auccuagg accagaagga gcccaagaac aagaccuucc uccgcugcga ggccaagaac 420

uacuccggcc gguucacgug cugguggcug accaccauca gcaccgaccu gaccuucucc 480

gucaagagcu cccgcgggag cuccgacccg cagggcguga cgugcggggc cgccacccuc 540

agcgcggagc gggugcgcgg cgacaacaag gaguacgagu acuccgugga gugccaggag 600

gacagcgccu gccccgccgc cgaggagucc cugcccaucg aggugauggu cgacgcggug 660

cacaagcuga aguacgagaa cuacaccagc agcuucuuca uccgggacau caucaagccc 720

gacccgccca agaaccucca gcugaagccc cugaagaacu cccgccaggu ggaggucagc 780

ugggaguacc ccgacaccug guccacgccg cacagcuacu ucucccucac cuucugcguc 840

caggugcagg gcaagagcaa gcgggagaag aaggaccgcg uguucaccga caagaccucc 900

gccacgguga ucugccggaa gaacgccagc aucuccgugc gcgccggaga ccgguacuac 960

agcuccagcu gguccgagug ggccagcguc cccugcuccg gcagcaccuc cgggagcggc 1020

aagcccgggu ccggcgaggg gagcaccaag ggccggaacc ugccgguggc cacccccgac 1080

cccggcaugu uccccugccu gcaccacagc cagaaccucc ugcgcgccgu guccaacaug 1140

cugcagaagg cccggcagac gcucgaguuc uacccgugca ccagcgagga gaucgaccac 1200

gaggacauca ccaaggacaa gaccuccacg gucgaggccu gccugccccu ggagcucacc 1260

aagaacgaga gcugccugaa cucccgcgag accagcuuca ucaccaacgg guccugccug 1320

gcgagccgga agacguccuu caugauggcc cucugccuga gcuccaucua cgaggaccug 1380

aagauguacc agguggaguu caagaccaug aacgccaagc uccugaugga ccccaagcgc 1440

cagaucuucc uggaccagaa caugcucgcc gugaucgacg agcugaugca ggcgcugaac 1500

1560

aagaucaagc ugugcauccu gcuccacgcc uuccggaucc gcgccgugac gaucgaccgg 1620

gugauguccu accugaacgc cagcugagga cuaguuauaa gacugacuag cccgaugggc 1680

cucccaacgg gcccuccucc ccuccuugca cggagauuaa uaaaaaaaaa aaaaaaaaaa 1740

1800

cccccccccc cccccccccc caaaggcucu uuucagagcc accagaauu 1849

<210> 993

<211> 2014

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12_opt1_gen5

<400> 993

ggggcgcugc cuacggaggu ggcagccauc uccuucucgg caucaagcuu accaugugcc 60

accagcagcu ggugaucagc ugguucuccc ucgucuuccu ggccagcccc cugguggcca 120

ucgggagcu caagaaggac guguacgucg uggagcugga cugguacccg gacgcgcccg 180

gcgagauggu gguccugacc ugcgacaccc ccgaggagga cgggaucacg uggacccucg 240

accaguccag cgaggugcug ggcuccggga agacccugac cauccaggug aaggaguucg 300

gcgacgccgg gcaguacacg ugccacaagg gcggcgaggu ccucagccac ucccugcugc 360

uccugcacaa gaaggaggac gggaucugga gcaccgacau ccugaaggac cagaaggagc 420

ccaagaacaa gaccuuccuc cgcugcgagg ccaagaacua cuccggccgg uucacgugcu 480

gguggcugac caccaucagc accgaccuga ccuucuccgu caagagcucc cgcgggagcu 540

ccgacccgca gggcgugacg ugcggggccg ccacccucag cgcggagcgg gugcgcggcg 600

acaacaagga guacgaguac uccguggagu gccaggagga cagcgccugc cccgccgccg 660

aggagucccu gcccaucgag gugauggucg acgcggugca caagcugaag uacgagaacu 720

acaccagcag cuucuucauc cgggacauca ucaagcccga cccgcccaag aaccuccagc 780

ugaagccccu gaagaacucc cgccaggugg aggucagcug ggaguacccc gacaccuggu 840

ccacgccgca cagcuacuuc ucccucaccu ucugcgucca ggugcaggggc aagagcaagc 900

gggagaagaa ggaccgcgug uucaccgaca agaccuccgc cacggugauc ugccggaaga 960

acgccagcau cuccgugcgc gcccaggacc gguacuacag cuccagcugg uccgaguggg 1020

ccagcguccc cugcuccggc agcaccuccg ggagcggcaa gcccgggucc ggcgagggga 1080

1140

accacagcca gaaccuccug cgcgccgugu ccaacaugcu gcagaaggcc cggcagacgc 1200

ucgaguucua cccgugcacc agcgaggaga ucgaccacga ggacaucacc aaggacaaga 1260

ccuccacggu cgaggccugc cugccccugg agcucaccaa gaacgagagc ugccugaacu 1320

1380

ugaggcccu cugccuagc uccaucuacg aggaccugaa gauguaccag guggaguuca 1440

agaccaugaa cgccaagcuc cugauggacc ccaagcgcca gaucuuccug gaccagaaca 1500

ugcucgccgu gaucgacgag cugaugcagg cgcugaacuu caacagcgag accguccccc 1560

agaaguccag ccucgaggag ccggacuucu acaagaccaa gaucaagcug ugcauccugc 1620

uccacgccuu ccggauccgc gccgugacga ucgaccgggu gauguccuac cugaacgcca 1680

1740

1800

ccugucuuaaa aaacauaaau uucuuuaauc auuuugccuc uuuucucugu gcuucaauua 1860

1920

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa ugcauccccc cccccccccc cccccccccc 1980

ccccccaaag gcucuuuuca gagccaccag aauu 2014

<210> 994

<211> 42

<212>RNA

<213> Artificial Sequence

<220>

<223> 1368_5UTR

<400> 994

ggcgcugccu acggaggugg cagccaucuc cuucucggca uc 42

<210> 995

<211> 34

<212>RNA

<213> Artificial Sequence

<220>

<223> 1412_5UTR

<400> 995

ggagcgggcg gcggcguugg cggcuugugc agca 34

<210> 996

<211> 34

<212>RNA

<213> Artificial Sequence

<220>

<223> 1413_5UTR

<400> 996

ggccgggaacc gccaucuucc aguaauucgc caaa 34

<210> 997

<211> 75

<212>RNA

<213> Artificial Sequence

<220>

<223> 1414_5UTR

<400> 997

gcggcucggc cauuuugucc cagucagucc ggaggcugcg gcugcagaag uaccgccugc 60

ggaguaacug caaag 75

<210> 998

<211> 62

<212>RNA

<213> Artificial Sequence

<220>

<223> 1415_5UTR

<400> 998

gucccgcagu cggcguccag cggcucugcu uguucgugug ugugucguug caggccuuau 60

uc62

<210> 999

<211> 31

<212>RNA

<213> Artificial Sequence

<220>

<223> 1416_5UTR

<400> 999

gccgcccagc cgguccaggc cucuggcgaa c 31

<210> 1000

<211> 56

<212>RNA

<213> Artificial Sequence

<220>

<223> 1417_5UTR

<400> 1000

agucaggaag gacguuggug uugagguuag cauacguauc aaggacagua acuacc 56

<210> 1001

<211> 42

<212>RNA

<213> Artificial Sequence

<220>

<223> 1418_5UTR

<400> 1001

gccucugcug gaguccgggg aguggcguug gcugcuagag cg 42

<210> 1002

<211> 34

<212>RNA

<213> Artificial Sequence

<220>

<223> 1419_5UTR

<400> 1002

ggccgccgca gccaucuucc aguaacucgc caaa 34

<210> 1003

<211> 53

<212>RNA

<213> Artificial Sequence

<220>

<223> 1420_5UTR

<400> 1003

gccaucuugg cgccugugga ggccugcugg gaacaggacu ucuaacagca agu 53

<210> 1004

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> 1368_5UTR

<400> 1004

ggcgctgcct acggaggtgg cagccatctc cttctcggca tc 42

<210> 1005

<211> 34

<212> DNA

<213> Artificial Sequence

<220>

<223> 1412_5UTR

<400> 1005

ggagcgggcg gcggcgttgg cggcttgtgc agca 34

<210> 1006

<211> 34

<212> DNA

<213> Artificial Sequence

<220>

<223> 1413_5UTR

<400> 1006

ggccgggaacc gccatcttcc agtaattcgc caaa 34

<210> 1007

<211> 75

<212> DNA

<213> Artificial Sequence

<220>

<223> 1414_5UTR

<400> 1007

gcggctcggc cattttgtcc cagtcagtcc ggaggctgcg gctgcagaag taccgcctgc 60

ggagtaactg caaag 75

<210> 1008

<211> 62

<212> DNA

<213> Artificial Sequence

<220>

<223> 1415_5UTR

<400> 1008

gtcccgcagt cggcgtccag cggctctgct tgttcgtgtg tgtgtcgttg caggccttat 60

tc62

<210> 1009

<211> 31

<212> DNA

<213> Artificial Sequence

<220>

<223> 1416_5UTR

<400> 1009

gccgcccagc cggtccaggc ctctggcgaa c 31

<210> 1010

<211> 56

<212> DNA

<213> Artificial Sequence

<220>

<223> 1417_5UTR

<400> 1010

agtcaggaag gacgttggtg ttgaggttag catacgtatc aaggacagta actacc 56

<210> 1011

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> 1418_5UTR

<400> 1011

gcctctgctg gagtccgggg agtggcgttg gctgctagag cg 42

<210> 1012

<211> 34

<212> DNA

<213> Artificial Sequence

<220>

<223> 1419_5UTR

<400> 1012

ggccgccgca gccatcttcc agtaactcgc caaa 34

<210> 1013

<211> 53

<212> DNA

<213> Artificial Sequence

<220>

<223> 1420_5UTR

<400> 1013

gccatcttgg cgcctgtgga ggcctgctgg gaacaggact tctaacagca agt 53

<210> 1014

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R3630_(a249g)_Ndel

<400> 1014

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauaugg uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacagugcu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R3630_(g241a)_Nsil

<400> 1015

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

augcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacagugcu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 1016

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R3630_no_BglII

<400> 1016

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccagauca ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacagugcu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 1017

<211> 14

<212> PRT

<213> Artificial Sequence

<220>

<223> W(Arg12)Cys

<400> 1017

Trp Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Arg Cys

1 5 10

<210> 1018

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1018

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu cuuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuu 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca ccuuauccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagauuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca aaccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagggggccu caguccccug cagcuga 987

<210> 1019

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1019

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccuggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagggggccu caguccccug cagcuga 987

<210> 1020

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1020

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagggggccu caguccccug cagcuga 987

<210> 1021

<211> 987

<212>RNA

<213> Artificial Sequence

<220>

<223> IL12B

<400> 1021

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccuggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagggggccu caguccccug cagcuga 987

<210> 1022

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1

<400> 1022

augcaaauac cccaagcccc cuggccgguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccucgauuc ccccgaccgc ccguggaauc cgcccccuu cucccccgcc 120

cucuuagucg ucaccgaagg cgacaacgcg accuucaccu guuccuuuuc gaacaccuca 180

gaauccuucg uccucaacug guaccgcaug uccccccucca accaaaccga caaacucgcc 240

gccuuccccg aagaccgauc ccaacccggc caagauugcc gcuuccgcgu cacacaauua 300

cccaauggac gcgacuuuca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc guuagccccc aaagcccaaa ucaaagaauc gcucagagcc 420

gaauuacgcg ucaccgaacg gcgcgccgaa guccccug cgcaccccuc ccccucgccc 480

cgccccgccg gccaauucca aacccucguc gucggcguug ucggcggcuu auuaggcuca 540

cucguccucc ucgucugggu acucgccguc aucugcuccc gcgccgcgcg cggcaccauc 600

ggcgcgcgcc gcaccggaca acccuuaaaa gaagaccccu ccgccguccc cgucuucucc 660

gucgacuacg gcgaacucga cuuccaaugg cgcgaaaaaa cgccggaacc acccgucccg 720

ugcguccccg aacaaacaga auacgcgacc aucgucuucc cguccggcau gggcacaucc 780

ucacccgccc gccgaggcuc cgccgacggc ccccgauccg cccaacccuu acgccccgaa 840

gacggccacu gcuccuggcc cuuauga 867

<210> 1023

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1

<400> 1023

augcaaaucc cccaagcccc cuggccgguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccucgacuc ccccgaccgc ccguggaauc cgcccccuu cucccccgcc 120

cucuuagucg ucaccgaagg cgacaacgcg accuucaccu guuccuucuc gaacaccuca 180

gaauccuucg uccucaacug guaccgcaug uccccccucca accaaaccga caaacucgcc 240

gccuuccccg aagaccgauc ccaacccggc caagacugcc gcuuccgcgu cacacaauua 300

cccaauggac gcgacuuuca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc guuagccccc aaagcccaaa ucaaagaauc gcucagagcc 420

gaauuacgcg ucaccgaacg gcgcgccgaa guccccug cgcaccccuc ccccucgccc 480

cgccccgccg gccaauucca aacccucguc gucggcguug ucggcggcuu auuaggcuca 540

cucguccucc ucgucugggu acucgccguc aucugcuccc gcgccgcgcg cggcaccauc 600

ggcgcgcgcc gcaccggaca acccuuaaaa gaagaccccu ccgccguccc cgucuucucc 660

gucgacuacg gcgaacucga cuuccaaugg cgcgaaaaaa cgccggaacc acccgucccg 720

ugcguccccg aacaaacaga auacgcgacc aucgucuucc cguccggcau gggcacaucc 780

ucacccgccc gccgaggcuc cgccgacggc ccccgauccg cccaacccuu acgccccgaa 840

gacggccacu gcuccuggcc ccucuga 867

<210> 1024

<211> 867

<212>RNA

<213> Artificial Sequence

<220>

<223> PDCD1

<400> 1024

augcaaaucc cccaagcccc cuggccgguc gucugggccg uccuccaacu cggcuggcgc 60

ccgggauggu uccucgacuc ccccgaccgc ccguggaauc cgcccccuu cucccccgcc 120

cucuuagucg ucaccgaagg cgacaacgcg accuucaccu guuccuucuc gaacaccuca 180

gaauccuucg uccucaacug guaccgcaug uccccccucca accaaaccga caaacucgcc 240

gccuuccccg aagaccgauc ccaacccggc caagacugcc gcuuccgcgu cacacaauua 300

cccaacggac gcgacuuuca cauguccguc guccgcgccc gccgcaacga cuccggcacc 360

uaccucugcg gcgccaucuc gcucgccccc aaagcccaaa ucaaagaauc gcucagagcc 420

gaacccgcg ucaccgaacg gcgcgccgaa guccccug cgcaccccuc ccccucgccc 480

cgccccgccg gccaauucca aacccucguc gucggcguug ucggcggccu cuuaggcuca 540

cucguccucc ucgucugggu acucgccguc aucugcuccc gcgccgcgcg cggcaccauc 600

ggcgcgcgcc gcaccggaca acccuuaaaa gaagaccccu ccgccguccc cgucuucucc 660

gucgacuacg gcgaacucga cuuccaaugg cgcgaaaaaa cgccggaacc acccgucccg 720

ugcguccccg aacaaacaga auacgcgacc aucgucuucc cguccggcau gggcacaucc 780

ucacccgccc gccgaggcuc cgccgacggc ccccgauccg cccaacccuu acgccccgaa 840

gacggccacu gcuccuggcc ccucuga 867

<210> 1025

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 1025

augaucgaaa ccuacaauca aaccucgccc cgcagcgccg caacaggccu ccccaucucc 60

augaaaaucu ucauguaccu ccucaccguc uuccuaauca cccaaaugau cggcuccgcc 120

uuauucgccg ucuaccucca ccgccgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuuug ucuucaugaa aacuauccaa cgaugcaaca ccggcgaacg aucccuaucc 240

cucuuaaacu gcgaagaaau aaaaucgcaa uucgaaggau ucgucaaaga caucaugcua 300

aacaaagaag aaaccaaaaa agaaaauucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaaucgcag cccacgucau cucagaagca ucuuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac caugucaaac aaccucguca cgcucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg cuuauacuac aucuacgcac aagucaccuu cugcuccaac 540

cgcgaagcau ccucccaagc ccccuucauc gccucccucu gucucaaauc ccccggccgc 600

uucgaacgca uccuccuccg cgccgcaaau acccauuccu ccgccaaacc augcggccaa 660

caauccaucc accucggcgg cgucuucgaa cuccaacccg gcgccuccgu cuucgucaac 720

gucaccgacc ccucccaagu aucccaugga accggcuuca ccuccuucgg ccuccucaaa 780

cucuga 786

<210> 1026

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 1026

augaucgaaa ccuacaauca aaccucgccc cgcagcgccg caacaggccu ccccaucucc 60

augaaaaucu ucauguaccu ccucaccguc uuccuaauca cccaaaugau cggcuccgcc 120

uuauucgccg ucuaccucca ccgccgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuuug ucuucaugaa aacuauccaa cgaugcaaca ccggcgaacg aucccuaucc 240

cuccucaacu gcgaagaaau aaaaucgcaa uucgaaggau ucgucaaaga caucaugcua 300

aacaaagaag aaaccaaaaa agaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaaucgcag cccacgucau cucagaagca ucuuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac caugucaaac aaccucguca cgcucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg ccucuacuac aucuacgcac aagucaccuu cugcuccaac 540

cgcgaagcau ccucccaagc ccccuucauc gccucccucu gccucaaauc ccccggccgc 600

uucgaacgca uccuccuccg cgccgcaaau acccauuccu ccgccaaacc augcggccaa 660

caauccaucc accucggcgg cgucuucgaa cuccaacccg gcgccuccgu cuucgucaac 720

gucaccgacc ccucccaagu aucccaugga accggcuuca ccuccuucgg ccuccucaaa 780

cucuga 786

<210> 1027

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 1027

augaucgaaa ccuacaauca aaccucgccc cgcagcgccg caacaggccu ccccaucucc 60

augaaaaucu ucauguaccu ccucaccguc uuccuaauca cccaaaugau cggcuccgcc 120

cuauucgccg ucuaccucca ccgccgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuuug ucuucaugaa aacuauccaa cgaugcaaca ccggcgaacg aucccuaucc 240

cuccucaacu gcgaagaaau aaaaucccaa uucgaaggau ucgucaaaga caucaugcua 300

aacaaagaag aaaccaaaaa agaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaaucgcag cccacgucau cucagaagca ucuuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac caugucaaac aaccucguca cccucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg ccucuacuac aucuacgcac aagucaccuu cugcuccaac 540

cgcgaagcau ccucccaagc ccccuucauc gccucccucu gccucaaauc ccccggccgc 600

uucgaacgca uccuccuccg cgccgcaaau acccacuccu ccgccaaacc augcggccaa 660

caauccaucc accucggcgg cgucuucgaa cuccaacccg gcgccuccgu cuucgucaac 720

gucaccgacc ccucccaagu aucccaugga accggcuuca ccuccuucgg ccuccucaaa 780

cucuga 786

<210> 1028

<211> 786

<212>RNA

<213> Artificial Sequence

<220>

<223> CD40LG

<400> 1028

augaucgaaa ccuacaauca aaccucgccc cgcagcgccg caacaggccu ccccaucucc 60

augaaaaucu ucauguaccu ccucaccguc uuccuaauca cccaaaugau cggcuccgcc 120

cuauucgccg ucuaccucca ccgccgccuc gacaaaaucg aagacgaacg caaccuccac 180

gaagacuuug ucuucaugaa aacuauccaa cgaugcaaca ccggcgaacg aucccuaucc 240

cuccucaacu gcgaagaaau aaaaucccaa uucgaaggau ucgucaaaga caucaugcua 300

aacaaagaag aaaccaaaaa agaaaacucc uucgaaaugc aaaaaggcga ccaaaacccc 360

caaaucgcag cccacgucau cucagaagca ucuuccaaaa ccaccuccgu ccuccaaugg 420

gccgaaaaag gcuacuacac caugucaaac aaccucguca cccucgaaaa cggcaaacaa 480

cucaccguca aacgccaagg ccucuacuac aucuacgcac aagucaccuu cugcuccaac 540

cgcgaagcau ccucccaagc ccccuucauc gccucccucu gccucaaauc ccccggccgc 600

uucgaacgca uccuccuccg cgccgcaaau acccacuccu ccgccaaacc augcggccaa 660

caauccaucc accucggcgg cgucuucgaa cuccaacccg gcgccuccgu cuucgucaac 720

gucaccgacc ccucccaagu aucccaugga accggcuuca ccuccuucgg ccuccucaaa 780

cucuga 786

<210> 1029

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1029

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cgucggucgu cacggucccg ucgucgucgc ucgggacgca gacguacauc 600

ugcaacguca accacaagcc gucgaacacg aaggucgaca agcgggucga gccgaagucg 660

ugcgacaaga cgcacacgug cccgccgugc ccggcgccgg aguuauuagg ggggccgucg 720

gucuuccucu ucccgccgaa gccgaaggac acguuaauga ucucgcgcac gccggagguc 780

acgugcgucg ucgucgacgu cucgcacgag gacccgggagg ucaaguucaa cugguacguc 840

gacggggucg agguccacaa cgcgaagacg aagccgcggg aggagcagua caacucgacg 900

uaccgcgucg ucucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1030

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1030

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguca accacaagcc gucgaacacg aaggucgaca agcgggucga gccgaagucg 660

ugcgacaaga cgcacacgug cccgccgugc ccggcgccgg aguuauuagg ggggccgucg 720

gucuuccucu ucccgccgaa gccgaaggac acguuaauga ucucgcgcac gccggagguc 780

acgugcgucg ucgucgacgu cucgcacgag gacccgggagg ucaaguucaa cugguacguc 840

gacggggucg agguccacaa cgcgaagacg aagccgcggg aggagcagua caacucgacg 900

uaccgcgucg ucucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1031

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1031

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagucg 660

ugcgacaaga cccacacgug cccgccgugc ccggcgccgg aguuauuagg ggggccgucg 720

gucuuccucu ucccgccgaa gccgaaggac acguuaauga ucucgcgcac gccggagguc 780

acgugcgucg ucgucgacgu cucgcacgag gacccgggagg ucaaguucaa cugguacguc 840

gacggggucg agguccacaa cgcgaagacg aagccgcggg aggagcagua caacucgacg 900

uaccgcgucg ucucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1032

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1032

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagucg 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg aguuauuagg cgggcccucc 720

gucuuccucu ucccgccgaa gccgaaggac acguuaauga ucucgcgcac gccggagguc 780

acgugcgucg ucgucgacgu cucgcacgag gacccgggagg ucaaguucaa cugguacguc 840

gacggggucg agguccacaa cgcgaagacg aagccgcggg aggagcagua caacucgacg 900

uaccgcgucg ucucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1033

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1033

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagucg 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg aguuauuagg cgggcccucc 720

guguuccucu ucccgcccaa gcccaaggac accuuaauga ucucgcgcac ccccgaggug 780

acgugcgucg ucgucgacgu cucgcacgag gacccgggagg ucaaguucaa cugguacguc 840

gacggggucg agguccacaa cgcgaagacg aagccgcggg aggagcagua caacucgacg 900

uaccgcgucg ucucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1034

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1034

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagucg 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg aguuauuagg cgggcccucc 720

guguuccucu ucccgcccaa gcccaaggac accuuaauga ucucgcgcac ccccgaggug 780

accugcgucg uggucgacgu guccicgag gacccgggagg ucaaguucaa cugguacgug 840

gacggcgugg agguccacaa cgcgaagacg aagccgcggg aggagcagua caacucgacg 900

uaccgcgucg ucucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1035

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1035

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagucg 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg aguuauuagg cgggcccucc 720

guguuccucu ucccgcccaa gcccaaggac accuuaauga ucucgcgcac ccccgaggug 780

accugcgucg uggucgacgu guccicgag gacccgggagg ucaaguucaa cugguacgug 840

gacggcgugg agguccacaa cgccaagacc aagccccggg aggagcagua caacucgacc 900

uaccgcgugg ugucggucuu aacgguccuc caccaggacu gguuaaacgg gaaggaguac 960

aagugcaagg ucucgaacaa ggcguuaccg gcgccgaucg agaagacgau cucgaaggcg 1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1036

<211> 1347

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_HC

<400> 1036

caggugcagu uagucgaguc gggcgggggc guggugcagc ccgggcgcuc ccuccgguua 60

ucgugcgccg ccuccggcuu caccuucucg uccuacacca ugcacugggu ccgccaggcg 120

ccggggaagg gcuuagagug ggugacguuc aucucguacg acggcaacaa caaguacuac 180

gccgacuccg ugaaggggcg guucaccauc ucgcgcgaca acuccaagaa cacccucuac 240

uuacagauga acucguuacg ggccgaggac accgccaucu acuacugcgc ccgcacggggc 300

uggcucgggc ccuucgacua cuggggccag gggaccuuag ucaccguguc cucggcgucc 360

accaagggcc ccucgguguu ccccuuagcc ccguccucga aguccacguc gggcgggacc 420

gccgcccucg gcugcuuagu caaggacuac uuccccgagc ccgugaccgu gucciggaac 480

ucgggggcgu uaaccucggg cguccacacg uuccccgccg ugcuccaguc cucgggcuua 540

uacuccuuau cguccguggu caccgugccg ucguccucgc ucgggaccca gaccuacauc 600

ugcaacguga accacaagcc cuccaacacg aaggucgaca agcgggugga gcccaagucg 660

ugcgacaaga cccacacgug cccgcccugc cccgcccccg aguuauuagg cgggcccucc 720

guguuccucu ucccgcccaa gcccaaggac accuuaauga ucucgcgcac ccccgaggug 780

accugcgucg uggucgacgu guccicgag gacccgggagg ucaaguucaa cugguacgug 840

gacggcgugg agguccacaa cgccaagacc aagccccggg aggagcagua caacucgacc 900

uaccgcgugg uguccgucuu aacggugcuc caccaggacu gguuaaacgg gaaggaguac 960

1020

aaggggcagc cgcgggagcc gcaggucuac acgcucccgc cgucgcgcga cgaguuaacg 1080

aagaaccagg ucucguuaac gugccucguc aagggguucu acccgucgga caucgcgguc 1140

gagugggagu cgaacgggca gccggagaac aacuacaaga cgacgccgcc ggucuuagac 1200

ucggacgggu cguucuucuu auacucgaag cucacggucg acaagucgcg guggcagcag 1260

gggaacgucu ucucgugcuc ggucaugcac gaggcguuac acaaccacua cacgcagaag 1320

ucguuaucgc ucucgccggg gaaguga 1347

<210> 1037

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_LC

<400> 1037

gagaucgugu uaacccaguc gcccggcacc cucuccuuau cgccggggga gcgcgccacg 60

uuauccugcc gggccucgca guccgucggc ucguccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgcuu auuaaucuac ggcgccuucu cgcggggccac cgggaucccc 180

gaccgcuucu ccggcucggg cuccgggacc gacuucaccc ucacgaucuc gcgguuuagag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccucgcccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 360

cccucggacg agcaguuaaa guccgggacg gccucggugg ucugccucuu aaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag gucgacaacg cguuacaguc ggggaacucg 480

caggagucgg ucacggagca ggacucgaag gacucgacgu acucgcucuc gucgacguua 540

acguuaucga aggcggacua cgagaagcac aaggucuacg cgugcgaggu cacgcaccag 600

gggcucucgu cgccggucac gaagucguuc aaccgcgggg agugcuga 648

<210> 1038

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_LC

<400> 1038

gagaucgugu uaacccaguc gcccggcacc cucuccuuau cgccggggga gcgcgccacg 60

uuauccugcc gggccucgca guccgucggc ucguccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgcuu auuaaucuac ggcgccuucu cgcggggccac cgggaucccc 180

gaccgcuucu ccggcucggg cuccgggacc gacuucaccc ucacgaucuc gcgguuuagag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccucgcccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 360

cccucggacg agcaguuaaa guccgggacg gccucggugg ucugccucuu aaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag guggacaacg cguuacaguc cggcaacucg 480

caggagucgg ucacggagca ggacucgaag gacucgacgu acucgcucuc gucgacguua 540

acguuaucga aggcggacua cgagaagcac aaggucuacg cgugcgaggu cacgcaccag 600

gggcucucgu cgccggucac gaagucguuc aaccgcgggg agugcuga 648

<210> 1039

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_LC

<400> 1039

gagaucgugu uaacccaguc gcccggcacc cucuccuuau cgccggggga gcgcgccacg 60

uuauccugcc gggccucgca guccgucggc ucguccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgcuu auuaaucuac ggcgccuucu cgcggggccac cgggaucccc 180

gaccgcuucu ccggcucggg cuccgggacc gacuucaccc ucacgaucuc gcgguuuagag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccucgcccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 360

cccucggacg agcaguuaaa guccgggacg gccucggugg ucugccucuu aaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag guggacaacg cguuacaguc cggcaacucg 480

caggagucgg ucaccgagca ggacuccaag gacucgaccu acucgcucuc gucgacguua 540

acguuaucga aggcggacua cgagaagcac aaggucuacg cgugcgaggu cacgcaccag 600

gggcucucgu cgccggucac gaagucguuc aaccgcgggg agugcuga 648

<210> 1040

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_LC

<400> 1040

gagaucgugu uaacccaguc gcccggcacc cucuccuuau cgccggggga gcgcgccacg 60

uuauccugcc gggccucgca guccgucggc ucguccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgcuu auuaaucuac ggcgccuucu cgcggggccac cgggaucccc 180

gaccgcuucu ccggcucggg cuccgggacc gacuucaccc ucacgaucuc gcgguuuagag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccucgcccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 360

cccucggacg agcaguuaaa guccgggacg gccucggugg ucugccucuu aaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag guggacaacg cguuacaguc cggcaacucg 480

caggagucgg ucaccgagca ggacuccaag gacucgaccu acucccucuc guccaccuua 540

acguuaucga aggcggacua cgagaagcac aaggucuacg cgugcgaggu cacgcaccag 600

gggcucucgu cgccggucac gaagucguuc aaccgcgggg agugcuga 648

<210> 1041

<211> 648

<212>RNA

<213> Artificial Sequence

<220>

<223> Ipilimumab_LC

<400> 1041

gagaucgugu uaacccaguc gcccggcacc cucuccuuau cgccggggga gcgcgccacg 60

uuauccugcc gggccucgca guccgucggc ucguccuacc ucgcguggua ccagcagaag 120

cccggggcagg cgccccgcuu auuaaucuac ggcgccuucu cgcggggccac cgggaucccc 180

gaccgcuucu ccggcucggg cuccgggacc gacuucaccc ucacgaucuc gcgguuuagag 240

ccggaggacu ucgccgugua cuacugccag caguacggcu ccucgcccug gaccuucggg 300

cagggcacca agguggagau caagcgcacc gucgccgccc ccuccguguu caucuucccg 360

cccucggacg agcaguuaaa guccgggacg gccucggugg ucugccucuu aaacaacuuc 420

uacccccggg aggccaaggu gcaguggaag guggacaacg cguuacaguc cggcaacucg 480

caggagucgg ucaccgagca ggacuccaag gacucgaccu acucccucuc guccaccuua 540

acguuaucga aggccgacua cgagaagcac aagguguacg ccugcgaggu gacgcaccag 600

gggcucucgu cgccggucac gaagucguuc aaccgcgggg agugcuga 648

<210> 1042

<211> 162

<212> PRT

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1042

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln

1 5 10 15

Leu Gly Trp Arg Pro Gly Trp Phe Leu Ala Leu Leu Val Val Thr Glu

20 25 30

Gly Asp Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser

35 40 45

Phe Val Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys

50 55 60

Leu Ala Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg

65 70 75 80

Phe Arg Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val

85 90 95

Val Arg Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile

100 105 110

Ser Leu Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu

115 120 125

Arg Val Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro

130 135 140

Ser Pro Arg Pro Ala Gly Gln Pro Glu Phe Arg Gly Gly Gly Ser Gly

145 150 155 160

Gly Gly

<210> 1043

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1043

augcagaucc cccaggcccc guggcccgug gucugggccg ugcugcagcu cggcuggcgc 60

cccggggggu uccggcgcu gcucgugguc accgagggcg acaacgccac cuucacgugc 120

agcuucucca acaccagcga guccuucgug cugaacuggu accggaugag ccccuccaac 180

cagaccgaca agcuggccgc cuucccggag gaccgcagcc agcccggggca ggacugccgg 240

uuccgcguga cccagcuccc caacggccgg gacuuccaca uguccgucgu gcgcgcccgg 300

cgcaacgaca gcgggacgua ccugugcggc gcgaucuccc uggcccccaa ggcccagauc 360

agggagcc uccgggccga gcugcgcgug accgagcggc gcgcggaggu cccgaccgcc 420

caccccuccc ccagcccccg gccggccggc cagcccgagu uccgcggggg cggguccggc 480

gggggc 486

<210> 1044

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1044

augcagaucc cccaggcccc cuggcccguc gucugggccg uccuccagcu cggcuggcgc 60

cccggcuggu uccucgcccu ccucgucguc accgagggcg acaacgccac cuucaccugc 120

uccuucucca acaccuccga guccuucguc cucaacuggu accgcauguc ccccuccaac 180

cagaccgaca agcucgccgc cuuccccgag gaccgcuccc agcccggcca ggacugccgc 240

uuccgcguca cccagcuccc caacggccgc gacuuccaca uguccgucgu ccgcgcccgc 300

cgcaacgacu ccggcaccua ccucugcggc gccaucuccc ucgcccccaa ggcccagauc 360

aaggaguccc uccgcgccga gcuccgcguc accgagcgcc gcgccgaggu ccccaccgcc 420

caccccuccc ccuccccccg ccccgccggc cagcccgagu uccgcggcgg cggcuccggc 480

ggcggc 486

<210> 1045

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1045

augcagaucc cccaagcccc uuggccagug gucugggcug uucugcagcu cggcuggaga 60

ccgggguggu uccuugcacu guugguggua accgagggag acaacgccac auuuacuugc 120

agcuucucca auacgucuga aucauuugug uuaaacuggu acaggaugag ucccagcaau 180

cagaccgaua agcuggcggc uuucccugag gaccgguccc agccagguca agauugucgc 240

uuucgaguca cacagcuacc caacggccgu gacuuccaca ugucuguggu uagagccagg 300

cggaaugauu cggggacuua ucucugcgga gcaauuucac uggccccuaa agcucagaua 360

aaggaaagcc uucgcgcaga gcugagagug accgaaaggc gggccgaggu cccaacagcu 420

caucccaguc cuuccccacg cccggccggc cagcccgagu uucgaggugg gggaucuggc 480

gggggg 486

<210> 1046

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1046

augcagaucc cccaggcccc cuggcccgug gugugggccg ugcugcagcu gggcuggaga 60

cccggcuggu uccggcccu gcugguggug accgagggcg acaacgccac cuucaccugc 120

agcuucagca acaccagcga gagcuucgug cugaacuggu acagaaugag ccccagcaac 180

cagaccgaca agcuggccgc cuuccccgag gacagaagcc agcccggcca ggacugcaga 240

uucagaguga cccagcugcc caacggcaga gacuuccaca ugagcguggu gagagccaga 300

agaaacgaca gcggcaccua ccugugcggc gccaucagcc uggcccccaa ggcccagauc 360

aggagagcc ugagagccga gcugagagug accgagagaa gagccgaggu gcccaccgcc 420

caccccagcc ccagccccag acccgccggc cagcccgagu ucagaggcgg cggcagcggc 480

ggcggc 486

<210> 1047

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1047

augcagaucc cccaagcccc uuggccggug gucugggcug uucugcagcu cggcuggaga 60

ccgggguggu uccggcccu ucugguggug accgagggag acaacgcgac auuuacgugc 120

agcuucucca auaccucuga gagcuuuguc cucaacuggu accggauguc cccuucuaau 180

cagacagaua agcuggcugc cuuccccgaa gaccgcagcc agccuggcca agauuguaga 240

uuucggguga cccagcuucc caacgggcgc gacuuccaca uguccguugu gagagcccgg 300

cgcaaugauu cuggaacaua ucugugcggc gcuauuagcc ucgccccuaa agcucagauc 360

aaggaauccc ugagagccga gcugcggguc accgaacgca gagcggaggu gccgacagcc 420

caucccagcc cuucuccccg gccugcuggg cagcccgagu uucgcgggagg cggcuccgggg 480

ggaggc 486

<210> 1048

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1048

augcaaauac cacaagcucc auggccagua guaugggcag uauuacaauu aggauggaga 60

120

aguuuuucaa auacaucaga aucauuugua uuaaauuggu auagaauguc accaucaaau 180

caaacagaua aauuagcagc auuuccagaa gacagaucac aaccaggaca agauugcaga 240

uucagaguaa cacaauuacc aaacggaaga gacuuucaua ugucaguagu aagagcaaga 300

agaaaugacu caggaacuua uuuaugcgga gcaauauucau uagcaccaaa agcacaaaua 360

aaagaaucac uaaagcaga auuaagagua acagaaagaa gagcagaagu ucccacagca 420

cauccaucac caucaccaag accagcagga caaccagaau uuagaggagg aggaucagga 480

ggaga 486

<210> 1049

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1049

augcagaucc cccaagcccc auggccggug gucugggcag ugcugcagcu cggcuggagg 60

ccgggguggu uccggccuu gcugguagug accgagggug acaacgcgac uuuuaccugc 120

agcuucucca auacgaguga auccuuuguc cucaacuggu accggauguc cccaaguaau 180

cagacugaua agcuggccgc auuccccgag gaccgcagcc agccaggcca agauuguagg 240

uuucggguga cccaguugcc caacgggcgc gacuuccaca uguccguggu cagggcccgg 300

cgcaaugaua gcggcaccua ucugugcggu gcaauuuccc ucgccccaaa agcgcagauc 360

aaggaaaguc ugagggccga gcugcgggug acugaacgca gggcagaggu accgaccgcc 420

caucccagcc caagcccccg gccagccggg cagcccgagu uucgcggcgg cgggagcggu 480

gggggg 486

<210> 1050

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1050

augcaaaucc cacaagcccc auggcccguc gucugggccg uccuccaacu cggcuggcgc 60

ccaggcuggu uccuagcacu ccuagucguc accgaaggcg acaacgcaac cuucaccugc 120

uccuucucca acaccucaga aucauucguc cucaacuggu accgcauguc ccccuccaac 180

caaaccgaca aacucgcagc cuuccccgaa gacagaucac aacccggcca agacugcaga 240

uuccgcguca cccaacuccc caacggacgc gacuuccaca uguccguagu ccgcgcccgc 300

cgaaacgacu ccggcaccua ccuaugcggc gccaucucac ucgccccaaa agcacaaauc 360

aaagaaucac ucagagcaga acuacgaguc accgaaagac gcgcagaagu accaaccgcc 420

cacccauccc ccucaccccg acccgccggc caacccgaau uccgcgggagg cggcuccggc 480

ggcggc 486

<210> 1051

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1051

augcaaaucc cacaagcccc cuggcccguc gucugggccg uacuacaacu cggauggcga 60

cccggcuggu uccuagcccu ccuagucguc accgaaggcg acaacgccac cuucaccugc 120

uccuucucaa acacauccga aucauucguc cucaacuggu accgcauguc ccccuccaac 180

caaaccgaca aacucgccgc cuuccccgaa gaccgauccc aacccggcca agacugccga 240

uuccgcguca cccaacuacc caacggccgc gacuuccaca uguccgucgu ccgcgcccgc 300

cgcaacgacu caggcaccua ccucuguggc gccaucuccc ucgcaccaaa agcccaaauc 360

aaagaauccc uccgcgccga acuccgcguc acagaacgca gagccgaagu ccccaccgca 420

cacccaucac cauccccccg cccagccggc caacccgaau uccgcggagg cggauccggc 480

ggcgga 486

<210> 1052

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1052

augcaaaucc cccaagcccc auggcccguc gucugggccg uccuacaacu cggcuggcgc 60

cccggcuggu uccucgcccu ccucgucguc accgaaggcg acaacgccac cuucaccugc 120

uccuucucca acacaucaga auccuucguc cucaacuggu accgaauguc ccccucaaac 180

caaaccgaca aacucgccgc cuuccccgaa gaccgcuccc aacccggcca agacugccgc 240

uuccgaguca cccaacuacc caacggccgc gacuuccaca uguccgucgu ccgcgcccgc 300

cgcaacgacu ccggcaccua ccuaugcggc gccaucuccc ucgcccccaa agcccaaauc 360

aaagaaucac uccgcgccga acccgcguc accgaacgcc gcgccgaagu ccccaccgcc 420

caccccuccc ccuccccccg ccccgccgga caacccgaau uccgcggcgg cggaucaggc 480

ggcggc 486

<210> 1053

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1053

augcaaauac cacaagcacc auggccugua guaugggcag uauuacaauu aggauggaga 60

120

ucauuuagua auacaucaga aucauuugua uuaaauuggu auagaaugag uccaaguaau 180

caaacagaua aauuagcagc auuuccagaa gacagaagcc aaccaggaca agauuguaga 240

uuuagaguaa cacaauuacc aaauggaaga gauuuucaua ugaguguagu aagagcaaga 300

agaaaugacu caggaacaua ucuaugcgga gcaauaagcu uagcaccaaa agcacaaaua 360

aaagaaagcu uaagagcaga auuaagagua acagaaagaa gagcagaagu accaacagca 420

cauccaaguc caaguccaag accagcagga caaccagaau uuagaggagg aggaaguggg 480

ggaga 486

<210> 1054

<211> 486

<212>RNA

<213> Artificial Sequence

<220>

<223> solPD1

<400> 1054

augcaaauac cacaagcacc aggccagua guaugggcag uauuacaauu aggauggaga 60

120

ucauuuucaa auacaucaga aucauuugua cuaaauuggu auagaauguc accaucaaau 180

240

uucagaguaa cacaacuacc aaauggaaga gacuuucaua ugucaguagu aaagcaaga 300

agaaaugauu caggaacaua ucuaugugga gcaauauucau uagcuccaaa agcacaaaua 360

aaagaaucau uaagagcaga auuaagagua acagaaagaa gagcagaagu accaacagca 420

cauccaucac caagcccaag accagcagga caaccagaau uuagaggagg aggaucagga 480

ggaga 486

<210> 1055

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R3630_SalI

<400> 1055

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgacuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacuuc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacagugcu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 1056

<211> 547

<212>RNA

<213> Artificial Sequence

<220>

<223> R3630_AatII

<400> 1056

60

uuuuuuuuuuuuuuuuuuga ccgucucaag guccaaguua gucugccuau aaaggugcgg 120

180

uuuuuaguaa augcgucuac ugaauccagc gaugaugcug gccgaucu ucgaccacaa 240

gugcauauag uagucaucga gggucgccuu uuuuuuuuuu uuuuuuuuuu uggcccaguu 300

cugagacguc gcuagagacu acaguuacag cugcaguagu aaccacugcg gcuauugcag 360

gaaaucccgu ucagguuuuu uuuuuuuuuu uuuuuuccgc ucacuaugau uaagaaccag 420

guggaguguc acugcucucg aggucucacg agagcgcucg auacagugcu uggaagaauc 480

uuuuuuuuuu uuuuuuuuuu uugugcgacg aucacagaga acuucuauuc augcaggucu 540

gcucuag 547

<210> 1057

<211> 18

<212> PRT

<213> Artificial Sequence

<220>

<223> CysPeptid CysHis6Arg4His6Cys

<400> 1057

Cys His His His His His His Arg Arg Arg Arg His His His His His His

1 5 10 15

His Cys

<210> 1058

<211> 1632

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12

<400> 1058

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagcggcagc accuccggga gcggcaagcc cggguccggc 1020

gaggggagca ccaagggccg gaaccugccg guggccaccc ccgaccccgg cauguucccc 1080

ugccugcacc acagccagaa ccuccugcgc gccgugucca acaugcugca gaaggcccgg 1140

cagacgcucg aguucuaccc gugcaccagc gaggagaucg accacgagga caucaccaag 1200

gacaagaccu ccacggucga ggccugccug ccccuggagc ucaccaagaa cgagagcugc 1260

1320

uccuucauga uggccucug ccugagcucc aucuacgagg accugaagau guaccaggug 1380

gaguucaaga ccaugaacgc caagcuccug auggaccca agcgccagau cuuccuggac 1440

1500

gucccccaga aguccagccu cgaggagccg gacuucuaca agaccaagau caagcugugc 1560

1620

aacgccagcu ga 1632

<210> 1059

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1059

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu cuuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuu 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca ccuuauccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagauuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca aaccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagc 984

<210> 1060

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1060

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagc 984

<210> 1061

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1061

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccuggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagc 984

<210> 1062

<211> 984

<212>RNA

<213> Artificial Sequence

<220>

<223>IL12B

<400> 1062

60

gucgccaucu gggaacucaa aaaagacgua uacgucgucg aacucgacug guaccccgac 120

gccccaggag aaauggucgu ccuaaccugc gacacaccg aagaagacgg uaucaccugg 180

acccucgacc aauccuccga aguccuaggc uccggcaaga cccucaccau ccaagucaaa 240

gaauuuggcg acgcaggaca auacaccugu cacaaaggcg gcgaaguccu cagccacagc 300

cuucuccuac uccauaaaaa agaagacggc aucuggucca cugacauccu caaagaccaa 360

aaagaaccca aaaauaaaac cuuccuccgc ugcgaagcca aaaacuacuc cggccgauuc 420

accuguuggu ggcuaaccac aaucagcacc gaccucaccu ucucagucaa auccucccgc 480

ggcucaucug acccccaagg cgucacaugc ggcgccgcca cccucuccgc cgaacgcguc 540

cgcggcgaca acaaagaaua cgaauacucc gucgaauguc aagaagacuc cgccugcccc 600

gccgccgaag aaucacuccc caucgaaguc auggucgacg caguccacaa acucaaauac 660

gaaaacuaca ccuccuccuu cuucauccgc gacauaauaa aacccgaccc acccaaaaac 720

cuccaacuca agccacucaa aaacucccga caagucgaag ucuccggga guaccccgac 780

accuggucca caccacacuc cuacuucucc cucaccuucu gcguccaagu ccaaggcaaa 840

uccaaacgcg aaaaaaaaga ccgcguuuuc acagacaaaa ccuccgccac aguaauauugc 900

cgcaaaaacg ccuccaucuc cguccgggcc caagaccgcu acuacuccuc cuccuggucc 960

gagugggccu caguccccug cagc 984

<---

Claims (113)

1. The use of an immunostimulatory RNA (isRNA) which contains the nucleotide sequence shown in SEQ ID NO: 433 for the treatment or prevention of a neoplastic or cancerous disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC) , head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC) where the tumor or cancer is at an advanced stage and/or is resistant to standard therapy by introducing isRNA into the tumor. 2. The use of isRNA according to claim 1, where the introduction of isRNA is carried out by injection. 3. The use of an isRNA according to claim 1 or 2 as part of a complex with a cationic or polycationic compound, preferably with a cationic or polycationic polymer, a cationic or polycationic peptide or protein, a cationic or polycationic polysaccharide and/or a cationic or polycationic lipid. 4. The use of an isRNA according to claim 3, wherein the cationic or polycationic compound is a polymeric carrier. 5. The use of an isRNA according to claim 4, wherein the polymeric carrier is formed by a disulfide crosslinked cationic component, preferably a disulfide crosslinked cationic component, preferably a disulfide crosslinked cationic peptide, wherein the disulfide crosslinked cationic peptide preferably comprises formula V peptide (Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x , (formula (V), wherein l + m + n + o + x is 8-15 and l, m, n or o can each independently be any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provided that the total content of Arg, Lys, His and Orn is at least 50% of the total amino acid content of the oligopeptide; and Xaa may be any amino acid selected from native (ie, naturally occurring) or non-naturally occurring amino acids with the exception of Arg, Lys, His, or Orn; and x may be any number selected from 0, 1, 2, 3, or 4, provided that the total Xaa content does not exceed 50% of the total amino acid content of the oligopeptide; peptide of formula Va {(Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa') _x (Cys) _y } formula (Va), in which (Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o and x have the meanings indicated for formula V, Xaa' denotes any amino acid selected from native (i.e. occurring naturally) or non-naturally occurring amino acids other than Arg, Lys, His, Orn, or Cys, and y is any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-90, provided that the total content of Arg (arginine), Lys (lysine), His (histidine) and Orn (ornithine) is at least 10% of all amino acids of the oligopeptide; peptide of formula Vb Cys1 {(Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x } Cys2, formula (Vb), in which the empirical formula {(Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x } corresponds to formula (V) and forms the core of the amino acid sequence corresponding to the (semi-empirical) formula (V), and in which Cys1 and Cys2 are cysteine residues located proximal or terminal relative to (Arg) _l ;(Lys) _m ;(His) _n ;(Orn) _o ;(Xaa) _x . 6. The use of an isRNA according to claim 4 or 5, wherein the polymeric carrier comprises at least one of the disulfide crosslinked cationic peptides Cys-Arg ₁₂ or Cys-Arg ₁₂ -Cys. 7. The use of isRNA according to any one of paragraphs. 3-6, wherein the N/P ratio of isRNA and cationic or polycationic compound, preferably a cationic or polycationic peptide or protein, is in the range of about 0.1-10, including a range of about 0.3-4, about 0 .5-2, about 0.7-2 and about 0.7-1.5. 8. The use of an isRNA according to any of the preceding paragraphs, as part of a complex with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes. 9. The use of an isRNA according to any one of the preceding claims, in conjunction with at least one additional pharmaceutically active ingredient. 10. The use of an isRNA according to claim 9, wherein at least one additional pharmaceutically active ingredient is a compound that is used to treat a tumor or cancer, preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC ), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the neoplastic or cancerous disease is preferably located on advanced stage and/or resistant to standard therapy. 11. The use of an isRNA according to claim 9 or 10, wherein at least one additional pharmaceutically active ingredient is a checkpoint modulator, or a fragment or variant thereof. 12. Use of an isRNA according to claim 11 wherein the checkpoint modulator is selected from the group consisting of PD-1 inhibitor, PD-L1 inhibitor, CTLA-4 inhibitor, LAG3 inhibitor, TIM3 inhibitor, TIGIT inhibitor, OX40 stimulator, 4-1BB stimulator , a CD40L stimulator, a CD28 stimulator, and a GITR stimulator, or a fragment or variant of any of these checkpoint modulators. 13. The use of an isRNA according to claim 12, wherein the checkpoint modulator is a PD-1 inhibitor or a PD-L1 inhibitor, wherein the PD-1 inhibitor is preferably an anti-PD-1 antagonist antibody and the PD-L1 inhibitor is an anti-PD antagonist antibody -L1 or fragment or variant of said antibody. 14. The use of an isRNA according to claim 12, wherein the checkpoint modulator is a CTLA-4 inhibitor, preferably an anti-CTLA4 antagonist antibody, or a fragment or variant thereof. 15. The use of an isRNA according to claim 9 or 10, wherein at least one additional pharmaceutically active ingredient is an interleukin, preferably IL-12, or a fragment or variant thereof. 16. The use of isRNA according to any one of paragraphs. 1-15 together with at least one coding RNA, preferably at least one mRNA. 17. The use of isRNA according to claim 16, where at least one coding RNA contains at least one coding region that encodes at least one peptide or protein, which is at least one peptide or protein selected from the group that consists from - IL-12, - CD40L, - PD-1 decoy receptor and - antagonistic antibody against CTLA4, or a fragment or variant of any of these compounds. 18. The use of an isRNA according to claim 16 or 17, wherein at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, or a fragment or variant thereof. 19. The use of an isRNA according to claim 16 or 17, wherein at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L or a CD40L analog, or a fragment or variant thereof. 20. The use of an isRNA according to claim 16 or 17, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor or a PD-1 decoy receptor analogue, or its fragment, or variant. 21. The use of an isRNA according to claim 16 or 17, wherein at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antagonist antibody or analog, or fragment, or variant. 22. The use of an isRNA according to claim 16 or 17, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, or a fragment or variant thereof, the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L, or a fragment or variant thereof, the same or another coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antagonist antibody, or a fragment or variant thereof, and optionally, the same or another coding RNA contains at least one coding sequence that encodes a PD-1 decoy receptor-containing peptide or protein, or a fragment or variant thereof. 23. The use of isRNA according to any one of paragraphs. 16-22 without using a PD-1 or PD-L1 antagonist and together with at least one PD-1 decoy receptor-containing peptide or protein, or fragment or variant thereof, or together with a nucleotide sequence that encodes at least at least one PD-1 decoy receptor-containing peptide or protein, or fragment or variant thereof. 24. The use of an isRNA according to claim 22 or 23, where the coding sequence that encodes a peptide or protein containing IL-12, or a fragment thereof, or a variant encoding a sequence that encodes a peptide or protein containing CD40L, or a fragment thereof, or a variant encoding a sequence that encodes a peptide or protein containing an anti-CTLA4 antagonist antibody, or a fragment or variant thereof, and optionally a coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof , are localized to different coding RNAs, preferably different mRNAs. 25. The use of an isRNA according to claim 22 or 23, wherein at least two of the coding sequences that encode a peptide or protein containing IL-12, or a fragment or variant thereof, encode a peptide or protein containing CD40L, or a fragment thereof, or a variant, encoding a peptide or protein containing an anti-CTLA4 antagonist antibody, or a fragment or variant thereof, and optionally encoding a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof, located on the same coding RNA, which is preferably bi- or polycistronic RNA. 26. The use of isRNA according to any one of paragraphs. 16-25 by co-injection into the tumor with at least one coding RNA. 27. The use of isRNA according to claim 24 by co-administration into the tumor with one preparative form, including different coding RNAs. 28. The use of isRNA according to any one of paragraphs. 16-27 formulated in combination with at least one coding RNA. 29. The use of isRNA according to any one of paragraphs. 16-28, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing IL-12, preferably at least one of IL-12A or IL-12B, or a fragment, or a variant of any from these proteins. 30. The use of an isRNA according to claim 29, wherein the encoded peptide or protein contains an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-8, or a fragment or variant of any of these sequences. 31. The use of an isRNA according to claim 29 or 30, wherein at least one coding sequence contains a nucleotide sequence selected from the group consisting of SEQ ID NOs: 440-445, or a fragment or variant of any of these sequences. 32. The use of isRNA according to any one of paragraphs. 29-31, where the encoded peptide or protein contains IL-12A and IL-12B, or a fragment or variant of each of these proteins. 33. The use of an isRNA according to claim 32, wherein the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 10, or a fragment or variant thereof. 34. The use of isRNA according to any one of paragraphs. 29-33, where at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 447, or a fragment or variant thereof. 35. The use of isRNA according to any one of paragraphs. 16-34, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing CD40L, or a fragment, or a variant, where the encoded peptide or protein preferably contains the amino acid sequence shown in SEQ ID NO : 11, or a fragment of it, or a variant. 36. The use of an isRNA according to claim 35, wherein at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 448, or a fragment or variant thereof. 37. The use of isRNA according to any one of paragraphs. 16-36, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing a PD-1 decoy receptor, or a fragment or variant thereof, preferably the extracellular part of the PD-1 receptor, or a fragment or variant of it. 38. The use of an isRNA according to claim 37, wherein the decoy PD-1 receptor is a peptide or protein containing soluble PD-1, or a fragment or variant thereof. 39. The use of an isRNA according to claim 37 or 38, wherein the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 2, or a fragment or variant thereof. 40. The use of isRNA according to any one of paragraphs. 37-39, in which at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 439, or a fragment or variant thereof. 41. The use of isRNA according to any one of paragraphs. 16-40, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing an anti-CTLA4 antagonist antibody, or a fragment or variant thereof. 42. The use of an isRNA according to claim 41, wherein the encoded peptide or protein contains the amino acid sequence shown in SEQ ID NO: 645 and/or 677, or a fragment thereof, or a variant of any of the indicated amino acid sequences. 43. The use of an isRNA according to claim 41 or 42, wherein at least one coding sequence contains the nucleotide sequence shown in SEQ ID NO: 646 and/or 678, or a fragment or variant of any of said nucleotide sequences. 44. The use of isRNA according to any one of paragraphs. 16-43, where at least one coding RNA contains at least one coding sequence that encodes a peptide or protein containing a tumor antigen, or fragment, or variant. 45. The use of isRNA according to claim 44, where the tumor antigen is preferably selected from the following group: 1A01 HLA-A/m; 1A02; 5T4; ACRBP; AFP; AKAP4; alpha-actinin-4/m; alpha-methylacyl-coenzyme A-racemase; ANDR; ART-4; ARTC1/m; AURKB; B2MG; B3GN5; B4GN1; B7H4; BAGE-1; BASI; BCL-2; bcr/abl; beta-catenin/m; BING-4; BIRC7; BRCA1/m; BY55; calreticulin; CAMEL; CASP-8/m; CASPA; cathepsin B; cathepsin L; CD1A; CD1B; CD1C; CD1D; CD1E; CD20; CD22; CD276; CD33; CD3E; CD3Z; CD44 isoform 1; CD44 isoform 6; CD4; CD52; CD55; CD56; CD80; CD86; CD8A; CDC27/m; CDE30; CDK4/m; CDKN2A/m; CEA; CEAM6; CH3L2; CLCA2; CML28; CML66; COA-1/m; coactosin-like protein; collagen XXIII; COX-2; CP1B1; CSAG2; CT45A1; CT55; CT-9/BRD6; CTAG2 isoform LAGE-1A; CTAG2 isoform LAGE-1B; CTCFL; cten; cyclin B1; cyclin D1; cyp-B; DAM-10; DEP1A; E7; EF1A2; EFTUD2/m; EGFR; EGLN3; ELF2/m; EMMPRIN; Epcam; EphA2; EphA3; ErbB3; ERBB4; erg; ETV6; EWS; EZH2; FABP7; FCGR3A version 1; FCGR3A version 2; FGF5; FGFR2; fibronectin; FOS; FOXP3; FUT1; G250; GAGE-1; GAGE-2; GAGE-3; GAGE-4; GAGE-5; GAGE-6; GAGE7b; GAGE-8 (GAGE-2D); GASR; GnT-V; GPC3; GPNMB/m; GRM3; HAGE; hepsin; Her2/neu; HLA-A2/m; homeobox NKX3.1; HOMTES-85; HPG1; HS71A; HS71B; HST-2; hTERT; iCE; IF2B3; IL10; IL-13Ra2; IL2-RA; IL2-RB; IL2-RG; IL-5; IMP3; ITA5; ITB1; ITB6; kallikrein-2; kallikrein-3; kallikrein-4; KI20A; KIAA0205; KIF2C; KK-LC-1; LDLR; LGMN; LIRB2; LY6K; MAGA5; MAGA8; MAGAB; MAGE-A10; MAGE-A12; MAGE-A1; MAGE-A2; MAGE-A3; MAGE-A4; MAGE-A6; MAGE-A9; MAGE-B10; MAGE-B16; MAGE-B17; MAGE-B1; MAGE-B2; MAGE-B3; MAGE-B4; MAGE-B5; MAGE-B6; MAGE-C1; MAGE-C2; MAGE-C3; MAGE-D1; MAGE-D2; MAGE-D4; MAGE-E1; MAGE10 E1 (MAGE1); MAGE-E2; MAGE-F1; MAGE-H1; MAGEL2; mammaglobin A; MART-1/melan-A; MART-2; MC1R; M-CSF; mesothelin; MITF; MMP1 1; MMP7; MUC-1; MUM-1/m; MUM-2/m; MYCN; MYO1A; MYO1B; MYO1C; MYO1D; MYO1E; MYO1F; MYO1G; MYO1H; NA17; NA88-A; Neo-PAP; NFYC/m; NGEP; NPM; NRCAM; NSE; NUF2; NY-ESO-1; OA1; OGT; OS-9; osteocalcin; osteopontin; p53; PAGE-4; PAI-1; PAI-2; PAP; PATE; PAX3; PAX5; PD1L1; PDCD1; PDEF; PECA1; PGCB; PGFRB; Pim-1 kinase; Pin-1; PLAC1; PMEL; PML; POTEF; POTE; PRAME; PRDX5/m; PRM2; protein; proteinase-3; PSA; PSB9; PSCA; PSGR; PSM; PTPRC; RAB8A; RAGE-1; RARA; RASH; RASK; RASN; RGS5; RHAMM/CD168; RHOC; RSSA; RU1; RU2; RUNX1; S-100; SAGE; SART-_1; SART-2; SART-3; SEPR; serpin B5; SIA7F; SIA8A; SIAT9; SIRT2/m; SOX10; SP17; SPNXA; SPXN3; SSX-1; SSX-2; SSX3; SSX-4; ST1A1; STAG2; STAMP-1; STEAP-1; survivin-2B; survivin; SYCP1; SYT-SSX-1; SYT-SSX-2; TARP; TCRg; TF2AA; TGFB1; TGFR2; TGM-4; TIE2; TKTL1; TPI/m; TRGV11; TRGV9; TRPC1; TRP-p8; TSG10; TSPY1; TVC_(TRGV3); TX101; tyrosinase; TYRP1; TYRP2; UPA; VEGFR1; WT1 and XAGE1. 46. The use of an isRNA according to claim 44 or 45, wherein at least one coding RNA is not introduced into the tumor. 47. The use of isRNA according to any one of paragraphs. 44-46, wherein at least one coding RNA is administered intradermally, intramuscularly, or subcutaneously. 48. The use of isRNA according to any one of paragraphs. 16-47, where at least one coding RNA contains at least one coding sequence containing a nucleotide sequence that is modified compared to the nucleotide sequence of the coding sequence corresponding to the wild-type RNA, and where the amino acid sequence encoded by said coding sequence is preferably is not modified from the amino acid sequence encoded by the corresponding wild-type RNA coding sequence. 49. The use of isRNA according to claim 48, where at least one coding sequence contains a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 25-30; 36-41; 47-52; 58-63; 69-74; 80-85; 91-96; 102-107; 113-118; 124-129; 135-140; 601-606; 612-617; 623-628; 716-725; 727; 1018-1021 and 1059-1062, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 32; 43; 54; 65; 76; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632-644; 726 and 1058, or a fragment or variant of any of these sequences; b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 44; 55; 66; 77; 88; 99; 110; 121; 132; 143; 609; 620; 631; 728-738 and 1025-1028, or a fragment or variant of any of these sequences; c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 646-660; 662-676; 678-692; 694-705; 707-715 or 1029-1041, or a fragment, or a variant of any of these sequences; and/or d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 23; 34; 45; 56; 67; 78; 89; 100; 111; 122; 133; 599; 610; 621; 1022-1024, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 24; 35; 46; 57; 68; 79; 90; 101; 112; 123; 134; 600; 611; 622 and 1043-1054, or a fragment or variant of any of these sequences. 50. The use of isRNA according to any one of paragraphs. 16-49, where at least one coding RNA contains at least one coding sequence having a modified, preferably increased, G/C content compared to the G/C content in the coding sequence corresponding to the wild-type RNA, and where the amino acid sequence, encoded by said coding sequence is preferably not modified from the amino acid sequence encoded by the coding sequence corresponding to the wild-type RNA. 51. The use of isRNA according to claim 50, where at least one coding sequence contains a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 25-30; 80-85; 91-96; 102-107; 113-118; 601-606; 124-129; 135-140; 612-617; 623-628; 716-725 and 72, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 32; 87; 98; 109; 120; 131; 142; 608; 619; 630; 632; 636-644 and 726, or a fragment or variant of any of these sequences; b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 33; 88; 99; 110; 121; 132; 143; 609; 620; 631 and 728-738, or a fragment or variant of any of these sequences; and/or c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 646; 650-658; 662; 666-674; SEQ ID NO: 678; 682-690; 694; 698 705; 707; 710 and 713, or a fragment or variant of any of these sequences; and/or d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 23; 78; 89; 100; 111; 122; 133; 599; 610 and 621, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 24; 79; 90; 101; 112; 123; 134; 600; 611 and 622, or a fragment or variant of any of these sequences. 52. The use of isRNA according to any one of paragraphs. 16-51, where at least one coding RNA contains a 5' cap structure. 53. The use of isRNA according to any one of paragraphs. 16-52, where at least one coding RNA contains a 5'-UTR element and/or a 3'-UTR element. 54. The use of isRNA according to any one of paragraphs. 16-53, wherein at least one coding RNA contains a poly(A) sequence and/or a poly(C) sequence. 55. The use of isRNA according to any one of paragraphs. 16-54, wherein at least one coding RNA contains a stem-loop histone structure sequence. 56. The use of isRNA according to any one of paragraphs. 16-55, where at least one coding RNA contains a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 146-151; 451-456; 157-162; 168-173; 179-184; 190-195; 201-206; 212-217; 223-228; 234-239; 245-250; 256-261 and 267-272, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 153; 458; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263, 274; 992 and 598, or a fragment or variant of any of the indicated sequences, b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 459; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264, 275 and 596, or a fragment or variant of any of the indicated sequences, c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 594; 595; 860-925, or a fragment or variant of any of the indicated sequences, and/or d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 144; 449; 155; 166; 177; 188; 199; 210; 221; 232; 243; 254 and 265, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 145; 450; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266 and 597, or a fragment or variant of any of these sequences. 57. The use of isRNA according to any one of paragraphs. 16-56, where together with at least three coding RNAs, where the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992; 458 and 598, or a fragment or variant of any of the indicated sequences, the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275; 459 and 596, or a fragment or variant of any of the indicated sequences, and the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 920-922 or 923-925, or a fragment or variant of any of these sequences, and optionally the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266; 450 and 597, or a fragment or variant of any of these sequences. 58. The use of isRNA according to any one of paragraphs. 16-57 together with at least four coding RNAs, where the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 153; 164; 175; 186; 197; 208; 219; 230; 241; 252; 263; 274; 992; 458 and 598, or a fragment or variant of any of the indicated sequences, the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 154; 165; 176; 187; 198; 209; 220; 231; 242; 253; 264; 275; 459 and 596, or a fragment or variant of any of the indicated sequences, the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NOs: 594 and 860-874, or a fragment, or a variant of any of these sequences, the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NOs: 595 and 890-904, or a fragment or variant of any of these sequences, and optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 145; 156; 167; 178; 189; 200; 211; 222; 233; 244; 255; 266; 450 and 597, or a fragment or variant of any of these sequences. 59. The use of isRNA according to any one of paragraphs. 16-58, where at least one coding RNA contains: a) a nucleotide sequence selected from the group consisting of SEQ ID NO: 278-283; 289-294; 300-305; 311-316; 322-327; 333-338; 344-349; 355-360; 366-371; 377-382; 388-393; 399-404 and 462-467, or a fragment or variant of any of these sequences, preferably selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of the indicated sequences, b) a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment, or a variant of any of the indicated sequences, c) a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-955, or a fragment or variant of any of the indicated nucleotide sequences, and a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-985, or a fragment or variant of any of the indicated nucleotide sequences, or a nucleotide sequence selected from the group consisting of SEQ ID NO: 986-991, or a fragment or variant of any of the indicated nucleotide sequences, and/or d) optionally a nucleotide sequence selected from the group consisting of SEQ ID NO: 276; 287; 298; 309; 320; 331; 342; 353; 364; 375; 386; 460 and 397, or a fragment or variant of any of these sequences, preferably selected from the group which consists of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 461; 387 and 398, or a fragment or variant of any of these sequences. 60. The use of isRNA according to any one of paragraphs. 16-59 together with at least four coding RNAs, where the first coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 285; 296; 307; 318; 329; 340; 351; 362; 373; 384; 395; 406; 430; 469 and 992, or a fragment or variant of any of the indicated sequences, the second coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 286; 297; 308; 319; 330; 341; 352; 363; 374; 385; 396; 470 and 407, or a fragment, or a variant of any of the indicated sequences, the third coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 926-940, or a fragment or variant of any of the indicated sequences, the fourth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 956-970, or a fragment or variant of any of the indicated sequences, and optionally, the fifth coding RNA contains a nucleotide sequence selected from the group consisting of SEQ ID NO: 277; 288; 299; 310; 321; 332; 343; 354; 365; 376; 387; 461 and 398, or a fragment or variant of any of these sequences. 61. The use of isRNA according to any one of paragraphs. 16-60 complexed with one or more cationic or polycationic compounds and at least one coding RNA, preferably mRNA, as free RNA or complexed with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes. 62. The use of isRNA according to any one of paragraphs. 1-61 in conjunction with chemotherapy, radiation therapy and/or surgery. 63. A pharmaceutical composition for the treatment of a tumor or cancer, preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T α-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the neoplastic or cancerous disease is advanced and/or resistant to standard therapy, containing an immunostimulatory RNA (isRNA) that contains a nucleotide the sequence shown in SEQ ID NO: 433, and a pharmaceutically acceptable carrier and/or excipient. 64. The pharmaceutical composition according to claim 63, which contains at least one additional pharmaceutically active ingredient, as defined in any of paragraphs. 9-57. 65. A kit for the treatment of a neoplastic or cancerous disease, preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T- cellular lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the tumor or cancer is advanced and/or resistant to standard therapy, containing an isRNA that contains the nucleotide sequence shown in SEQ ID NO: 433, or a pharmaceutical composition as defined in any of paragraphs. 63, 64, and technical instructions with information about the introduction and administered doses when injected into the tumor. 66. A method of treating or preventing a disorder selected from the group consisting of a neoplastic or cancerous disease, preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of the mycotic fungoid subtype, and vulvar squamous cell carcinoma (VSCC), where the tumor or cancer is advanced and/or resistant to standard therapy, where the method includes introducing into the tumor of an individual who needs it, an effective amount of isRNA, which contains the nucleotide sequence presented in SEQ ID NO: 433, a pharmaceutical composition according to any one of paragraphs. 63, 64 or set according to item 65.

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